[Effect of jiaotai pill on pancreatic fat accumulation and islet cell apoptosis in rats with type 2 diabetes].

PubMed

Zou, Xin; Liu, De-Liang; Lu, Fu-Er; Dong, Hui; Xu, Li-Jun; Luo, Yun-Huan; Wang, Kai-Fu

2014-06-01

In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.

Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

PubMed Central

Kelly, Karen B.; Kennelly, John P.; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

2016-01-01

Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

Influence of muscle fiber type composition on early fat accumulation under high-fat diet challenge.

PubMed

Hua, Ning; Takahashi, Hirokazu; Yee, Grace M; Kitajima, Yoichiro; Katagiri, Sayaka; Kojima, Motoyasu; Anzai, Keizo; Eguchi, Yuichiro; Hamilton, James A

2017-01-01

To investigate whether differences in muscle fiber types affect early-stage fat accumulation, under high fat diet challenge in mice. Twelve healthy male C57BL/6 mice experienced with short-term (6 weeks) diet treatment for the evaluation of early pattern changes in muscular fat. The mice were randomly divided into two groups: high fat diet (n = 8) and normal control diet (n = 4). Extra- and intra-myocellular lipid (EMCL and IMCL) in lumbar muscles (type I fiber predominant) and tibialis anterior (TA) muscle (type II fiber predominant) were determined using magnetic resonance spectroscopy (MRS). Correlation of EMCL, IMCL and their ratio between TA and lumbar muscles was evaluated. EMCL increased greatly in both muscle types after high fat diet. IMCL in TA and lumbar muscles increased to a much lower extent, with a slightly greater increase in TA muscles. EMCLs in the 2 muscles were positively correlated (r = 0.84, p = 0.01), but IMCLs showed a negative relationship (r = -0.84, p = 0.01). In lumbar muscles, high fat diet significantly decreased type I fiber while it increased type II fiber (all p≤0.001). In TA muscle, there was no significant fiber type shifting (p>0.05). Under short-time high fat diet challenge, lipid tends to initially accumulate extra-cellularly. In addition, compared to type II dominant muscle, Type I dominant muscle was less susceptible to IMCL accumulation but more to fiber type shifting. These phenomena might reflect compensative responses of skeletal muscle to dietary lipid overload in order to regulate metabolic homeostasis.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.

PubMed

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-04-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.

Coconut oil enhances tomato carotenoid tissue accumulation compared to safflower oil in the Mongolian gerbil ( Meriones unguiculatus ).

PubMed

Conlon, Lauren E; King, Ryan D; Moran, Nancy E; Erdman, John W

2012-08-29

Evidence suggests that monounsaturated and polyunsaturated fats facilitate greater absorption of carotenoids than saturated fats. However, the comparison of consuming a polyunsaturated fat source versus a saturated fat source on tomato carotenoid bioaccumulation has not been examined. The goal of this study was to determine the influence of coconut oil and safflower oil on tomato carotenoid tissue accumulation in Mongolian gerbils ( Meriones unguiculatus ) fed a 20% fat diet. Coconut oil feeding increased carotenoid concentrations among many compartments including total carotenoids in the serum (p = 0.0003), adrenal glandular phytoene (p = 0.04), hepatic phytofluene (p = 0.0001), testicular all-trans-lycopene (p = 0.01), and cis-lycopene (p = 0.006) in the prostate-seminal vesicle complex compared to safflower oil. Safflower oil-fed gerbils had greater splenic lycopene concentrations (p = 0.006) compared to coconut oil-fed gerbils. Coconut oil feeding increased serum cholesterol (p = 0.0001) and decreased hepatic cholesterol (p = 0.0003) compared to safflower oil. In summary, coconut oil enhanced tissue uptake of tomato carotenoids to a greater degree than safflower oil. These results may have been due to the large proportion of medium-chain fatty acids in coconut oil, which might have caused a shift in cholesterol flux to favor extrahepatic carotenoid tissue deposition.

Femoral adipose tissue may accumulate the fat that has been recycled as VLDL and nonesterified fatty acids.

PubMed

McQuaid, Siobhán E; Humphreys, Sandy M; Hodson, Leanne; Fielding, Barbara A; Karpe, Fredrik; Frayn, Keith N

2010-10-01

Gluteo-femoral, in contrast to abdominal, fat accumulation appears protective against diabetes and cardiovascular disease. Our objective was to test the hypothesis that this reflects differences in the ability of the two depots to sequester fatty acids, with gluteo-femoral fat acting as a longer-term "sink." A total of 12 healthy volunteers were studied after an overnight fast and after ingestion of a mixed meal. Blood samples were taken from veins draining subcutaneous femoral and abdominal fat and compared with arterialized blood samples. Stable isotope-labeled fatty acids were used to trace specific lipid fractions. In 36 subjects, adipose tissue blood flow in the two depots was monitored with (133)Xe. Blood flow increased in response to the meal in both depots, and these responses were correlated (r(s) = 0.44, P < 0.01). Nonesterified fatty acid (NEFA) release was suppressed after the meal in both depots; it was lower in femoral fat than in abdominal fat (P < 0.01). Plasma triacylglycerol (TG) extraction by femoral fat was also lower than that by abdominal fat (P = 0.05). Isotopic tracers showed that the difference was in chylomicron-TG extraction. VLDL-TG extraction and direct NEFA uptake were similar in the two depots. Femoral fat shows lower metabolic fluxes than subcutaneous abdominal fat, but differs in its relative preference for extracting fatty acids directly from the plasma NEFA and VLDL-TG pools compared with chylomicron-TG.

Femoral Adipose Tissue May Accumulate the Fat That Has Been Recycled as VLDL and Nonesterified Fatty Acids

PubMed Central

McQuaid, Siobhán E.; Humphreys, Sandy M.; Hodson, Leanne; Fielding, Barbara A.; Karpe, Fredrik; Frayn, Keith N.

2010-01-01

OBJECTIVE Gluteo-femoral, in contrast to abdominal, fat accumulation appears protective against diabetes and cardiovascular disease. Our objective was to test the hypothesis that this reflects differences in the ability of the two depots to sequester fatty acids, with gluteo-femoral fat acting as a longer-term “sink.” RESEARCH DESIGN AND METHODS A total of 12 healthy volunteers were studied after an overnight fast and after ingestion of a mixed meal. Blood samples were taken from veins draining subcutaneous femoral and abdominal fat and compared with arterialized blood samples. Stable isotope-labeled fatty acids were used to trace specific lipid fractions. In 36 subjects, adipose tissue blood flow in the two depots was monitored with 133Xe. RESULTS Blood flow increased in response to the meal in both depots, and these responses were correlated (rs = 0.44, P < 0.01). Nonesterified fatty acid (NEFA) release was suppressed after the meal in both depots; it was lower in femoral fat than in abdominal fat (P < 0.01). Plasma triacylglycerol (TG) extraction by femoral fat was also lower than that by abdominal fat (P = 0.05). Isotopic tracers showed that the difference was in chylomicron-TG extraction. VLDL-TG extraction and direct NEFA uptake were similar in the two depots. CONCLUSIONS Femoral fat shows lower metabolic fluxes than subcutaneous abdominal fat, but differs in its relative preference for extracting fatty acids directly from the plasma NEFA and VLDL-TG pools compared with chylomicron-TG. PMID:20682685

Fatty acid profiles and adipogenic gene expression of various fat depots in Japanese Black and Holstein steers.

PubMed

Shirouchi, Bungo; Albrecht, Elke; Nuernberg, Gerd; Maak, Steffen; Olavanh, Samadmanivong; Nakamura, Yoshinori; Sato, Masao; Gotoh, Takafumi; Nuernberg, Karin

2014-01-01

Objective of the study was to assess the breed effect on fatty acid (FA) composition of different adipose tissues and on mRNA expression of genes involved in adipogenesis and fat metabolism. Japanese Black (JB) and Holstein (HS) steers were kept under equivalent conditions with high energy intake resulting in large differences in intramuscular fat (IMF) accumulation in longissimus muscle (LM). The relative FA composition of muscle, intermuscular fat, visceral fat, and perirenal fat was comparable between JB and HS steers. Circulating fatty acids were also similar in both breeds. Most relevant breed effects were identified in IMF, underlining the uniqueness of this adipose tissue site. JB steers had more monounsaturated FA and less saturated FA. Perilipin 1 and adipose differentiation-related protein (ADFP) mRNA levels were higher in IMF of JB. The results suggest advanced maturity of IMF cells in JB and altered local conditions in muscle influencing IMF accumulation and composition. © 2013.

The increase in fat content in the warm-acclimated striped hamsters is associated with the down-regulated metabolic thermogenesis.

PubMed

Tan, Song; Wen, Jing; Shi, Lu-Lu; Wang, Chun-Ming; Wang, Gui-Ying; Zhao, Zhi-Jun

2016-11-01

It has been well known that metabolic thermogenesis plays an important role in the thermoregulation of small mammals under different temperatures, while its role in fat accumulation is far from clear. In the present study, several physiological, hormonal, and biochemical measures indicative of metabolic thermogenesis were measured in the weaning striped hamsters after acclimated to a warm condition (30°C) for 1, 3 and 4months. The warm-acclimated groups significantly decreased energy intake, and simultaneously decreased nonshivering thermogenesis compared to those housed at 21°C. Body fat content increased by 29.9%, 22.1% and 19.6% in the hamsters acclimated to 1, 3 or 4months, respectively relative to their counterparts maintain at 21°C (P<0.05). The cytochrome c oxidase (COX) activity of brain, liver, heart and skeletal muscle, and the ratio of serum tri-iodothyronine to thyroxine significantly decreased in warm-acclimated groups compared with 21°C group. COX activity and uncoupling protein 1 (UCP1) mRNA expression of brown adipose tissue (BAT) were significantly down-regulated under the warm conditions. COX activity of BAT, liver, heart and muscle were significantly negatively correlated with body fat content, and the correlation between UCP1 expression and body fat content tended to be negative. These findings suggest that the decrease in the energy spent on metabolic thermogenesis plays an important role in the fat accumulation. The attenuation of COX and UCP1-based BAT activity may be involved in body fat accumulation in animals under warm conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation

PubMed Central

Li, Chang-Jun; Cheng, Peng; Liang, Meng-Ke; Chen, Yu-Si; Lu, Qiong; Wang, Jin-Yu; Xia, Zhu-Ying; Zhou, Hou-De; Cao, Xu; Xie, Hui; Liao, Er-Yuan; Luo, Xiang-Hang

2015-01-01

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra–bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss. PMID:25751060

The Influence of Dietary Fat on Liver Fat Accumulation

PubMed Central

Green, Charlotte J.; Hodson, Leanne

2014-01-01

Obesity is a known risk factor for the development of non-alcoholic fatty liver disease (NAFLD); however, it has been suggested that dietary fat, both amount and composition, may play a pivotal role in its development, independent of body fatness. Studies that have investigated the role of dietary fat on liver fat accumulation are reasonably sparse. We review here the available work that has investigated the impact of dietary fat: amount, composition and frequency, on liver fat accumulation in human observational and intervention studies. Overall, it would seem that total calorie consumption, rather than dietary fat composition, is an important factor in the development of fatty liver disease in humans. PMID:25389901

Milk processing quality of suckled/milked goats: effects of milk accumulation interval and milking regime.

PubMed

Högberg, M; Dahlborn, K; Hydbring-Sandberg, E; Hartmann, E; Andrén, A

2016-05-01

Milk with a high concentration of fat and casein is required for cheese production, and these components have a major impact for both quality and yield of the curd. Recent observations have shown that suckling can elevate milk fat concentration in goats and our aim was therefore to check the hypothesis that animal welfare and cheese-processing properties of goat milk could be optimised by appropriate management of suckled/milked goats. Twelve Swedish dairy goats were kept together with one kid each in 4 different mixed management-systems (milking combined with partial suckling) in a cross-over design. Two milk accumulation intervals were tested; Short = dams and kids were together for 16 h (T16) and Long = ; dams and kids were together for 8 h (T8 h). In addition, two milking regimes were used; Suckled Before Milking = S and Milked Before Suckling = M. Milk accumulation interval referred to how long dams and kids were separated. The milk yield available for processing (milk offtake), was weighed and analysed from each milking occasion and the suckled milk yield was estimated by a weigh-suckle-weigh method (WSW) in combination with observing the suckling behaviour during the free suckling periods. Milking managements, such as 'suckling before milking (S)', increased milk fat concentration compared to milking before suckling (M) and 'Short accumulation treatments (T16)' gave higher milk fat, casein concentration and individual curd yield (%) compared to the 'Long accumulation treatment (T8)'. The total individual curd yield (g) was the same despite treatment, but the animal welfare was most likely higher in T16 where dams and kids spent more time together.

Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Son, Kuk Hui; Son, Myeongjoo; Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon

Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneousmore » and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. - Highlights: • The age-related AGE-albumin accumulation and S100β were more prominent in visceral than subcutaneous fat. • The age-related RAGE expression were more prominent in visceral than subcutaneous fat. • The inflammatory signal pathway were more activated in aged animal visceral than subcutaneous fat. • The results suggested visceral fat is involved in inflammation-induced diseases in the elderly.« less

Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets

PubMed Central

Shin, Sunhye

2018-01-01

Dietary fatty acids play important roles in the regulation of fat accumulation or metabolic phenotype of adipocytes, either as brown or beige fat. However, a systematic comparison of effects of diets with different composition of 18-C fatty acids on browning/beiging phenotype has not been done. In this study, we compared the effects of different dietary fats, rich in specific 18-carbon fatty acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON) or high-fat diets (HFD) containing 25% kcal from lard and 20% kcal fat from shea butter (stearic acid-rich fat; SHB), olive oil (oleic acid-rich oil; OO), safflower oil (linoleic acid-rich oil; SFO), or soybean oil (mixed oleic, linoleic, and α-linolenic acids; SBO) ad libitum for 12 weeks, with or without a terminal 4-h norepinephrine (NE) treatment. When compared to SHB, feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had the highest thermogenesis level, which resulted in lower body fat accumulation and improved glucose and lipid metabolism. Feeding SFO downregulated expression of lipid oxidation-related genes and upregulated expression of lipogenic genes, perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1 expression in both subcutaneous and epididymal white adipose tissue, and suppressed NE-induced Pgc1a expression in brown adipose tissue. These results suggest that the position of double bonds in dietary fatty acids, as well as the quantity of dietary fat, may have a significant effect on the regulation of oxidative and thermogenic conditions in vivo. PMID:29473916

Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets.

PubMed

Shin, Sunhye; Ajuwon, Kolapo M

2018-02-23

Dietary fatty acids play important roles in the regulation of fat accumulation or metabolic phenotype of adipocytes, either as brown or beige fat. However, a systematic comparison of effects of diets with different composition of 18-C fatty acids on browning/beiging phenotype has not been done. In this study, we compared the effects of different dietary fats, rich in specific 18-carbon fatty acids, on thermogenesis and lipid metabolism. Male C57BL/6 mice were fed a control diet containing 5.6% kcal fat from lard and 4.4% kcal fat from soybean oil (CON) or high-fat diets (HFD) containing 25% kcal from lard and 20% kcal fat from shea butter (stearic acid-rich fat; SHB), olive oil (oleic acid-rich oil; OO), safflower oil (linoleic acid-rich oil; SFO), or soybean oil (mixed oleic, linoleic, and α-linolenic acids; SBO) ad libitum for 12 weeks, with or without a terminal 4-h norepinephrine (NE) treatment. When compared to SHB, feeding OO, SFO, and SBO resulted in lower body weight gain. The OO fed group had the highest thermogenesis level, which resulted in lower body fat accumulation and improved glucose and lipid metabolism. Feeding SFO downregulated expression of lipid oxidation-related genes and upregulated expression of lipogenic genes, perhaps due to its high n-6:n-3 ratio. In general, HFD-feeding downregulated Ucp1 expression in both subcutaneous and epididymal white adipose tissue, and suppressed NE-induced Pgc1a expression in brown adipose tissue. These results suggest that the position of double bonds in dietary fatty acids, as well as the quantity of dietary fat, may have a significant effect on the regulation of oxidative and thermogenic conditions in vivo.

Blood orange juice inhibits fat accumulation in mice.

PubMed

Titta, L; Trinei, M; Stendardo, M; Berniakovich, I; Petroni, K; Tonelli, C; Riso, P; Porrini, M; Minucci, S; Pelicci, P G; Rapisarda, P; Reforgiato Recupero, G; Giorgio, M

2010-03-01

To analyze the effect of the juice obtained from two varieties of sweet orange (Citrus sinensis L. Osbeck), Moro (a blood orange) and Navelina (a blond orange), on fat accumulation in mice fed a standard or a high-fat diet (HFD). Obesity was induced in male C57/Bl6 mice by feeding a HFD. Moro and Navelina juices were provided instead of water. The effect of an anthocyanin-enriched extract from Moro oranges or purified cyanidin-3-glucoside (C3G) was also analyzed. Body weight and food intake were measured regularly over a 12-week period. The adipose pads were weighted and analyzed histologically; total RNA was also isolated for microarray analysis. Dietary supplementation of Moro juice, but not Navelina juice significantly reduced body weight gain and fat accumulation regardless of the increased energy intake because of sugar content. Furthermore, mice drinking Moro juice were resistant to HFD-induced obesity with no alterations in food intake. Only the anthocyanin extract, but not the purified C3G, slightly affected fat accumulation. High-throughput gene expression analysis of fat tissues confirmed that Moro juice could entirely rescue the high fat-induced transcriptional reprogramming. Moro juice anti-obesity effect on fat accumulation cannot be explained only by its anthocyanin content. Our findings suggest that multiple components present in the Moro orange juice might act synergistically to inhibit fat accumulation.

Effects of Visceral Fat Accumulation Awareness on a Web-Based Weight-Loss Program: Japanese Study of Visceral Adiposity and Lifestyle Information-Utilization and Evaluation (J-VALUE).

PubMed

Sakane, Naoki; Dohi, Seitaro; Sakata, Koichi; Hagiwara, Shin-Ichi; Morimoto, Toshihisa; Uchida, Takanobu; Katashima, Mitsuhiro; Yanagisawa, Yoshiko; Yasumasu, Takeshi; Study Group, J-Value

2013-01-01

A reduction of visceral fat is important for improvement of metabolic risk. This study was designed to compare the effects of a web-based program alone or together with measurement and self-awareness of accumulated visceral fat in Japanese workers. A new noninvasive device to measure visceral fat accumulation was introduced, and efficacy on weight-loss and improvement of healthy behaviors were examined. This study was conducted according to Helsinki declaration and approved by the ethical committee of Japan Hospital Organization, National Kyoto Hospital. Two-hundred and sixteen overweight and obese males with BMI of more than 23 participated from 8 healthcare offices of 3 Japanese private companies. Subjects were randomly allocated into control group, Web-based weight-loss program (Web), or Web + Visceral fat measurement group (Web + VFA). Eighty-one percent of participants completed the study. Reductions of body weight, waist circumference, and BMI were the largest in Web + VFA group, and the differences between groups were significant by ANOVA. Improvements of healthy behaviors were the largest in Web + VFA group, and the differences of healthy eating improvement scores between Web + VFA and control groups were significant. Our findings suggest that measurement and awareness of visceral fat are effective in weight reduction in overweight and obese males in the workplace.

Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis

PubMed Central

Smagris, Eriks; BasuRay, Soumik; Li, John; Huang, Yongcheng; Lai, Ka-man V; Gromada, Jesper; Cohen, Jonathan C; Hobbs, Helen H

2015-01-01

A sequence polymorphism (rs738409, I148M) in patatin-like phospholipid domain containing protein 3 (PNPLA3) is strongly associated with nonalcoholic fatty liver disease (NAFLD), but the mechanistic basis for this association remains enigmatic. Neither ablation nor overexpression of wild-type PNPLA3 affects liver fat content in mice, whereas hepatic overexpression of the human 148M transgene causes steatosis. To determine whether the 148M allele causes fat accumulation in the liver when expressed at physiological levels, we introduced a methionine codon at position 148 of the mouse Pnpla3 gene. Knockin mice had normal levels of hepatic fat on a chow diet, but when challenged with a high-sucrose diet their liver fat levels increased 2 to 3-fold compared to wild-type littermates without any associated changes in glucose homeostasis. The increased liver fat in the knockin mice was accompanied by a 40-fold increase in PNPLA3 on hepatic lipid droplets, with no increase in hepatic PNPLA3 messenger RNA (mRNA). Similar results were obtained when the catalytic dyad of PNPLA3 was inactivated by substituting the catalytic serine with alanine (S47A). Conclusion: These data provide the first direct evidence that physiological expression of PNPLA3 148M variant causes NAFLD, and that the accumulation of catalytically inactive PNPLA3 on the surfaces of lipid droplets is associated with the accumulation of TG in the liver. (Hepatology 2015;61:108–118) PMID:24917523

Age-related accumulation of advanced glycation end-products-albumin, S100β, and the expressions of advanced glycation end product receptor differ in visceral and subcutaneous fat.

PubMed

Son, Kuk Hui; Son, Myeongjoo; Ahn, Hyosang; Oh, Seyeon; Yum, Yoonji; Choi, Chang Hu; Park, Kook Yang; Byun, Kyunghee

2016-08-19

Visceral fat induces more inflammation by activating macrophages than subcutaneous fat, and inflammation is an underlying feature of the pathogeneses of various diseases, including cardiovascular disease and diabetes. Advanced glycation end products (AGEs), S100β, and their receptors, the receptor for advanced glycation end products (RAGE), lead to macrophage activation. However, little information is available regarding the differential accumulations of AGE-albumin (serum albumin modified by AGEs), S100β, or expressions of RAGE in different adipocyte types in fat tissues. In this study, the authors investigated whether age-related AGE-albumin accumulations S100β level, and RAGE expressions differ in subcutaneous and visceral fat tissues. Subcutaneous and visceral fat were harvested from 3- and 28-week-old rats. Macrophage activation was confirmed by Iba1 staining, and AGE-albumin accumulations and RAGE expressions were assessed by confocal microscopy. S100β were analyzed by immunoblotting. It was found that activated macrophage infiltration, AGE-albumin accumulation, and S100β in visceral fat was significantly greater in 28-week-old rats than in 3-week-old rats, but similar in subcutaneous fat. The expression of RAGE in visceral fat was much greater in 28-week-old rats, but its expression in subcutaneous fat was similar in 3- and 28-week-old rats. Furthermore, inflammatory signal pathways (NFκB, TNF-α) and proliferation pathways (FAK) in visceral fat were more activated in 28-week-old rats. These results imply that age-related AGE-albumin accumulation, S100β, and RAGE expression are more prominent in visceral than in subcutaneous fat, suggesting that visceral fat is involved in the pathogenesis of inflammation-induced diseases in the elderly. Copyright © 2016 Elsevier Inc. All rights reserved.

Maternal fat supplementation during late pregnancy and lactation influences the development of hepatic steatosis in offspring depending on the fat source.

PubMed

Llopis, Marina; Sánchez, Juana; Priego, Teresa; Palou, Andreu; Picó, Catalina

2014-02-19

In this study we investigate the effects of maternal supplementation with different fat sources (margarine, olive oil, or butter) during pregnancy and lactation on offspring metabolic health in adulthood and under obesogenic conditions. In adulthood and under a high-fat (HF) diet, the margarine group showed lower body fat content than the butter group and was also protected against the increase in hepatic lipid content occurring in the other groups, whereas the butter group showed signs of more advanced hepatic steatosis. Under an HF diet, all fat-supplemented animals showed greater hepatic expression levels of fatty acid oxidation-related genes compared to their normal-fat diet counterparts, with higher levels in the margarine group. Under these conditions, the margarine group also showed higher white adipose tissue mRNA levels of adipogenic genes than the other fat-supplemented groups. Thus, compared to other fat sources, offspring from margarine-supplemented dams seem to be more protected from metabolic alterations related to the HF diet, particularly concerning hepatic fat accumulation.

Gender differences in fat distribution and inflammatory markers among Arabs.

PubMed

Farooq, Abdulaziz; Knez, Wade L; Knez, Kelly; Al-Noaimi, Asma; Grantham, Justin; Mohamed-Ali, Vidya

2013-01-01

Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS). To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n = 58) were matched for age, gender, and body mass index. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. Women had more adipose tissue in the total abdominal (P = 0.04) and abdominal subcutaneous (P = 0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men.

Gender Differences in Fat Distribution and Inflammatory Markers among Arabs

PubMed Central

Farooq, Abdulaziz; Knez, Wade L.; Knez, Kelly; Al-Noaimi, Asma; Grantham, Justin; Mohamed-Ali, Vidya

2013-01-01

Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS). Objective. To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n = 58) were matched for age, gender, and body mass index. Methods. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. Results. Women had more adipose tissue in the total abdominal (P = 0.04) and abdominal subcutaneous (P = 0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. Conclusion. In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men. PMID:24227909

Usefulness of chemical-shift MRI in discriminating increased liver echogenicity in glycogenosis.

PubMed

Pozzato, C; Dall'asta, C; Radaelli, G; Torcoletti, M; Formenti, A; Riva, E; Cornalba, G; Pontiroli, A E

2007-11-01

Glycogen storage diseases are inherited defects which cause accumulation of glycogen in the tissues. Hepatic steatosis is defined as accumulation of fat within hepatocytes. On sonography, liver shows increased echogenicity both in glycogen storage diseases and steatosis. Liver hyperechogenicity in glycogen storage diseases may depend on accumulation of glycogen and/or fat. Chemical-shift magnetic resonance imaging can discriminate tissues only containing water from those containing both fat and water. The primary aim of the present study was to evaluate the usefulness of liver chemical-shift magnetic resonance imaging for detecting liver steatosis in patients with metabolic impairment due to glycogen storage diseases. Twelve patients with type I (n=8) or type III (n=4) glycogen storage diseases were studied and compared to 12 obese-overweight subjects with known liver steatosis. As control group 12 lean normal voluntary subjects were recruited. Liver was evaluated by sonography and chemical-shift magnetic resonance imaging to calculate hepatic fat fraction. A significant difference in echogenicity between patients with glycogen storage diseases and normal subjects was observed (p<0.05), while this difference was not present between overweight-obese and glycogen storage diseases patients. On the contrary, fat fraction was similar between glycogen storage diseases patients and normal subjects and different between glycogen storage diseases patients and overweight-obese (p<0.05). The present data suggest that chemical-shift magnetic resonance imaging may exclude fat deposition as a cause of liver hyperechogenicity in subjects with glycogen storage diseases.

Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis.

PubMed

Smagris, Eriks; BasuRay, Soumik; Li, John; Huang, Yongcheng; Lai, Ka-man V; Gromada, Jesper; Cohen, Jonathan C; Hobbs, Helen H

2015-01-01

A sequence polymorphism (rs738409, I148M) in patatin-like phospholipid domain containing protein 3 (PNPLA3) is strongly associated with nonalcoholic fatty liver disease (NAFLD), but the mechanistic basis for this association remains enigmatic. Neither ablation nor overexpression of wild-type PNPLA3 affects liver fat content in mice, whereas hepatic overexpression of the human 148M transgene causes steatosis. To determine whether the 148M allele causes fat accumulation in the liver when expressed at physiological levels, we introduced a methionine codon at position 148 of the mouse Pnpla3 gene. Knockin mice had normal levels of hepatic fat on a chow diet, but when challenged with a high-sucrose diet their liver fat levels increased 2 to 3-fold compared to wild-type littermates without any associated changes in glucose homeostasis. The increased liver fat in the knockin mice was accompanied by a 40-fold increase in PNPLA3 on hepatic lipid droplets, with no increase in hepatic PNPLA3 messenger RNA (mRNA). Similar results were obtained when the catalytic dyad of PNPLA3 was inactivated by substituting the catalytic serine with alanine (S47A). These data provide the first direct evidence that physiological expression of PNPLA3 148M variant causes NAFLD, and that the accumulation of catalytically inactive PNPLA3 on the surfaces of lipid droplets is associated with the accumulation of TG in the liver. © 2014 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

Anthocyanin-rich Phytochemicals from Aronia Fruits Inhibit Visceral Fat Accumulation and Hyperglycemia in High-fat Diet-induced Dietary Obese Rats.

PubMed

Takahashi, Azusa; Shimizu, Hisae; Okazaki, Yukako; Sakaguchi, Hirohide; Taira, Toshio; Suzuki, Takashi; Chiji, Hideyuki

2015-01-01

Aronia fruits (chokeberry: Aronia melanocarpa E.) containing phenolic phytochemicals, such as cyanidin 3-glycosides and chlorogenic acid, have attracted considerable attention because of their potential human health benefits in humans including antioxidant activities and ability to improved vision. In the present study, the effects of anthocyanin-rich phytochemicals from aronia fruits (aronia phytochemicals) on visceral fat accumulation and fasting hyperglycemia were examined in rats fed a high-fat diet (Experiment 1). Total visceral fat mass was significantly lower in rats fed aronia phytochemicals than that in both the control group and bilberry phytochemicals-supplemented rats (p < 0.05). Moreover, perirenal and epididymal adipose tissue mass in rats fed aronia phytochemicals was significantly lower than that in both the control and bilberry phytochemicals group. Additionally, the mesenteric adipose tissue mass in aronia phytochemicals-fed rats was significantly low (p < 0.05). Furthermore, the fasting blood glucose levels significantly decreased in rats fed aronia phytochemicals for 4 weeks compared to that in the control rats (p < 0.05). Therefore, we investigated the effects of phytochemicals on postprandial hyperlipidemia after corn oil loading in rats, pancreatic lipase activity in vitro, and the plasma glycemic response after sucrose loading in order to elucidate the preventive factor of aronia phytochemical on visceral fat accumulation. In the oral corn oil tolerance tests (Experiment 2), aronia phytochemicals significantly inhibited the increases in plasma triglyceride levels, with a half-maximal inhibitory concentration (IC(50)) of 1.50 mg/mL. However, the inhibitory activity was similar to that of bilberry and tea catechins. In the sucrose tolerance tests (Experiment 3), aronia phytochemicals also significantly inhibited the increases in blood glucose levels that were observed in the control animals (p < 0.05). These results suggest that anthocyanin-rich phytochemicals in aronia fruits suppress visceral fat accumulation and hyperglycemia by inhibiting pancreatic lipase activity and/or intestinal lipid absorption.

Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat Accumulation in High-Fat Diet-Fed Mice.

PubMed

Tamura, Shohei; Honda, Kazuhisa; Morinaga, Ryoji; Saneyasu, Takaoki; Kamisoyama, Hiroshi

2017-01-01

The combination of diet and exercise is the first choice for the treatment of obesity and metabolic syndrome. We previously reported that enzymatically synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats. However, the effect of the combination of ESG and exercise on abdominal fat accumulation has not yet been investigated. Our goal in this study was therefore to evaluate the effects of dietary ESG and its combination with exercise on abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25 m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG and exercise significantly reduced the weights of abdominal adipose tissues. In addition, the combination of ESG and exercise significantly suppressed abdominal fat accumulation, suggesting that ESG and exercise showed an additive effect. Exercise significantly increased the mRNA levels of lipid metabolism-related genes such as lipoprotein lipase, peroxisome proliferator-activated receptor delta; factor-delta (PPARδ), carnitin palmitoyltransferase b, adipose triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle. On the other hand, dietary ESG significantly decreased the mRNA levels of PPARδ and ATGL in the gastrocnemius muscle. These results suggest that the combined treatment of ESG and exercise effectively suppresses abdominal fat accumulation in HFD-fed mice by different mechanisms.

Effects of Persian leek (Allium ampeloprasum) on hepatic lipids and the expression of proinflammatory gene in hamsters fed a high-fat/ high-cholesterol diet.

PubMed

Fatoorechi, Vahideh; Rismanchi, Marjan; Nasrollahzadeh, Javad

2016-01-01

Persian leek is one of the most widely used herbal foods among Iranians. In this study, effects of oral administration of Persian leek on plasma and liver lipids were examined in hamster. Male Syrian hamsters were randomly divided into three groups: control (standard diet), high fat control (high-fat/high-cholesterol diet), Persian leek (high-fat/high-cholesterol diet + 1% per weight of diet from dried powdered Persian leek) for 14 weeks. High fat diet increased plasma and liver lipids as compared to standard diet. Adding Persian leek to the high-fat/high-cholesterol diet resulted in no significant changes in the concentration of the plasma lipids or liver cholesterol. However, liver triglycerides (TG), plasma Alanine aminotransferase and gene expression of tumor necrosis factor- α were decreased in hamsters fed high-fat diet containing Persian leek as compared to high-fat diet only. Persian leek might be considered as a herbal food that can reduce liver TG accumulation induced by high fat diets.

Increased Epicardial Adipose Tissue Volume in HIV-Infected Men and Relationships to Body Composition and Metabolic Parameters

PubMed Central

Lo, Janet; Abbara, Suhny; Rocha-Filho, Jose A.; Shturman, Leon; Wei, Jeffrey; Grinspoon, Steven K.

2011-01-01

Summary Epicardial fat accumulation may have important clinical consequences, yet little is known regarding this depot in HIV patients. We compared epicardial fat volume in 78 HIV-infected men and 32 HIV-negative controls. Epicardial fat volume was higher in HIV than control subjects (p=0.04). In HIV patients, epicardial fat volume was strongly associated with visceral adipose tissue area (VAT)(ρ = 0.76, p<0.0001), fasting glucose (ρ = 0.41, p=0.001) and insulin (ρ = 0.44, p=0.0003). Relationships with glucose and insulin remained significant controlling for age, race, BMI, adiponectin, VAT, and antiretroviral therapy. Epicardial fat may be an important fat depot in HIV-infected patients. PMID:20588167

Deiodinase 2 expression is increased in dorsocervical fat of patients with HIV-associated lipohypertrophy syndrome.

PubMed

Torriani, Martin; Fitch, Kathleen; Stavrou, Eleni; Bredella, Miriam A; Lim, Ruth; Sass, Christina A; Cypess, Aaron M; Grinspoon, Steven

2012-04-01

The pathogenesis and function of dorsocervical sc adipose tissue (DSAT) accumulation in HIV-infected patients is not known. Previous investigations using either UCP-1 expression or positron emission tomography have been inconclusive as to whether this depot represents brown adipose tissue (BAT). We investigated DSAT gene expression, including DIO2, a deiodinase that contributes to increased thermogenesis in brown fat, and simultaneously determined [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake in lipodystrophic HIV and healthy control subjects. Thirteen HIV-infected and three non-HIV-infected men were recruited. HIV-infected subjects had evidence of significant lipodystrophy, including fat atrophy of the face, arms, and legs, and/or fat accumulation of the neck and abdomen. Subjects were cooled, followed by [¹⁸F]FDG positron emission tomography/computed tomography, fat biopsy of DSAT, and measurement of resting energy expenditure (REE). HIV-infected subjects were characterized as lipohypertrophic and lipoatrophic and compared. Mean standardized uptake value of [¹⁸F]FDG and UCP-1 expression were not significantly different in DSAT among the groups. However, lipohypertrophic subjects demonstrated increased expression of DIO2 in DSAT compared with lipoatrophic subjects (P = 0.03). Among HIV-infected patients, DIO2 expression was strongly related to REE (r = 0.78, P = 0.002) and was a predictor of REE in multivariate modeling controlling for age, TSH, and lean body mass (r² = 0.79, P = 0.008). One control subject demonstrated typical BAT in the supraclavicular area. Adipose tissue accumulating in the dorsocervical area in HIV lipodystrophy does not appear to be classical BAT. However, DIO2 expression is increased in DSAT among patients with HIV lipodystrophy, particularly those with increased visceral adiposity, and is positively associated with energy expenditure.

Increased fat deposition in injured skeletal muscle is regulated by sex-specific hormones

PubMed Central

McHale, Matthew J.; Sarwar, Zaheer U.; Cardenas, Damon P.; Porter, Laurel; Salinas, Anna S.; Michalek, Joel E.; McManus, Linda M.

2012-01-01

Sex differences in skeletal muscle regeneration are controversial; comparisons of regenerative events between sexes have not been rigorously defined in severe injury models. We comprehensively quantified inflammation and muscle regeneration between sexes and manipulated sex-specific hormones to determine effects on regeneration. Cardiotoxin injury was induced in intact, castrated and ovariectomized female and male mice; ovariectomized mice were replaced with low- or high-dose 17-β estradiol (E2) or progesterone (P4). Extent of injury was comparable between intact mice, but females were more efficient in removal of necrotic debris, despite similar tissue levels of inflammatory cells and chemokines. Myofiber size during regeneration was equivalent between intact mice and after castration or ovariectomy (OVX) but was decreased (P < 0.001) in ovariectomized mice with high-dose E2 replacement. Intermuscular adipocytes were absent in uninjured muscle, whereas adipocyte area was increased among regenerated myofibers in all groups. Interestingly, intermuscular fat was greater (P = 0.03) in intact females at day 14 compared with intact males. Furthermore, castration increased (P = 0.01) and OVX decreased adipocyte accumulation. After OVX, E2, but not P4, replacement decreased (P ≤ 0.03) fat accumulation. In conclusion, sex-dependent differences in regeneration consisted of more efficient removal of necrosis and increased fat deposition in females with similar injury, inflammation, and regenerated myofiber size; high-dose E2 decreased myofiber size and fat deposition. Adipocyte accumulation in regenerating muscle was influenced by sex-specific hormones. Recovery following muscle injury was different between males and females, and sex-specific hormones contributed to these differences, suggesting that sex-specific treatments could be beneficial after injury. PMID:22116509

fat-1 mice prevent high-fat plus high-sugar diet-induced non-alcoholic fatty liver disease.

PubMed

Guo, Xiao-Fei; Gao, Jin-Long; Li, Jiao-Mei; Li, Duo

2017-11-15

High-fat and high-sugar (HFS) diets have been suggested to play a causal role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate whether fat-1 transgenic mice with a higher tissue content of n-3 polyunsaturated fatty acids (PUFAs) could prevent HFS diet-induced NAFLD, compared with wild-type mice. The fat-1 and wild-type littermates had free access to a 15% fructose solution plus high-fat diet, a 15% glucose solution plus high-fat diet, or a 15% sucrose solution plus high-fat diet, respectively. Caloric intake, weight gain, biochemical parameters, histology, and gene and protein expression levels were measured after 8 weeks of intervention. Liquid intake in glucose- or sucrose-fed mice was about 2-fold compared with that in fructose-fed mice. The wild-type mice given glucose showed the highest total caloric intake and weight gain compared to the other groups. The serum concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and alanine transaminase (ALT) were significantly lowered in fat-1 groups compared with their paired wild-type groups. Histological analysis showed that the wild-type groups fed the HFS diets developed hepatic lipid accumulation and steatosis, compared with the fat-1 groups. The gene and protein expression levels involved in fatty acid synthesis and the toll-like receptor (TLR)-4 signaling pathway were significantly inhibited in the fat-1 groups compared with the wild-type groups. The endogenously synthesized n-3 PUFAs of the three fat-1 groups, which inhibit fatty acid synthesis and the TLR-4 signaling pathway, prevent HFS diet-induced NAFLD.

Relationship between delayed embryonic development and metabolic factors and fat deposition in fruit bat Cynopterus sphinx.

PubMed

Banerjee, Arnab; Meenakumari, K J; Krishna, Amitabh

2007-01-01

The present study was undertaken in the fruit bat Cynopterus sphinx, which breeds twice in quick succession at Varanasi, India. Its gestation period varies significantly in the two successive pregnancies of the year owing to delayed embryonic development during the first (winter) pregnancy. The primary aim of the present study was to determine the role of metabolic factors in delayed embryonic development in the fruit bat C. sphinx. Variation in bodyweight, fat deposition, oxygen (O(2)) consumption rate, basal metabolic rate (BMR), body temperature (Tb) and hepatic succinate dehydrogenase (SDH) activity, along with circulating levels of thyroid hormones (tri-iodothyronine and thyroxine), were examined as metabolic factors during the two successive pregnancies in C. sphinx. The increase in bodyweight observed in November was due to accumulation of white adipose tissue in the posterior abdominal region. A significant decline in O(2) consumption rate, BMR, Tb and SDH activity was found in early winter in November-December, which coincides closely with the period of fat accumulation and with the period of delayed embryonic development in C. sphinx. A significantly higher O(2) consumption rate, BMR, Tb and SDH activity was noted during the second pregnancy in, when embryonic development was relatively faster. Thyroid hormone levels were high during the period of embryonic delay compared with levels during the remaining months. The results of the present study suggest that the delayed embryonic development in C. sphinx during early winter may be due to a low O(2) consumption rate, BMR, Tb and SDH activity in November-December. The energy saved by suppressing embryonic development in this species may be advantageous for fat accumulation. Increased thyroid hormone levels during the early winter period might facilitate fat accumulation in C. sphinx.

Creatine supplementation prevents fatty liver in rats fed choline-deficient diet: a burden of one-carbon and fatty acid metabolism.

PubMed

Deminice, Rafael; de Castro, Gabriela Salim Ferreira; Francisco, Lucas Vieira; da Silva, Lilian Eslaine Costa Mendes; Cardoso, João Felipe Rito; Frajacomo, Fernando Tadeu Trevisan; Teodoro, Bruno Gonzaga; Dos Reis Silveira, Leonardo; Jordao, Alceu Afonso

2015-04-01

To examine the effects of creatine (Cr) supplementation on liver fat accumulation in rats fed a choline-deficient diet. Twenty-four rats were divided into 3 groups of 8 based on 4 weeks of feeding an AIN-93 control diet (C), a choline-deficient diet (CDD) or a CDD supplemented with 2% Cr. The CDD diet was AIN-93 without choline. The CDD significantly increased plasma homocysteine and TNFα concentration, as well as ALT activity. In liver, the CDD enhanced concentrations of total fat (55%), cholesterol (25%), triglycerides (87%), MDA (30%), TNFα (241%) and decreased SAM concentrations (25%) and the SAM/SAH ratio (33%). Cr supplementation prevented all these metabolic changes, except for hepatic SAM and the SAM/SAH ratio. However, no changes in PEMT gene expression or liver phosphatidylcholine levels were observed among the three experimental groups, and there were no changes in hepatic triglyceride transfer protein (MTP) mRNA level. On the contrary, Cr supplementation normalized expression of the transcription factors PPARα and PPARγ that were altered by the CDD. Further, the downstream targets and fatty acids metabolism genes, UCP2, LCAD and CPT1a, were also normalized in the Cr group as compared to CDD-fed rats. Cr supplementation prevented fat liver accumulation and hepatic injures in rats fed with a CDD for 4 weeks. Our results demonstrated that one-carbon metabolism may have a small role in mitigating hepatic fat accumulation by Cr supplementation. The modulation of key genes related to fatty acid oxidation pathway suggests a new mechanism by which Cr prevents liver fat accumulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Joint water-fat separation and deblurring for spiral imaging.

PubMed

Wang, Dinghui; Zwart, Nicholas R; Pipe, James G

2018-06-01

Most previous approaches to spiral Dixon water-fat imaging perform the water-fat separation and deblurring sequentially based on the assumption that the phase accumulation and blurring as a result of off-resonance are separable. This condition can easily be violated in regions where the B 0 inhomogeneity varies rapidly. The goal of this work is to present a novel joint water-fat separation and deblurring method for spiral imaging. The proposed approach is based on a more accurate signal model that takes into account the phase accumulation and blurring simultaneously. A conjugate gradient method is used in the image domain to reconstruct the deblurred water and fat iteratively. Spatially varying convolutions with a local convergence criterion are used to reduce the computational demand. Both simulation and high-resolution brain imaging have demonstrated that the proposed joint method consistently improves the quality of reconstructed water and fat images compared with the sequential approach, especially in regions where the field inhomogeneity changes rapidly in space. The loss of signal-to-noise-ratio as a result of deblurring is minor at optimal echo times. High-quality water-fat spiral imaging can be achieved with the proposed joint approach, provided that an accurate field map of B 0 inhomogeneity is available. Magn Reson Med 79:3218-3228, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Leisure-time physical activity and intra-abdominal fat in young adulthood: A monozygotic co-twin control study.

PubMed

Rottensteiner, Mirva; Leskinen, Tuija; Järvelä-Reijonen, Elina; Väisänen, Karoliina; Aaltonen, Sari; Kaprio, Jaakko; Kujala, Urho M

2016-05-01

To investigate differences in abdominal fat compartments between young adult monozygotic twin pairs discordant for leisure-time physical activity. Ten young adult male monozygotic twin pairs (age range 32-36 years) discordant for leisure-time physical activity during the past 3 years were systematically selected from a population-based Finnish twin cohort. Magnetic resonance image at the level of the L2-L3 intervertebral disc was used to predict intra-abdominal and subcutaneous abdominal fat masses. Dietary intake was assessed with a 4-day food diary. Inactive twins had 31% more intra-abdominal fat than their active co-twins (mean difference 0.52 kg, 95% CI 0.12 to 0.91, P = 0.016), whereas the difference in subcutaneous abdominal fat was only 13% (P = 0.21) and 3% in body mass index (P = 0.28). Intraperitoneal fat mass was 41% higher among inactive twins compared to their active co-twins (mean difference 0.41 kg, 95% CI 0.11 to 0.70, P = 0.012). Dietary intake did not differ between co-twins. A lower level of physical activity is related to greater accumulation of intra-abdominal fat among healthy adult males in their mid-30s. The findings highlight the importance of leisure-time physical activity independent of genes and diet in the prevention of intra-abdominal fat accumulation from early adulthood onward. © 2016 The Obesity Society.

Diffuse lipomatosis of the thyroid gland with papillary microcarcinoma: Report of a rare entity.

PubMed

Nandyala, Hariharanadha Sarma; Madapuram, Srinivasulu; Yadav, Megha; Katamala, Sudheer Kumar

2015-01-01

Presence of lobules of adipose tissue either focally or diffusely is very rare in the thyroid gland. Fat accumulation can be macroscopic or microscopic. Focal infiltrates of fat have been reported in conditions such as adenolipoma, intrathyroid lipoma, and encapsulated papillary carcinoma. Diffuse lipomatosis has been reported in conditions such as amyloid goitre, heterotopic fat nests, thyrolipoma and liposarcoma. The exact mechanism of fat accumulation is not known although there are many theories postulated. Investigations such as ultrasound, computed tomography scan, and magnetic resonance imaging can detect the presence of macroscopic fat in the thyroid gland. Accurate diagnosis of the type of fat accumulation is necessary because tumorous and nontumorous conditions fall into the differential diagnosis. Only nine cases of papillary carcinoma associated with lipomatosis of thyroid are reported so far. We report possibly the first case of diffuse lipomatosis of the thyroid gland with a focus of papillary microcarcinoma.

Kefir prevented excess fat accumulation in diet-induced obese mice.

PubMed

Choi, Jae-Woo; Kang, Hye Won; Lim, Won-Chul; Kim, Mi-Kyoung; Lee, In-Young; Cho, Hong-Yon

2017-05-01

Excessive body fat accumulation can result in obesity, which is a serious health concern. Kefir, a probiotic, has recently shown possible health benefits in fighting obesity. This study investigated the inhibitory effects of 0.1 and 0.2% kefir powder on fat accumulation in adipose and liver tissues of high-fat diet (HFD)-induced obese mice. Kefir reduced body weight and epididymal fat pad weight and decreased adipocyte diameters in HFD-induced obese mice. This was supported by decreased expression of genes related to adipogenesis and lipogenesis as well as reduced proinflammatory marker levels in epididymal fat. Along with reduced hepatic triacylglycerol concentrations and serum alanine transaminase and aspartate transaminase activities, genes related to lipogenesis and fatty acid oxidation were downregulated and upregulated, respectively, in liver tissue. Kefir also decreased serum triacylglycerol, total cholesterol, and low-density lipoprotein-cholesterol concentrations. Overall, kefir has the potential to prevent obesity.

A choline-deficient diet exacerbates fatty liver but attenuates insulin resistance and glucose intolerance in mice fed a high-fat diet.

PubMed

Raubenheimer, Peter J; Nyirenda, Moffat J; Walker, Brian R

2006-07-01

Liver fat accumulation is proposed to link obesity and insulin resistance. To dissect the role of liver fat in the insulin resistance of diet-induced obesity, we altered liver fat using a choline-deficient diet. C57Bl/6 mice were fed a low-fat (10% of calories) or high-fat (45% of calories) diet for 8 weeks; during the final 4 weeks, diets were either choline deficient or choline supplemented. In choline replete animals, high-fat feeding induced weight gain, elevated liver triglycerides (171%), hyperinsulinemia, and glucose intolerance. Choline deficiency did not affect body or adipose depot weights but amplified liver fat accumulation with high-fat diet (281%, P < 0.01). However, choline deficiency lowered fasting plasma insulin (from 983 +/- 175 to 433 +/- 36 pmol/l, P < 0.01) and improved glucose tolerance on a high-fat diet. In mice on 30% fat diet, choline deficiency increased liver mRNA levels of the rate-limiting enzyme in phosphatidylcholine synthesis and of enzymes involved in free fatty acid esterification, without affecting those of de novo lipogenesis or fatty acid oxidation. We conclude that liver fat accumulation per se does not cause insulin resistance during high-fat feeding and that choline deficiency may shunt potentially toxic free fatty acids toward innocuous storage triglyceride in the liver.

Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial.

PubMed

Gepner, Yftach; Shelef, Ilan; Schwarzfuchs, Dan; Cohen, Noa; Bril, Nitzan; Rein, Michal; Tsaban, Gal; Zelicha, Hila; Yaskolka Meir, Anat; Tene, Lilac; Sarusy, Benjamin; Rosen, Philip; Hoffman, Jay R; Stout, Jeffrey R; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Stampfer, Meir J; Shai, Iris

2017-01-01

Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among participants with abdominal fat, remain unclear. In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28g·day-1 of walnuts). After 6-months, the participants were re-randomized to moderate intense physical activity (PA+) or non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats. Across the 277 participants [86% men, age = 48 years, body-mass-index (BMI) = 31kg/m2, visceral fat = 33%] 86% completed the 18-m trial. At baseline, women had higher IMTG than men (3.4% vs. 2.3%, p<0.001) and increased IMTG was associated with aging and higher BMI, visceral and intermuscular fats, HbA1c%, HDL-c and leptin(p<0.05), but not with intra-hepatic fat. After 18 month of intervention and a -3 kg mean weight loss, participants significantly increased IMTG by 25%, with a distinct effect in the MED/LCPA+ group as compared to the other intervention groups (57% vs. 9.5-18.5%, p<0.05). Changes in IMTG were associated with visceral and intermuscular fat, metabolic syndrome, insulin and leptin (p<0.05 for all), however, these associations did not remain after adjustment for visceral fat changes. Lifestyle strategies differentially affect IMTG accumulation; combination of exercise with decreased carbohydrate/increased unsaturated fat proportion intake greatly increase IMTG. Our findings suggest that increased IMTG during diet-induced moderate weight loss may not be directly related to cardiometabolic risk. ClinicalTrials.gov NCT01530724.

Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

PubMed

Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

2016-05-01

Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

TRPV1 agonist monoacylglycerol increases UCP1 content in brown adipose tissue and suppresses accumulation of visceral fat in mice fed a high-fat and high-sucrose diet.

PubMed

Iwasaki, Yusaku; Tamura, Yasuko; Inayoshi, Kimiko; Narukawa, Masataka; Kobata, Kenji; Chiba, Hiroshige; Muraki, Etsuko; Tsunoda, Nobuyo; Watanabe, Tatsuo

2011-01-01

The administration of such a transient receptor potential vanilloid 1 (TRPV1) agonist as capsaicin, which is a pungent ingredient of red pepper, promotes energy metabolism and suppresses visceral fat accumulation. We have recently identified monoacylglycerols (MGs) having an unsaturated long-chain fatty acid as the novel TRPV1 agonist in foods. We investigated in this present study the effects of dietary MGs on uncoupling protein 1 (UCP1) expression in interscapular brown adipose tissue (IBAT) and on fat accumulation in mice fed with a high-fat, high-sucrose diet. The MG30 diet that substituted 30% of all lipids for MGs (a mixture of 1-oleoylglycerol, 1-linoleoylglycerol and 1-linolenoylglycerol) significantly increased the UCP1 content of IBAT and decreased the weight of epididymal white adipose tissue, and the serum glucose, total cholesterol and free fatty acid levels. The diet containing only 1-oleoylglycerol as MG also increased UCP1 expression in IBAT. MGs that activated TRPV1 also therefore induced the expression of UCP 1 and prevented visceral fat accumulation as well as capsaicin.

MCD-induced steatohepatitis is associated with hepatic adiponectin resistance and adipogenic transformation of hepatocytes.

PubMed

Larter, Claire Z; Yeh, Matthew M; Williams, Jacqueline; Bell-Anderson, Kim S; Farrell, Geoffrey C

2008-09-01

In these studies, we tested the hypothesis that increased lipid intake would exacerbate the severity of nutritional steatohepatitis. C57Bl/6J mice were fed methionine-and-choline deficient (MCD) diets containing 20% (high) or 5% (low) fat by weight for 3 weeks and compared to lipid-matched controls. MCD feeding increased serum ALT levels and induced hepatic steatosis, lobular inflammation and ballooning degeneration of hepatocytes, irrespective of dietary fat content. Hepatic triglyceride accumulation was similar between high and low-fat MCD-fed mice, but lipoperoxide levels were approximately 3-fold higher in the high-fat MCD-fed animals. Serum adiponectin levels increased in MCD-fed mice, although to a lesser extent in high-fat fed animals. AMPK phosphorylation was correspondingly increased in muscle of MCD-fed mice, but hepatic AMPK phosphorylation decreased, and there was little evidence of PPAR alpha activation, suggesting impaired adiponectin action in the livers of MCD-fed animals. Hepatocyte PPAR gamma mRNA levels increased in MCD-fed mice, and were associated with increased aP2 expression, indicating adipogenic transformation of hepatocytes. Increased dietary lipid intake did not alter steatohepatitis severity in MCD-fed mice despite increased lipoperoxide accumulation. Instead, steatohepatitis was associated with impaired hepatic adiponectin action, and adipogenic transformation of hepatocytes in both low and high-fat MCD-fed mice.

Diet-driven microbiota dysbiosis is associated with vagal remodeling and obesity.

PubMed

Sen, Tanusree; Cawthon, Carolina R; Ihde, Benjamin Thomas; Hajnal, Andras; DiLorenzo, Patricia M; de La Serre, Claire B; Czaja, Krzysztof

2017-05-01

Obesity is one of the major health issues in the United States. Consumption of diets rich in energy, notably from fats and sugars (high-fat/high-sugar diet: HF/HSD) is linked to the development of obesity and a popular dietary approach for weight loss is to reduce fat intake. Obesity research traditionally uses low and high fat diets and there has been limited investigation of the potential detrimental effects of a low-fat/high-sugar diet (LF/HSD) on body fat accumulation and health. Therefore, in the present study, we investigated the effects of HF/HSD and LF/HSD on microbiota composition, gut inflammation, gut-brain vagal communication and body fat accumulation. Specifically, we tested the hypothesis that LF/HSD changes the gut microbiota, induces gut inflammation and alters vagal gut-brain communication, associated with increased body fat accumulation. Sprague-Dawley rats were fed an HF/HSD, LF/HSD or control low-fat/low-sugar diet (LF/LSD) for 4weeks. Body weight, caloric intake, and body composition were monitored daily and fecal samples were collected at baseline, 1, 6 and 27days after the dietary switch. After four weeks, blood and tissues (gut, brain, liver and nodose ganglia) were sampled. Both HF/HSD and LF/HSD-fed rats displayed significant increases in body weight and body fat compared to LF/LSD-fed rats. 16S rRNA sequencing showed that both HF/HSD and LF/HSD-fed animals exhibited gut microbiota dysbiosis characterized by an overall decrease in bacterial diversity and an increase in Firmicutes/Bacteriodetes ratio. Dysbiosis was typified by a bloom in Clostridia and Bacilli and a marked decrease in Lactobacillus spp. LF/HSD-fed animals showed a specific increase in Sutterella and Bilophila, both Proteobacteria, abundances of which have been associated with liver damage. Expression of pro-inflammatory cytokines, such as IL-6, IL-1β and TNFα, was upregulated in the cecum while levels of tight junction protein occludin were downregulated in both HF/HSD and LF/HSD fed rats. HF/HSD and LF/HSD-fed rats also exhibited an increase in cecum and serum levels of lipopolysaccharide (LPS), a pro-inflammatory bacterial product. Immunofluorescence revealed the withdrawal of vagal afferents from the gut and at their site of termination the nucleus of the solitary tract (NTS) in both the HF/HSD and LF/HSD rats. Moreover, there was significant microglia activation in the nodose ganglia, which contain the vagal afferent neuron cell bodies, of HF/HSD and LF/HSD rats. Taken together, these data indicate that, similar to HF/HSD, consumption of an LF/HSD induces dysbiosis of gut microbiota, increases gut inflammation and alters vagal gut-brain communication. These changes are associated with an increase in body fat accumulation. © 2016.

Visceral adiposity as a target for the management of the metabolic syndrome.

PubMed

Kishida, Ken; Funahashi, Tohru; Matsuzawa, Yuji; Shimomura, Iichiro

2012-05-01

Atherosclerosis, the underlying cause of atherosclerotic cardiovascular disease (ACVD), develops due not only to a single cardiovascular risk factor but to a variety of complex factors. The concept of the multiple cardiometabolic risk factor clustering syndrome has been proposed as a highly atherogenic state, independent of hypercholesterolemia and smoking. Body fat distribution, especially visceral fat accumulation, is a major correlate of a cluster of diabetogenic, atherogenic, prothrombotic, and proinflammatory metabolic abnormalities referred to as the metabolic syndrome, with dysfunctional adipocytes and dysregulated production of adipocytokines (hypoadiponectinemia). Medical research has focused on visceral adiposity as an important component of the syndrome in Japanese subjects with a mild degree of adiposity compared with Western subjects. For the prevention of ACVD at least in Japan, it might be practical to stratify subjects with multiple risk factors for atherosclerotic cardiovascular disease based on visceral fat accumulation. Visceral fat reduction through health promotion programs using risk factor-oriented approaches may be effective in reducing ACVD events, as well as producing improvement in risks and hypoadiponectinemia. This review article discusses visceral adiposity as a key player in the syndrome. Visceral fat reduction with life-style modification is a potentially useful strategy in the prevention of ACVD in patients with the metabolic syndrome.

Comparison of efficacy of low-carbohydrate and low-fat diet education programs in non-alcoholic fatty liver disease: A randomized controlled study.

PubMed

Jang, Eun Chul; Jun, Dae Won; Lee, Seung Min; Cho, Yong Kyun; Ahn, Sang Bong

2018-02-01

Composition of macronutrients is important in non-alcoholic fatty liver disease (NAFLD). Diet education programs that mainly emphasize reducing fat consumption have been used for NAFLD patients. We compared the efficacy of conventional low-fat diet education with low-carbohydrate diet education in Korean NAFLD patients. One hundred and six NAFLD patients were randomly allocated to low-fat diet education or low-carbohydrate education groups for 8 weeks. Liver chemistry, liver / spleen ratio, and visceral fat using abdominal tomography were measured. Intrahepatic fat accumulation decreased significantly in the low-carbohydrate group compared to low-fat group (liver/spleen 0.85 vs. 0.92, P < 0.05). Normalization of ALT activity at week 8 was 38.5% for the low-carbohydrate and 16.7% for the low-fat group (P = 0.016). Not only liver enzyme, but also low density lipoprotein cholesterol and blood pressure levels significantly decreased in the low-carbohydrate group. Total energy intake was also further decreased in the low-carbohydrate group compared to the low-fat group. Although body weight changes were not different between the two groups, the carbohydrate group had a lower total abdominal fat amount. A low-carbohydrate diet program is more realistic and effective in reducing total energy intake and hepatic fat content in Korean NAFLD patients. This trial is registered with the National Research Institute of Health: KCT0000970 (https://cris.nih.go.kr/cris/index.jsp). © 2017 The Japan Society of Hepatology.

Influence of extracurricular sport activities on body composition and physical fitness in boys: a 3-year longitudinal study.

PubMed

Ara, I; Vicente-Rodriguez, G; Perez-Gomez, J; Jimenez-Ramirez, J; Serrano-Sanchez, J A; Dorado, C; Calbet, J A L

2006-07-01

To analyse the effect of extracurricular physical activities on fat mass accumulation and physical fitness during growth in early pubertal males. Longitudinal study. A total of 42 male children (9.4+/-1.4 years, Tanner I-II and 12.7+/-1.5 years, Tanner III-IV, before and after the 3.3 years follow-up, respectively), randomly sampled from the population of Gran Canaria (Spain), 26 of them physically active (PA, at least 3 h per week during 3 years) and 16 non-physically active (non-PA). Body composition (dual-energy X-ray absorptiometry), anthropometrics (body circumferences and skinfolds) and physical fitness variables (dynamic and isometric force, anaerobic capacity and maximal aerobic power) were determined in all subjects. Both groups had comparable body sizes at the start and the end of the study. Body mass index increased with growth more in the PA than in the non-PA group (P<0.05). However, fat mass accumulation with growth was lower in the PA than in the non-PA (P<0.05). There was a positive relationship between the increment of total and trunkal fat mass, especially in non-active children (r2=0.93). In contrast, there was an inverse relationship between the total lean mass growth and the accumulation of total and regional fat mass (r=-0.37 to -0.41, all P<0.05). Physical fitness was maintained in the PA, while it worsened in the non-PA children. Without any dietary intervention, children who regularly participate in at least 3 h per week of sports activities are more protected against total and regional fat mass accumulation. They also increase their total lean and bone mass to a greater extent than children who do not participate in extracurricular sport activities. In addition, PA children maintain their physical fitness during growth, while it deteriorates in the non-PA children.

A long-term high-fat diet changes iron distribution in the body, increasing iron accumulation specifically in the mouse spleen.

PubMed

Yamano, Noriko; Ikeda, Yasumasa; Sakama, Minoru; Izawa-Ishizawa, Yuki; Kihira, Yoshitaka; Ishizawa, Keisuke; Miyamoto, Licht; Tomita, Shuhei; Tsuchiya, Koichiro; Tamaki, Toshiaki

2015-01-01

Although iron is an essential trace metal, its presence in excess causes oxidative stress in the human body. Recent studies have indicated that iron storage is a risk factor for type 2 diabetes mellitus. Dietary iron restriction or iron chelation ameliorates symptoms of type 2 diabetes in mouse models. However, whether iron content in the body changes with the development of diabetes is unknown. Here, we investigated the dynamics of iron accumulation and changes in iron absorption-related genes in mice that developed obesity and diabetes by consuming a high-fat diet (HFD-fed mice). HFD-fed mice (18-20 wk) were compared with control mice for hematologic features, serum ferritin levels, and iron contents in the gastrocnemius muscle, heart, epididymal fat, testis, liver, duodenum, and spleen. In addition, the spleen was examined histologically. Iron absorption-related gene expression in the liver and duodenum was also examined. Hemoglobin and serum ferritin levels were increased in HFD-fed mice. The HFD-fed mice showed iron accumulation in the spleen, but not in the heart or liver. Increased percentages of the splenic red pulp and macrophages were observed in HFD-fed mice and iron accumulation in the spleen was found mainly in the splenic red pulp. The HFD-fed mice also showed decreased iron content in the duodenum. The mRNA expression of divalent metal transporter-1 (DMT-1), an iron absorption-related gene, was elevated in the duodenum of HFD-fed mice. These results indicate that iron accumulation (specifically accumulation in the spleen) is enhanced by the development of type 2 diabetes induced by HFD.

The influence of high fat diets with different ketogenic ratios on the hippocampal accumulation of creatine - FTIR microspectroscopy study

NASA Astrophysics Data System (ADS)

Skoczen, A.; Setkowicz, Z.; Janeczko, K.; Sandt, Ch.; Borondics, F.; Chwiej, J.

2017-09-01

The main purpose of this study was the determination and comparison of anomalies in creatine (Cr) accumulation occurring within CA3 and DG areas of hippocampal formation as a result of two high-fat, carbohydrate-restricted ketogenic diets (KD) with different ketogenic ratio (KR). To reach this goal, Fourier transformed infrared microspectroscopy with synchrotron radiation source (SRFTIR microspectroscopy) was applied for chemical mapping of creatine absorption bands, occurring around 1304, 1398 and 2800 cm- 1. The samples were taken from three groups of experimental animals: control group (N) fed with standard laboratory diet, KD1 and KD2 groups fed with high-fat diets with KR 5:1 and 9:1 respectively. Additionally, the possible influence on the phosphocreatine (PhCr, the high energetic form of creatine) content was evaluated by comparative analysis of chemical maps obtained for creatine and for compounds containing phosphate groups which manifest in the spectra at the wavenumbers of around 1240 and 1080 cm- 1. Our results showed that KD2 strongly modifies the frequency of Cr inclusions in both analyzed hippocampal areas. Statistical analysis, performed with Mann-Whitney U test revealed increased accumulation of Cr within CA3 and DG areas of KD2 fed rats compared to both normal rats and KD1 experimental group. Moreover, KD2 diet may modify the frequency of PhCr deposits as well as the PhCr to Cr ratio.

Matured Hop Bittering Components Induce Thermogenesis in Brown Adipose Tissue via Sympathetic Nerve Activity.

PubMed

Morimoto-Kobayashi, Yumie; Ohara, Kazuaki; Takahashi, Chika; Kitao, Sayoko; Wang, Guanying; Taniguchi, Yoshimasa; Katayama, Mikio; Nagai, Katsuya

2015-01-01

Obesity is the principal symptom of metabolic syndrome, which refers to a group of risk factors that increase the likelihood of atherosclerosis. In recent decades there has been a sharp rise in the incidence of obesity throughout the developed world. Iso-α-acids, the bitter compounds derived from hops in beer, have been shown to prevent diet-induced obesity by increasing lipid oxidation in the liver and inhibition of lipid absorption from the intestine. Whereas the sharp bitterness induced by effective dose of iso-α-acids precludes their acceptance as a nutrient, matured hop bittering components (MHB) appear to be more agreeable. Therefore, we tested MHB for an effect on ameliorating diet-induced body fat accumulation in rodents. MHB ingestion had a beneficial effect but, compared to iso-α-acids and despite containing structurally similar compounds, acted via different mechanisms to reduce body fat accumulation. MHB supplementation significantly reduced body weight gain, epididymal white adipose tissue weight, and plasma non-esterified free fatty acid levels in diet-induced obese mice. We also found that uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) was significantly increased in MHB-fed mice at both the mRNA and protein levels. In addition, MHB administration in rats induced the β-adrenergic signaling cascade, which is related to cAMP accumulation in BAT, suggesting that MHB could modulate sympathetic nerve activity innervating BAT (BAT-SNA). Indeed, single oral administration of MHB elevated BAT-SNA in rats, and this elevation was dissipated by subdiaphragmatic vagotomy. Single oral administration of MHB maintained BAT temperature at a significantly higher level than in control rats. Taken together, these findings indicate that MHB ameliorates diet-induced body fat accumulation, at least partly, by enhancing thermogenesis in BAT via BAT-SNA activation. Our data suggests that MHB is a useful tool for developing functional foods or beverages to counteract the accumulation of body fat.

Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance.

PubMed

Nishimoto, Sachiko; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Murata, Chie; Kim-Kaneyama, Joo-Ri; Sato, Fukiko; Bando, Masahiro; Yagi, Shusuke; Soeki, Takeshi; Hayashi, Tetsuya; Imoto, Issei; Sakaue, Hiroshi; Shimabukuro, Michio; Sata, Masataka

2016-03-01

Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Here we showed that obesity-related adipocyte degeneration causes release of cell-free DNA (cfDNA), which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9 (TLR9), originally known as a sensor of exogenous DNA fragments. Fat-fed obese wild-type mice showed increased release of cfDNA, as determined by the concentrations of single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in plasma. cfDNA released from degenerated adipocytes promoted monocyte chemoattractant protein-1 (MCP-1) expression in wild-type macrophages, but not in TLR9-deficient (Tlr9 (-/-) ) macrophages. Fat-fed Tlr9 (-/-) mice demonstrated reduced macrophage accumulation and inflammation in adipose tissue and better insulin sensitivity compared with wild-type mice, whereas bone marrow reconstitution with wild-type bone marrow restored the attenuation of insulin resistance observed in fat-fed Tlr9 (-/-) mice. Administration of a TLR9 inhibitory oligonucleotide to fat-fed wild-type mice reduced the accumulation of macrophages in adipose tissue and improved insulin resistance. Furthermore, in humans, plasma ssDNA level was significantly higher in patients with computed tomography-determined visceral obesity and was associated with homeostasis model assessment of insulin resistance (HOMA-IR), which is the index of insulin resistance. Our study may provide a novel mechanism for the development of sterile inflammation in adipose tissue and a potential therapeutic target for insulin resistance.

Body fat composition and weight changes during pregnancy and 6-8 months post-partum in primiparous and multiparous women.

PubMed

To, William W K; Wong, Margaret W N

2009-02-01

To compare changes in maternal weight and body fat composition from early to late pregnancy and 6-8 months postnatally between primiparous and multiparous patients. Maternal weight and body fat percentage were assessed in a cohort of low-risk uncomplicated women in a general antenatal clinic at 14-20 weeks gestation, after 36 weeks, and around six to eight months after delivery using a Tanita TBF 105 Fat Analyser. Maternal epidemiological and anthropometric data, as well as pregnancy characteristics and perinatal outcome, were derived from standard antenatal records after delivery. The cohort was stratified into primiparous and multiparous women for comparison. In a cohort of 104 women, 55 (52.8%) were primiparous and 49 (47.1%) were multiparous. A relatively good overall correlation between body fat percentage gain and weight gain was observed (correlation coefficient 0.33) from early to late pregnancy. Primiparous women had higher weight gain (12 kg) and higher body fat gain (7.7%) during the pregnancy compared to multiparous women (10.8 kg and 6%, respectively), and they also retained more of the fat accumulated during pregnancy (1.92% vs - 0.44%, P < 0.001) when assessed over six months after their delivery. The findings could represent more exaggerated physiological responses to the pregnant state in the primiparous woman as compared to multiparous women.

Effects of Yogurt Containing Fermented Pepper Juice on the Body Fat and Cholesterol Level in High Fat and High Cholesterol Diet Fed Rat.

PubMed

Yeon, Su-Jung; Hong, Go-Eun; Kim, Chang-Kyu; Park, Woo Joon; Kim, Soo-Ki; Lee, Chi-Ho

2015-01-01

This experiment investigated whether yogurt containing fermented pepper juice (FPJY) affects cholesterol level in high fat and high cholesterol diet (HFCD) fed rat. Twenty five Sprague-Dawley male rats of 7 wk were divided into 5 groups, and fed following diets for 9 wk; CON (control diet), HFCD (HFCD), PY (HFCD supplemented with 2% of plain yogurt), LFY (HFCD supplemented with 2% of FPJY), and HFY (HFCD supplemented with 5% of FPJY). In the LFY group, hepatic total lipid level decreased significantly compared to the HFCD group (p<0.05). Serum HDL cholesterol level tended to increase and hepatic total cholesterol level decreased and were comparable to the CON group (p>0.05). In HFY group, body weight and hepatic total lipid level significantly decreased over the HFCD group (p<0.05). Serum and hepatic total cholesterol level, kidney, and body fat weights decreased, and were compared to the CON group (p>0.05). Liver weight decreased as FPJY content was increased. Results suggested FPJY would inhibit organ hypertrophy and accumulation of body fat, hepatic lipid, and cholesterol in HFCD fed rat.

Interaction of unsaturated fat or coconut oil with monensin in lactating dairy cows fed 12 times daily. II. Fatty acid flow to the omasum and milk fatty acid profile.

PubMed

Reveneau, C; Ribeiro, C V D M; Eastridge, M L; Firkins, J L

2012-04-01

Feeding animal-vegetable (AV) fat or medium-chain fatty acids (FA) to dairy cows can decrease ruminal protozoal counts. However, combining moderate to large amounts of AV fat with monensin (tradename: Rumensin, R) could increase the risk for milk fat depression (MFD), whereas it is not known if diets supplemented with coconut oil (CNO; rich in medium-chain FA) with R would cause MFD. In a 6 × 6 Latin square design with a 2 × 3 factorial arrangement of treatments, 6 rumen-cannulated cows were fed diets without or with R (12 g/909 kg) and either control (no fat), 5% AV fat, or 5% CNO. Diets were balanced to have 21.5% forage neutral detergent fiber, 16.8% crude protein, and 42% nonfiber carbohydrates. Omasal flows of FA were characterized by an increased percentage of trans 18:1 for AV fat and CNO diets compared with the control, a higher percentage of 12:0 and 14:0 for CNO, and higher cis 18:1 for AV fat. Milk FA composition reflected the changes observed for omasal FA digesta flow. The de novo FA synthesis in the mammary gland was decreased by the main effects of R compared without R (averaged over fat treatments) and for added fat (AV fat and CNO) versus control (averaged over R). The percentages of 6:0, 8:0, and 10:0 in milk fat were lower for R and for AV fat and CNO compared with the control. The percentage of trans 18:1 FA in milk fat also higher for AV fat and CNO compared with the control. Against our hypotheses, the feeding of CNO did not prevent MFD, and few interactions between R and fat source were detected. The feeding of CNO did compromise ruminal biohydrogenation, with accumulation of trans 18:1 in the rumen and in milk fat. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice

PubMed Central

Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

2012-01-01

Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day−1). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training. PMID:22674717

Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice.

PubMed

Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

2012-09-01

Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.

Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver.

PubMed

Dongiovanni, P; Stender, S; Pietrelli, A; Mancina, R M; Cespiati, A; Petta, S; Pelusi, S; Pingitore, P; Badiali, S; Maggioni, M; Mannisto, V; Grimaudo, S; Pipitone, R M; Pihlajamaki, J; Craxi, A; Taube, M; Carlsson, L M S; Fargion, S; Romeo, S; Kozlitina, J; Valenti, L

2018-04-01

Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance. We performed a Mendelian randomization analysis using risk alleles in PNPLA3, TM6SF2, GCKR and MBOAT7, and a polygenic risk score for hepatic fat, as instruments. We evaluated complementary cohorts of at-risk individuals and individuals from the general population: 1515 from the liver biopsy cohort (LBC), 3329 from the Swedish Obese Subjects Study (SOS) and 4570 from the population-based Dallas Heart Study (DHS). Hepatic fat was epidemiologically associated with liver damage, insulin resistance, dyslipidemia and hypertension. The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation. Genetically determined hepatic fat was associated with aminotransferases, and with inflammation, ballooning and fibrosis in the LBC. Furthermore, in the LBC, the causal association between hepatic fat and fibrosis was independent of disease activity, suggesting that a causal effect of long-term liver fat accumulation on liver disease is independent of inflammation. Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS. However, this association was dependent on liver damage severity. Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available databases. These data suggest that long-term hepatic fat accumulation plays a causal role in the development of chronic liver disease. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

The fate of vicilins, 7S storage globulins, in larvae and adult Callosobruchus maculatus (Coleoptera: Chrysomelidae: Bruchinae).

PubMed

Souza, Sheila M; Uchôa, Adriana F; Silva, José R; Samuels, Richard I; Oliveira, Antônia E A; Oliveira, Eliana M; Linhares, Ricardo T; Alexandre, Daniel; Silva, Carlos P

2010-09-01

The fate of vicilins ingested by Callosobruchus maculatus and the physiological importance of these proteins in larvae and adults were investigated. Vicilins were quantified by ELISA in the haemolymph and fat body during larval development (2nd to 4th instars), in pupae and adults, as well as in ovaries and eggs. Western blot analysis demonstrated that the majority of absorbed vicilins were degraded in the fat body. Tracing the fate of vicilins using FITC revealed that the FITC-vicilin complex was present inside cells of the fat body of the larvae and in the fat bodies of both male and female adult C. maculatus. Labelled vicilin was also detected in ovocytes and eggs. Based on the results presented here, we propose that following absorption, vicilins accumulate in the fat body, where they are partially degraded. These peptides are retained throughout the development of the insects and eventually are sequestered by the eggs. It is possible that accumulation in the eggs is a defensive strategy against pathogen attack as these peptides are known to have antimicrobial activity. Quantifications performed on internal organs from larvae of C. maculatus exposed to extremely dry seeds demonstrated that the vicilin concentration in the haemolymph and fat body was significantly higher when compared to larvae fed on control seeds. These results suggest that absorbed vicilins may also be involved in the survival of larvae in dry environments.

Remodeling of skeletal muscle mitochondrial proteome with high-fat diet involves greater changes to β-oxidation than electron transfer proteins in mice.

PubMed

Dasari, Surendra; Newsom, Sean A; Ehrlicher, Sarah E; Stierwalt, Harrison D; Robinson, Matthew M

2018-05-29

Excess fat intake can increase lipid oxidation and expression of mitochondrial proteins, indicating remodeling of the mitochondrial proteome. Yet intermediates of lipid oxidation also accumulate and indicate a relative insufficiency to completely oxidize lipids. We investigated remodeling of the mitochondrial proteome to determine mechanisms of changes to lipid oxidation following high-fat feeding. C57BL/6J mice consumed either a high-fat diet (HFD, 60% fat from lard) or low fat diet (LFD, 10% fat) for 12 weeks. Mice were fasted 4 hours then anaesthetized by sodium pentobarbital for tissue collection. A mitochondrial-enriched fraction was prepared from gastrocnemius muscles and underwent proteomic analysis by high-resolution mass spectrometry. Mitochondrial respiratory efficiency was measured as ATP production per oxygen consumption (P:O). Intramuscular acyl-carnitines were measured by liquid-chromatography mass spectrometry. A total of 658 mitochondrial proteins were identified with 40 having higher and 14 having lower abundance in mice consuming a HFD compared to LFD. Individual proteins that changed with HFD were primarily related to β-oxidation with fewer changes to the electron transfer system. Gene set enrichment analysis identified HFD increased pathways of lipid metabolism and β-oxidation. Intramuscular concentrations of select acyl-carnitines (C18:0) were greater with HFD and reflected dietary lipid composition. Mitochondrial respiratory P:O for lipids was not different between LFD and HFD. Following the 60% fat diet, remodeling of the mitochondrial proteome revealed up-regulation of proteins regulating lipid oxidation that was not evident for all mitochondrial pathways. The accumulation of lipid metabolites with obesity may occur without intrinsic dysfunction to mitochondrial lipid oxidation.

Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet

PubMed Central

Garbow, Joel R.; Doherty, Jason M.; Schugar, Rebecca C.; Travers, Sarah; Weber, Mary L.; Wentz, Anna E.; Ezenwajiaku, Nkiruka; Cotter, David G.; Brunt, Elizabeth M.

2011-01-01

Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis. PMID:21454445

Diet-induced thermogenesis is lower in rats fed a lard diet than in those fed a high oleic acid safflower oil diet, a safflower oil diet or a linseed oil diet.

PubMed

Takeuchi, H; Matsuo, T; Tokuyama, K; Shimomura, Y; Suzuki, M

1995-04-01

The objectives of the present study were to examine the effects of dietary fats differing in fatty acid composition on diet-induced thermogenesis, sympathetic activity in brown adipose tissue and body fat accumulation in rats. Rats were meal-fed for 12 wk an isoenergetic diet based on lard, high oleic acid safflower oil, safflower oil or linseed oil, and norepinephrine turnover rates in brown adipose tissue were then estimated. Whole-body oxygen consumption after the meal indicated that diet-induced thermogenesis was significantly lower in rats fed the lard diet than in those fed the other diets. The norepinephrine turnover rate in the interscapular brown adipose tissue was also significantly lower in the lard diet group than in the other diet groups. The carcass fat content was significantly higher in the lard diet group than in the other diet groups, whereas the abdominal adipose tissue weights were the same in all diet groups. These results suggest that the intake of animal fats rich in saturated fatty acids, compared with the intake of vegetable oils rich in monounsaturated or polyunsaturated fatty acids, decreases diet-induced thermogenesis by a decline of sympathetic activity in brown adipose tissue, resulting in the promotion of body fat accumulation.

Differential Effects of Bariatric Surgery Versus Exercise on Excessive Visceral Fat Deposits

PubMed Central

Wu, Fu-Zong; Huang, Yi-Luan; Wu, Carol C.; Wang, Yen-Chi; Pan, Hsiang-Ju; Huang, Chin-Kun; Yeh, Lee-Ren; Wu, Ming-Ting

2016-01-01

Abstract The aim of the present study was to compare differential impacts of bariatric surgery and exercise-induced weight loss on excessive abdominal and cardiac fat deposition. Excessive fat accumulation around the heart may play an important role in the pathogenesis of cardiovascular disease. Recent evidences have suggested that bariatric surgery results in relatively less decrease in epicardial fat compared with abdominal visceral fat and paracardial fat. Sixty-four consecutive overweight or obese subjects were enrolled in the study. Clinical characteristics and metabolic profiles were recorded. The volumes of abdominal visceral adipose tissue (AVAT), abdominal subcutaneous adipose tissue (ASAT), epicardial (EAT), and paracardial adipose tissue (PAT) were measured by computed tomography in the bariatric surgery group (N = 25) and the exercise group (N = 39) at baseline and 3 months after intervention. Subjects in both the surgery and exercise groups showed significant reduction in body mass index (15.97%, 7.47%), AVAT (40.52%, 15.24%), ASAT (31.40, 17.34%), PAT (34.40%, 12.05%), and PAT + EAT (22.31%, 17.72%) (all P < 0.001) after intervention compared with baseline. In both the groups, the decrease in EAT was small compared with the other compartments (P < 0.01 in both groups). Compared with the exercise group, the surgery group had greater loss in abdominal and cardiac visceral adipose tissue (AVAT, ASAT, PAT, EAT+PAT) (P < 0.001), but lesser loss in EAT (P = 0.037). Compared with the exercise group, bariatric surgery results in significantly greater percentage loss of excessive fat deposits except for EAT. EAT, but not PAT, was relatively preserved despite weight reduction in both the groups. The physiological impact of persistent EAT deserves further investigation. PMID:26844473

How to get fat: nutritional mechanisms of seasonal fat accumulation in migratory songbirds

NASA Astrophysics Data System (ADS)

Bairlein, Franz

2002-01-01

Many migratory birds accumulate large amounts of lipids as the prime energy source for their long-distance flights. This fat accumulation is mostly under endogenous control, reflecting genetically programmed temporal shifts of the body mass set point. It is accompanied by an increase in daily food intake and food utilisation efficiency and by a seasonal shift in food selection. In particular, seasonal frugivory appears to play a key role in many migrants. Fruits have a high content of fatty acids indispensable for building up the specific depot lipids. In addition, plant secondary compounds seem to play some kind of supportive role, but the mechanisms are not yet known. The effect of being fat on the metabolic situation in migrant birds appears to be similar to the metabolic syndrome in obese humans. The fat migratory bird provides a model through which to study nutritional factors as well as the biochemical and endocrine regulation of food intake, body mass and obesity.

Computed tomography of deep fat masses in multiple symmetrical lipomatosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Enzi, G.; Biondetti, P.R.; Fiore, D.

1982-07-01

Deep fat masses were evaluated by computed tomography (CT) in 15 patients with multiple symmetrical lipomatosis. In 4 patients, peritracheal accumulations of fat were observed. In 3 of them, tracheal compression by lipomatous tissue was demonstrated: 2 were asymptomatic and the third severe respiratory insufficiency secondary to blockage of the air was by the vocal cords as the result of recurrent nerve palsy. In 6 patients, lipomatous tissue occupied the potential space between the spina scapulae and the trapezius, supraspinatus, and infraspinatus muscles. In 2, calcification of lipomatous masses was observed. There was no relationship between extension of subcutaneous fatmore » and accumulation at deep sites. CT facilitates early detection of peritracheal lipomatous tissue and is helpful in follow-up when deep fat accumulation is responsible for space-occupying lesions requiring surgery.« less

Intramyocellular triacylglycerol accumulation across weight loss strategies; Sub-study of the CENTRAL trial

PubMed Central

Gepner, Yftach; Shelef, Ilan; Schwarzfuchs, Dan; Cohen, Noa; Bril, Nitzan; Rein, Michal; Tsaban, Gal; Zelicha, Hila; Yaskolka Meir, Anat; Tene, Lilac; Sarusy, Benjamin; Rosen, Philip; Hoffman, Jay R.; Stout, Jeffrey R.; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Stampfer, Meir J.; Shai, Iris

2017-01-01

Background Intramyocellular triacylglycerol (IMTG) is utilized as metabolic fuel during exercise and is linked to insulin resistance, but the long-term effect of weight loss strategies on IMTG among participants with abdominal fat, remain unclear. Methods In an 18-month trial, sedentary participants with abdominal fat/dyslipidemia were randomized to either a low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC) diet (including 28g·day-1 of walnuts). After 6-months, the participants were re-randomized to moderate intense physical activity (PA+) or non-physical activity (PA-). Magnetic resonance imaging (MRI) was used to quantify changes of IMTG, abdominal sub-depots, hepatic and intermuscular fats. Results Across the 277 participants [86% men, age = 48 years, body-mass-index (BMI) = 31kg/m2, visceral fat = 33%] 86% completed the 18-m trial. At baseline, women had higher IMTG than men (3.4% vs. 2.3%, p<0.001) and increased IMTG was associated with aging and higher BMI, visceral and intermuscular fats, HbA1c%, HDL-c and leptin(p<0.05), but not with intra-hepatic fat. After 18 month of intervention and a -3 kg mean weight loss, participants significantly increased IMTG by 25%, with a distinct effect in the MED/LCPA+ group as compared to the other intervention groups (57% vs. 9.5–18.5%, p<0.05). Changes in IMTG were associated with visceral and intermuscular fat, metabolic syndrome, insulin and leptin (p<0.05 for all), however, these associations did not remain after adjustment for visceral fat changes. Conclusions Lifestyle strategies differentially affect IMTG accumulation; combination of exercise with decreased carbohydrate/increased unsaturated fat proportion intake greatly increase IMTG. Our findings suggest that increased IMTG during diet-induced moderate weight loss may not be directly related to cardiometabolic risk. Trial registration ClinicalTrials.gov NCT01530724 PMID:29190720

Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

ERIC Educational Resources Information Center

Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

2002-01-01

Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

Fatty Liver

MedlinePlus

... Drug Information, Search Drug Names, Generic and Brand Natural Products, ... fat to accumulate in liver cells by causing the body to synthesize more fat or by processing (metabolizing) and excreting fat more slowly. As a ...

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials

PubMed Central

Ma, Jiantao; Karlsen, Micaela C.; Chung, Mei; Jacques, Paul F.; Saltzman, Edward; Smith, Caren E.; Fox, Caroline S.

2016-01-01

Context: The effect of added sugar intake on ectopic fat accumulation is a subject of debate. Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. Data Sources: MEDLINE, CAB Abstracts, CAB Global Health, and EBM (Evidence-Based Medicine) Reviews – Cochrane Central Register of Controlled Trials databases were searched for studies published from 1973 to September 2014. Data Extraction: RCTs with a minimum of 6 days’ duration of added sugar exposure in the intervention group were selected. The dosage of added sugar intake as a percentage of total energy was extracted or calculated. Means and standard deviations of pre- and post-test measurements or changes in ectopic fat depots were collected. Data Synthesis: Fourteen RCTs were included. Most of the studies had a medium to high risk of bias. Meta-analysis showed that, compared with eucaloric controls, subjects who consumed added sugar under hypercaloric conditions likely increased ectopic fat, particularly in the liver (pooled standardized mean difference = 0.9 [95%CI, 0.6–1.2], n = 6) and muscles (pooled SMD = 0.6 [95%CI, 0.2–1.0], n = 4). No significant difference was observed in liver fat, visceral adipose tissue, or muscle fat when isocaloric intakes of different sources of added sugars were compared. Conclusions: Data from a limited number of RCTs suggest that excess added sugar intake under hypercaloric diet conditions likely increases ectopic fat depots, particularly in the liver and in muscle fat. There are insufficient data to compare the effect of different sources of added sugars on ectopic fat deposition or to compare intake of added sugar with intakes of other macronutrients. Future well-designed RCTs with sufficient power and duration are needed to address the role of sugars on ectopic fat deposition. PMID:26518034

Hyperspectral Stimulated Raman Scattering Microscopy Unravels Aberrant Accumulation of Saturated Fat in Human Liver Cancer.

PubMed

Yan, Shuai; Cui, Sishan; Ke, Kun; Zhao, Bixing; Liu, Xiaolong; Yue, Shuhua; Wang, Ping

2018-06-05

Lipid metabolism is dysregulated in human cancers. The analytical tools that could identify and quantitatively map metabolites in unprocessed human tissues with submicrometer resolution are highly desired. Here, we implemented analytical hyperspectral stimulated Raman scattering microscopy to map the lipid metabolites in situ in normal and cancerous liver tissues from 24 patients. In contrast to the conventional wisdom that unsaturated lipid accumulation enhances tumor cell survival and proliferation, we unexpectedly visualized substantial amount of saturated fat accumulated in cancerous liver tissues, which was not seen in majority of their adjacent normal tissues. Further analysis by mass spectrometry confirmed significant high levels of glyceryl tripalmitate specifically in cancerous liver. These findings suggest that the aberrantly accumulated saturated fat may have great potential to be a metabolic biomarker for liver cancer.

Transcriptome Profile Reveals that Pu-Erh Tea Represses the Expression of Vitellogenin Family to Reduce Fat Accumulation in Caenorhabditis elegans.

PubMed

Xiao, Ru-Yue; Hao, Junjun; Ding, Yi-Hong; Che, Yan-Yun; Zou, Xiao-Ju; Liang, Bin

2016-10-17

Due to misbalanced energy surplus and expenditure, obesity has become a common chronic disorder that is highly associated with many metabolic diseases. Pu-erh tea, a traditional Chinese beverage, has been believed to have numerous health benefits, such as anti-obesity. However, the underlying mechanisms of its anti-obesity effect are yet to be understood. Here, we take the advantages of transcriptional profile by RNA sequencing (RNA-Seq) to view the global gene expression of Pu-erh tea. The model organism Caenorhabditis elegans was treated with different concentrations of Pu-erh tea water extract (PTE, 0 g/mL, 0.025 g/mL, and 0.05 g/mL). Compared with the control, PTE indeed decreases lipid droplets size and fat accumulation. The high-throughput RNA-Sequence technique detected 18073 and 18105 genes expressed in 0.025 g/mL and 0.05 g/mL PTE treated groups, respectively. Interestingly, the expression of the vitellogenin family ( vit-1 , vit-2 , vit-3, vit-4 and vit-5 ) was significantly decreased by PTE, which was validated by qPCR analysis. Furthermore, vit-1(ok2616) , vit-3(ok2348) and vit-5(ok3239) mutants are insensitive to PTE triggered fat reduction. In conclusion, our transcriptional profile by RNA-Sequence suggests that Pu-erh tea lowers the fat accumulation primarily through repression of the expression of vit (vitellogenin) family, in addition to our previously reported (sterol regulatory element binding protein) SREBP-SCD (stearoyl-CoA desaturase) axis.

Alpha-Lipoic Acid Reduces LDL-Particle Number and PCSK9 Concentrations in High-Fat Fed Obese Zucker Rats

PubMed Central

Carrier, Bradley; Wen, Shin; Zigouras, Sophia; Browne, Richard W.; Li, Zhuyun; Patel, Mulchand S.; Williamson, David L.; Rideout, Todd C.

2014-01-01

We characterized the hypolipidemic effects of alpha-lipoic acid (LA, R-form) and examined the associated molecular mechanisms in a high fat fed Zucker rat model. Rats (n = 8) were assigned to a high fat (HF) diet or the HF diet with 0.25% LA (HF-LA) for 30 days and pair fed to remove confounding effects associated with the anorectic properties of LA. Compared with the HF controls, the HF-LA group was protected against diet-induced obesity (102.5±3.1 vs. 121.5±3.6,% change BW) and hypercholesterolemia with a reduction in total-C (−21%), non-HDL-C (−25%), LDL-C (−16%), and total LDL particle number (−46%) and an increase in total HDL particles (∼22%). This cholesterol-lowering response was associated with a reduction in plasma PCSK9 concentration (−70%) and an increase in hepatic LDLr receptor protein abundance (2 fold of HF). Compared with the HF-fed animals, livers of LA-supplemented animals were protected against TG accumulation (−46%), likely through multiple mechanisms including: a suppressed lipogenic response (down-regulation of hepatic acetyl-CoA carboxylase and fatty acid synthase expression); enhanced hepatic fat oxidation (increased carnitine palmitoyltransferase Iα expression); and enhanced VLDL export (increased hepatic diacylglycerol acyltransferase and microsomal triglyceride transfer protein expression and elevated plasma VLDL particle number). Study results also support an enhanced fatty acid uptake (2.8 fold increase in total lipase activity) and oxidation (increased CPT1β protein abundance) in muscle tissue in LA-supplemented animals compared with the HF group. In summary, in the absence of a change in caloric intake, LA was effective in protecting against hypercholesterolemia and hepatic fat accumulation under conditions of strong genetic and dietary predisposition toward obesity and dyslipidemia. PMID:24595397

Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits.

PubMed

Prior, Larissa J; Eikelis, Nina; Armitage, James A; Davern, Pamela J; Burke, Sandra L; Montani, Jean-Pierre; Barzel, Benjamin; Head, Geoffrey A

2010-04-01

The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively (P<0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher (P<0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin (r=0.87; P<0.01). Intracerebroventricular leptin administration (5 to 100 microg) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: -54%, paraventricular: -69%, and dorsomedial hypothalamus: -65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked "selective leptin resistance" in these animals.

Tissue Specific Expression Of Sprouty1 In Mice Protects Against High Fat Diet Induced Fat Accumulation, Bone Loss, And Metabolic Dysfunction

PubMed Central

Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J.; Liaw, Lucy

2012-01-01

We recently characterized Sprouty1 (Spry1), a growth factor signaling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue specific Spry1 expression in mice resulted in increased bone mass and reduced body fat while conditional knockout of Spry1 had the opposite effect with decreased bone and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high fat diet-induced obesity, bone loss, and associated lipid abnormalities and demonstrate that Spry1 has a long-term protective effect on mice fed a high caloric diet. We studied diet-induced obesity in mice with fatty acid binding promoter (aP2)-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1 null mice, high fat diet increased body fat by 40%, impaired glucose regulation, and led to liver steatosis. However, over-expression of Spry1 led to 35% lower body fat, reduced bone loss, and normal metabolic function compared to single transgenics. This protective phenotype was associated with decreased circulating insulin (70%) and leptin (54%) compared to controls on a high fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45%. We show that conditional Spry1 expression in adipose tissue protects against high fat diet-induced obesity and associated bone loss. PMID:22142492

Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction.

PubMed

Urs, Sumithra; Henderson, Terry; Le, Phuong; Rosen, Clifford J; Liaw, Lucy

2012-09-28

We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

Relationships between body fat accumulation, aerobic capacity and insulin resistance in Japanese participants.

PubMed

Yoshimura, Eiichi; Kumahara, Hideaki; Tobina, Takuro; Ayabe, Makoto; Matono, Sakiko; Anzai, Keizo; Higaki, Yasuki; Kiyonaga, Akira; Tanaka, Hiroaki

2011-01-01

This study evaluated the relationships between body fat accumulation, aerobic capacity and insulin resistance (HOMA-IR) in 61 Japanese participants. The participants were middle-aged to elderly (age: 33-73; BMI: 21.6-38.5). Body fat mass (FM) was evaluated by hydrostatic weighing. Computed tomography was used to evaluate visceral and subcutaneous fat areas (VFA and SFA), liver to spleen ratio (L/S), and low-density muscle area (LDMA). To assess aerobic capacity, VO2 at the lactate threshold (VO2@LT) and VO2 peak were measured using a bicycle ergometer. FM, VFA, SFA, LDMA and L/S significantly correlated with HOMA-IR, but VO2@LT and VO2 peak did not. Analysis of covariance after adjustment for VFA or other body fat distribution and aerobic capacity showed that HOMA-IR had a significant linear trend across the tertile groups of L/S. However, for FM, VFA, SFA, LDMA and VO2@LT or VO2 peak, no significant trend was observed between the tertiles and insulin resistance. Ectopic fat deposition in the liver may influence insulin resistance independently of other body fat accumulation and aerobic capacity in Japanese participants. © 2011 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

Pancreatic Fat Accumulation, Fibrosis, and Acinar Cell Injury in the Zucker Diabetic Fatty Rat Fed a Chronic High-Fat Diet

PubMed Central

Matsuda, Akiko; Makino, Naohiko; Tozawa, Tomohiro; Shirahata, Nakao; Honda, Teiichiro; Ikeda, Yushi; Sato, Hideyuki; Ito, Miho; Kakizaki, Yasuharu; Akamatsu, Manabu; Ueno, Yoshiyuki; Kawata, Sumio

2014-01-01

Objective The histological alteration of the exocrine pancreas in obesity has not been clarified. In the present study, we investigated biochemical and histological changes in the exocrine pancreas of obese model rats. Methods Zucker lean rats were fed a standard diet, and Zucker diabetic fatty (ZDF) rats were divided into 2 groups fed a standard diet and a high-fat diet, respectively. These experimental groups were fed each of the diets from 6 weeks until 12, 18, 24 weeks of age. We performed blood biochemical assays and histological analysis of the pancreas. Results In the ZDF rats fed a high-fat diet, the ratio of accumulated pancreatic fat area relative to exocrine gland area was increased significantly at 18 weeks of age in comparison with the other 2 groups (P < 0.05), and lipid droplets were observed in acinar cells. Subsequently, at 24 weeks of age in this group, pancreatic fibrosis and the serum exocrine pancreatic enzyme levels were increased significantly relative to the other 2 groups (P < 0.01). Conclusions In ZDF rats fed a chronic high-fat diet, fat accumulates in pancreatic acinar cells, and this fatty change seems to be related to subsequent pancreatic fibrosis and acinar cell injury. PMID:24717823

Beneficial Effect of Bis(Hinokitiolato)Zn Complex on High-fat Diet-induced Lipid Accumulation in Mouse Liver and Kidney.

PubMed

Naito, Yuki; Yoshikawa, Yutaka; Yoshizawa, Katsuhiko; Takenouchi, Akiko; Yasui, Hiroyuki

2017-01-01

Metabolic syndrome-induced lifestyle-related diseases include diabetes mellitus (DM) and hypertension, and Zn-based compounds have effects on DM. We aimed to investigate the ameliorating effects of bis(hinokitiolato)Zn, [Zn(hkt) 2 ] on lipid metabolism in the liver and kidney, histopathologically. We used a high-fat diet (HFD)-fed C57BL/6J mouse model and administered a diet containing 10-20 mg Zn/kg body weight (BW) or 20 mg pioglitazone/kg BW as the positive control. After the treatments, we collected blood, liver, and kidney samples and morphologically evaluated the mouse organs for fat accumulation. After a 4-month HFD administration, ectopic fat deposition was detected in the liver and kidney. Furthermore, Zn accumulation in the liver and kidney increased following [Zn(hkt) 2 ] treatment, that reduced lipid accumulations and lipid toxicity in these tissues. The results of this study suggest that [Zn(hkt) 2 ] could be a novel anti-dyslipidaemia compound for treating diet-induced obesity. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cuphea wrightii thioesterases have unexpected broad specificities on saturated fatty acids.

PubMed

Leonard, J M; Slabaugh, M B; Knapp, S J

1997-07-01

Cuphea wrightii A. Gray is an herbaceous annual that accumulates 30% caprate (10:0) and 54% laurate (12:0) in seed storage lipids. We investigated the role of acyl-acyl carrier protein (ACP) thioesterases (TE) in acyl chain-length regulation in C. wrightii. Two embryo-derived cDNAs, encoding the TEs Cw FatB1 and Cw FatB2, were isolated. Both proteins were detected in developing embryos and mature seeds but not in other tissues, suggesting involvement in seed oil synthesis. Although expected to be 10:0/12:0-ACP-specific, these genes produced a broad range of fatty acids (12:0, 14:0, and 16:0) in transgenic Arabidopsis with the greatest accumulation at 14:0. Cw FatB2 transformants also accumulated small amounts of 10:0. Because C. wrightii accumulates only ca. 5% 14:0 and ca. 2% 16:0, we tested the possibility that gene dosage effects might significantly alter the overall kinetics of the pathway. Phenotypic comparisons of progeny segregating for the transgenes individually and in a hybrid population demonstrated that increased enzyme pools in vivo had a minor effect on diverting fatty acid production to shorter chains. We propose that Cw FatB1 and Cw FatB2 may be necessary but not sufficient determinants of the C. wrightii phenotype.

A high-fat meal promotes lipid-load and apolipoprotein B-48 receptor transcriptional activity in circulating monocytes.

PubMed

Varela, Lourdes M; Ortega, Almudena; Bermudez, Beatriz; Lopez, Sergio; Pacheco, Yolanda M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G

2011-05-01

The postprandial metabolism of dietary fats results in the production of apolipoprotein B-48 (apoB48)-containing triglyceride-rich lipoproteins (TRLs), which cause rapid receptor-mediated macrophage lipid engorgement via the apoB48 cell surface receptor (apoB48R). Monocytes circulate together with apoB48-containing TRLs in the postprandial bloodstream and may start accumulating lipids even before their migration to tissues and differentiation to macrophages. We sought to determine whether circulating monocytes are equipped with apoB48R and whether, in the postprandial state, circulating monocytes accumulate lipids and modulate apoB48R transcriptional activity after intake of a high-fat meal. In a crossover design, we studied the effect of a high-fat meal on fasting and postprandial concentrations of triglycerides, free fatty acids, cholesterol, and insulin in 12 healthy men. TRLs and monocytes were freshly isolated at fasting, hourly until the postprandial peak, and at the late postprandial phase. TRLs were subjected to triglycerides, apoB48, and apolipoprotein B-100 analyses; and lipid accumulation and apoB48R mRNA expression levels were measured in monocytes. Monocytes showed a time-dependent lipid accumulation in response to the high-fat meal, which was paralleled by an increase in apoB48R mRNA expression levels. These effects were coincident only with an increase in apoB48-containing TRLs in the postprandial phase and were also observed ex vivo in freshly isolated monocytes incubated with apoB48-containing TRLs. In a setting of abundant plasma apoB48-containing TRLs, these findings highlight the role of dietary fat in inducing lipid accumulation and apoB48R gene transcription in circulating monocytes.

Artemisia scoparia Enhances Adipocyte Development and Endocrine Function In Vitro and Enhances Insulin Action In Vivo

PubMed Central

Richard, Allison J.; Fuller, Scott; Fedorcenco, Veaceslav; Beyl, Robbie; Burris, Thomas P.; Mynatt, Randall; Ribnicky, David M.; Stephens, Jacqueline M.

2014-01-01

Background Failure of adipocytes to expand during periods of energy excess can result in undesirable metabolic consequences such as ectopic fat accumulation and insulin resistance. Blinded screening studies have indicated that Artemisia scoparia (SCO) extracts can enhance adipocyte differentiation and lipid accumulation in cultured adipocytes. The present study tested the hypothesis that SCO treatment modulates fat cell development and function in vitro and insulin sensitivity in adipose tissue in vivo. Methods In vitro experiments utilized a Gal4-PPARγ ligand binding domain (LBD) fusion protein-luciferase reporter assay to examine PPARγ activation. To investigate the ability of SCO to modulate adipogenesis and mature fat cell function in 3T3-L1 cells, neutral lipid accumulation, gene expression, and protein secretion were measured by Oil Red O staining, qRT-PCR, and immunoblotting, respectively. For the in vivo experiments, diet-induced obese (DIO) C57BL/6J mice were fed a high-fat diet (HFD) or HFD containing 1% w/w SCO for four weeks. Body weight and composition, food intake, and fasting glucose and insulin levels were measured. Phospho-activation and expression of insulin-sensitizing proteins in epididymal adipose tissue (eWAT) were measured by immunoblotting. Results Ethanolic extracts of A. scoparia significantly activated the PPARγ LBD and enhanced lipid accumulation in differentiating 3T3-L1 cells. SCO increased the transcription of several PPARγ target genes in differentiating 3T3-L1 cells and rescued the negative effects of tumor necrosis factor α on production and secretion of adiponectin and monocyte chemoattractant protein-1 in fully differentiated fat cells. DIO mice treated with SCO had elevated adiponectin levels and increased phosphorylation of AMPKα in eWAT when compared to control mice. In SCO-treated mice, these changes were also associated with decreased fasting insulin and glucose levels. Conclusion SCO has metabolically beneficial effects on adipocytes in vitro and adipose tissue in vivo, highlighting its potential as a metabolically favorable botanical supplement. PMID:24915004

Characterization of fat metabolism in the fatty liver caused by a high-fat, low-carbohydrate diet: A study under equal energy conditions.

PubMed

Kurosaka, Yuka; Shiroya, Yoko; Yamauchi, Hideki; Kitamura, Hiromi; Minato, Kumiko

2017-05-20

The pathology of fatty liver due to increased percentage of calories derived from fat without increased overall caloric intake is largely unclear. In this study, we aimed to characterize fat metabolism in rats with fatty liver resulting from consumption of a high-fat, low-carbohydrate (HFLC) diet without increased caloric intake. Four-week-old male Sprague-Dawley rats were randomly assigned to the control (Con) and HFLC groups, and rats were fed the corresponding diets ad libitum. Significant decreases in food intake per gram body weight were observed in the HFLC group compared with that in the Con group. Thus, there were no significant differences in body weights or caloric intake per gram body weight between the two groups. Marked progressive fat accumulation was observed in the livers of rats in the HFLC group, accompanied by suppression of de novo lipogenesis (DNL)-related proteins in the liver and increased leptin concentrations in the blood. In addition, electron microscopic observations revealed that many lipid droplets had accumulated within the hepatocytes, and mitochondrial numbers were reduced in the hepatocytes of rats in the HFLC group. Our findings confirmed that consumption of the HFLC diet induced fatty liver, even without increased caloric intake. Furthermore, DNL was not likely to be a crucial factor inducing fatty liver with standard energy intake. Instead, ultrastructural abnormalities found in mitochondria, which may cause a decline in β-oxidation, could contribute to the development of fatty liver. Copyright © 2017 Elsevier Inc. All rights reserved.

Substantial replacement of lactose with fat in a high-lactose milk replacer diet increases liver fat accumulation but does not affect insulin sensitivity in veal calves.

PubMed

Pantophlet, A J; Gerrits, W J J; Vonk, R J; van den Borne, J J G C

2016-12-01

In veal calves, the major portion of digestible energy intake originates from milk replacer (MR), with lactose and fat contributing approximately 45 and 35%, respectively. In veal calves older than 4 mo, prolonged high intakes of MR may lead to problems with glucose homeostasis and insulin sensitivity, ultimately resulting in sustained insulin resistance, hepatic steatosis, and impaired animal performance. The contribution of each of the dietary energy sources (lactose and fat) to deteriorated glucose homeostasis and insulin resistance is currently unknown. Therefore, an experiment was designed to compare the effects of a high-lactose and a high-fat MR on glucose homeostasis and insulin sensitivity in veal calves. Sixteen male Holstein-Friesian calves (120±2.8kg of BW) were assigned to either a high-lactose (HL) or a high-fat (HF) MR for 13 consecutive weeks. After at least 7 wk of adaptation, whole-body insulin sensitivity and insulin secretion were assessed by euglycemic-hyperinsulinemic and hyperglycemic clamps, respectively. Postprandial blood samples were collected to assess glucose, insulin, and triglyceride responses to feeding, and 24-h urine was collected to quantify urinary glucose excretion. At the end of the trial, liver and muscle biopsies were taken to assess triglyceride contents in these tissues. Long-term exposure of calves to HF or HL MR did not affect whole-body insulin sensitivity (averaging 4.2±0.5×10 -2 [(mg/kg∙min)/(μU/mL)]) and insulin secretion. Responses to feeding were greater for plasma glucose and tended to be greater for plasma insulin in HL calves than in HF calves. Urinary glucose excretion was substantially higher in HL calves (75±13g/d) than in HF calves (21±6g/d). Muscle triglyceride content was not affected by treatment and averaged 4.5±0.6g/kg, but liver triglyceride content was higher in HF calves (16.4±0.9g/kg) than in HL calves (11.2±0.7g/kg), indicating increased hepatic fat accumulation. We conclude that increasing the contribution of fat to the digestible energy intake from the MR from 20 to 50%, at the expense of lactose does not affect whole-body insulin sensitivity and insulin secretion in calves. However, a high-lactose MR increases postprandial glucose and insulin responses, whereas a high-fat MR increases fat accumulation in liver but not muscle. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

NOX1-induced accumulation of reactive oxygen species in abdominal fat-derived mesenchymal stromal cells impinges on long-term proliferation

PubMed Central

Sela, M; Tirza, G; Ravid, O; Volovitz, I; Solodeev, I; Friedman, O; Zipori, D; Gur, E; Krelin, Y; Shani, N

2015-01-01

Mesenchymal stromal cells (MSCs) are multipotent and can be derived from different adult tissues including fat. Our repeated attempts to produce long-term proliferative cultures of rat abdominal adipose stem cells (aASCs) under normal oxygen concentration (21%) were unsuccessful. We set to examine the events controlling this cytostasis of aASCs and found that it resulted from overproduction of reactive oxygen species (ROS) that led to apoptosis. ROS overproduction in aASCs was accompanied by increased expression of NOX1 but not of NOX2 or NOX4. NOX family members are an important source of intracellular ROS pointing to NOX1 involvement in ROS accumulation. This was verified when aASCs that were grown under 3% oxygen conditions expanded long term, displaying reduced NOX1 expression and decreased ROS accumulation. NOX1 involvement in aASC cytostasis was reaffirmed when cells that were expanded under normoxic conditions in the presence of a specific NOX1 inhibitor, ML171, demonstrated reduced ROS accumulation, reduced apoptosis and long-term expansion. aASC expansion arrest was accompanied also by a weak fat differentiation and migratory potential, which was enhanced by NOX1 inhibition. This suggests an inhibitory role for NOX1-induced ROS overproduction on aASCs, their fat differentiation and migratory potential. In contrast to aASCs, similar cells produced from subcutaneous fat were easily expanded in normoxic cultures, exhibiting low ROS concentrations, a low number of apoptotic cells and improved fat differentiation and migration. Taken together, our results show, for the first time, that NOX1-induced ROS accumulation halts ASC expansion and reduces their differentiation and migratory potential under normoxic conditions. Importantly, this phenotype comprises a tissue-specific signature as it was evident in aASCs but not in subcutaneous ASCs. NOX-induced ROS accumulation and cytokine production by fat are part of the metabolic syndrome. The similarity of this phenomenon to aASC phenotype may indicate that they arise from similar molecular mechanisms. PMID:25880095

Ginsenoside Rb1 ameliorates liver fat accumulation by upregulating perilipin expression in adipose tissue of db/db obese mice

PubMed Central

Yu, Xizhong; Ye, Lifang; Zhang, Hao; Zhao, Juan; Wang, Guoqiang; Guo, Chao; Shang, Wenbin

2014-01-01

Background Ginsenoside Rb1 (G-Rb1), the major active constituent of ginseng, improves insulin sensitivity and exerts antidiabetic effects. We tested whether the insulin-sensitizing and antidiabetic effects of G-Rb1 results from a reduction in ectopic fat accumulation, mediated by inhibition of lipolysis in adipocytes. Methods Obese and diabetic db/db mice were treated with daily doses of 20 mg/kg G-Rb1 for 14 days. Hepatic fat accumulation was evaluated by measuring liver weight and triglyceride content. Levels of blood glucose and serum insulin were used to evaluate insulin sensitivity in db/db mice. Lipolysis in adipocytes was evaluated by measuring plasma-free fatty acids and glycerol release from 3T3-L1 adipocytes treated with G-Rb1. The expression of relevant genes was analyzed by western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay kit. Results G-Rb1 increased insulin sensitivity and alleviated hepatic fat accumulation in obese diabetic db/db mice, and these effects were accompanied by reduced liver weight and hepatic triglyceride content. Furthermore, G-Rb1 lowered the levels of free fatty acids in obese mice, which may contribute to a decline in hepatic lipid accumulation. Corresponding to these results, G-Rb1 significantly suppressed lipolysis in 3T3-L1 adipocytes and upregulated the perilipin expression in both 3T3-L1 adipocytes and mouse epididymal fat pads. Moreover, G-Rb1 increased the level of adiponectin and reduced that of tumor necrosis factor-α in obese mice, and these effects were confirmed in 3T3-L1 adipocytes. Conclusion G-Rb1 may improve insulin sensitivity in obese and diabetic db/db mice by reducing hepatic fat accumulation and suppressing adipocyte lipolysis; these effects may be mediated via the upregulation of perilipin expression in adipocytes. PMID:26199550

Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation

PubMed Central

Martius, Gesa; Alwahsh, Salamah Mohammad; Rave-Fränk, Margret; Hess, Clemens Friedrich; Christiansen, Hans; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

2014-01-01

Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot analysis and RT-PCR in liver, respectively. Changes in FAT/CD36 expression were studied in-vitro in a human monocyte cell line U937 after irradiation in presence or absence of infliximab (IFX). Nile Red staining of liver cryosections showed a quick (12-48 h) increase in fat droplets. Accordingly, hepatic triglycerides (TG) and free fatty acids (FFA) were elevated. An early increase (3-6 h) in the serum level of HDL-C, TG and cholesterol was measured after single dose irradiation followed by a decrease thereafter. Furthermore, expression of the fat transporter protein FAT/CD36 was increased, immunohistochemistry revealed basolateral and cytoplasmic expression in hepatocytes. Moreover, apolipoprotein-B100, -C3 and enzymes (acetyl-CoA carboxylase, lipoprotein-lipase, carnitine-palmitoyltransferase, malonyl-CoA-decarboxylase) involved in fat metabolism were induced at 12-24 h. Early activation of the NFkβ pathway (IκBα) by TNF-α was seen, followed by a significant elevation of serum markers for liver damage (AST and GLDH). TNF-α blockage by anti-TNF-α in cell culture (U937) prevented the increase of FAT/CD36 caused by irradiation. Selective liver irradiation is a model for rapid induction of steatosis hepatis and fat accumulation could be triggered by irradiation-induced inflammatory mediators (e.g. TNF-α). PMID:25197426

Browning of subcutaneous fat and higher surface temperature in response to phenotype selection for advanced endurance exercise performance in male DUhTP mice.

PubMed

Brenmoehl, J; Ohde, D; Albrecht, E; Walz, C; Tuchscherer, A; Hoeflich, A

2017-02-01

For the assessment of genetic or conditional factors of fat cell browning, novel and polygenic animal models are required. Therefore, the long-term selected polygenic mouse line DUhTP originally established in Dummerstorf for high treadmill performance is used. DUhTP mice are characterized by increased fat accumulation in the sedentary condition and elevated fat mobilization during mild voluntary physical activity. In the present study, the phenotype of fat cell browning of subcutaneous fat and a potential effect on oral glucose tolerance, an indicator of metabolic health, were addressed in DUhTP mice. Analysis of peripheral fat pads revealed increased brite (brown-in-white) subcutaneous adipose tissues and in subcutaneous fat from DUhTP mice higher levels of irisin and different markers of fat cell browning like T-box transcription factor (Tbx1), PPARα, and uncoupling protein (UCP1) (P < 0.05) when compared to unselected controls. UCP1 was further increased in subcutaneous fat from DUhTP mice in response to mild exercise (fourfold, P < 0.05). In addition, surface temperature of DUhTP mice was increased when compared to controls indicating a physiological effect of increased UCP1 expression. The present study suggests that DUhTP mice exhibit different markers of mitochondrial biogenesis and fat browning without external stimuli. At an age of 43 days, sedentary DUhTP mice have improved metabolic health as judged from lower levels of blood glucose after an oral glucose tolerance test. Consequently, the non-inbred mouse model DUhTP represents a novel model for the identification of fat cell browning mechanisms in white adipose tissues.

Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.

PubMed

Geng, Shanshan; Zhu, Weiwei; Xie, Chunfeng; Li, Xiaoting; Wu, Jieshu; Liang, Zhaofeng; Xie, Wei; Zhu, Jianyun; Huang, Cong; Zhu, Mingming; Wu, Rui; Zhong, Caiyun

2016-04-01

The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice. Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF-MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis. Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK. Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

Cynanchum wilfordii Radix attenuates liver fat accumulation and damage by suppressing hepatic cyclooxygenase-2 and mitogen-activated protein kinase in mice fed with a high-fat and high-fructose diet.

PubMed

Jang, Seon-A; Lee, SungRyul; Sohn, Eun-Hwa; Yang, Jaehyuk; Park, Dae Won; Jeong, Yong Joon; Kim, Inhye; Kwon, Jung Eun; Song, Hae Seong; Cho, Young Mi; Meng, Xue; Koo, Hyun Jung; Kang, Se Chan

2016-09-01

Excessive consumption of fat and fructose augments the pathological progression of nonalcoholic fatty liver disease through hepatic fibrosis, inflammation, and hepatic de novo lipogenesis. We hypothesized that supplementation with Cynanchum wilfordii extract (CWE) decreases fat accumulation in the liver by suppressing cyclooxygenase-2 (COX-2), the nuclear translocation of nuclear factor κB (NF-κB), and p38 mitogen-activated protein kinase (MAPK). The beneficial effect of CWE was evaluated in a murine model of nonalcoholic fatty liver disease. Mice were fed either a normal diet or an atherogenic diet with fructose (ATHFR) in the presence or absence of CWE (50, 100, or 200 mg/kg; n=6/group). Treatment with ATHFR induced a hepatosplenomegaly-like condition (increased liver and spleen weight); this pathological change was attenuated in the presence of CWE. The ATHFR group exhibited impaired liver function, as evidenced by increased blood levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, fat accumulation in the liver, and lipid profiles. Supplementation of CWE (100 and 200 mg/kg, P<.05) ameliorated these impaired liver functions. Atherogenic diet with fructose increased the protein levels of COX-2 and p38 MAPK, as well as the nuclear translocation of NF-κB. These signaling pathways, which are associated with the inflammatory response, were markedly suppressed after CWE treatment (100 and 200 mg/kg). In summary, CWE supplementation reduced high-fat and high-fructose diet-induced fat accumulation and damage in the liver by suppressing COX-2, NF-κB, and p38 MAPK. Copyright © 2016 Elsevier Inc. All rights reserved.

Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats.

PubMed

Lu, Yi; Wu, Qing; Liu, Long-Zhu; Yu, Xiao-Jiang; Liu, Jin-Jun; Li, Man-Xiang; Zang, Wei-Jin

2018-04-01

Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1α pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue. Copyright © 2018 Elsevier B.V. All rights reserved.

The subcutaneous abdominal fat and not the intraabdominal fat compartment is associated with anovulation in women with obesity and infertility.

PubMed

Kuchenbecker, Walter K H; Groen, Henk; Zijlstra, Tineke M; Bolster, Johanna H T; Slart, Riemer H J; van der Jagt, Erik J; Kobold, Anneke C Muller; Wolffenbuttel, Bruce H R; Land, Jolande A; Hoek, Annemieke

2010-05-01

Abdominal fat contributes to anovulation. We compared body fat distribution measurements and their contribution to anovulation in obese ovulatory and anovulatory infertile women. Seventeen ovulatory and 40 anovulatory women (age, 30 +/- 4 yr; body mass index, 37.7 +/- 6.1 kg/m(2)) participated. Body fat distribution was measured by anthropometrics, dual-energy x-ray absorptiometry, and single-sliced abdominal computed tomography scan. Multiple logistic regression analysis was applied to determine which fat compartments significantly contributed to anovulation. Anovulatory women had a higher waist circumference (113 +/- 11 vs. 104 +/- 9 cm; P < 0.01) and significantly more trunk fat (23.0 +/- 5.3 vs. 19.1 +/- 4.2 kg; P < 0.01) and abdominal fat (4.4 +/- 1.3 kg vs. 3.5 +/- 0.9 kg; P < 0.05) on dual-energy x-ray absorptiometry scan than ovulatory women despite similar body mass index. The volume of intraabdominal fat on single-sliced abdominal computed tomography scan was not significantly different between the two groups (203 +/- 56 vs. 195 +/- 71 cm(3); P = 0.65), but anovulatory women had significantly more sc abdominal fat (SAF) (992 +/- 198 vs. 864 +/- 146 cm(3); P < 0.05). After multiple logistic regression analysis, only trunk fat, abdominal fat, and SAF were associated with anovulation. Abdominal fat is increased in anovulatory women due to a significant increase in SAF and not in intraabdominal fat. SAF and especially abdominal and trunk fat accumulation are associated with anovulation.

Tangeretin and 3',4',3,5,6,7,8-heptamethoxyflavone decrease insulin resistance, fat accumulation and oxidative stress in mice fed high-fat diet

USDA-ARS?s Scientific Manuscript database

Tangeretin and heptamethoxyflavone were investigated for their ability to repair metabolic damage caused by high-fat diet in C57BL/6J mice. In the first four weeks, induction of obesity was performed and the mice received standard diet (11% kcal from fat) or high-fat diet (45% kcal from fat). After ...

Quantitative Proton Magnetic Resonance Techniques for Measuring Fat

PubMed Central

Harry, Houchun; Kan, Hermien E.

2014-01-01

Accurate, precise, and reliable techniques for quantifying body and organ fat distributions are important tools in physiology research. They are critically needed in studies of obesity and diseases involving excess fat accumulation. Proton magnetic resonance methods address this need by providing an array of relaxometry-based (T1, T2) and chemical-shift-based approaches. These techniques can generate informative visualizations of regional and whole-body fat distributions, yield measurements of fat volumes within specific body depots, and quantify fat accumulation in abdominal organs and muscles. MR methods are commonly used to investigate the role of fat in nutrition and metabolism, to measure the efficacy of short and long-term dietary and exercise interventions, to study the implications of fat in organ steatosis and muscular dystrophies, and to elucidate pathophysiological mechanisms in the context of obesity and its comorbidities. The purpose of this review is to provide a summary of mainstream MR strategies for fat quantification. The article will succinctly describe the principles that differentiate water and fat proton signals, summarize advantages and limitations of various techniques, and offer a few illustrative examples. The article will also highlight recent efforts in MR of brown adipose tissue and conclude by briefly discussing some future research directions. PMID:24123229

Long term highly saturated fat diet does not induce NASH in Wistar rats

PubMed Central

Romestaing, Caroline; Piquet, Marie-Astrid; Bedu, Elodie; Rouleau, Vincent; Dautresme, Marianne; Hourmand-Ollivier, Isabelle; Filippi, Céline; Duchamp, Claude; Sibille, Brigitte

2007-01-01

Background Understanding of nonalcoholic steatohepatitis (NASH) is hampered by the lack of a suitable model. Our aim was to investigate whether long term high saturated-fat feeding would induce NASH in rats. Methods 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (MCD) diet, a non physiological model of NASH. Results MCDD fed rats rapidly lost weight and showed NASH features. Rats fed coconut (86% of saturated fatty acid) or butter (51% of saturated fatty acid) had an increased caloric intake (+143% and +30%). At the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45%) and butter (42%) groups than in the standard (7%) diet group. No change in body mass was observed as compared with standard rats at the end of the experiment. However, high fat fed rats were fattier with enlarged white and brown adipose tissue (BAT) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. Absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in BAT uncoupling protein UCP1 (+25–28% vs standard). Conclusion Long term high saturated fat feeding led to increased "peripheral" fat storage and BAT thermogenesis but did not induce hepatic steatosis and NASH. PMID:17313679

Bone marrow fat accumulation accelerated by high fat diet is suppressed by exercise

PubMed Central

Styner, Maya; Thompson, William R.; Galior, Kornelia; Uzer, Gunes; Wu, Xin; Kadari, Sanjay; Case, Natasha; Xie, Zhihui; Sen, Buer; Romaine, Andrew; Pagnotti, Gabriel M.; Rubin, Clinton T.; Styner, Martin A.; Horowitz, Mark C.; Rubin, Janet

2014-01-01

Marrow adipose tissue (MAT), associated with skeletal fragility and hematologic insufficiency, remains poorly understood and difficult to quantify. We tested the response of MAT to high fat diet (HFD) and exercise using a novel volumetric analysis, and compared it to measures of bone quantity. We hypothesized that HFD would increase MAT and diminish bone quantity, while exercise would slow MAT acquisition and promote bone formation. Eight week-old female C57BL/6 mice were fed a regular (RD) or HFD, and exercise groups were provided voluntary access to running wheels (RD-E, HFD-E). Femoral MAT was assessed by μCT (lipid binder osmium) using a semi-automated approach employing rigid co-alignment, regional bone masks and was normalized for total femoral volume (TV) of the bone compartment. MAT was 2.6-fold higher in HFD relative to RD mice. Exercise suppressed MAT in RD-E mice by more than half compared with RD. Running similarly inhibited MAT acquisition in HFD mice. Exercise significantly increased bone quantity in both diet groups. Thus, HFD caused significant accumulation of MAT; importantly running exercise limited MAT acquisition while promoting bone formation during both diets. That MAT is exquisitely responsive to diet and exercise, and its regulation by exercise appears to be inversely proportional to effects on exercise induced bone formation, is relevant for an aging and sedentary population. PMID:24709686

Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects.

PubMed

Yoshizane, Chiyo; Mizote, Akiko; Yamada, Mika; Arai, Norie; Arai, Shigeyuki; Maruta, Kazuhiko; Mitsuzumi, Hitoshi; Ariyasu, Toshio; Ushio, Shimpei; Fukuda, Shigeharu

2017-02-06

Trehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and incretin responses after trehalose ingestion in healthy Japanese volunteers. In a crossover study, 20 fasted healthy volunteers consumed 25 g trehalose or glucose in 100 mL water. Blood samples were taken frequently over the following 3 h, and blood glucose, insulin, active gastric inhibitory polypeptide (GIP) and active glucagon-like peptide-1 (GLP-1) levels were measured. Trehalose ingestion did not evoke rapid increases in blood glucose levels, and had a lower stimulatory potency of insulin and active GIP secretion compared with glucose ingestion. Conversely, active GLP-1 showed higher levels from 45 to 180 min after trehalose ingestion as compared with glucose ingestion. Specifically, active GIP secretion, which induces fat accumulation, was markedly lower after trehalose ingestion. Our findings indicate that trehalose may be a useful saccharide for good health because of properties that do not stimulate rapid increases in blood glucose and excessive secretion of insulin and GIP promoting fat accumulation.

Characterization of fat metabolism in the fatty liver caused by a high-fat, low-carbohydrate diet: A study under equal energy conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurosaka, Yuka; Shiroya, Yoko; Yamauchi, Hideki

The pathology of fatty liver due to increased percentage of calories derived from fat without increased overall caloric intake is largely unclear. In this study, we aimed to characterize fat metabolism in rats with fatty liver resulting from consumption of a high-fat, low-carbohydrate (HFLC) diet without increased caloric intake. Four-week-old male Sprague-Dawley rats were randomly assigned to the control (Con) and HFLC groups, and rats were fed the corresponding diets ad libitum. Significant decreases in food intake per gram body weight were observed in the HFLC group compared with that in the Con group. Thus, there were no significant differencesmore » in body weights or caloric intake per gram body weight between the two groups. Marked progressive fat accumulation was observed in the livers of rats in the HFLC group, accompanied by suppression of de novo lipogenesis (DNL)-related proteins in the liver and increased leptin concentrations in the blood. In addition, electron microscopic observations revealed that many lipid droplets had accumulated within the hepatocytes, and mitochondrial numbers were reduced in the hepatocytes of rats in the HFLC group. Our findings confirmed that consumption of the HFLC diet induced fatty liver, even without increased caloric intake. Furthermore, DNL was not likely to be a crucial factor inducing fatty liver with standard energy intake. Instead, ultrastructural abnormalities found in mitochondria, which may cause a decline in β-oxidation, could contribute to the development of fatty liver. - Highlights: • The high-fat, low-carbohydrate diet did not affect body weight or caloric intake. • The high-fat, low-carbohydrate diet caused fatty liver in rats. • De novo lipogenesis was not a crucial factor in fatty liver. • Mitochondria were altered in fatty livers of rats consuming this diet.« less

Short-term hyperthyroidism modulates adenosine receptors and catalytic activity of adenylate cyclase in adipocytes.

PubMed Central

Rapiejko, P J; Malbon, C C

1987-01-01

The effects of short-term hyperthyroidism in vivo on the status of the components of the fat-cell hormone-sensitive adenylate cyclase were investigated. The number of beta-adrenergic receptors was elevated by about 25% in membranes of fat-cells isolated from hyperthyroid rats as compared with euthyroid rats, but their affinity for radioligand was unchanged. Membranes of hyperthyroid-rat fat-cells displayed less than 65% of the normal complement of receptors for [3H]cyclohexyladenosine. The affinity of the receptors for this ligand was normal. In contrast with the marked increase in the amounts of the alpha-subunits of the guanine nucleotide-binding proteins Gi (Mr 41,000) and Go (Mr 39,000) observed in the hypothyroid state [Malbon, Rapiejko & Mangano (1985) J. Biol. Chem. 260, 2558-2564], the amounts of alpha-Gi, alpha-Go as well as alpha-Gs subunits [Mr 42,000 (major) and 46,000/48,000 (minor)] were not changed by hyperthyroidism. Adenylate cyclase activity in response to forskolin, guanosine 5'-[gamma-thio]triphosphate or isoprenaline, in contrast, was decreased by 30-50% in fat-cell membranes from hyperthyroid rats. Fat-cells isolated from hyperthyroid rats accumulated cyclic AMP to less than 50% of the extent in their euthyroid counterparts in the presence of adenosine deaminase and either adrenaline or forskolin, suggesting a decrease in the amount or activity of the catalytic subunit of adenylate cyclase. In the absence of exogenous adenosine deaminase, cyclic AMP accumulation in response to adrenaline was elevated rather than decreased in fat-cells from hyperthyroid rats. The inhibitory influence of adenosine is apparently limited in the hyperthyroid state by the decreased complement of inhibitory R-site purinergic receptors in these fat-cells. Short-term hyperthyroidism modulates the fat-cell adenylate cyclase system at the receptor level (beta-receptor number increased, R-site purinergic-receptor number decreased) and the catalytic subunit of adenylate cyclase. Images Fig. 2. PMID:3036073

Effects of different ratios of monounsaturated and polyunsaturated fatty acids to saturated fatty acids on regulating body fat deposition in hamsters.

PubMed

Liao, Fang-Hsuean; Liou, Tsan-Hon; Shieh, Ming-Jer; Chien, Yi-Wen

2010-01-01

Effects of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid consumption on regulating body fat accumulation and body weight gain are controversial between animal and human studies. We designed a 2 x 2 factorial study, with two levels of MUFAs (60% and 30%) and two levels of polyunsaturated-to-saturated fatty acid (P/S) ratio (5 and 3) to prepare four kinds of experimental oils consisting of 60% MUFAs with a high or low P/S ratio (HMHR or HMLR, respectively) or 30% MUFAs with a high or low P/S ratio (LMHR or LMLR, respectively). Thirty-two male golden Syrian hamsters were randomly divided into four groups and fed the experimental diets containing 15% (w/w) fat for 12 wk. No difference was observed in the mean daily food intake. Hamsters fed the LMLR diet had increased weight gain, epididymal and retroperitoneal white adipose tissues, plasma non-esterified fatty acids, insulin, hepatic acetyl coenzyme A carboxylase and malic enzyme activities, and mRNA expressions of peroxisome proliferator-activated receptor-alpha and sterol regulatory element-binding protein-1c among all groups (P < 0.05). Hamsters fed the HMHR diet had lower plasma insulin levels and hepatic acetyl coenzyme A carboxylase activities among groups (P < 0.05) and elevated hepatic acyl coenzyme A oxidase and carnitine palmitoyltransferase-I activities compared with those fed the LMLR diet (P < 0.05). Hamsters fed the LMLR diet had increased weight gain and body fat accumulation, whereas the HMHR diet appeared to be beneficial in preventing white adipose tissue accumulation by decreasing plasma insulin levels and increasing hepatic lipolytic enzyme activities involved in beta-oxidation. 2010 Elsevier Inc. All rights reserved.

A mircroarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice

USDA-ARS?s Scientific Manuscript database

A sexual dimorphism exists in body fat distribution; females deposit relatively more fat in subcutaneous/inguinal depots whereas males deposit more fat in the intra-abdominal/gonadal depot. Our objective was to systematically document depot- and sex-related differences in the accumulation of adipose...

Screening for Bioactive Metabolites in Plant Extracts Modulating Glucose Uptake and Fat Accumulation

PubMed Central

El-Houri, Rime B.; Kotowska, Dorota; Olsen, Louise C. B.; Bhattacharya, Sumangala; Christensen, Lars P.; Oksbjerg, Niels; Færgeman, Nils; Kristiansen, Karsten; Christensen, Kathrine B.

2014-01-01

Dichloromethane and methanol extracts of seven different food and medicinal plants were tested in a screening platform for identification of extracts with potential bioactivity related to insulin-dependent glucose uptake and fat accumulation. The screening platform included a series of in vitro bioassays, peroxisome proliferator-activated receptor (PPAR) γ-mediated transactivation, adipocyte differentiation of 3T3-L1 cell cultures, and glucose uptake in both 3T3-L1 adipocytes and primary porcine myotubes, as well as one in vivo bioassay, fat accumulation in the nematode Caenorhabditis elegans. We found that dichloromethane extracts of aerial parts of golden root (Rhodiola rosea) and common elder (Sambucus nigra) as well as the dichloromethane extracts of thyme (Thymus vulgaris) and carrot (Daucus carota) were able to stimulate insulin-dependent glucose uptake in both adipocytes and myotubes while weekly activating PPARγ without promoting adipocyte differentiation. In addition, these extracts were able to decrease fat accumulation in C. elegans. Methanol extracts of summer savory (Satureja hortensis), common elder, and broccoli (Brassica oleracea) enhanced glucose uptake in myotubes but were not able to activate PPARγ, indicating a PPARγ-independent effect on glucose uptake. PMID:25254050

Non-linear imaging techniques visualize the lipid profile of C. elegans

NASA Astrophysics Data System (ADS)

Mari, Meropi; Petanidou, Barbara; Palikaras, Konstantinos; Fotakis, Costas; Tavernarakis, Nektarios; Filippidis, George

2015-07-01

The non-linear techniques Second and Third Harmonic Generation (SHG, THG) have been employed simultaneously to record three dimensional (3D) imaging and localize the lipid content of the muscular areas (ectopic fat) of Caenorhabditis elegans (C. elegans). Simultaneously, Two-Photon Fluorescence (TPEF) was used initially to localize the stained lipids with Nile Red, but also to confirm the THG potential to image lipids successfully. In addition, GFP labelling of the somatic muscles, proves the initial suggestion of the existence of ectopic fat on the muscles and provides complementary information to the SHG imaging of the pharynx. The ectopic fat may be related to a complex of pathological conditions including type-2 diabetes, hypertension and cardiovascular diseases. The elucidation of the molecular path leading to the development of metabolic syndrome is a vital issue with high biological significance and necessitates accurate methods competent of monitoring lipid storage distribution and dynamics in vivo. THG microscopy was employed as a quantitative tool to monitor the lipid accumulation in non-adipose tissues in the pharyngeal muscles of 12 unstained specimens while the SHG imaging revealed the anatomical structure of the muscles. The ectopic fat accumulation on the pharyngeal muscles increases in wild type (N2) C. elegans between 1 and 9 days of adulthood. This suggests a correlation of the ectopic fat accumulation with the aging. Our results can provide new evidence relating the deposition of ectopic fat with aging, but also validate SHG and THG microscopy modalities as new, non-invasive tools capable of localizing and quantifying selectively lipid accumulation and distribution.

Evolutionarily conserved gene family important for fat storage

PubMed Central

Kadereit, Bert; Kumar, Pradeep; Wang, Wen-Jun; Miranda, Diego; Snapp, Erik L.; Severina, Nadia; Torregroza, Ingrid; Evans, Todd; Silver, David L.

2008-01-01

The ability to store fat in the form of cytoplasmic triglyceride droplets is conserved from Saccharomyces cerevisiae to humans. Although much is known regarding the composition and catabolism of lipid droplets, the molecular components necessary for the biogenesis of lipid droplets have remained obscure. Here we report the characterization of a conserved gene family important for lipid droplet formation named fat-inducing transcript (FIT). FIT1 and FIT2 are endoplasmic reticulum resident membrane proteins that induce lipid droplet accumulation in cell culture and when expressed in mouse liver. shRNA silencing of FIT2 in 3T3-LI adipocytes prevents accumulation of lipid droplets, and depletion of FIT2 in zebrafish blocks diet-induced accumulation of lipid droplets in the intestine and liver, highlighting an important role for FIT2 in lipid droplet formation in vivo. Together these studies identify and characterize a conserved gene family that is important in the fundamental process of storing fat. PMID:18160536

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials.

PubMed

Ma, Jiantao; Karlsen, Micaela C; Chung, Mei; Jacques, Paul F; Saltzman, Edward; Smith, Caren E; Fox, Caroline S; McKeown, Nicola M

2016-01-01

The effect of added sugar intake on ectopic fat accumulation is a subject of debate. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. MEDLINE, CAB Abstracts, CAB Global Health, and EBM (Evidence-Based Medicine) Reviews - Cochrane Central Register of Controlled Trials databases were searched for studies published from 1973 to September 2014. RCTs with a minimum of 6 days' duration of added sugar exposure in the intervention group were selected. The dosage of added sugar intake as a percentage of total energy was extracted or calculated. Means and standard deviations of pre- and post-test measurements or changes in ectopic fat depots were collected. Fourteen RCTs were included. Most of the studies had a medium to high risk of bias. Meta-analysis showed that, compared with eucaloric controls, subjects who consumed added sugar under hypercaloric conditions likely increased ectopic fat, particularly in the liver (pooled standardized mean difference = 0.9 [95%CI, 0.6-1.2], n = 6) and muscles (pooled SMD = 0.6 [95%CI, 0.2-1.0], n = 4). No significant difference was observed in liver fat, visceral adipose tissue, or muscle fat when isocaloric intakes of different sources of added sugars were compared. Data from a limited number of RCTs suggest that excess added sugar intake under hypercaloric diet conditions likely increases ectopic fat depots, particularly in the liver and in muscle fat. There are insufficient data to compare the effect of different sources of added sugars on ectopic fat deposition or to compare intake of added sugar with intakes of other macronutrients. Future well-designed RCTs with sufficient power and duration are needed to address the role of sugars on ectopic fat deposition. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Toward production of jet fuel functionality in oilseeds: identification of FatB acyl-acyl carrier protein thioesterases and evaluation of combinatorial expression strategies in Camelina seeds

PubMed Central

Kim, Hae Jin; Silva, Jillian E.; Vu, Hieu Sy; Mockaitis, Keithanne; Nam, Jeong-Won; Cahoon, Edgar B.

2015-01-01

Seeds of members of the genus Cuphea accumulate medium-chain fatty acids (MCFAs; 8:0–14:0). MCFA- and palmitic acid- (16:0) rich vegetable oils have received attention for jet fuel production, given their similarity in chain length to Jet A fuel hydrocarbons. Studies were conducted to test genes, including those from Cuphea, for their ability to confer jet fuel-type fatty acid accumulation in seed oil of the emerging biofuel crop Camelina sativa. Transcriptomes from Cuphea viscosissima and Cuphea pulcherrima developing seeds that accumulate >90% of C8 and C10 fatty acids revealed three FatB cDNAs (CpuFatB3, CvFatB1, and CpuFatB4) expressed predominantly in seeds and structurally divergent from typical FatB thioesterases that release 16:0 from acyl carrier protein (ACP). Expression of CpuFatB3 and CvFatB1 resulted in Camelina oil with capric acid (10:0), and CpuFatB4 expression conferred myristic acid (14:0) production and increased 16:0. Co-expression of combinations of previously characterized Cuphea and California bay FatBs produced Camelina oils with mixtures of C8–C16 fatty acids, but amounts of each fatty acid were less than obtained by expression of individual FatB cDNAs. Increases in lauric acid (12:0) and 14:0, but not 10:0, in Camelina oil and at the sn-2 position of triacylglycerols resulted from inclusion of a coconut lysophosphatidic acid acyltransferase specialized for MCFAs. RNA interference (RNAi) suppression of Camelina β-ketoacyl-ACP synthase II, however, reduced 12:0 in seeds expressing a 12:0-ACP-specific FatB. Camelina lines presented here provide platforms for additional metabolic engineering targeting fatty acid synthase and specialized acyltransferases for achieving oils with high levels of jet fuel-type fatty acids. PMID:25969557

Toward production of jet fuel functionality in oilseeds: Identification of FatB acyl-acyl carrier protein thioesterases and evaluation of combinatorial expression strategies in Camelina seeds

DOE PAGES

Kim, Hae Jin; Silva, Jillian E.; Vu, Hieu Sy; ...

2015-05-11

Seeds of members of the genus Cuphea accumulate medium-chain fatty acids (MCFAs; 8:0–14:0). MCFA- and palmitic acid- (16:0) rich vegetable oils have received attention for jet fuel production, given their similarity in chain length to Jet A fuel hydrocarbons. Studies were conducted to test genes, including those from Cuphea, for their ability to confer jet fuel-type fatty acid accumulation in seed oil of the emerging biofuel crop Camelina sativa. Transcriptomes from Cuphea viscosissima and Cuphea pulcherrima developing seeds that accumulate >90% of C8 and C10 fatty acids revealed three FatB cDNAs ( CpuFatB3, CvFatB1, and CpuFatB4) expressed predominantly in seedsmore » and structurally divergent from typical FatB thioesterases that release 16:0 from acyl carrier protein (ACP). Expression of CpuFatB3 and CvFatB1 resulted in Camelina oil with capric acid (10:0), and CpuFatB4 expression conferred myristic acid (14:0) production and increased 16:0. Co-expression of combinations of previously characterized Cuphea and California bay FatBs produced Camelina oils with mixtures of C8–C16 fatty acids, but amounts of each fatty acid were less than obtained by expression of individual FatB cDNAs. Increases in lauric acid (12:0) and 14:0, but not 10:0, in Camelina oil and at the sn-2 position of triacylglycerols resulted from inclusion of a coconut lysophosphatidic acid acyltransferase specialized for MCFAs. RNA interference (RNAi) suppression of Camelina β-ketoacyl-ACP synthase II, however, reduced 12:0 in seeds expressing a 12:0-ACP-specific FatB. Here, Camelina lines presented here provide platforms for additional metabolic engineering targeting fatty acid synthase and specialized acyltransferases for achieving oils with high levels of jet fuel-type fatty acids.« less

The Effects of Diet Composition on Body Fat and Hepatic Steatosis in an Animal (Peromyscus californicus) Model of the Metabolic Syndrome

PubMed Central

Krugner-Higby, Lisa; Caldwell, Stephen; Coyle, Kathryn; Bush, Eugene; Atkinson, Richard; Joers, Valerie

2011-01-01

The objective of this research was to determine body composition, total fat content, fat distribution, and serum leptin concentration in hyperlipidemic (high responder, HR) and normolipidemic (low responder, LR) California mice (Peromyscus californicus). In our initial experiments, we sought to determine whether differences in regional fat storage were associated with hyperlipidemia in this species. To further characterize the hepatic steatosis in the mice, we performed 2 additional experiments by using a diet containing 45% of energy as fat. The body fat content of mice fed a low fat-diet (12.3% energy as fat) was higher than that of mice fed a moderate-fat diet (25.8% energy as fat). Total body fat did not differ between HR and LR mice. There was no significant difference between intraabdominal, gonadal, or inguinal fat pad weights. Liver weights of HR mice fed the moderate-fat diet were higher than those of LR mice fed the same diet, and the moderate-fat diet was associated with nonalcoholic fatty liver (NAFL). Mice fed the 45% diet had higher histologic score for steatosis but very little inflammatory response. Chemical analysis indicated increased lipid in the livers of mice fed the high-fat diet compared with those fed the low-fat diet. HR and LR mice had similar serum leptin concentrations. California mice develop NAFL without excess fat accumulation elsewhere. NAFL was influenced by genetic and dietary factors. These mice may be a naturally occuring model of partial lipodystrophy. PMID:21819679

Carotenoids and fat-soluble vitamins in horse tissues: a comparison with cattle.

PubMed

Álvarez, R; Meléndez-Martínez, A J; Vicario, I M; Alcalde, M J

2015-07-01

Carotenoids are important for human health because of their provitamin A function among other biological actions. Their implication on consumer point of view of cattle products have been widely studied, but very little information is available for horse products. The aim of this study was to study the accumulation of carotenoids, retinoids and tocopherol by HPLC and HPLC-MS analysis in different horse tissues (plasma, milk, adipose tissue and liver) and compare it with that of cattle. Fat color was also studied. Four groups of animals were studied (15 animals within each group): lactating mares (709.82±23.09 kg) and cows (576.93±31.94 kg) reared outdoors; and foals (556.8±25.9 kg, 14 months old) and calves (474.7±36.2 kg, 14 months old) reared indoors. Both mares and foals were from the Hispano-Breton breed, whereas both cows and calves belonged to the commercial crossbred Limousine-Retinta. Differences in plasma and milk carotenoids (P0.05). Both species showed different levels of accumulation of retinoids in the liver, with the foal having better accumulation (P<0.01, P<0.001). These results indicate that there are species-specific differences in the accumulation of carotenoids, retinol and tocopherol, but further studies are required to establish the mechanism of these differences.

Identification of Sphingolipid Metabolites That Induce Obesity via Misregulation of Appetite, Caloric Intake and Fat Storage in Drosophila

PubMed Central

Walls, Stanley M.; Attle, Steve J.; Brulte, Gregory B.; Walls, Marlena L.; Finley, Kim D.; Chatfield, Dale A.; Herr, Deron R.; Harris, Greg L.

2013-01-01

Obesity is defined by excessive lipid accumulation. However, the active mechanistic roles that lipids play in its progression are not understood. Accumulation of ceramide, the metabolic hub of sphingolipid metabolism, has been associated with metabolic syndrome and obesity in humans and model systems. Here, we use Drosophila genetic manipulations to cause accumulation or depletion of ceramide and sphingosine-1-phosphate (S1P) intermediates. Sphingolipidomic profiles were characterized across mutants for various sphingolipid metabolic genes using liquid chromatography electrospray ionization tandem mass spectroscopy. Biochemical assays and microscopy were used to assess classic hallmarks of obesity including elevated fat stores, increased body weight, resistance to starvation induced death, increased adiposity, and fat cell hypertrophy. Multiple behavioral assays were used to assess appetite, caloric intake, meal size and meal frequency. Additionally, we utilized DNA microarrays to profile differential gene expression between these flies, which mapped to changes in lipid metabolic pathways. Our results show that accumulation of ceramides is sufficient to induce obesity phenotypes by two distinct mechanisms: 1) Dihydroceramide (C14:0) and ceramide diene (C14:2) accumulation lowered fat store mobilization by reducing adipokinetic hormone- producing cell functionality and 2) Modulating the S1P: ceramide (C14:1) ratio suppressed postprandial satiety via the hindgut-specific neuropeptide like receptor dNepYr, resulting in caloric intake-dependent obesity. PMID:24339790

Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets

NASA Astrophysics Data System (ADS)

Brackmann, Christian; Gabrielsson, Britt; Svedberg, Fredrik; Holmäng, Agneta; Sandberg, Ann-Sofie; Enejder, Annika

2010-11-01

Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.

Nonlinear microscopy of lipid storage and fibrosis in muscle and liver tissues of mice fed high-fat diets.

PubMed

Brackmann, Christian; Gabrielsson, Britt; Svedberg, Fredrik; Holmaang, Agneta; Sandberg, Ann-Sofie; Enejder, Annika

2010-01-01

Hallmarks of high-fat Western diet intake, such as excessive lipid accumulation in skeletal muscle and liver as well as liver fibrosis, are investigated in tissues from mice using nonlinear microscopy, second harmonic generation (SHG), and coherent anti-Stokes Raman scattering (CARS), supported by conventional analysis methods. Two aspects are presented; intake of standard chow versus Western diet, and a comparison between two high-fat Western diets of different polyunsaturated lipid content. CARS microscopy images of intramyocellular lipid droplets in muscle tissue show an increased amount for Western diet compared to standard diet samples. Even stronger diet impact is found for liver samples, where combined CARS and SHG microscopy visualize clear differences in lipid content and collagen fiber development, the latter indicating nonalcoholic fatty liver disease (NAFLD) and steatohepatitis induced at a relatively early stage for Western diet. Characteristic for NAFLD, the fibrous tissue-containing lipids accumulate in larger structures. This is also observed in CARS images of liver samples from two Western-type diets of different polyunsaturated lipid contents. In summary, nonlinear microscopy has strong potential (further promoted by technical advances toward clinical use) for detection and characterization of steatohepatitis already in its early stages.

Differential effects of dietary fats on sympathetic nervous system activity in the rat.

PubMed

Young, J B; Walgren, M C

1994-01-01

Fat feeding stimulates sympathetic nervous system (SNS) activity in rats. To determine if fats vary in their potency as stimulants of the SNS, [3H]norepinephrine ([3H]NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of animals fed lab chow diets supplemented with safflower oil, coconut oil, or medium-chain triglycerides (MCT). At 5 days, all three fats accelerated [3H]NE turnover in heart and did so equally, but only when the fat supplement represented an increase in energy intake. However, after 14 days, safflower oil and coconut oil but not MCT increased [3H]NE turnover in heart compared with turnover rates obtained in animals fed isoenergetic amounts of chow. Furthermore, the stimulatory effect of safflower oil on [3H]NE turnover was statistically greater than that seen in animals fed equivalent amounts of coconut oil. In vivo synthesis of NE assessed by accumulation of dopamine (DA) in heart following inhibition of dopamine-beta-hydroxylase (D beta H) was likewise highest in safflower oil-fed rats and lowest in those fed MCT. Thus, sympathetic activation by dietary fat varies among different fats, suggesting a role for fatty acid intake in dietary regulation of the SNS.

The reduction of starch in finishing diets supplemented with oil does not prevent the accumulation of trans-10 18:1 in lamb meat.

PubMed

Costa, M; Alves, S P; Francisco, A; Almeida, J; Alfaia, C M; Martins, S V; Prates, J A M; Santos-Silva, J; Doran, O; Bessa, R J B

2017-08-01

The experiment was conducted to test the hypothesis that the replacement of cereal with low-starch feed ingredients in lambs' finishing diets supplemented with oils could prevent the accumulation of -10-18:1 in meat. Forty lambs were fed 1 of 4 diets supplemented with soybean oil (5.9%) and fish oil (1%) for 6 wk before slaughter. The control (CON) diet contained 43% barley, and in the other diets, barley was completely replaced by dehydrated citrus pulp (DCP), dehydrated sugar beet pulp (DBP), or soybean hulls (SH). Growth performance, feed intake, and carcass and meat quality traits were analyzed. At slaughter, LM samples were collected for gene expression evaluation, and 3 d after slaughter, LM and subcutaneous (s.c.) fat samples were collected for fatty acid analysis. None of the diets affected meat quality, but the DCP diet reduced ADG ( < 0.05) and the DCP and SH diets decreased the feed-to-gain ratio ( < 0.01). The DCP diet increased ( < 0.05) the risk of parakeratosis and the severity of the lesions. Moreover, the DBP treatment led to increased a* (redness) and b* (yellowness) in s.c. fat compared with the CON treatment ( < 0.05). The lipid content of LM did not differ ( > 0.05) with treatment and averaged 34.4 g/kg of meat. Diets had no effect ( > 0.05) on SFA, PUFA, and -MUFA sums and on the -6:-3 ratio in both LM and s.c. fat. A lower expression of fatty acid synthase (FASN) was found with the DCP treatment than with the other treatments ( < 0.001). All treatments showed a high accumulation of -10-18:1, averaging 91 mg/g fatty acid in LM and 147 mg/g fatty acid in s.c. fat. The concentration of -11-18:1 in the tissues was considerably lower than that of -10-18:1, and thus the -10-18:1:-11-18:1 ratio was above 3 with all treatments. Despite this, the SH diet clearly promoted a larger deposition of -11-18:1 and -9,-11-18:2 in tissues compared with the other treatments. () gene expression and SCD activity index in LM were reduced with the SH diet compared with the CON and DCP diets. Overall, these results clearly showed, for the first time, that low-starch/high-NDF diets are not able to prevent the establishment of -10 shifted rumen biohydrogenation pathways, evaluated by the deposition of biohydrogenation intermediates in lamb meat and fat.

Effects of berberine on the growth and immune performance in response to ammonia stress and high-fat dietary in blunt snout bream Megalobrama amblycephala.

PubMed

Chen, Qing-Qing; Liu, Wen-Bin; Zhou, Man; Dai, Yong-Jun; Xu, Chao; Tian, Hong-Yan; Xu, Wei-Na

2016-08-01

This study aimed to figure out the effects of berberine on growth performance, immunity, oxidative stress and hepatocyte apoptosis of blunt snout bream (Megalobrama amblycephala) fed with high-fat diet. 320 fish (80.00 ± 0.90 g) were divided randomly into four trial groups (each with four replicates) and fed with 4 diets (normal diet, normal diet with 50 mg/kg berberine, high-fat diet, high-fat diet with 50 mg/kg berberine), respectively. At the end of the feeding trial, ammonia stress test was carried out for 5 days. The result showed the growth performance, immune parameters including plasm acid phosphatase (ACP) activities, lysozyme (LYZ) activities and alternative complement C3 and C4 contents were suppressed in fish fed with high-fat diets but improved in berberine diets compared with control (normal diet). Hepatopancreas oxidative status, the malondialdehyde (MDA), protein carbonyl (PC) and lipid peroxide (LPO) were increased significantly (P < 0.05) when fish were fed with high-fat diets. Berberine could slow the progression of the oxidative stress induced by high-fat through increasing superoxide dismutase (SOD) activities and total sulfydryl (T-SH) levels of fish. And the hepatocyte apoptosis in the high-fat group could also be alleviated by berberine. After the ammonia stress test, the accumulative mortality was extremely (P < 0.05) low in fish fed high-fat diet with berberine compared to other groups. It was concluded berberine as a functional feed additive significantly inhibited the progression of oxidative stress, reduced the apoptosis and enhanced the immunity of fish fed with high-fat diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

Background diet and fat type alters plasma lipoprotein response but not aortic cholesterol accumulation in F1B Golden Syrian hamsters.

PubMed

Dillard, Alice; Matthan, Nirupa R; Spartano, Nicole L; Butkowski, Ann E; Lichtenstein, Alice H

2013-12-01

Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat type on aortic cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and 0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and safflower oil, respectively), and lower HDL-C (-47 and -45 %, coconut oil and safflower oil, respectively) concentrations. Plasma triacylglycerol concentrations in the hamsters fed the non-purified coconut oil-supplemented diets were three- to fourfold higher than non-purified safflower oil-supplemented, and both semi-purified diets. With the exception of HDL-C, a significant effect of fat type was observed in TC, nHDL-C and triacylglycerol (all P < 0.05) concentrations. Regardless of diet induced differences in lipoprotein profiles, there was no significant effect on aortic cholesterol accumulation. There was an inverse relationship between plasma nHDL-C and triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal transfer protein) were not reflected in protein concentrations. Although hamsters fed non-purified and/or saturated fatty acid-supplemented diets had more atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or polyunsaturated fatty acid-supplemented diets these differences were not reflected in aortic cholesterol accumulation.

Ipragliflozin Improves Hepatic Steatosis in Obese Mice and Liver Dysfunction in Type 2 Diabetic Patients Irrespective of Body Weight Reduction.

PubMed

Komiya, Chikara; Tsuchiya, Kyoichiro; Shiba, Kumiko; Miyachi, Yasutaka; Furuke, Shunsaku; Shimazu, Noriko; Yamaguchi, Shinobu; Kanno, Kazuo; Ogawa, Yoshihiro

2016-01-01

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis.

Comparison of Anti-Obesity Effect between Two Types of Syrup Containing Rare Sugars in Wistar Rats.

PubMed

Ochiai, Masaru; Misaki, Kohei; Yamada, Takako; Iida, Tetsuo; Okuma, Kazuhiro; Matsuo, Tatsuhiro

2017-01-01

D-Allulose-containing rare sugar sweeteners have been categorized into two types, rare sugar syrup (RSS), consisting of 4 rare monosaccharides, and modified glucose syrup (MGS), rich in D-allulose, which was previously referred to D-psicose. The anti-obesity effect of RSS and D-allulose has been already clarified, but that of rare monosaccharides other than D-allulose in RSS has not yet been well understood. Here, we investigated and compared the anti-obesity effect of RSS and MGS in rats. Male Wistar rats were divided into 4 dietary groups: a high-sucrose control diet group (S), a high-fructose corn syrup diet group (HFCS), an RSS diet group (RSS), and an MGS diet group (MGS). RSS significantly suppressed abdominal adipose tissue weight and total body fat accumulation in comparison to sucrose. On the other hand, MGS reduced body weight gain, but not abdominal fat accumulation, relative to sucrose. The weight of the liver and kidneys was significantly higher in the RSS and MGS groups than in the S and HFCS groups, but serum biochemical parameters and hepatic lipids contents were not significantly different among the groups. The present study shows that two types of D-allulose-containing rare sugar sweeteners can suppress body fat accumulation or weight gain in a different manner and that RSS could be used as more effective sweeteners in place of sucrose and HFCS to maintain healthy body weight.

[Healthy obesity? Why the adiposity paradox is only seemingly paradox].

PubMed

Ströhle, Alexander; Worm, Nicolai

2014-02-01

The health consequences of being overweight have been discussed controversially. Indeed, from a metabolic point of view, overweight and obese people are quite heterogenous. The body mass index (BMI) is not suitable to predict health oriented outcomes on an individual level without taking into account further parameters such as waist circumference, blood pressure, serum glucose, serum lipids, and physical fitness. The BMI does not distinguish between metabolically healthy and metabolically unhealthy. Of upmost importance for health consequences of obesity is body fat distribution. Two types of principally different fat distribution can be identified: abdominal and gluteofemoral fat. Waist circumference and hip circumference can be utilized to distinguish between those two types. People with accumulation of body fat in the abdominal region have a markedly higher risk of developing type-2-diabetes and cardiovascular disease. Moreover, their total mortality is increased. On the other hand, waist circumference is not sufficiently capable of indicating individual risk. Instead, the amount of visceral fat is believed to be a primary risk factor because of its metabolic characteristics (i. e. increased lipolysis, diabetogenic and atherogenic adipokine profile). Recent findings point to visceral fat being more an indicator of the parallel accumulation of fat deposits in organs placed in the abdomen. The accumulation of lipids in tissues not primary intended for fat storage is called,,ectopic fat". It can be found in muscle, liver, pancreas, and kidney. The fattening of those organs is now considered to have the key role in the pathogenesis of type-2-diabetes. The pathophysiological effects of ectopic fat and the associated metabolic derangements can solve the conflicting findings concerning health consequences of BMI--at least in part. Moreover, these findings may have therapeutic consequences. The reduction of ectopic fat as well as the modification of its metabolic effects - via dietetic, bariatric or pharmaceutic means - opens up the pathway to counteract impaired glucose tolerance early and in a causal way.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hae Jin; Silva, Jillian E.; Vu, Hieu Sy

Seeds of members of the genus Cuphea accumulate medium-chain fatty acids (MCFAs; 8:0–14:0). MCFA- and palmitic acid- (16:0) rich vegetable oils have received attention for jet fuel production, given their similarity in chain length to Jet A fuel hydrocarbons. Studies were conducted to test genes, including those from Cuphea, for their ability to confer jet fuel-type fatty acid accumulation in seed oil of the emerging biofuel crop Camelina sativa. Transcriptomes from Cuphea viscosissima and Cuphea pulcherrima developing seeds that accumulate >90% of C8 and C10 fatty acids revealed three FatB cDNAs ( CpuFatB3, CvFatB1, and CpuFatB4) expressed predominantly in seedsmore » and structurally divergent from typical FatB thioesterases that release 16:0 from acyl carrier protein (ACP). Expression of CpuFatB3 and CvFatB1 resulted in Camelina oil with capric acid (10:0), and CpuFatB4 expression conferred myristic acid (14:0) production and increased 16:0. Co-expression of combinations of previously characterized Cuphea and California bay FatBs produced Camelina oils with mixtures of C8–C16 fatty acids, but amounts of each fatty acid were less than obtained by expression of individual FatB cDNAs. Increases in lauric acid (12:0) and 14:0, but not 10:0, in Camelina oil and at the sn-2 position of triacylglycerols resulted from inclusion of a coconut lysophosphatidic acid acyltransferase specialized for MCFAs. RNA interference (RNAi) suppression of Camelina β-ketoacyl-ACP synthase II, however, reduced 12:0 in seeds expressing a 12:0-ACP-specific FatB. Here, Camelina lines presented here provide platforms for additional metabolic engineering targeting fatty acid synthase and specialized acyltransferases for achieving oils with high levels of jet fuel-type fatty acids.« less

Maternal consumption of a cafeteria diet during lactation in rats leads the offspring to a thin-outside-fat-inside phenotype.

PubMed

Pomar, C A; van Nes, R; Sánchez, J; Picó, C; Keijer, J; Palou, A

2017-08-01

The suckling period is a critical phase of development, in which maternal overnutrition may program the susceptibility of developing chronic diseases and disorders, such as obesity and metabolic alterations, in adult life. Here, we questioned whether the consumption of a cafeteria diet throughout lactation in rats affects the macronutrient composition of milk and whether it results in permanent metabolic effects in the offspring. Nursing rats were fed a control diet or a cafeteria diet during lactation. Milk was obtained at different time points of lactation. Offspring (males and females) were weaned onto a control diet until the age of 6 months. Circulating parameters were measured under ad libitum feeding and under 12-h fasting conditions at weaning and at 3 and 6 months of age. An oral glucose tolerance test (OGTT) was performed at 3 and 6 months of age. Rats fed a cafeteria diet during lactation consumed an unbalanced diet, with lower protein and higher fat content versus controls, which was reflected in the composition of the milk. The offspring of rats fed a cafeteria diet during lactation showed lower body weight and lower lean mass, but greater fat accumulation, compared with controls. They also displayed hyperleptinaemia, altered lipid profile and impaired response to an OGTT. Maternal consumption of a cafeteria diet throughout lactation in rats produces lasting effects in the metabolic health of their offspring, which are not associated with a higher body weight but with a greater fat accumulation, similarly to the thin-outside-fat-inside phenotype.

Evaluation of portal venous velocity with Doppler ultrasound in patients with nonalcoholic fatty liver disease.

PubMed

Ulusan, Serife; Yakar, Tolga; Koc, Zafer

2011-01-01

We examined the relationship between portal venous velocity and hepatic-abdominal fat in patients with nonalcoholic fatty liver disease (NAFLD), using spectral Doppler ultrasonography (US) and magnetic resonance imaging (MRI). In this prospective study, 35 patients with NAFLD and 29 normal healthy adults (control group) underwent portal Doppler US. The severity of hepatic steatosis in patients with NAFLD was assessed by MRI through chemical shift imaging, using a modification of the Dixon method. Abdominal (intra-abdominal and subcutaneous) fat was measured by MRI. The difference in portal venous velocity between the patients with NAFLD and the control group was significant (p < 0.0001). There was no correlation between the degree of abdominal or hepatic fat and portal venous velocity (p > 0.05). There were strong correlations between the hepatic fat fraction and subcutaneous adiposity (p < 0.0001), intraperitoneal fat accumulation (p = 0.017), and retroperitoneal fat accumulation (p < 0.0001). Our findings suggest that patients with NAFLD have lower portal venous velocities than normal healthy subjects.

Carnosic acid attenuates obesity-induced glucose intolerance and hepatic fat accumulation by modulating genes of lipid metabolism in C57BL/6J-ob/ob mice.

PubMed

Park, Mi-Young; Sung, Mi-Kyung

2015-03-15

Carnosic acid (CA), a major bioactive component of rosemary (Rosmarinus officinalis) leaves, is known to possess antioxidant and anti-adipogenic activities. In this study it was hypothesized that CA would ameliorate obesity-induced glucose intolerence and hepatic fat accumulation, and possible mechanisms are suggested. It was observed that a 0.02% (w/w) CA diet effectively decreased body weight, liver weight and blood triglyceride (TG) and total cholesterol levels (P < 0.05) compared with the control diet. CA at 0.02% significantly improved glucose tolerance, and hepatic TG accumulation was reduced in a dose-dependent manner. Hepatic lipogenic-related gene (L-FABP, SCD1 and FAS) expression decreased whereas lipolysis-related gene (CPT1) expression increased in animals fed the 0.02% CA diet (P < 0.05). Long-chain fatty acid content and the ratio of C18:1/C18:0 fatty acids were decreased in adipose tissue of animals fed the 0.02% CA diet (P < 0.05). Serum inflammatory mediators were also decreased significantly in animals fed the 0.02% CA diet compared with those of the obese control group (P < 0.05). These results suggest that CA is an effective anti-obesity agent that regulates fatty acid metabolism in C57BL/6J-ob/ob mice. © 2014 Society of Chemical Industry.

Probiotic supplementation attenuates increases in body mass and fat mass during high-fat diet in healthy young adults.

PubMed

Osterberg, Kristin L; Boutagy, Nabil E; McMillan, Ryan P; Stevens, Joseph R; Frisard, Madlyn I; Kavanaugh, John W; Davy, Brenda M; Davy, Kevin P; Hulver, Matthew W

2015-12-01

The objective was to determine the effects of the probiotic, VSL#3, on body and fat mass, insulin sensitivity, and skeletal muscle substrate oxidation following 4 weeks of a high-fat diet. Twenty non-obese males (18-30 years) participated in the study. Following a 2-week eucaloric control diet, participants underwent dual X-ray absorptiometry to determine body composition, an intravenous glucose tolerance test to determine insulin sensitivity, and a skeletal muscle biopsy for measurement of in vitro substrate oxidation. Subsequently, participants were randomized to receive either VSL#3 or placebo daily during 4 weeks of consuming a High-fat (55% fat), hypercaloric diet (+1,000 kcal day(-1) ). Participants repeated all measurements following the intervention. Body mass (1.42 ± 0.42 kg vs. 2.30 ± 0.28 kg) and fat mass (0.63 ± 0.09 kg vs. 1.29 ± 0.27 kg) increased less following the High-fat diet in the VSL#3 group compared with placebo. However, there were no significant changes in insulin sensitivity or in vitro skeletal muscle pyruvate and fat oxidation with the High-fat diet or VSL#3. VSL#3 supplementation appears to have provided some protection from body mass gain and fat accumulation in healthy young men consuming a High-fat and high-energy diet. © 2015 The Obesity Society.

Sodium-Glucose Cotransporter 2 Inhibitor and a Low Carbohydrate Diet Affect Gluconeogenesis and Glycogen Content Differently in the Kidney and the Liver of Non-Diabetic Mice.

PubMed

Atageldiyeva, Kuralay; Fujita, Yukihiro; Yanagimachi, Tsuyoshi; Mizumoto, Katsutoshi; Takeda, Yasutaka; Honjo, Jun; Takiyama, Yumi; Abiko, Atsuko; Makino, Yuichi; Haneda, Masakazu

2016-01-01

A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin. We compared metabolic parameters, gene expression for transcripts related to glucose and fat metabolism, and glycogen content in the kidney and the liver among the groups. SGLT2i but not LCHD improved glucose excursion after an oral glucose load compared to NCHD, although all groups presented comparable non-fasted glycemia. Both the LCHD and SGLT2i treatments increased calorie-intake, whereas only the LCHD increased body weight compared to the NCHD, epididimal fat mass and developed insulin resistance. Gene expression of certain gluconeogenic enzymes was simultaneously upregulated in the kidney of SGLT2i treated group, as well as in the liver of the LCHD treated group. The SGLT2i treated groups showed markedly lower glycogen content in the liver, but induced glycogen accumulation in the kidney. We conclude that LCHD induces deleterious metabolic changes in the non-diabetic mice. Our results suggest that SGLT2i induced gluconeogenesis mainly in the kidney, whereas for LCHD it was predominantly in the liver.

Sodium-Glucose Cotransporter 2 Inhibitor and a Low Carbohydrate Diet Affect Gluconeogenesis and Glycogen Content Differently in the Kidney and the Liver of Non-Diabetic Mice

PubMed Central

Atageldiyeva, Kuralay; Fujita, Yukihiro; Yanagimachi, Tsuyoshi; Mizumoto, Katsutoshi; Takeda, Yasutaka; Honjo, Jun; Takiyama, Yumi; Abiko, Atsuko; Makino, Yuichi; Haneda, Masakazu

2016-01-01

A low carbohydrate diet (LCHD) as well as sodium glucose cotransporter 2 inhibitors (SGLT2i) may reduce glucose utilization and improve metabolic disorders. However, it is not clear how different or similar the effects of LCHD and SGLT2i are on metabolic parameters such as insulin sensitivity, fat accumulation, and especially gluconeogenesis in the kidney and the liver. We conducted an 8-week study using non-diabetic mice, which were fed ad-libitum with LCHD or a normal carbohydrate diet (NCHD) and treated with/without the SGLT-2 inhibitor, ipragliflozin. We compared metabolic parameters, gene expression for transcripts related to glucose and fat metabolism, and glycogen content in the kidney and the liver among the groups. SGLT2i but not LCHD improved glucose excursion after an oral glucose load compared to NCHD, although all groups presented comparable non-fasted glycemia. Both the LCHD and SGLT2i treatments increased calorie-intake, whereas only the LCHD increased body weight compared to the NCHD, epididimal fat mass and developed insulin resistance. Gene expression of certain gluconeogenic enzymes was simultaneously upregulated in the kidney of SGLT2i treated group, as well as in the liver of the LCHD treated group. The SGLT2i treated groups showed markedly lower glycogen content in the liver, but induced glycogen accumulation in the kidney. We conclude that LCHD induces deleterious metabolic changes in the non-diabetic mice. Our results suggest that SGLT2i induced gluconeogenesis mainly in the kidney, whereas for LCHD it was predominantly in the liver. PMID:27327650

Optimized Rapeseed Oils Rich in Endogenous Micronutrients Protect High Fat Diet Fed Rats from Hepatic Lipid Accumulation and Oxidative Stress

PubMed Central

Xu, Jiqu; Liu, Xiaoli; Gao, Hui; Chen, Chang; Deng, Qianchun; Huang, Qingde; Ma, Zhonghua; Huang, Fenghong

2015-01-01

Micronutrients in rapeseed exert a potential benefit to hepatoprotection, but most of them are lost during the conventional refining processing. Thus some processing technologies have been optimized to improve micronutrient retention in oil. The aim of this study is to assess whether optimized rapeseed oils (OROs) have positive effects on hepatic lipid accumulation and oxidative stress induced by a high-fat diet. Methods: Rats received experiment diets containing 20% fat and refined rapeseed oil or OROs obtained with various processing technologies as lipid source. After 10 weeks of treatment, liver was assayed for lipid accumulation and oxidative stress. Results: All OROs reduced hepatic triglyceride contents. Microwave pretreatment-cold pressing oil (MPCPO) which had the highest micronutrients contents also reduced hepatic cholesterol level. MPCPO significantly decreased hepatic sterol regulatory element-binding transcription factor 1 (SREBP1) but increased peroxisome proliferator activated receptor α (PPARα) expressions, and as a result, MPCPO significantly suppressed acetyl CoA carboxylase and induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression. Hepatic catalase (CAT) and glutathione peroxidase (GPx) activities as well as reduced glutathione (GSH) contents remarkably increased and lipid peroxidation levels decreased in parallel with the increase of micronutrients. Conclusion: OROs had the ability to reduce excessive hepatic fat accumulation and oxidative stress, which indicated that OROs might contribute to ameliorating nonalcoholic fatty liver induced by high-fat diet. PMID:26473919

Impact of high-protein diets with either moderate or low carbohydrate on weight loss, body composition, blood pressure and glucose tolerance in rats.

PubMed

Lobley, Gerald E; Bremner, David M; Holtrop, Grietje; Johnstone, Alexandra M; Maloney, Christopher

2007-06-01

One approach to achieve weight loss and decrease both obesity and associated morbidities involves high-protein, low-carbohydrate (HPLC) diets. This study compares the impact on metabolic health of HPLC and high-protein, medium-carbohydrate (HPMC) diets offered to diet-induced obese (DIO) rats. Weanling male rats were fed either a 37 % fat diet (n 48) or stock pellets (n 12) for 22 weeks. Rats fed the 37 % fat diet accumulated more body fat (26.6 versus 14.8 % body weight, P < 0.001) compared with those on stock diet. The DIO rats had higher systolic blood pressure (+6.6 mmHg, P = 0.002), fasting insulin (+63 % P = 0.006) and areas under the glucose (+21 %, P < 0.001) and insulin (+81 %, P < 0.001) curves following an oral glucose tolerance test. DIO rats were then separated into four groups and offered for 8 weeks either: (1) the 37 % fat diet; (2) an HPLC or (3) HPMC diet; or (4) fed the 37 % fat diet to the intake of the HPMC group. Rats offered the 37 % fat or HPLC diets gained while those on HPMC lost body fat. Blood pressure was not altered by the dietary switch. Both HPLC and HPMC rats had lowered fasting insulin (P = 0.027) and improved homeostatic assessment (HOMA; P = 0.011) that was not different from those of stock animals. These improvements occurred despite differences in fat gain, and indicate that both weight loss and macronutrient intake can impact favourably on obesity-associated morbidities.

Do South Indian newborn babies have higher fat percentage for a given birth weight?

PubMed

Kv, Radha Krishna; Hemalatha, Rajkumar; Mamidi, Raja Sriswan; Jj, Babu Geddam; Balakrishna, N

2016-05-01

India is experiencing rapidly escalating epidemics of diabetes and cardiovascular disease. High fat percent in Indian adults may have its origins at birth (Fetal origin hypothesis). Conflicting evidence from India have shown increased or similar fat mass in Indian newborn babies compared to western countries. To compare body composition of term infants with data from similar studies in India and developed countries. Cross-sectional study in newborn infants at the antenatal ward of a tertiary care hospital in South India. 626 mothers and their newborn babies. Maternal body weight and height, baby weight, length, head circumference, skin folds at three sites. Body fat, arm muscle area and arm muscle index were calculated based on known methods. Mean (SD) birth weight of newborn babies was 2.80 (0.37) kg and 43% of them were small for gestational age. Birth weight was significantly related to subscapular (r=0.445; p<0.001) and triceps (r=0.567; p<0.001) skin fold thickness. Mean (CI) Subscapular skin fold thickness and total body fat % was 3.81mm (3.74-3.97) and 10.5% (10.2-10.8). Mean total body fat % for small for gestational age (SGA) (9.57%) was significantly lower than appropriate for gestational age (AGA) babies (11.7%). The mean body fat percent in AGA infants was similar to that of studies reported on term infants of developed countries, suggesting that South Indian babies may accumulate similar fat mass with increasing birth weight and gestational age. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Emulsion Stability Modulates Gastric Secretion and Its Mixing with Emulsified Fat in Healthy Adults in a Randomized Magnetic Resonance Imaging Study.

PubMed

Liu, Dian; Parker, Helen L; Curcic, Jelena; Kozerke, Sebastian; Steingoetter, Andreas

2016-10-01

Oil-in-water emulsions have recently become of interest to nutritional sciences because of their ability to influence gastrointestinal digestive processes and ultimately benefit human health. MRI offers the potential to noninvasively characterize the interaction between emulsified lipids and gastric secretion within the stomach. We determined noninvasively how emulsion stability modulates volumes of fat and secretion, layering of fat, and the mixing of emulsified fat with secretion within the stomach. This required the development of MRI technology for quantifying fat and secretion concentrations inside the stomach. Twenty-one healthy adults [13 men, mean ± SD age: 22.5 ± 2.5 y, mean ± SD body mass index (in kg/m 2 ): 22.7 ± 1.8] were analyzed in a single-blind, randomized, parallel design. MRI was used to acquire the distributions of fat and secretion in the stomach after ingestion of 2 emulsions: a stable emulsion (E1) or an unstable emulsion (E4) with 20% fat fraction and ∼0.3 mm droplet sizes. Layer, volume, and mixing variables were fitted to the data and compared between the 2 emulsions. The intragastric mixing between fat and secretion was better with the E4 than the E1 [increase in content heterogeneity of 17.1% (95% CI: 12.3%, 21.9%)]. The E4 demonstrated a linear relation [slope 1.57 (95% CI: 0.86, 2.29)] between the degree of layering and mixing. In contrast, no such relation was detected for the E1. Accumulated secretion volume in the stomach was lower with the E4 [decrease in volume variable k s of 2.3 (95% CI: -3.9, -0.7)] and correlated with the degree of layering (r = 0.62, P < 0.001). In healthy adults, intragastric fat layering was influenced mainly by the degree of intragastric mixing, rather than the overall dominance of secretion. The E1 triggered a higher accumulation of gastric secretion, which in turn facilitated homogenization of intragastric content in comparison with its unstable counterpart. This trial was registered at clinicaltrials.gov as NCT02602158. © 2016 American Society for Nutrition.

Effects of dietary heme iron and exercise training on abdominal fat accumulation and lipid metabolism in high-fat diet-fed mice.

PubMed

Katsumura, Masanori; Takagi, Shoko; Oya, Hana; Tamura, Shohei; Saneyasu, Takaoki; Honda, Kazuhisa; Kamisoyama, Hiroshi

2017-08-01

Animal by-products can be recycled and used as sources of essential nutrients. Water-soluble heme iron (WSHI), a functional food additive for supplementing iron, is produced by processing animal blood. In this study, we investigated the effects of dietary supplementation of 3% WSHI and exercise training for 4 weeks on the accumulation of abdominal fat and lipid metabolism in mice fed high-fat diet. Exercise-trained mice had significantly less perirenal adipose tissue, whereas WSHI-fed mice tended to have less epididymal adipose tissue. In addition, total weight of abdominal adipose tissues was significantly decreased in the Exercise + WSHI group. Dietary WSHI significantly increased the messenger RNA (mRNA) levels of lipoprotein lipase and hormone-sensitive lipase. WSHI-fed mice also tended to show increased mRNA levels of adipose triglyceride lipase in their epididymal adipose tissue. Dietary WSHI also significantly decreased the mRNA levels of fatty acid oxidation-related enzymes in the liver, but did not influence levels in the Gastrocnemius muscle. Exercise training did not influence the mRNA levels of lipid metabolism-related enzymes in the epididymal adipose tissue, liver or the Gastrocnemius muscle. These findings suggest that the accumulation of abdominal fat can be efficiently decreased by the combination of dietary WSHI and exercise training in mice fed high-fat diet. © 2016 Japanese Society of Animal Science.

Dietary salecan reverts partially the metabolic gene expressions and NMR-based metabolomic profiles from high-fat-diet-induced obese rats.

PubMed

Sun, Qi; Li, Minghui; Yang, Xiao; Xu, Xi; Wang, Junsong; Zhang, Jianfa

2017-09-01

Previous studies suggest that dietary salecan (a water-soluble β-glucan) effectively reduces high-fat-diet-induced adiposity through disturbing bile-acid-promoted emulsification in mice. However, the effects of salecan on metabolic genes and metabolites involved in lipid accumulation are mostly unknown. Here, we confirmed that dietary 3% and 6% salecan for 4 weeks markedly decreased fat accumulation in liver and adipose tissue in high-fat-diet rats, displaying a decrease in mRNA levels of SREBP1-C, FAS, SCD1 and ACC1 involved in de novo lipogenesis and a reduction of levels of GPAT1, DGAT1 and DGAT2 related to triglyceride synthesis. Dietary salecan also increased the mRNA levels of PPARα and CYP7A1, which are related to fatty acid oxidation and cholesterol decomposition, respectively. In the 1 H nuclear magnetic resonance metabolomic analysis, both the serum and liver metabolite profiles differed among the control groups, and the metabolic profiles of the salecan groups were shifted toward that of the low-fat-diet group. Metabolites analysis showed that salecan significantly increased hepatic glutathione and betaine levels which are related to regulation of cellular reactive oxygen species. These data demonstrate that dietary salecan not only disturbed fat digestion and absorption but also influenced lipid accumulation and metabolism in diet-induced obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

CSFII Analysis of Fat Intake Distributions 94-96 (1998 Survey Data)

EPA Science Inventory

Certain chemicals, such as dioxins tend to accumulate in fat tissue. Information about the total animal fat intake is necessary to adequately assess exposures and risks from these chemicals. Under this project, NCEA will desegregate the components of the various food items in the...

Colestipol

MedlinePlus

... used with diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and ... substances in your blood. Accumulation of cholesterol and fats along the walls of your arteries (a process ...

Micronutrients-fortified rapeseed oil improves hepatic lipid accumulation and oxidative stress in rats fed a high-fat diet

PubMed Central

2013-01-01

Intake of high-fat diet is associated with increased fatty livers. Hepatic lipid accumulation and oxidative stress are key pathophysiological mechanisms in this disease. Micronutrients polyphenols, tocopherols and phytosterols in rapeseed exert potential benefit to hepatoprotection, but most of these micronutrients are removed by the traditional refining process. The purpose of the present study was to determine whether rapeseed oil fortified with these micronutrients can decrease hepatic lipid accumulation and oxidative stress induced by high-fat diet. Sprague–Dawley rats received rodent diet contained 20% fat whose source was refined rapeseed oil (RRO) or fortified RRO with low, middle and high quantities of these micronutrients for 10 weeks. Intake of RRO caused a remarkable hepatic steatosis. Micronutrients supplementation was effective in reducing steatosis as well as total triglyceride and total cholesterol contents in liver. These micronutrients also significantly increased hepatic antioxidant defense capacities, as evaluated by the significant elevation in the activities of SOD and GPx as well as the level of GSH, and the significant decline in lipid peroxidation. These findings suggest that rapeseed oil fortified with micronutrients polyphenols, tocopherols and phytosterols may contribute to prevent fatty livers such as nonalcoholic fatty liver disease by ameliorating hepatic lipid accumulation and oxidative stress. PMID:23510587

Alternate-Day High-Fat Diet Induces an Increase in Mitochondrial Enzyme Activities and Protein Content in Rat Skeletal Muscle.

PubMed

Li, Xi; Higashida, Kazuhiko; Kawamura, Takuji; Higuchi, Mitsuru

2016-04-06

Long-term high-fat diet increases muscle mitochondrial enzyme activity and endurance performance. However, excessive calorie intake causes intra-abdominal fat accumulation and metabolic syndrome. The purpose of this study was to investigate the effect of an alternating day high-fat diet on muscle mitochondrial enzyme activities, protein content, and intra-abdominal fat mass in rats. Male Wistar rats were given a standard chow diet (CON), high-fat diet (HFD), or alternate-day high-fat diet (ALT) for 4 weeks. Rats in the ALT group were fed a high-fat diet and standard chow every other day for 4 weeks. After the dietary intervention, mitochondrial enzyme activities and protein content in skeletal muscle were measured. Although body weight did not differ among groups, the epididymal fat mass in the HFD group was higher than those of the CON and ALT groups. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities in the plantaris muscle of rats in HFD and ALT were significantly higher than that in CON rats, whereas there was no difference between HFD and ALT groups. No significant difference was observed in muscle glycogen concentration or glucose transporter-4 protein content among the three groups. These results suggest that an alternate-day high-fat diet induces increases in mitochondrial enzyme activities and protein content in rat skeletal muscle without intra-abdominal fat accumulation.

Head fat is a novel method of measuring metabolic disorder in Chinese obese patients

PubMed Central

2014-01-01

Background Body adiposity, especially ectopic fat accumulation, has a range of metabolic and cardiovascular effects. The aim of this study was to investigate the association between head fat and metabolic values in Chinese obese patients. Methods Data of this cross-sectional study from 66 obese patients were collected. Fat distribution was measured by dual-energy X-ray absorptiometry, and data of body weight, body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC), visceral index, basal metabolism (BM), glucose metabolism, lipid levels, uric acid (UA) had been collected. Results 1) Head fat was significantly associated with BMI, WC, HC, visceral index, BM, total fat and total fat excluding head fat in both males and females (p < 0.05). Head fat was positively correlated with upper limb fat, trunk fat, weight, fasting plasma C peptide, fasting plasma insulin and UA in women(p < 0.05), and the association was not statistically significant in male (p > 0.05). Head fat was positively corrected with NC in males (p < 0.05) but not females (p > 0.05). There was no significant correlation between head fat and fasting plasma glucose, total choleslerolemia, triglyceridemia, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and free fat acid in either gender (p > 0.05). 2) Receiver operating characteristic analysis showed that a head fat of 1925.6 g and a head fat of 1567.85 g were the best cut-off values to determine subjects with low high-density lipoprotein cholesterol and hyperuricemia respectively. Conclusions Head fat accumulation was closely associated with increased body fat, hyperinsulinemia, hyperuricemia, and impared lipid profile, suggesting it might be used as an indicator for dyslipidemia and hyperuricemia. PMID:25015267

Comparison of Antiobesity Effects Between Gochujangs Produced Using Different Koji Products and Tabasco Hot Sauce in Rats Fed a High-Fat Diet.

PubMed

Son, Hee-Kyoung; Shin, Hye-Won; Jang, Eun-Seok; Moon, Byoung-Seok; Lee, Choong-Hwan; Lee, Jae-Joon

2018-03-01

In this study, we compared the antiobesity effects between gochujangs prepared using different koji products and Tabasco hot sauce in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats were fed HFD containing four different types of 10% gochujang powder or 0.25% commercial Tabasco sauce powder for 8 weeks. The body weight gain, liver and epididymal and mesenteric fat pad weights, serum leptin levels, and lipogenesis-related mRNA levels of HFD-gochujang supplementation groups were significantly decreased compared with those of the HFD group. In addition, gochujang supplement significantly reduced adipocyte size; hepatic triglyceride and total cholesterol levels; the occurrence of fatty liver deposits and steatosis by inhibiting lipogenesis through downregulation of fatty acid synthase, acetly-CoA carboxylase, and glucose-6-phosphate-dehydrogenase. These effects were greater in the gochujang-supplemented groups than the Tabasco hot sauce-supplemented group. The gochujang prepared by nutritious giant embryo rice koji and soybean koji was most effective in terms of antiobesity effects, compared with the other tested gochujangs. In gochujangs, the antiobesity effects are mediated by high levels of secondary metabolites such as isoflavone, soyasaponin, capsaicin, and lysophosphatidylcholine. The current results indicated that the gochujang products have the potential to reduce fat accumulation and obesity.

Beneficial effect of low carbohydrate in low calorie diets on visceral fat reduction in type 2 diabetic patients with obesity.

PubMed

Miyashita, Yoh; Koide, Nobukiyo; Ohtsuka, Masaki; Ozaki, Hiroshi; Itoh, Yoshiaki; Oyama, Tomokazu; Uetake, Takako; Ariga, Kiyoko; Shirai, Kohji

2004-09-01

The adequate composition of carbohydrate and fat in low calorie diets for type 2 diabetes mellitus patients with obesity is not fully established. The aim of this study was to investigate the effects of low carbohydrate diet on glucose and lipid metabolism, especially on visceral fat accumulation, and comparing that of a high carbohydrate diet. Obese subjects with type 2 diabetes mellitus were randomly assigned to take a low calorie and low carbohydrate diet (n = 11, 1000 kcal per day, protein:carbohydrate:fat = 25:40:35) or a low calorie and high carbohydrate diet (n = 11, 1000 kcal per day, protein:carbohydrate:fat = 25:65:10) for 4 weeks. Similar decreases in body weight and serum glucose levels were observed in both groups. Fasting serum insulin levels were reduced in the low carbohydrate diet group compared to the high carbohydrate diet group (-30% versus -10%, P < 0.05). Total serum cholesterol and triglyceride levels decreased in both groups, but were not significantly different from each other. High-density lipoprotein-cholesterol (HDL-C) increased in the low carbohydrate diet group but not in the high carbohydrate diet group (+15% versus 0%, P < 0.01). There was a larger decrease in visceral fat area measured by computed tomography in the low carbohydrate diet group compared to the high carbohydrate diet group (-40 cm(2) versus -10 cm(2), P < 0.05). The ratio of visceral fat area to subcutaneous fat area did not change in the high carbohydrate diet group (from 0.70 to 0.68), but it decreased significantly in the low carbohydrate diet group (from 0.69 to 0.47, P < 0.005). These results suggest that, when restrict diet was made isocaloric, a low calorie/low carbohydrate diet might be more effective treatment for a reduction of visceral fat, improved insulin sensitivity and increased in HDL-C levels than low calorie/high carbohydrate diet in obese subjects with type 2 diabetes mellitus.

Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner.

PubMed

Ortega-Gómez, Almudena; Varela, Lourdes M; López, Sergio; Montserrat de la Paz, Sergio; Sánchez, Rosario; Muriana, Francisco J G; Bermúdez, Beatriz; Abia, Rocío

2017-09-01

Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of monounsaturated fatty acids (MUFAs) MUFAs, omega-3 polyunsaturated fatty acids (PUFAs) PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe -/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs, or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular triglycerides (TGs) TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-α and IL-1β mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex vivo suggesting cell priming/activation. Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro and in vivo inhibition of aldose reductase and advanced glycation end products by phloretin, epigallocatechin 3-gallate and [6]-gingerol.

PubMed

Sampath, Chethan; Sang, Shengmin; Ahmedna, Mohamed

2016-12-01

Hyperglycemic stress activates polyol pathway and aldose reductase (AR) key enzyme responsible for generating secondary complications during diabetes. In this study the therapeutic potential of phloretin, epigallocatechin 3-gallate (EGCG) and [6]-gingerol were evaluated for anti-glycating and AR inhibitory activity in vitro and in vivo systems. Human retinal pigment epithelial (HRPE) cells were induced with high glucose supplemented with the phloretin, EGCG and [6]-gingerol. Aldose reductase activity, total advanced glycation end products (AGEs) and enzyme inhibitor kinetics were assessed. Male C57BL/6J mice were randomly assigned to one of the different treatments (bioactive compounds at 2 concentrations each) with either a low fat diet or high fat diet (HFD). After sixteen weeks, AGE accumulation and AR activity was determined in heart, eyes and kidney. High glucose induced toxicity decreased cell viability compared to the untreated cells and AR activity increased to 2-5 folds from 24 to 96h. Pre-treatment of cells with phloretin, EGCG and [6]-gingerol improved cell viability and inhibited AR activity. The enzyme inhibition kinetics followed a non-competitive mode of inhibition for phloretin and EGCG whereas [6]-gingerol indicated uncompetitive type of inhibition against AR. Data from the animal studies showed high plasma glucose levels in HFD group over time, compared to the low fat diet. HFD group developed cataract and AR activity increased to 4 folds compared to the group with low fat diet. Administration of EGCG, phloretin and [6]-gingerol significantly reduced blood sugar levels, AGEs accumulation, and AR activity. These findings could provide a basis to consider using the selected dietary components alone or in combination with other therapeutic approaches to prevent diabetes-related complications in humans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Central Effects of Estradiol in the Regulation of Adiposity

PubMed Central

Brown, LM; Clegg, DJ

2010-01-01

In recent years, obesity and its associated health disorders and costs have increased. Accumulation of adipose tissue, or fat, in the intra-abdominal adipose depot is associated with an increased risk of developing cardiovascular problems, type-2 diabetes mellitus, certain cancers, and other disorders like the metabolic syndrome. Males and females differ in terms of how and where their body fat is stored, in their hormonal secretions, and in their neural responses to signals regulating weight and body fat distribution. Men and post-menopausal women accumulate more fat in their intra-abdominal depots than pre-menopausal women, resulting in a greater risk of developing complications associated with obesity. The goal of this review is to discuss the current literature on sexual dimorphisms in body weight regulation, adipose tissue accrual and deposition. PMID:20035866

Monte Carlo modeling (MCML) of light propagation in skin layers for detection of fat thickness

NASA Astrophysics Data System (ADS)

Nilubol, Chonnipa; Treerattrakoon, Kiatnida; Mohammed, Waleed S.

2010-05-01

Nowadays, most activities require lesser physical actions, which could ultimately lead to accumulation of excessive body fat. The main roles of body fat are to store energy and acts as various kinds of insulators for the body. The thickness of fat layers can be measured to indicate fat-body weight ratio. Exceeding the body-mass index (BMI) could lead to many illnesses regarding obesity. Consequently, many studies have proposed various principles and techniques to measure the amount of fat within one's body. In this paper, infrared interactance in skin layers is studied for investigation of the influence of fat thickness upon photon travelling pattern in skin tissues using Monte Carlo model (MCML). Photon propagation is numerically simulated in simplified multi-layered tissues. The optical coefficients of each skin layers are accounted for different traveling paths of photons that move through random motion. The thickness of fat layer is varied, and changing in optical parameters is observed. Then the statistically obtained data are computed and analyzed for the effect of the fat layer upon reflection percentage using different wavelengths. The calculations have shown increment in the slope of change of reflection percentage versus fat thickness, when using infrared compare to visible light. This technique can be used to construct a mobile device that is capable of measuring the volume fraction of melanin and blood in the epidermis layer and dermis layer, to calculate for the necessary optical coefficients that would be necessary for measurement of fat thickness.

The role of pericardial adipose tissue in the heart of obese minipigs.

PubMed

Wang, Chia-Yu; Li, Sin-Jin; Wu, Twin-Way; Lin, Han-Jen; Chen, Jyun-Wei; Mersmann, Harry J; Ding, Shih-Torng; Chen, Ching-Yi

2018-04-23

Pericardial adipose tissue (PAT) volume is highly associated with the presence and severity of cardiometabolic diseases, but the underlying mechanism is unknown. We previously demonstrated that a high-fat diet (HFD) induced metabolic dysregulation, cardiac fibrosis and accumulation of more PAT in minipigs. This study used our obese minipig model to investigate the characteristics of PAT and omental visceral fat (VAT) induced by a HFD, and the potential link between PAT and HFD-related myocardial fibrosis. Five-month-old Lee-Sung minipigs were made obese by feeding a HFD for 6 months. The HFD induced dyslipidemia, cardiac fibrosis and more fat accumulation in the visceral and pericardial depots. The HFD changes the fatty acid composition in the adipose tissue by decreasing the portion of linoleic acid in the VAT and PAT. No arachidonic acid was detected in the VAT and PAT of control pigs, whereas it existed in the same tissues of obese pigs fed the HFD. Compared with the control pigs, elevated levels of malondialdehyde and TNFα were exhibited in the plasma and PAT of obese pigs. HFD induced greater size of adipocytes in VAT and PAT. Higher levels of GH, leptin, OPG, PDGF, resistin, SAA and TGFβ were observed in obese pig PAT compared to VAT. This study demonstrated the similarities and dissimilarities between PAT and VAT under HFD stimulus. In addition, this study suggested that alteration in PAT contributed to the myocardial damage. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Proteomic Analyses of Cysteine Redox in High-Fat-Fed and Fasted Mouse Livers: Implications for Liver Metabolic Homeostasis.

PubMed

Li, Yixing; Luo, Zupeng; Wu, Xilong; Zhu, Jun; Yu, Kai; Jin, Yi; Zhang, Zhiwang; Zhao, Shuhong; Zhou, Lei

2018-01-05

Intensive oxidative stress occurs during high-fat-diet-induced hepatic fat deposition, suggesting a critical role for redox signaling in liver metabolism. Intriguingly, evidence shows that fasting could also result in redox-profile changes largely through reduced oxidant or increased antioxidant levels. However, a comprehensive landscape of redox-modified hepatic substrates is lacking, thereby hindering our understanding of liver metabolic homeostasis. We employed a proteomic approach combining iodoacetyl tandem mass tag and nanoliquid chromatography tandem mass spectrometry to quantitatively probe the effects of high-fat feeding and fasting on in vivo redox-based cysteine modifications. Compared with control groups, ∼60% of cysteine residues exhibited downregulated oxidation ratios by fasting, whereas ∼94% of these ratios were upregulated by high-fat feeding. Importantly, in fasted livers, proteins exhibiting diminished cysteine oxidation were annotated in pathways associated with fatty acid metabolism, carbohydrate metabolism, insulin, peroxisome proliferator-activated receptors, and oxidative respiratory chain signaling, suggesting that fasting-induced redox changes targeted major metabolic pathways and consequently resulted in hepatic lipid accumulation.

Toward production of jet fuel functionality in oilseeds: identification of FatB acyl-acyl carrier protein thioesterases and evaluation of combinatorial expression strategies in Camelina seeds.

PubMed

Kim, Hae Jin; Silva, Jillian E; Vu, Hieu Sy; Mockaitis, Keithanne; Nam, Jeong-Won; Cahoon, Edgar B

2015-07-01

Seeds of members of the genus Cuphea accumulate medium-chain fatty acids (MCFAs; 8:0-14:0). MCFA- and palmitic acid- (16:0) rich vegetable oils have received attention for jet fuel production, given their similarity in chain length to Jet A fuel hydrocarbons. Studies were conducted to test genes, including those from Cuphea, for their ability to confer jet fuel-type fatty acid accumulation in seed oil of the emerging biofuel crop Camelina sativa. Transcriptomes from Cuphea viscosissima and Cuphea pulcherrima developing seeds that accumulate >90% of C8 and C10 fatty acids revealed three FatB cDNAs (CpuFatB3, CvFatB1, and CpuFatB4) expressed predominantly in seeds and structurally divergent from typical FatB thioesterases that release 16:0 from acyl carrier protein (ACP). Expression of CpuFatB3 and CvFatB1 resulted in Camelina oil with capric acid (10:0), and CpuFatB4 expression conferred myristic acid (14:0) production and increased 16:0. Co-expression of combinations of previously characterized Cuphea and California bay FatBs produced Camelina oils with mixtures of C8-C16 fatty acids, but amounts of each fatty acid were less than obtained by expression of individual FatB cDNAs. Increases in lauric acid (12:0) and 14:0, but not 10:0, in Camelina oil and at the sn-2 position of triacylglycerols resulted from inclusion of a coconut lysophosphatidic acid acyltransferase specialized for MCFAs. RNA interference (RNAi) suppression of Camelina β-ketoacyl-ACP synthase II, however, reduced 12:0 in seeds expressing a 12:0-ACP-specific FatB. Camelina lines presented here provide platforms for additional metabolic engineering targeting fatty acid synthase and specialized acyltransferases for achieving oils with high levels of jet fuel-type fatty acids. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Disrupted fat distribution and composition due to medium-chain triglycerides in mice with a β-oxidation defect.

PubMed

Tucci, Sara; Flögel, Ulrich; Sturm, Marga; Borsch, Elena; Spiekerkoetter, Ute

2011-08-01

Because of the enhanced recognition of inherited long-chain fatty acid oxidation disorders by worldwide newborn screening programs, an increasing number of asymptomatic patients receive medium-chain triglyceride (MCT) supplements to prevent the development of cardiomyopathy and myopathy. MCT supplementation has been recognized as a safe dietary intervention, but long-term observations into later adulthood are still not available. We investigated the consequences of a prolonged MCT diet on abdominal fat distribution and composition and on liver fat. Mice with very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD(-/-)) were supplemented for 1 y with a diet in which MCTs replaced long-chain triglycerides without increasing the total fat content. The dietary effects on abdominal fat accumulation and composition were analyzed by in vivo (1)H- and (13)C-magnetic resonance spectroscopy (9.4 Tesla). After 1 y of MCT supplementation, VLCAD(-/-) mice accumulated massive visceral fat and had a dramatic increase in the concentration of serum free fatty acids. Furthermore, we observed a profound shift in body triglyceride composition, ie, concentrations of physiologically important polyunsaturated fatty acids dramatically decreased. (1)H-Magnetic resonance spectroscopy analysis and histologic evaluation of the liver also showed pronounced fat accumulation and marked oxidative stress. Although the MCT-supplemented diet has been reported to prevent the development of cardiomyopathy and skeletal myopathy in fatty acid oxidation disorders, our data show that long-term MCT supplementation results in a severe clinical phenotype similar to that of nonalcoholic steatohepatitis and the metabolic syndrome.

Verification regarding changing construction in accumulation of fat for BMI based on change with age estimated from body composition balance.

PubMed

Fujii, Katsunori; Tanaka, Nozomi; Mishima, Takaaki

2013-12-01

In the present study, a regression analysis of BMI and body fat percentage in each school year was performed with cross-sectional data in school-aged children. The qualitative changes in physique during the school-age years were examined by showing the changes in the level of body fat accu- mulation with age. The subjects were 789 boys and girls (469 boys, 320 girls) aged 7 to 14 years who participated in regular sports activities. Height, weight and body fat percentage were measured. Fat free mass was calculated by subtracting fat mass from body weight. BMI was calculated as body weight (kg) divided by the square of height (m). Regression analysis was conducted for fat percentage against BMI in boys and girls of all school years, and the level of body fat accumulation was considered, the distributions of the frequency of age change were examined. As a result, in the frequency distribution charts there was a shift from excessive fat to low fat from age 7 to 14 years. A χ2 test was then performed for these frequency distribution charts, and the results showed a significant difference in the frequency distribution in each year (P < 0.01). This trend was clearly in boys, and meaning was found in clarifying the changes with age in the body composition balance in boys and girls.

Ezetimibe reduced hepatic steatosis induced by dietary oxysterols in nonhuman primates.

PubMed

Deushi, Michiyo; Osaka, Mizuko; Nakano, Kaku; Osada, Kyoichi; Egashira, Kensuke; Yoshida, Masayuki

2016-10-01

Oxidized cholesterol (oxysterols) plays an important and multifaceted role in lipid metabolism. Here we examined whether dietary oxysterols accelerate hepatic lipid accumulation and inflammation in nonhuman primates. We also examined the effect of the Niemann-Pick C1-like1 inhibitor, ezetimibe (Ez). Macaca fascicularis (5-year-old males) were fed either regular cholesterol + high-fat diet (control-HFD) or oxysterols + high-fat diet (ox-HFD; with 0.015% of oxysterols cholesterol) for 24 weeks. Compared with control-HFD, ox-HFD did not affect plasma lipid levels, but it did affect hepatic lipid levels [total cholesterol, 40.9 mg·g -1 (ox-HFD) versus 3.2 (control-HFD) mg·g -1 ; triglycerides, 28.0 (ox-HFD) versus 5.7 (control-HFD) mg·g -1 ]. Ox-HFD increased lipid accumulation as well as recruitment of inflammatory cells when compared to control-HFD. We then examined the effects of Ez, 0.2 mg·kg -1 ·day -1 for 12 weeks. In addition to a significant reduction in dyslipidemia, Ez alleviated biochemical and pathological aspects of steatosis. Dietary oxysterols aggravate steatosis in nonhuman primates. Treatment with Ez may be a novel therapeutic approach to NAFLD by alleviating dyslipidemia.

High-Fat Diet-Induced Adiposity, Adipose Inflammation, Hepatic Steatosis and Hyperinsulinemia in Outbred CD-1 Mice

PubMed Central

Gao, Mingming; Ma, Yongjie; Liu, Dexi

2015-01-01

High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population. PMID:25768847

High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

PubMed

Gao, Mingming; Ma, Yongjie; Liu, Dexi

2015-01-01

High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population.

Effect of High Sugar Intake on Glucose Transporter and Weight Regulating Hormones in Mice and Humans

PubMed Central

Ritze, Yvonne; Bárdos, Gyöngyi; D’Haese, Jan G.; Ernst, Barbara; Thurnheer, Martin; Schultes, Bernd; Bischoff, Stephan C.

2014-01-01

Objective Sugar consumption has increased dramatically over the last decades in Western societies. Especially the intake of sugar-sweetened beverages seems to be a major risk for the development of obesity. Thus, we compared liquid versus solid high-sugar diets with regard to dietary intake, intestinal uptake and metabolic parameters in mice and partly in humans. Methods Five iso-caloric diets, enriched with liquid (in water 30% vol/vol) or solid (in diet 65% g/g) fructose or sucrose or a control diet were fed for eight weeks to C57bl/6 mice. Sugar, liquid and caloric intake, small intestinal sugar transporters (GLUT2/5) and weight regulating hormone mRNA expression, as well as hepatic fat accumulation were measured. In obese versus lean humans that underwent either bariatric surgery or small bowel resection, we analyzed small intestinal GLUT2, GLUT5, and cholecystokinin expression. Results In mice, the liquid high-sucrose diet caused an enhancement of total caloric intake compared to the solid high-sucrose diet and the control diet. In addition, the liquid high-sucrose diet increased expression of GLUT2, GLUT5, and cholecystokinin expression in the ileum (P<0.001). Enhanced liver triglyceride accumulation was observed in mice being fed the liquid high-sucrose or -fructose, and the solid high-sucrose diet compared to controls. In obese, GLUT2 and GLUT5 mRNA expression was enhanced in comparison to lean individuals. Conclusions We show that the form of sugar intake (liquid versus solid) is presumably more important than the type of sugar, with regard to feeding behavior, intestinal sugar uptake and liver fat accumulation in mice. Interestingly, in obese individuals, an intestinal sugar transporter modulation also occurred when compared to lean individuals. PMID:25010715

Effect of the inclusion time of dietary saturated and unsaturated fats before slaughter on the accumulation and composition of abdominal fat in female broiler chickens.

PubMed

Sanz, M; Lopez-Bote, C J; Flores, A; Carmona, J M

2000-09-01

The aim of this experiment was to assess the effects of four different feeding programs designed to include tallow, a saturated fat at 0, 8, 12, and 28 d prior to slaughter on female broiler performance and the deposition, fatty acid profile, and melting point of abdominal fat. The following treatment groups were established according to dietary inclusion--from 21 to 49 d of age--of: sunflower oil (SUN), sunflower oil followed by tallow during the last 8 d (SUN + 8TALL), sunflower oil followed by tallow during the last 12 d (SUN + 12TALL), and tallow (TALL). The diets were designed to be isoenergetic and isonitrogenous. Abdominal fat deposition increased linearly with increasing number of days in which birds were fed the tallow-enriched diet. However, linear and quadratic response patterns were found between days before slaughter in which the birds were fed the tallow-enriched diet and abdominal fat melting points. This result suggested an exponential response in which 85% of the maximum level was already attained when the dietary fat type changed from an unsaturated to a saturated condition during the last 8 d of the feeding period. The use of an unsaturated fat source during the first stages of growth, and the substitution of a saturated fat for a few days before slaughter, may offer the advantage of lower abdominal fat deposition and an acceptable fat fluidity compared with the use of a saturated fat source during the whole growing and finishing period.

Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects.

PubMed

Haufe, Sven; Engeli, Stefan; Kast, Petra; Böhnke, Jana; Utz, Wolfgang; Haas, Verena; Hermsdorf, Mario; Mähler, Anja; Wiesner, Susanne; Birkenfeld, Andreas L; Sell, Henrike; Otto, Christoph; Mehling, Heidrun; Luft, Friedrich C; Eckel, Juergen; Schulz-Menger, Jeanette; Boschmann, Michael; Jordan, Jens

2011-05-01

Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (-30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids. A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet. Copyright © 2011 American Association for the Study of Liver Diseases.

Arboreal adaptations of body fat in wild toque macaques (Macaca sinica) and the evolution of adiposity in primates.

PubMed

Dittus, Wolfgang P J

2013-11-01

There is a paucity of information on body composition and fat patterning in wild nonhuman primates. Dissected adipose tissue from wild toque macaques (Macaca sinica) (WTM), feeding on a natural diet, accounted for 2.1% of body weight. This was far less than fatness reported for nonhuman primates raised in captivity or for contemporary humans. In WTM, fatness increased with age and diet richness, but did not differ by sex. In WTM (none of which were obese) intra-abdominal fat filled first, and "excess" fat was stored peripherally in a ratio of about 6:1. Intermuscular fat was minimal (0.1%). The superficial paunch held <15% of subcutaneous fat weight in contrast to its much larger proportions in obese humans and captive monkeys where most added fat accumulates subcutaneously. With increasing total adiposity, accumulating fat shifted in its distribution among eight different main internal and peripheral deposit areas-consistent with maintaining body balance and a low center of gravity. The available data suggest that, in arboreal primates, adaptations for agile locomotion and terminal branch feeding set constraints on the quantity and distribution of fat. The absence of a higher percentage of body fat in females and neonates (as are typical of humans) suggests that arboreal adaptations preclude the development of fat-dependent, large-brained infants and the adipose-rich mothers needed to sustain them. The lifestyle and body composition of wild primates represent a more appropriate model for early human foragers than well-fed captive monkeys do. Copyright © 2013 Wiley Periodicals, Inc.

Ghrelin receptor null mice have reduced visceral fat and improved insulin sensitivity during aging

USDA-ARS?s Scientific Manuscript database

Aging is associated with a higher incidence of Type 2 diabetes; one in five Americans over age 65 has diabetes. Loss of lean mass and accumulation of fat, particularly visceral fat, during aging result in increased insulin resistance. Insulin resistance is a major pathogenic factor for Type 2 diabet...

Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice

USDA-ARS?s Scientific Manuscript database

Adipose tissue macrophages play an important role in the pathogenesis of obese type 2 diabetes. High-fat diet-induced obesity has been shown to lead to adipose tissue macrophages accumulation in rodents;however, the impact of hyperglycemia on adipose tissue macrophages dynamics in high-fat diet-fed ...

Rhododendron oldhamii leaf extract improves fatty liver syndrome by increasing lipid oxidation and decreasing the lipogenesis pathway in mice.

PubMed

Liu, Ya-Ling; Lin, Lei-Chen; Tung, Yu-Tang; Ho, Shang-Tse; Chen, Yao-Li; Lin, Chi-Chen; Wu, Jyh-Horng

2017-01-01

Some members of Rhododendron genus are traditionally used as medicinal plants for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases. To the best of our knowledge, there is no report on the protective effects of R. oldhamii leaf extract on non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro . In this study, the effects of R. oldhamii leaf extract on inhibiting the free fatty acid (FFA)-induced accumulation of fat in HepG2 cells and on improving fatty liver syndrome in mice with high fat diet (HFD)-induced NAFLD were investigated. For the in vitro assay, HepG2 cells were treated with FFAs (oleate/palmitate = 2:1) with or without treatment with R. oldhamii leaf ethyl acetate (EtOAc) fraction to observe lipid accumulation using Nile red and oil red O stains. For the in vivo assay, C57BL/6 mice were randomly assigned to three groups ( n = 5), including the normal diet group, the HFD group and the HFD+EtOAc group. After 11 weeks, body weight, serum biochemical indices and the mRNA expressions of the liver tissue, as well as the outward appearance, weight and histopathological analysis of liver and adipose tissues were evaluated. Among the fractions derived from R. oldhamii leaf, the EtOAc fraction exhibited a strong fat-accumulation inhibitory activity. Following reverse-phase high-performance liquid chromatography (HPLC), four specific phytochemicals, including (2 R , 3 R )-astilbin (AS), hyposide (HY), guaijaverin (GU) and quercitrin (QU), were isolated and identified from the EtOAc fraction of R. oldhamii leaf extract. Among them, AS and HY showed excellent fat-accumulation inhibitory activity. Thus, the EtOAc fraction of R. oldhamii leaf and its derived phytochemicals have great potential in preventing FFA-induced fat accumulation. In addition, the EtOAc fraction of R. oldhamii leaf significantly improved fatty liver syndrome and reduced total cholesterol (TC) and triglyceride (TG) in HFD-induced NAFLD mice at a dosage of 200 mg/kg BW. These results demonstrated that the methanolic extracts from R. oldhamii leaf have excellent inhibitory activities against fat accumulation and anti-NAFLD activities and thus have great potential as a natural health product.

Effect of Sea-Buckthorn (Hippophaë rhamnoides L.) Pulp Oil Consumption on Fatty Acids and Vitamin A and E Accumulation in Adipose Tissue and Liver of Rats.

PubMed

Czaplicki, Sylwester; Ogrodowska, Dorota; Zadernowski, Ryszard; Konopka, Iwona

2017-06-01

An in vivo experiment was conducted to determine the effect of sea-buckthorn pulp oil feeding on the fatty acid composition of liver and adipose tissue of Wistar rats and the liver accumulation of retinol, its esters and α-tocopherol. For a period of 28 days, rats were given a modified casein diet (AIN-93) in which sea-buckthorn pulp oil, soybean oil and pork lard were used as sources of fat. Compared to the other fat sources, sea-buckthorn pulp oil was the most abundant in C16 fatty acids, carotenoids (mainly β-carotene) and tocopherols (mainly α-tocopherol). Its consumption was reflected in an increased share of palmitoleic acid in adipose tissue and the liver and an increased level of retinol in liver tissues (this was not observed for its esters). Although the type of fat did not have a significant effect on the average content of α-tocopherol in the liver, the variation of saturation of this tissue with α-tocopherol was the lowest when rats were fed a diet containing sea-buckthorn oil. This experiment indicates the possibility of affecting adipose tissue and liver by a diet.

Antidiabetic effects of Artemisia sphaerocephala Krasch. gum, a novel food additive in China, on streptozotocin-induced type 2 diabetic rats.

PubMed

Xing, Xiao-Hui; Zhang, Zheng-Mao; Hu, Xin-Zhong; Wu, Rui-Qin; Xu, Chao

2009-09-25

Since ancient times, practicians of traditional Chinese medicine have discovered that Artemisia sphaerocephala Krasch. (Asteraceae) seed powder was useful for the treatment of diabetes. Artemisia sphaerocephala Krasch. gum (ASK gum), which is extracted from seed powder of the plant, is a novel food additive favored by the food industry in China. The objective of this study was to determine the antidiabetic function of ASK gum on type 2 diabetes. Type 2 diabetic rat model was induced with high fat diet and low dose of streptozotocin (STZ). The effects of ASK gum on hyperglycemia, hyperlipemia, insulin resistance, and liver fat accumulation in type 2 diabetic rats were evaluated. The results were compared to those of normal rats and diabetic rats treated with metformin. The addition of ASK gum to the rats' food supply significantly lowered fasting blood glucose, glycated serum protein, serum cholesterol, and serum triglyceride in type 2 diabetic rats, and significantly elevated liver glucokinase, liver glycogen, and serum high density protein cholesterol in the diabetic rats. ASK gum significantly reduced insulin resistance and liver fat accumulation of type 2 diabetes. Artemisia sphaerocephala Krasch. gum can alleviate hyperglycemia, hyperlipemia and insulin resistance of type 2 diabetes.

Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver.

PubMed

Davaatseren, Munkhtugs; Hur, Haeng Jeon; Yang, Hye Jeong; Hwang, Jin-Taek; Park, Jae Ho; Kim, Hyun-Jin; Kim, Min Jung; Kwon, Dae Young; Sung, Mi Jeong

2013-08-01

The purpose of this study is to determine the protective effect of Taraxacum official (dandelion) leaf extract (DLE) on high-fat-diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. To determine the hepatoprotective effect of DLE, we fed C57BL/6 mice with normal chow diet (NCD), high-fat diet (HFD), HFD supplemented with 2g/kg DLE DLE (DL), and HFD supplemented with 5 g/kg DLE (DH). We found that the HFD supplemented by DLE dramatically reduced hepatic lipid accumulation compared to HFD alone. Body and liver weights of the DL and DH groups were significantly lesser than those of the HFD group, and DLE supplementation dramatically suppressed triglyceride (TG), total cholesterol (TC), insulin, fasting glucose level in serum, and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) induced by HFD. In addition, DLE treatment significantly increased activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in liver and muscle protein. DLE significantly suppressed lipid accumulation in the liver, reduced insulin resistance, and lipid in HFD-fed C57BL/6 mice via the AMPK pathway. These results indicate that the DLE may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Interleukin-6 deficiency facilitates myocardial dysfunction during high fat diet-induced obesity by promoting lipotoxicity and inflammation.

PubMed

Chen, Fan; Chen, Dandan; Zhao, Xinmei; Yang, Shuai; Li, Zhe; Sanchis, Daniel; Jin, Liang; Qiang, Xizhe; Wang, Kaiye; Xu, Yitao; Zhang, Yubin; Ye, Junmei

2017-12-01

Obesity is associated with metabolic disorder and chronic inflammation that plays a crucial role in cardiovascular diseases. IL-6 is involved in regulating obesity-related lipid metabolism and inflammation. In this study, we sought to determine the role of IL-6 in high-fat diet (HFD)-induced cardiomyopathy and explore the signaling pathway. Female, 5-week-old IL-6 knockout (KO) and littermate mice were fed a normal diet (ND, 10% fat) or HFD (45% fat) for 14 weeks. At the end of treatment, cardiac function was assessed by echocardiography. Adipose tissues and plasma were collected for further measurement. Immunohistology of CD68 was performed to detect inflammation in the heart. Masson's trichrome staining and Oil Red O staining was applied to evaluated cardiac fibrosis and lipid accumulation. Real-time PCR and Western immunoblotting analyses on heart tissue were used to explore the underlying mechanism. IL-6 KO mice displayed increased insulin resistance compared to WT mice at baseline. When fed HFD, IL-6 KO mice showed decreased gains in body weight and fat mass, increased insulin resistance relative to IL-6 KO mice feed ND. Furthermore, IL-6 KO mice developed cardiac dysfunction during HFD-induced obesity. Histological analysis suggested increased lipid accumulation, fibrosis and inflammation without affecting cardiac morphology during HFD treatment in the heart of IL-6 KO mice. Finally, IL-6 deficiency increased the phosphorylation of AMPK and ACC in the heart during HFD-induced obesity. Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Milk fat globule membrane coating of large lipid droplets in the diet of young mice prevents body fat accumulation in adulthood.

PubMed

Baars, Annemarie; Oosting, Annemarie; Engels, Eefje; Kegler, Diane; Kodde, Andrea; Schipper, Lidewij; Verkade, Henkjan J; van der Beek, Eline M

2016-06-01

Epidemiological studies have demonstrated protective effects of breast-feeding on childhood obesity. Differences between human milk and infant milk formula (IMF) in dietary lipid structure may contribute to this effect. In our mouse model, feeding a diet containing large lipid droplets coated with phospholipids (PL) (Nuturis®; PL of milk fat globule membrane (MFGM) fraction origin) in early life protected against excessive body fat accumulation following a diet challenge in adult life. We now set out to determine the relevance of increased droplet size and/or MFGM lipid droplet coating to the observed anti-obesogenic effects in adult life. From day 16 to 42, male mouse pups were exposed to diets with small (S) or large (L) lipid droplets (0·3 v. 2·9 µm average mode diameter, respectively), either without MFGM or with MFGM coating around the lipid droplet, resulting in four groups: S (control diet), L, Scoating and Lcoating (Nuturis® IMF diet). Mice were subsequently challenged with a Western-style diet until dissection at postnatal day 98. A non-challenged group served as reference (REF). We repeatedly determined body composition between postnatal day 42 and 98. At day 98 plasma and gene expression measurements were performed. Only the Nuturis® IMF diet (Lcoating) in early life containing MFGM-coated large lipid droplets reduced body fat mass to a level comparable with the REF group. These data support the notion that the structural aspects of lipids in human milk, for example, both lipid droplet size as well as the MFGM coating, may contribute to its reported protective effect against obesity in later life.

Visceral Fat Accumulation Is Associated with Colorectal Cancer in Postmenopausal Women

PubMed Central

Lee, Jee-Yon; Lee, Hye-Sun; Lee, Duk-Chul; Chu, Sang-Hui; Jeon, Justin Y.

2014-01-01

Background Obesity is a known risk factor for colorectal cancer (CRC), and emerging data suggest that this association is mediated by visceral fat rather than total body fat. However, there is a lack of studies evaluating the association between visceral fat area and the prevalence of CRC. Methods To investigate the relationship between visceral adiposity and prevalence of CRC, data of 497 women diagnosed with CRC and 318 apparently healthy women were analysed and data of well-balanced 191 pairs of women with CRC and healthy women matched based on propensity scores were additionally analysed. Diagnosis of CRC was confirmed by colonoscopy and histology. Metabolic parameters were assessed, along with body composition, using computed tomography. Results The median visceral fat area was significantly higher in the CRC group compared with the control group before and after matching. The prevalence of CRC increased significantly with increasing visceral fat tertiles after matching (p for trend <0.01). A multivariate analysis showed that mean visceral fat area of individuals in the 67th percentile or greater group was associated with an increased prevalence of CRC (adjusted odds ratio: 1.80; 95% confidence interval: 1.12–2.91 before matching and adjusted odds ratio: 2.96; 95% confidence interval: 1.38–6.33) compared with that of individuals in the 33th percentile or lower group. Conclusion Thus, we conclude that visceral fat area is positively associated with the prevalence of CRC. Although we could not determine the causality, visceral adiposity may be associated with the risk of CRC. Further prospective studies are required to determine the benefits of controlling visceral obesity for reducing CRC risk. PMID:25402501

Prediabetic nephropathy as an early consequence of the high-calorie/high-fat diet: relation to oxidative stress.

PubMed

Shevalye, Hanna; Lupachyk, Sergey; Watcho, Pierre; Stavniichuk, Roman; Khazim, Khaled; Abboud, Hanna E; Obrosova, Irina G

2012-03-01

This study evaluated early renal functional, structural, and biochemical changes in high-calorie/high-fat diet fed mice, a model of prediabetes and alimentary obesity. Male C57BL6/J mice were fed normal (11 kcal% fat) or high-fat (58 kcal% fat) diets for 16 wk. Renal changes were evaluated by histochemistry and immunohistochemistry, Western blot analysis, ELISA, enzymatic assays, and chemiluminometry. High-fat diet consumption led to increased body and kidney weights, impaired glucose tolerance, hyperinsulinemia, polyuria, a 2.7-fold increase in 24-h urinary albumin excretion, 20% increase in renal glomerular volume, 18% increase in renal collagen deposition, and 8% drop of glomerular podocytes. It also resulted in a 5.3-fold increase in urinary 8-isoprostane excretion and a 38% increase in renal cortex 4-hydroxynonenal adduct accumulation. 4-hydroxynonenal adduct level and immunoreactivity or Sirtuin 1 expression in renal medulla were not affected. Studies of potential mechanisms of the high-fat diet induced renal cortex oxidative injury revealed that whereas nicotinamide adenine dinucleotide phosphate reduced form oxidase activity only tended to increase, 12/15-lipoxygenase was significantly up-regulated, with approximately 12% increase in the enzyme protein expression and approximately 2-fold accumulation of 12(S)-hydroxyeicosatetraenoic acid, a marker of 12/15-lipoxygenase activity. Accumulation of periodic acid-Schiff -positive material, concentrations of TGF-β, sorbitol pathway intermediates, and expression of nephrin, CAAT/enhancer-binding protein homologous protein, phosphoeukaryotic initiation factor-α, and total eukaryotic initiation factor-α in the renal cortex were indistinguishable between experimental groups. Vascular endothelial growth factor concentrations were reduced in high-fat diet fed mice. In conclusion, systemic and renal cortex oxidative stress associated with 12/15-lipoxygenase overexpression and activation is an early phenomenon caused by high-calorie/high-fat diet consumption and a likely contributor to kidney disease associated with prediabetes and alimentary obesity.

An infection of human adenovirus 31 affects the differentiation of preadipocytes into fat cells, its metabolic profile and fat accumulation.

PubMed

Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Sawicki, Grzegorz; Woźniak, Mieczysław

2016-03-01

The primary issue undertaken in this study was to test the hypothesis that preadipocytes would have intrinsically elevated propensity to differentiate into mature adipocytes due to HAdV31 infection. To prove that, the metabolic and molecular mechanisms responsible for HAdV31-induced adipogenesis were examined. 3T3L1 cells (mouse embryonic fibroblast, adipose like cell line) were used as a surrogate model to analyze an increased proliferation, differentiation, and maturation of preadipocytes infected with human adenovirus. An expression of E4orf1, C/EBP-β, PPAR-γ, GAPDH, aP2, LEP, and fatty acid synthase genes, intracellular lipid accumulation as well as cytokine release from the fat cells were assessed. Data showed that HAdV31 increased an expression of C/EBP-β and PPAR-γ genes leading to an enhanced differentiation of preadipocytes into fat cells. Besides, overexpression of GAPDH and fatty acid synthase, and decreased expression of leptin caused an increased accumulation of intracellular lipids. Secretion of TNF-α and IL-6 from HAdV31-infected cells was strongly decreased, leading to unlimited virus replication. The results obtained from this study provided the evidences that HAdV31, likewise previously documented HAdV36, is a subsequent human adenovirus affecting the differentiation and lipid accumulation of 3T3L1 cells. © 2015 Wiley Periodicals, Inc.

Associations of Erythrocyte Fatty Acids in the De Novo Lipogenesis Pathway with Proxies of Liver Fat Accumulation in the EPIC-Potsdam Study

PubMed Central

Jacobs, Simone; Jäger, Susanne; Jansen, Eugene; Peter, Andreas; Stefan, Norbert; Boeing, Heiner; Schulze, Matthias B.; Kröger, Janine

2015-01-01

Background Biomarker fatty acids (FAs) reflecting de novo lipogenesis (DNL) are strongly linked to the risk of cardiometabolic diseases. Liver fat accumulation could mediate this relation. There is very limited data from human population-based studies that have examined this relation. Objective The aim of this study was to investigate the relation between specific FAs in the DNL pathway and liver fat accumulation in a large population-based study. Methods We conducted a cross-sectional analysis of a subsample (n = 1,562) of the EPIC-Potsdam study, which involves 27,548 middle-aged men and women. Baseline blood samples have been analyzed for proportions of 32 FAs in erythrocyte membranes (determined by gas chromatography) and biomarker concentrations in plasma. As indicators for DNL, the DNL-index (16:0 / 18:2n-6) and proportions of individual blood FAs in the DNL pathway were used. Plasma parameters associated with liver fat content (fetuin-A, ALT, and GGT) and the algorithm-based fatty liver index (FLI) were used to reflect liver fat accumulation. Results The DNL-index tended to be positively associated with the FLI and was positively associated with GGT activity in men (p for trend: 0.12 and 0.003). Proportions of 14:0 and 16:0 in erythrocytes were positively associated with fetuin-A, whereas 16:1n-7 were positively associated with the FLI and GGT activity (all p for trends in both sexes at least 0.004). Furthermore, the proportion of 16:1n-7 was positively related to fetuin-A in women and ALT activity in men (all p for trend at least 0.03). The proportion of 16:1n-9 showed positive associations with the FLI and GGT activity in men and fetuin-A in both sexes, whereas 18:1n-7 was positively associated with GGT activity in men (all p for trend at least 0.048). Conclusion Findings from this large epidemiological study suggest that liver fat accumulation could link erythrocyte FAs in the DNL pathway to the risk of cardiometabolic diseases. PMID:25984792

Extent of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation and glycated hemoglobin of 5.6-6.4.

PubMed

Iwahashi, Hiromi; Noguchi, Midori; Okauchi, Yukiyoshi; Morita, Sachiko; Imagawa, Akihisa; Shimomura, Iichiro

2015-09-01

Weight reduction improves glycemic control in obese men with glycated hemoglobin (HbA1c) of 5.6-6.4%, suggesting that it can prevent the development of diabetes in these patients. The aim of the present study was to quantify the amount of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation. The study participants were 482 men with an estimated visceral fat area of ≥100 cm(2), HbA1c of 5.6-6.4%, fasting plasma glucose (FPG) of <126 mg/dL or casual plasma glucose <200 mg/dL. They were divided into two groups based on weight change at the end of the 3-year follow-up period (weight gain and weight loss groups). The weight loss group was classified into quartile subgroups (lowest group, 0 to <1.2%: second lowest group, ≥1.2 to <2.5%: second highest group, ≥2.5 to <4.3%: highest group, ≥4.3% weight loss). The development of diabetes at the end-point represented a rise in HbA1c to ≥6.5% or FPG ≥126 mg/dL, or casual plasma glucose ≥200 mg/dL. The cumulative incidence of diabetes at the end of the 3-year follow-up period was 16.2% in the weight gain group and 10.1% in the weight loss group (P not significant). The incidence of diabetes was significantly lower in the highest weight loss group (3.1%), but not in the second highest, the second lowest and the lowest weight loss groups (9.7, 10.1 and 18.3%), compared with the weight gain group. Minimization of the risk of diabetes in Japanese men with visceral fat accumulation requires a minimum of 4-5% weight loss in those with HbA1c of 5.6-6.4%.

Persistent organic pollutants in fat of three species of Pacific pelagic longline caught sea turtles: Accumulation in relation to ingested plastic marine debris

USGS Publications Warehouse

Clukey, Katharine; Lepczyk, Christopher A.; Balazs, George H.; Work, Thierry M.; Li, Qing X.; Bachman, Melanie J.; Lynch, Jennifer M.

2017-01-01

In addition to eating contaminated prey, sea turtles may be exposed to persistent organic pollutants (POPs) from ingesting plastic debris that has absorbed these chemicals. Given the limited knowledge about POPs in pelagic sea turtles and how plastic ingestion influences POP exposure, our objectives were to: 1) provide baseline contaminant levels of three species of pelagic Pacific sea turtles; and 2) assess trends of contaminant levels in relation to species, sex, length, body condition and capture location. In addition, we hypothesized that if ingesting plastic is a significant source of POP exposure, then the amount of ingested plastic may be correlated to POP concentrations accumulated in fat. To address our objectives we compared POP concentrations in fat samples to previously described amounts of ingested plastic from the same turtles. Fat samples from 25 Pacific pelagic sea turtles [2 loggerhead (Caretta caretta), 6 green (Chelonia mydas) and 17 olive ridley (Lepidochelys olivacea) turtles] were analyzed for 81 polychlorinated biphenyls (PCBs), 20 organochlorine pesticides, and 35 brominated flame-retardants. The olive ridley and loggerhead turtles had higher ΣDDTs (dichlorodiphenyltrichloroethane and metabolites) than ΣPCBs, at a ratio similar to biota measured in the South China Sea and southern California. Green turtles had a ratio close to 1:1. These pelagic turtles had lower POP levels than previously reported in nearshore turtles. POP concentrations were unrelated to the amounts of ingested plastic in olive ridleys, suggesting that their exposure to POPs is mainly through prey. In green turtles, concentrations of ΣPCBs were positively correlated with the number of plastic pieces ingested, but these findings were confounded by covariance with body condition index (BCI). Green turtles with a higher BCI had eaten more plastic and also had higher POPs. Taken together, our findings suggest that sea turtles accumulate most POPs through their prey rather than marine debris.

The Major Green Tea Polyphenol, (−)-Epigallocatechin-3-Gallate, Inhibits Obesity, Metabolic Syndrome, and Fatty Liver Disease in High-Fat–Fed Mice1,2

PubMed Central

Bose, Mousumi; Lambert, Joshua D.; Ju, Jihyeung; Reuhl, Kenneth R.; Shapses, Sue A.; Yang, Chung S.

2008-01-01

In this study, we investigated the effects of the major green tea polyphenol, (−)-epigallocatechin-3-gallate (EGCG), on high-fat–induced obesity, symptoms of the metabolic syndrome, and fatty liver in mice. In mice fed a high-fat diet (60% energy as fat), supplementation with dietary EGCG treatment (3.2 g/kg diet) for 16 wk reduced body weight (BW) gain, percent body fat, and visceral fat weight (P < 0.05) compared with mice without EGCG treatment. The BW decrease was associated with increased fecal lipids in the high-fat–fed groups (r2 = 0.521; P < 0.05). EGCG treatment attenuated insulin resistance, plasma cholesterol, and monocyte chemoattractant protein concentrations in high-fat–fed mice (P < 0.05). EGCG treatment also decreased liver weight, liver triglycerides, and plasma alanine aminotransferase concentrations in high-fat–fed mice (P < 0.05). Histological analyses of liver samples revealed decreased lipid accumulation in hepatocytes in mice treated with EGCG compared with high-fat diet-fed mice without EGCG treatment. In another experiment, 3-mo-old high-fat–induced obese mice receiving short-term EGCG treatment (3.2 g/kg diet, 4 wk) had decreased mesenteric fat weight and blood glucose compared with high-fat–fed control mice (P < 0.05). Our results indicate that long-term EGCG treatment attenuated the development of obesity, symptoms associated with the metabolic syndrome, and fatty liver. Short-term EGCG treatment appeared to reverse preexisting high-fat–induced metabolic pathologies in obese mice. These effects may be mediated by decreased lipid absorption, decreased inflammation, and other mechanisms. PMID:18716169

Milk production and composition, and progeny performance in young ewes with high merit for rapid growth and muscle and fat accumulation.

PubMed

Rosales Nieto, C A; Ferguson, M B; Macleay, C A; Briegel, J R; Wood, D A; Martin, G B; Bencini, R; Thompson, A N

2018-02-26

In ewe lambs, acceleration of growth and accumulation of both muscle and fat leads to earlier sexual maturity and better reproductive performance. The next stage in the development of this theme is to test whether these aspects of growth in young ewes affect milk production in their first lactation and the growth of their first progeny. We studied 75 young Merino ewes that had known phenotypic values for depth of eye muscle (EMD) and fat (FAT), and known Australian Sheep Breeding Values for post-weaning weight (PWT) and depths of eye muscle (PEMD) and fat (PFAT). They lambed for the first time at 1 year of age. Their lambs were weighed weekly from birth to weaning at 10 weeks to determine live weight gain and weaning weight. Progeny birth weight was positively associated with live weight gain and weaning weight (P0.05). The PWT of the sire was positively associated with live weight gain (P0.05). The concentrations of fat, protein, lactose and total solids in the milk were not affected by the phenotype or genotype of the mothers or of the sires of the mothers, or by the sex of the progeny (P>0.05). We conclude that selection of young Merino ewes for better growth, and more rapid accumulation of muscle and fat, will lead to progeny that are heavier at birth, grow faster and are heavier at weaning. Moreover, milk production and composition do not seem to be affected by the genetic merit of the mother for post-weaning live weight or PEMD or PFAT. Therefore, Merino ewes can lamb at 1 year of age without affecting the production objectives of the Merino sheep industry.

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials

USDA-ARS?s Scientific Manuscript database

Context: The effect of added sugar intake on ectopic fat accumulation is a subject of debate. Objective: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. Data Sources: MEDLINE, CA...

Fat digestion and absorption in spice-pretreated rats.

PubMed

Prakash, Usha N S; Srinivasan, Krishnapura

2012-02-01

A few common spices are known to stimulate secretion of bile with higher amount of bile acids which play a major role in digestion and absorption of dietary lipids. It would be appropriate to verify if these spices enable efficient digestion and absorption during high-fat intake. In this context, dietary ginger (0.05%), piperine (0.02%), capsaicin (0.015%), and curcumin (0.5%) were examined for their influence on bile secretion, digestive enzymes of pancreas and absorption of dietary fat in high-fat (30%) fed Wistar rats for 8 weeks. These spices enhanced the activity of pancreatic lipase, amylase, trypsin and chymotrypsin by 22-57%, 32-51%, 63-81% and 12-38%, respectively. Dietary intake of spices along with high-fat enhanced fat absorption. These dietary spices increased bile secretion with higher bile acid content. Stimulation of lipid mobilisation from adipose tissue was suggested by the decrease in perirenal adipose tissue weight by dietary capsaicin and piperine. This was also accompanied by prevention of the accumulation of triglyceride in liver and serum in high-fat fed rats. Activities of key lipogenic enzymes in liver were reduced which was accompanied by an increased activity of hormone-sensitive lipase. Thus, dietary ginger and other spice compounds enhance fat digestion and absorption in high-fat fed situation through enhanced secretion of bile salts and a stimulation of the activity pancreatic lipase. At the same time, the energy expenditure is facilitated by these spices to prevent the accumulation of absorbed fat. Copyright © 2011 Society of Chemical Industry.

Aerobic capacity mediates susceptibility for the transition from steatosis to steatohepatitis.

PubMed

Morris, E Matthew; McCoin, Colin S; Allen, Julie A; Gastecki, Michelle L; Koch, Lauren G; Britton, Steven L; Fletcher, Justin A; Fu, Xiarong; Ding, Wen-Xing; Burgess, Shawn C; Rector, R Scott; Thyfault, John P

2017-07-15

Low intrinsic aerobic capacity is associated with increased all-cause and liver-related mortality in humans. Low intrinsic aerobic capacity in the low capacity runner (LCR) rat increases susceptibility to acute and chronic high-fat/high-sucrose diet-induced steatosis, without observed increases in liver inflammation. Addition of excess cholesterol to a high-fat/high-sucrose diet produced greater steatosis in LCR and high capacity runner (HCR) rats. However, the LCR rat demonstrated greater susceptibility to increased liver inflammatory and apoptotic markers compared to the HCR rat. The progressive non-alcoholic fatty liver disease observed in the LCR rats following western diet feeding was associated with further declines in liver fatty acid oxidation and mitochondrial respiratory capacity compared to HCR rats. Low aerobic capacity increases risk for non-alcoholic fatty liver disease and liver-related disease mortality, but mechanisms mediating these effects remain unknown. We recently reported that rats bred for low aerobic capacity (low capacity runner; LCR) displayed susceptibility to high fat diet-induced steatosis in association with reduced hepatic mitochondrial fatty acid oxidation (FAO) and respiratory capacity compared to high aerobic capacity (high capacity runner; HCR) rats. Here we tested the impact of aerobic capacity on susceptibility for progressive liver disease following a 16-week 'western diet' (WD) high in fat (45% kcal), cholesterol (1% w/w) and sucrose (15% kcal). Unlike previously with a diet high in fat and sucrose alone, the inclusion of cholesterol in the WD induced hepatomegaly and steatosis in both HCR and LCR rats, while producing greater cholesterol ester accumulation in LCR compared to HCR rats. Importantly, WD-fed low-fitness LCR rats displayed greater inflammatory cell infiltration, serum alanine transaminase, expression of hepatic inflammatory markers (F4/80, MCP-1, TLR4, TLR2 and IL-1β) and effector caspase (caspase 3 and 7) activation compared to HCR rats. Further, LCR rats had greater WD-induced decreases in complete FAO and mitochondrial respiratory capacity. Intrinsic aerobic capacity had no impact on WD-induced hepatic steatosis; however, rats bred for low aerobic capacity developed greater hepatic inflammation, which was associated with reduced hepatic mitochondrial FAO and respiratory capacity and increased accumulation of cholesterol esters. These results confirm epidemiological reports that aerobic capacity impacts progression of liver disease and suggest that these effects are mediated through alterations in hepatic mitochondrial function. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Hyperphagia and increased fat accumulation in two models of chronic CNS glucagon-like peptide-1 loss of function.

PubMed

Barrera, Jason G; Jones, Kenneth R; Herman, James P; D'Alessio, David A; Woods, Stephen C; Seeley, Randy J

2011-03-09

Central administration of glucagon-like peptide-1 (GLP-1) causes a dose-dependent reduction in food intake, but the role of endogenous CNS GLP-1 in the regulation of energy balance remains unclear. Here, we tested the hypothesis that CNS GLP-1 activity is required for normal energy balance by using two independent methods to achieve chronic CNS GLP-1 loss of function in rats. Specifically, lentiviral-mediated expression of RNA interference was used to knock down nucleus of the solitary tract (NTS) preproglucagon (PPG), and chronic intracerebroventricular (ICV) infusion of the GLP-1 receptor (GLP-1r) antagonist exendin (9-39) (Ex9) was used to block CNS GLP-1r. NTS PPG knockdown caused hyperphagia and exacerbated high-fat diet (HFD)-induced fat accumulation and glucose intolerance. Moreover, in control virus-treated rats fed the HFD, NTS PPG expression levels correlated positively with fat mass. Chronic ICV Ex9 also caused hyperphagia; however, increased fat accumulation and glucose intolerance occurred regardless of diet. Collectively, these data provide the strongest evidence to date that CNS GLP-1 plays a physiologic role in the long-term regulation of energy balance. Moreover, they suggest that this role is distinct from that of circulating GLP-1 as a short-term satiation signal. Therefore, it may be possible to tailor GLP-1-based therapies for the prevention and/or treatment of obesity.

Quantification of Liver Fat with Magnetic Resonance Imaging

PubMed Central

Reeder, Scott B.; Sirlin, Claude

2010-01-01

Intracellular fat accumulation is common feature of liver disease. Intracellular fat (steatosis) is the histological hallmark of non-alcoholic fatty liver disease (NAFLD) but also may occur with alcohol abuse, viral hepatitis, HIV and genetic lipodystrophies, and chemotherapy. This article reviews emerging magnetic resonance imaging techniques that attempt to quantify liver fat. The content provides an overview of fatty liver disease and diseases where fat is an important disease feature. Also discussed is the current use and limitation of non-targeted biopsy in diffuse liver disease, and why quantitative non-invasive biomarkers of liver fat would be beneficial. PMID:21094444

ω-3 Fatty Acids Prevent Hepatic Steatosis, Independent of PPAR-α Activity, in a Murine Model of Parenteral Nutrition–Associated Liver Disease

PubMed Central

Prince, Esther; Lazare, Farrah B.; Treem, William R.; Xu, Jiliu; Iqbal, Jahangir; Pan, Xiaoyue; Josekutty, Joby; Walsh, Meghan; Anderson, Virginia; Hussain, M. Mahmood; Schwarz, Steven M.

2015-01-01

Objectives ω-3 Fatty acids (FAs), natural ligands for the peroxisome proliferator-activated receptor–α (PPAR-α), attenuate parenteral nutrition–associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω-3 FAs are still unknown. The aim of this study was to determine the effects of ω-3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR-α and microsomal triglyceride transfer protein (MTP) in this experimental setting. Methods 129S1/SvImJ wild-type or 129S4/SvJaePparatm/Gonz/J PPAR-α knockout mice were fed chow and water (controls); oral, fat-free PN solution only (PN-O); PN-O plus intraperitoneal (IP) ω-6 FA-predominant supplements (PN–ω-6); or PN-O plus IP ω-3 FA (PN–ω-3). Control and PN-O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR-α messenger RNA were assessed after 19 days. Results In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN-O and PN–ω-6 groups accumulated significantly greater amounts of TG when compared with PN–ω-3 mice. Studies in PPAR-α null animals showed that PN feeding increases hepatic TG as in wild-type mice. PPAR-α null mice in the PN-O and PN–ω-6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω-3 FAs. Conclusions PN induces TG accumulation (steatosis) in wild-type and PPAR-α null mice. In PN-fed wild-type and PPAR-α null mice given IP ω-3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω-3 FAs results from PPAR-α–independent pathways. PMID:23757305

Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change.

PubMed

Rinnankoski-Tuikka, Rita; Hulmi, Juha J; Torvinen, Sira; Silvennoinen, Mika; Lehti, Maarit; Kivelä, Riikka; Reunanen, Hilkka; Kujala, Urho M; Kainulainen, Heikki

2014-08-01

The relation between lipid accumulation and influence of exercise on insulin sensitivity is not straightforward. A proper balance between lipid droplet synthesis, lipolysis, and oxidative metabolism would ensure low local intramyocellular fatty acid levels, thereby possibly protecting against lipotoxicity-associated insulin resistance. This study investigated whether the accumulation of triglycerides and lipid droplets in response to high availability of fatty acids after high-fat feeding would parallel the abundance of intramyocellular perilipin proteins, especially PLIN5. The effects on these variables after diet change or voluntary running exercise intervention in skeletal muscle were also investigated. During a 19-week experiment, C57BL/6J mice were studied in six different groups: low-fat diet sedentary, low-fat diet active, high-fat diet sedentary, high-fat diet active and two groups which were high-fat sedentary for nine weeks, after which divided into low-fat sedentary or low-fat active groups. Myocellular triglyceride concentration and perilipin protein expression levels were assessed. We show that, concurrently with impaired insulin sensitivity, the expression level of PLIN5 and muscular triglyceride concentration increased dramatically after high-fat diet. These adaptations were reversible after the diet change intervention with no additional effect of exercise. After high-fat diet, lipid droplets become larger providing more surface area for PLIN5. We suggest that PLIN5 is an important regulator of lipid droplet turnover in altered conditions of fatty acid supply and consumption. Imbalances in lipid droplet metabolism and turnover might lead to lipotoxicity-related insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

Dermal Collagen and Lipid Deposition Correlate with Tissue Swelling and Hydraulic Conductivity in Murine Primary Lymphedema

PubMed Central

Rutkowski, Joseph M.; Markhus, Carl Erik; Gyenge, Christina C.; Alitalo, Kari; Wiig, Helge; Swartz, Melody A.

2010-01-01

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling—predominantly collagen and fat deposition—may dictate tissue swelling and govern interstitial transport in lymphedema. PMID:20110415

Dermal collagen and lipid deposition correlate with tissue swelling and hydraulic conductivity in murine primary lymphedema.

PubMed

Rutkowski, Joseph M; Markhus, Carl Erik; Gyenge, Christina C; Alitalo, Kari; Wiig, Helge; Swartz, Melody A

2010-03-01

Primary lymphedema is a congenital pathology of dysfunctional lymphatic drainage characterized by swelling of the limbs, thickening of the dermis, and fluid and lipid accumulation in the underlying tissue. Two mouse models of primary lymphedema, the Chy mouse and the K14-VEGFR-3-Ig mouse, both lack dermal lymphatic capillaries and exhibit a lymphedematous phenotype attributable to disrupted VEGFR-3 signaling. Here we show that the differences in edematous tissue composition between these two models correlated with drastic differences in hydraulic conductivity. The skin of Chy mice possessed significantly higher levels of collagen and fat, whereas K14-VEGFR-3-Ig mouse skin composition was relatively normal, as compared with their respective wild-type controls. Functionally, this resulted in a greatly increased dermal hydraulic conductivity in K14-VEGFR3-Ig, but not Chy, mice. Our data suggest that lymphedema associated with increased collagen and lipid accumulation counteracts an increased hydraulic conductivity associated with dermal swelling, which in turn further limits interstitial transport and swelling. Without lipid and collagen accumulation, hydraulic conductivity is increased and overall swelling is minimized. These opposing tissue responses to primary lymphedema imply that tissue remodeling--predominantly collagen and fat deposition--may dictate tissue swelling and govern interstitial transport in lymphedema.

Additive effects of nicotine and high-fat diet on hepatic steatosis in male mice.

PubMed

Friedman, Theodore C; Sinha-Hikim, Indrani; Parveen, Meher; Najjar, Sonia M; Liu, Yanjun; Mangubat, Michael; Shin, Chang-Sung; Lyzlov, Alexei; Ivey, Rasheed; Shaheen, Magda; French, Samuel W; Sinha-Hikim, Amiya P

2012-12-01

Smoking is a major risk factor for diabetes and cardiovascular disease and may contribute to nonalcoholic fatty liver disease. We hypothesize that in the presence of nicotine, high-fat diet (HFD) causes more severe hepatic steatosis in obese mice. Adult C57BL6 male mice were fed a normal chow diet or HFD and received twice daily injections of nicotine (0.75 mg/kg body weight, ip) or saline for 10 wk. Light microscopic image analysis revealed significantly higher lipid accumulation in livers from mice on HFD plus nicotine (190 ± 19 μm(2)), compared with mice on HFD alone (28 ± 1.2 μm(2)). A significant reduction in the percent volume of endoplasmic reticulum (67.8%) and glycogen (49.2%) was also noted in hepatocytes from mice on HFD plus nicotine, compared with mice on HFD alone. The additive effects of nicotine on the severity of HFD-induced hepatic steatosis was associated with significantly greater oxidative stress, increased hepatic triglyceride levels, higher incidence of hepatocellular apoptosis, inactivation (dephosphorylation) of AMP-activated protein kinase, and activation of its downstream target acetyl-coenzyme A-carboxylase. Treatment with acipimox, an inhibitor of lipolysis, significantly reduced nicotine plus HFD-induced hepatic lipid accumulation. We conclude that: 1) greater oxidative stress coupled with inactivation of AMP-activated protein kinase mediate the additive effects of nicotine and HFD on hepatic steatosis in obese mice and 2) increased lipolysis is an important contributor to hepatic steatosis. We surmise that nicotine exposure is likely to exacerbate the metabolic abnormalities induced by high-fat intake in obese patients.

Increased liver fat and glycogen stores after consumption of high versus low glycaemic index food: A randomized crossover study.

PubMed

Bawden, Stephen; Stephenson, Mary; Falcone, Yirga; Lingaya, Melanie; Ciampi, Elisabetta; Hunter, Karl; Bligh, Frances; Schirra, Jörg; Taylor, Moira; Morris, Peter; Macdonald, Ian; Gowland, Penny; Marciani, Luca; Aithal, Guruprasad P

2017-01-01

To investigate the acute and longer-term effects of low (LGI) versus high glycaemic index (HGI) diets on hepatic fat and glycogen accumulation and related blood measures in healthy volunteers. Eight healthy men (age 20.1 ± 0.4 years, body mass index 23.0 ± 0.9 kg/m 2 ) attended a test day before and after a 7-day macronutrient- and energy-matched HGI or LGI diet, followed by a minimum 4-week wash-out period, and then returned to repeat the intervention with the alternative diet. During test days, participants consumed either an HGI or an LGI test meal corresponding to their diet week, and liver fat [ 1 H magnetic resonance spectroscopy (MRS)], glycogen ( 13 C MRS) and gastric content volume (MRI) were measured. Blood samples were obtained regularly throughout the test day to assess plasma glucose and insulin levels. Plasma glucose and insulin peak values and area under the curve were significantly greater after the HGI test meal compared with the LGI test meal, as expected. Hepatic glycogen concentrations increased more after the HGI test meal ( P < .05) and peak levels were significantly greater after 7 days of HGI dietary intervention compared with those at the beginning of the intervention ( P < .05). Liver fat fractions increased significantly after the HGI dietary intervention compared with the LGI dietary intervention (two-way repeated-measures analysis of variance P ≤ .05). Compared with an LGI diet, a 1-week HGI diet increased hepatic fat and glycogen stores. This may have important clinical relevance for dietary interventions in the prevention and management of non-alcoholic fatty liver disease. © 2016 John Wiley & Sons Ltd.

Exacerbation of liver steatosis following exposure to famine and overnutrition.

PubMed

Ning, Zhiyuan; Zhang, Kun; Zhao, Li; Lu, You; Sun, Honglin; Chen, Chi; Nie, Xiaomin; Lu, Meng; Wang, Ningjian; Lu, Yingli

2017-10-01

People suffering from famine in early life and overnutrition in adulthood may have an increased risk for liver steatosis. We aimed to investigate the effects and mechanisms of early nutrition restriction and overnutrition on de novo lipogenesis in the liver. Three-wk-old male rats were food restricted for 4 wk and refed a high-fat or normal fat diet individually in metabolic cages for 9 wk. Weight-matched groups were also set up. Fatty acid synthetase expression was measured to estimate de novo lipogenesis in the liver. Parameters of glucose and lipid metabolism were measured with isotope assays. All four groups had comparable body weights. However, the famine high-fat diet group had the highest degree of liver steatosis, the greatest body fat ratio, and insulin resistance. Lipid accumulation, fatty acid synthetase expression, and gluconeogenesis in the liver were significantly higher in the famine and high-fat diet groups (p < 0.05). Moreover, these groups also had markedly lower muscle glucose uptake. Under famine and high-fat refeeding stress, rats were extremely susceptible to developing hepatic steatosis. This is presumably a consequence of upregulation of de novo lipogenesis and enhanced glucose flux from muscle to de novo lipogenesis in the liver. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fatty acid‐binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia‐inducible factor 1 in mice

PubMed Central

Lee, Yong‐Soo; Kim, Ja‐Yeon; Oh, Kyung‐Soo

2017-01-01

Abstract Background Fatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined. Fatty acid‐binding protein 4 (FABP4) is a carrier protein for fatty acids and is involved in fatty acid uptake, transport, and lipid metabolism. Rotator cuff tear (RCT) usually occurs in the elderly and is closely related with fatty infiltration in injured muscle. To investigate potential mechanisms for fatty infiltration other than adipogenic differentiation of muscle stem cells, we examined the role of FABP4 in muscle fatty infiltration in an RCT mouse model. Methods In the RCT model, we evaluated the expression of FABP4 by qRT‐PCR, western blotting, and immunohistochemical analyses. Histological changes such as inflammation and fat accumulation in the injured muscles were examined immunohistochemically. To evaluate whether hypoxia induces FABP4 expression, the levels of FABP4 mRNA and protein in C3H10T1/2 cells after hypoxia were examined. Using a transient transfection assay in 293T cells, we assessed the promoter activity of FABP4 by hypoxia‐inducible factors (HIFs). Additionally, we evaluated the reduction in FABP4 expression and fat accumulation using specific inhibitors for HIF1 and FABP4, respectively. Results FABP4 expression was significantly increased after RCT in mice, and its expression was localized in the intramuscular fatty region. Rotator cuff tear‐induced FABP4 expression was up‐regulated by hypoxia. HIF1α, which is activated by hypoxia, augmented the promoter activity of FABP4, together with HIF1β. Hypoxia‐induced FABP4 expression was significantly decreased by HIF1 inhibitor treatment. Furthermore, in RCT model mice, fat accumulation was remarkably reduced by FABP4 inhibitor treatment. Conclusions This study shows that RCT induces FABP4 expression, leading to fat accumulation in injured muscle. FABP4 transcription is regulated by the direct binding of HIF1 to the FABP4 promoter in the hypoxic condition induced by RCT. Fat accumulation in injured muscle was reduced by the inhibition of FABP4. Ultimately, in the RCT model, we identified a novel mechanism for fatty infiltration by FABP4, which differs from adipogenic differentiation of muscle stem cells, and we found that fatty infiltration might be regulated by inhibition of HIF1 or FABP4. PMID:28382782

DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS INCREASES CENTRAL BODY FAT ACCUMULATION IN MALES AFFECTED BY DIABETES MELLITUS AND LATE-ONSET HYPOGONADISM.

PubMed

Tirabassi, Giacomo; Muscogiuri, Giovanna; Colao, Annamaria; Balercia, Giancarlo

2016-04-01

Functional hypercortisolism (FH) is a condition which occurs in some clinical states, such as major depression, eating disorders, numerous psychiatric conditions, and diabetes mellitus (DM) and which exerts several negative systemic effects. No data exist on the potentially harmful role of FH on body composition. In this retrospective study, we evaluated the influence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation on body composition in men affected by DM-associated late-onset hypogonadism (LOH). Fourteen subjects affected by FH (FH-LOH) and 18 subjects not affected (N-LOH) were studied. Clinical, hormonal, and body composition measures were considered. The 2 groups had comparable age and weight. FH-LOH patients had lower levels of total (2 ± 0.27 ng/mL versus 2.31 ± 0.26 ng/mL; P = .003) and free (39.5 ± 6.44 pg/mL versus 46.8 ± 7.23 pg/mL; P = .005) (median, 38.7 [interquartile range, 36.1 to 41.3] pg/mL versus median, 46.1 [interquartile range, 40.4 to 52.7] pg/mL) testosterone compared to N-LOH patients. Abdominal fat amount was greater in FH-LOH than in N-LOH patients, even after adjustment for total testosterone. None of the bivariate correlations between body composition measures and hormonal variables were significant in N-LOH. Conversely, in FH-LOH, cortisol area under the curve (AUC) was found to be positively and significantly correlated with trunk (r = 0.933; P<.001) and abdominal fat (r = 0.852; P<.001) and negatively with lean leg (r = -0.607; P = .021). All of these associations were further confirmed upon linear regression analysis in FH-LOH (respectively, unstandardized β = 10.988 [P<.001]; β = 1.156 [P<.001]; β = -7.675 [P = .021]). Multivariate regression analysis confirmed AUC cortisol as a predictor of trunk and abdominal fat in FH-LOH. Dysregulation of the HPA axis in LOH-associated DM seems to be involved in abdominal fat accumulation.

Histochemical study of brown-fat cells in the golden hamster (Mesocricetus auratus) in cultures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sokolov, V.E.; Boyadzhieva-Mikhailova, A.; Koncheva, L.

1985-11-01

The authors undertake the task of studying the synthesis of certain hormones by brown-fat cells. The authors used brown-fat cells from the golden hamster. The metabolism of brown-fat cells was studied on precultured cells, which made it possible to detect the synthesis of the studied substances rather than their accumulation in the organ. The authors conducted three experiments. First, fragments of brown fat were cultivated in diffusion chambers in vivo. Pieces of brown fat were cultivated in parallel in vitro on agar (organotypic cultures) and on plasma (histotypic cultures). During cultivation in diffusion chambers, the chambers were implanted in themore » abdominal cavity of young white rats. For in vitro cultivation, TCM 199 plus 15-20% calf serum was used. A total of 36 cultures with 12 cultures in each series of experiments were performed. The auto-radiographic studies of brown-fat cells were conducted on 24-hour cultures and on brown-fat fragments taken from the intact animal. The cultures were incubated with isotopes for 1 h. Either (/sup 3/H)lysine (87.3 Ci/mM specific activity), (/sup 3/H)arginine (16.7 Ci/mM), (/sup 3/H)glycerol (43 Ci/mM), or (/sup 3/H)cholesterol (43 Ci/mM) were added to the medium. After incubation, the cultures were washed three times in pure medium, fixed in Sierra fluid, and embedded in paraffin. The paraffin sections were covered with Ilford K/sub 2/ emulsion, and the preparations were exposed for 20 days at 4/sup 0/C temperature. Radio-immunological methods were used to study the accumulation of estradiol-17-beta in the culture medium by the Dobson method and that of testerone. The culture medium was taken on cultivation days 2,4,6,8, and 10. The medium was changed during cultivation every third day, which made it possible to judge the rates of accumulation of material with increase in the cultivation times.« less

High- and low-throughput scoring of fat mass and body fat distribution in C. elegans

PubMed Central

Wählby, Carolina; Lee-Conery, Annie; Bray, Mark-Anthony; Kamentsky, Lee; Larkins-Ford, Jonah; Sokolnicki, Katherine L.; Veneskey, Matthew; Michaels, Kerry; Carpenter, Anne E.; O’Rourke, Eyleen J.

2014-01-01

Fat accumulation is a complex phenotype affected by factors such as neuroendocrine signaling, feeding, activity, and reproductive output. Accordingly, the most informative screens for genes and compounds affecting fat accumulation would be those carried out in whole living animals. Caenorhabditis elegans is a well-established and effective model organism, especially for biological processes that involve organ systems and multicellular interactions, such as metabolism. Every cell in the transparent body of C. elegans is visible under a light microscope. Consequently, an accessible and reliable method to visualize worm lipid-droplet fat depots would make C. elegans the only metazoan in which genes affecting not only fat mass but also body fat distribution could be assessed at a genome-wide scale. Here we present a radical improvement in oil red O worm staining together with high-throughput image-based phenotyping. The three-step sample preparation method is robust, formaldehyde-free, and inexpensive, and requires only 15 minutes of hands-on time to process a 96-well plate. Together with our free and user-friendly automated image analysis package, this method enables C. elegans sample preparation and phenotype scoring at a scale that is compatible with genome-wide screens. Thus we present a feasible approach to small-scale phenotyping and large-scale screening for genetic and/or chemical perturbations that lead to alterations in fat quantity and distribution in whole animals. PMID:24784529

Modulation of cAMP levels by high fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression

USDA-ARS?s Scientific Manuscript database

Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr-/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of f...

Historical perspective: visceral obesity and related comorbidity in Joannes Baptista Morgagni's 'De sedibus et causis morborum per anatomen indagata'.

PubMed

Enzi, G; Busetto, L; Inelmen, E M; Coin, A; Sergi, G

2003-04-01

In recent years, advances in epidemiological approaches and laboratory technology, along with the availability of sophisticated imaging methods to evaluate body fat distribution, made it possible to define the close correlation between visceral fat accumulation and the occurrence of metabolic abnormalities, cardiovascular diseases and respiratory disturbances in obese patients. Some 250 y ago, JB Morgagni with the help of only a knife for anatomical dissection, an acute mind, and an observational skillfulness was able to identify the intra-abdominal and mediastinal fat accumulation in android obesity. He clearly described the association between visceral obesity, hypertension, hyperuricemia, atherosclerosis and obstructive sleep apnea syndrome, long before the modern recognition of this syndrome.

MiR-103 Controls Milk Fat Accumulation in Goat (Capra hircus) Mammary Gland during Lactation

PubMed Central

Lin, Xianzi; Luo, Jun; Zhang, Liping; Wang, Wei; Gou, Deming

2013-01-01

Milk is the primary source of nutrition for young mammals including humans. The nutritional value of milk is mainly attributable to fats and proteins fractions. In comparison to cow milk, goat milk contains greater amounts of total fat, including much higher levels of the beneficial unsaturated fatty acids. MicroRNAs (miRNAs), a well-defined group of small RNAs containing about 22 nucleotides (nt), participate in various metabolic processes across species. However, little is known regarding the role of miRNAs in regulating goat milk composition. In the present study, we performed high-throughput sequencing to identify mammary gland-enriched miRNAs in lactating goats. We identified 30 highly expressed miRNAs in the mammary gland, including miR-103. Further studies revealed that miR-103 expression correlates with the lactation. Further functional analysis showed that over-expression of miR-103 in mammary gland epithelial cells increases transcription of genes associated with milk fat synthesis, resulting in an up-regulation of fat droplet formation, triglyceride accumulation, and the proportion of unsaturated fatty acids. This study provides new insight into the functions of miR-103, as well as the molecular mechanisms that regulate milk fat synthesis. PMID:24244462

Consumption of a Mango Fruit Powder Protects Mice from High-Fat Induced Insulin Resistance and Hepatic Fat Accumulation.

PubMed

Sabater, Agustín G; Ribot, Joan; Priego, Teresa; Vazquez, Itxaso; Frank, Sonja; Palou, Andreu; Buchwald-Werner, Sybille

2017-01-01

The aim of this study was to gain more insight into the beneficial effects of mango fruit powder on the early metabolic adverse effects of a high-fat diet. The progressive dose-response effects of mango fruit powder on body composition, circulating parameters, and the expression of genes related to fatty acid oxidation and insulin sensitivity in key tissues were studied in mice fed a moderate (45%) high-fat diet. Findings suggest that mango fruit powder exerts physiological protective effects in the initial steps of insulin resistance and hepatic lipid accumulation induced by a high-fat diet in mice. Moreover, AMPK and SIRT1 appear as key regulators of the observed improvement in fatty acid oxidation capacity, as well as of the improved insulin sensitivity and the increased glucose uptake and metabolism through the glycolytic pathway capacity in liver and skeletal muscle. In summary, this study provides evidence that the functional food ingredient (CarelessTM) from mango fruit prevents early metabolic alterations caused by a high-fat diet in the initial stages of the metabolic syndrome. © 2017 The Author(s). Published by S. Karger AG, Basel.

Enhanced cortisol production rates, free cortisol, and 11beta-HSD-1 expression correlate with visceral fat and insulin resistance in men: effect of weight loss.

PubMed

Purnell, Jonathan Q; Kahn, Steven E; Samuels, Mary H; Brandon, David; Loriaux, D Lynn; Brunzell, John D

2009-02-01

Controversy exists as to whether endogenous cortisol production is associated with visceral obesity and insulin resistance in humans. We therefore quantified cortisol production and clearance rates, abdominal fat depots, insulin sensitivity, and adipocyte gene expression in a cohort of 24 men. To test whether the relationships found are a consequence rather than a cause of obesity, eight men from this larger group were studied before and after weight loss. Daily cortisol production rates (CPR), free cortisol levels (FC), and metabolic clearance rates (MCR) were measured by stable isotope methodology and 24-h sampling; intra-abdominal fat (IAF) and subcutaneous fat (SQF) by computed tomography; insulin sensitivity (S(I)) by frequently sampled intravenous glucose tolerance test; and adipocyte 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD-1) gene expression by quantitative RT-PCR from subcutaneous biopsies. Increased CPR and FC correlated with increased IAF, but not SQF, and with decreased S(I). Increased 11beta-HSD-1 gene expression correlated with both IAF and SQF and with decreased S(I). With weight loss, CPR, FC, and MCR did not change compared with baseline; however, with greater loss in body fat than lean mass during weight loss, both CPR and FC increased proportionally to final fat mass and IAF and 11beta-HSD-1 decreased compared with baseline. These data support a model in which increased hypothalamic-pituitary-adrenal activity in men promotes selective visceral fat accumulation and insulin resistance and may promote weight regain after diet-induced weight loss, whereas 11beta-HSD-1 gene expression in SQF is a consequence rather than cause of adiposity.

Comparison of the effects of swimming and Tai Chi Chuan on body fat composition in elderly people.

PubMed

Yu, Tung-Yang; Pei, Yu-Cheng; Lau, Yiu-Chung; Chen, Chih-Kuang; Hsu, Hung-Chih; Wong, Alice M K

2007-01-01

Accumulation of fat and substantial loss of muscle mass are common phenomena in the elderly. In this study, we observed the effects of Tai Chi Chuan (TCC) and swimming, two exercises suitable for elderly people, on the percentage body fat and fat distribution by measuring subcutaneous adipose tissue thickness and body composition. Subjects were divided into three groups: regular swimmers (n = 20), regular TCC practitioners (n = 32), and age-matched control subjects (n = 31). Subcutaneous adipose tissue thickness was taken using a Lange skinfold caliper at the chests, abdomens, and thighs in the men, and the triceps, suprailium, and thighs in the women. Mid-arm circumference (MAC) was measured on the non-dominant upper arm using fiberglass tape. Body composition was analyzed using the Inbody 3.0 logo, a bioelectrical impedance analysis (BIA) system. No significant differences were found between the three test groups in relation to total body adiposity and arm muscle circumference in the men and women. There was significantly less subcutaneous adipose tissue at the abdomen (p = 0.011) and thigh (p < 0.001) of TCC-group men and at the thighs (p < 0.001) of the swimming group compared with the control group. In women, only the thigh skinfold (p = 0.002) showed a decrease in the TCC group compared with the control group. Swimming and TCC may not decrease total fat adiposity in elderly men and women, however, they may change body fat distribution due to certain muscle group usage. The differences observed in the effects of exercise on body fat distribution between elderly women and men may be gender-related.

Ubiquitin-like modifier FAT10 attenuates RIG-I mediated antiviral signaling by segregating activated RIG-I from its signaling platform

PubMed Central

Nguyen, Nhung T.H.; Now, Hesung; Kim, Woo-Jong; Kim, Nari; Yoo, Joo-Yeon

2016-01-01

RIG-I is a key cytosolic RNA sensor that mediates innate immune defense against RNA virus. Aberrant RIG-I activity leads to severe pathological states such as autosomal dominant multi-system disorder, inflammatory myophathies and dermatomyositis. Therefore, identification of regulators that ensure efficient defense without harmful immune-pathology is particularly critical to deal with RIG-I-associated diseases. Here, we presented the inflammatory inducible FAT10 as a novel negative regulator of RIG-I-mediated inflammatory response. In various cell lines, FAT10 protein is undetectable unless it is induced by pro-inflammatory cytokines. FAT10 non-covalently associated with the 2CARD domain of RIG-I, and inhibited viral RNA-induced IRF3 and NF-kB activation through modulating the RIG-I protein solubility. We further demonstrated that FAT10 was recruited to RIG-I-TRIM25 to form an inhibitory complex where FAT10 was stabilized by E3 ligase TRIM25. As the result, FAT10 inhibited the antiviral stress granules formation contains RIG-I and sequestered the active RIG-I away from the mitochondria. Our study presented a novel mechanism to dampen RIG-I activity. Highly accumulated FAT10 is observed in various cancers with pro-inflammatory environment, therefore, our finding which uncovered the suppressive effect of the accumulated FAT10 during virus-mediated inflammatory response may also provide molecular clue to understand the carcinogenesis related with infection and inflammation. PMID:26996158

Ubiquitin-like modifier FAT10 attenuates RIG-I mediated antiviral signaling by segregating activated RIG-I from its signaling platform.

PubMed

Nguyen, Nhung T H; Now, Hesung; Kim, Woo-Jong; Kim, Nari; Yoo, Joo-Yeon

2016-03-21

RIG-I is a key cytosolic RNA sensor that mediates innate immune defense against RNA virus. Aberrant RIG-I activity leads to severe pathological states such as autosomal dominant multi-system disorder, inflammatory myophathies and dermatomyositis. Therefore, identification of regulators that ensure efficient defense without harmful immune-pathology is particularly critical to deal with RIG-I-associated diseases. Here, we presented the inflammatory inducible FAT10 as a novel negative regulator of RIG-I-mediated inflammatory response. In various cell lines, FAT10 protein is undetectable unless it is induced by pro-inflammatory cytokines. FAT10 non-covalently associated with the 2CARD domain of RIG-I, and inhibited viral RNA-induced IRF3 and NF-kB activation through modulating the RIG-I protein solubility. We further demonstrated that FAT10 was recruited to RIG-I-TRIM25 to form an inhibitory complex where FAT10 was stabilized by E3 ligase TRIM25. As the result, FAT10 inhibited the antiviral stress granules formation contains RIG-I and sequestered the active RIG-I away from the mitochondria. Our study presented a novel mechanism to dampen RIG-I activity. Highly accumulated FAT10 is observed in various cancers with pro-inflammatory environment, therefore, our finding which uncovered the suppressive effect of the accumulated FAT10 during virus-mediated inflammatory response may also provide molecular clue to understand the carcinogenesis related with infection and inflammation.

Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.

PubMed

Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

2012-01-01

The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

Protective potentials of wild rice (Zizania latifolia (Griseb) Turcz) against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats.

PubMed

Han, Shu-Fen; Zhang, Hong; Zhai, Cheng-Kai

2012-07-01

The study evaluates the protective potentials of wild rice against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats. In addition to the rats of low-fat diet group, others animals were exposed to a high-fat/cholesterol diet condition for 8 weeks. The city diet (CD) is based on the diet consumed by urban residents in modern China, which is rich in fat/cholesterol and high in carbohydrates from white rice and processed wheat starch. The chief source of dietary carbohydrates of wild rice diet (WRD) is from Chinese wild rice and other compositions are the same with CD. Rats fed CD showed elevated body and liver organ weights, lipid profiles, free fatty acids (FFA) and leptin comparable with rats fed high-fat/cholesterol diet (HFD) known to induce obesity and hyperlipidaemia in this species. However, rats consuming WRD suppressed the increase of lipid droplets accumulation, FFA, and leptin, and the decrease of lipoprotein lipase and adipose triglyceride lipase. Meanwhile, WRD prevented high-fat/cholesterol diet-induced elevation in protein expression of sterol-regulatory element binding protein-1c, and gene expression of fatty acid synthase and acetyl-CoA carboxylase. These findings indicate that wild rice as a natural food has the potentials of preventing obesity and liver lipotoxicity induced by a high-fat/cholesterol diet in rats. Copyright © 2012 Elsevier Ltd. All rights reserved.

Weight increase and overweight are associated with DNA oxidative damage in skeletal muscle.

PubMed

de la Maza, María-Pía; Olivares, Daniela; Hirsch, Sandra; Sierralta, Walter; Gattás, Vivien; Barrera, Gladys; Bunout, Daniel; Leiva, Laura; Fernández, Mireya

2006-12-01

Weight maintenance within normal standards is recommended for prevention of conditions associated with oxidative injury. To compare oxidative damage in a post mitotic tissue, between adults differing in long-term energy balance. During hernia surgery, a sample of skeletal muscle was obtained in 17 non-obese adults. Subjects were divided into two groups according to their self-reported weight change: weight maintainers (WM) reported <4kg increase, and weight gainers (WG) reported >5kg increment. Muscle immunohistochemistry for 8-hydroxy-deoxyguanosine (8OHdG), 4-Hydroxy-2-nonenal (4HNE), and TNF-alpha, as markers of oxidative injury and inflammation, were performed. As known positive controls for oxidative injury, we included 10 elderly subjects (66-101yr). Anthropometric measures and blood samples for clinical laboratory and serum cytokines (TNF-alpha and IL-6) were obtained. 8OHdG was higher in WG compared with WM (149.1+/-16.2 versus 117.8+/-29.5, P=0.03), and was associated with anthropometric indicators of fat accumulation. 4HNE was similar in WG compared with WM (10.9+/-7.6 versus 9.8+/-6.3) but noticeably higher in elderly subjects (21.5+/-15.3, P=0.059). TNF-alpha protein in WG was higher compared with WM (114.0+/-41.7 versus 70.1+/-23.3, P=0.025), and was associated with weight increase. Moderate self-reported weight increase, and body fat accumulation, suggesting long-term positive energy balance is associated with muscle DNA oxidative injury and inflammation.

Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet.

PubMed

Navarro, V; Zabala, A; Macarulla, M T; Fernández-Quintela, A; Rodríguez, V M; Simón, E; Portillo, M P

2003-09-01

Conjugated linoleic acid (CLA) refers to a mixture of naturally occurring positional and geometric isomers of linoleic acid that exist in dairy products and meat. The aim of the present work was to study the effects of c-9,t-11 and t-10,c-12 CLA isomers on body fat accumulation and serum lipids in hamsters fed an atherogenic diet. Hamsters were divided in four groups: one group was fed a chow diet (control) and the other three groups were given semi-purified atherogenic diets with 0.5% linoleic acid (LA), c-9,t-11 or t-10,c-12 CLA. Body weight and food intake were measured daily. After 6 weeks, adipose tissues from different anatomical locations and liver were dissected and weighed. Serum glucose, total cholesterol, HDL-c, LDL-c and triacylglycerol levels, as well as total and free cholesterol, triacylglycerol and phospholipid content in liver were determined by enzymatic methods. No differences in either energy intake or final body weight were found. The addition of t-10,c-12 CLA reduced fat accumulation and led to lower serum cholesterol, as compared with LA group. Nevertheless the level remained higher than in the control animals. The reduction in serum cholesterol was limited to LDL-c. This isomer also reduced triacylglycerol content in liver but did not modify serum triacylglycerol level. In summary, the present study demonstrates that t-10,c-12 CLA is the biologically active agent when anti-obesity and hypocholesterolaemic properties of CLA are considered. In contrast, the isomer c-9,t-11 has no effect on lipid metabolism in hamsters.

Storage capacity of subcutaneous fat in Japanese adults.

PubMed

Sato, S; Demura, S; Nakai, M

2015-08-01

On the basis of our previous study, which examined the nonlinear relationship between visceral fat area (VFA) and percent regional fat mass in the trunk, we hypothesise the presence of some storage capacity of subcutaneous fat. This study aimed to examine the storage capacity of subcutaneous fat on the basis of subcutaneous fat area (SFA) and VFA in 791 Japanese adult males and 563 females. Regression analyses by using SFA as a dependent variable and VFA as an independent variable were performed for each group classified by visceral fat obesity (VO): VO (VFA ⩾ 100 cm(2)) and the no-VO (NVO) groups. To statistically identify an optimal critical point for subcutaneous fat accumulation, we changed the cutoff point for the VO group from 50-150 cm(2) in 10-cm(2) increments and confirmed the significance of the correlation between SFA and VFA for each obesity group, the statistical difference in correlations between NVO and VO groups, and the goodness of fit for the two regression lines using the standard error of estimation values. These analyses were conducted for each sex and age (<65 and ⩾ 65 years) group. The critical point for subcutaneous fat accumulation appears at the following cutoff points of VFA: 130 cm(2) in <65-year-old males, 110 cm(2) in ⩾ 65-year-old males and 100 cm(2) in both female groups. These results suggest the presence of some storage capacity of subcutaneous fat. As a further application, these findings may serve to improve the risk assessment of obesity-related diseases.

Android and gynoid fat percentages and serum lipid levels in United States adults.

PubMed

Min, Kyoung-Bok; Min, Jin-Young

2015-03-01

Accumulating evidence suggests that fat distribution is a better predictor of cardiovascular disease than body mass index (BMI). The aim of this study was to investigate the association of android and gynoid fat percentages with lipid profiles to determine whether android and/or gynoid fat percentages are associated with serum lipid levels. A population-based cross-sectional study. Five thousand six hundred and ninety-six adults (20 years and older) who participated in the National Health and Nutrition Examination Survey 2003-2006. The regional body composition in the android and gynoid regions was defined by dual energy X-ray absorptiometry (DXA). The estimation of lipid risk profiles included total cholesterol, high-density lipoprotein (HDL) -cholesterol, low-density lipoprotein (LDL) -cholesterol and triglycerides (TG). Regardless of gender, android and gynoid body fat percentages were positively and significantly correlated with BMI and waist circumference. After adjustment for age, ethnicity, education, smoking, alcohol consumption, dyslipidaemia and BMI, increases in android fat percentage were significantly associated with total cholesterol, TG and HDL cholesterol in males, and total cholesterol, HDL cholesterol and LDL cholesterol in females. The gynoid fat percentages showed a positive correlation with total cholesterol in males, whereas gynoid fat accumulation in females showed a favourable association with TG and HDL cholesterol. The observed associations differed according to ethnic groups. Our results suggest that regional fat distribution in the android and gynoid regions have different effects on lipid profiles, and that fat in the android region, rather than the gynoid region, may be an important factor in determining the risk of cardiovascular disease. © 2014 John Wiley & Sons Ltd.

Gastric bypass surgery is protective from high-fat diet-induced non-alcoholic fatty liver disease and hepatic endoplasmic reticulum stress.

PubMed

Mosinski, J D; Pagadala, M R; Mulya, A; Huang, H; Dan, O; Shimizu, H; Batayyah, E; Pai, R K; Schauer, P R; Brethauer, S A; Kirwan, J P

2016-06-01

High-fat diets are known to contribute to the development of obesity and related co-morbidities including non-alcoholic fatty liver disease (NAFLD). The accumulation of hepatic lipid may increase endoplasmic reticulum (ER) stress and contribute to non-alcoholic steatohepatitis and metabolic disease. We hypothesized that bariatric surgery would counter the effects of a high-fat diet (HFD) on obesity-associated NAFLD. Sixteen of 24 male Sprague Dawley rats were randomized to Sham (N = 8) or Roux-en-Y gastric bypass (RYGB) surgery (N = 8) and compared to Lean controls (N = 8). Obese rats were maintained on a HFD throughout the study. Insulin resistance (HOMA-IR), and hepatic steatosis, triglyceride accumulation, ER stress and apoptosis were assessed at 90 days post-surgery. Despite eating a HFD for 90 days post-surgery, the RYGB group lost weight (-20.7 ± 6%, P < 0.01) and improved insulin sensitivity (P < 0.05) compared to Sham. These results occurred with no change in food intake between groups. Hepatic steatosis and ER stress, specifically glucose-regulated protein-78 (Grp78, P < 0.001), X-box binding protein-1 (XBP-1) and spliced XBP-1 (P < 0.01), and fibroblast growth factor 21 (FGF21) gene expression, were normalized in the RYGB group compared to both Sham and Lean controls. Significant TUNEL staining in liver sections from the Obese Sham group, indicative of accelerated cell death, was absent in the RYGB and Lean control groups. Additionally, fasting plasma glucagon like peptide-1 was increased in RYGB compared to Sham (P < 0.02). These data suggest that in obese rats, RYGB surgery protects the liver against HFD-induced fatty liver disease by attenuating ER stress and excess apoptosis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues

USDA-ARS?s Scientific Manuscript database

Adipose tissue is one of the major sites for fatty acid synthesis and lipid storage. We generated adipose (fat)-specific ACC1 knockout (FACC1KO) mice using the aP2-Cre/loxP system. FACC1KO mice showed prenatal growth retardation; after weaning, however, their weight gain was comparable to that of wi...

Acidogenesis and Two-Phase Codigestion of Fats, Oils, and Greases and Municipal Biosolids.

PubMed

Varin, Ross; Novak, John; Bott, Charles

2016-11-01

  Acidogenic codigestion of fats, oils, and greases (FOG) was studied using suspended growth sludge digesters operated as batch fed reactors that were fed twice daily. The digesters were maintained at a 2-day retention time and at 37 °C to mimic the acid phase of an acid-gas digestion system. As FOG loading rates increased, volatile fatty acid (VFA) production was found to increase, although the percentage of VFA production compared to theoretical values decreased exponentially to just 20% at the highest loading rates. FOG matter was found to have accumulated in the reactor vessel in semi-solid balls that floated near the liquid surface. Two-phase codigestion of FOG was studied at 37 °C using Continuously Stirred Tank Reactors (CSTRs) as acid phase digesters (APD) operated with 2-day retention times, followed by gas phase digesters (GPD) with 15-day retention times. The two-phase systems were compared by FOG addition to the APD versus GPD. FOG addition to the APD resulted in 88% destruction of LCFAs, whereas FOG addition to the GPD resulted in 95% destruction of LCFAs. Accumulated LCFAs were found in the APD receiving FOG and were primarily composed palmitic acid (16:0), followed by oleic acid (18:1) and stearic acid (18:0).

Abdominal obesity: a marker of ectopic fat accumulation.

PubMed

Smith, Ulf

2015-05-01

In the early 1980s, we analyzed the metabolic profile of 930 men and women and concluded that an abdominal distribution of fat for a given BMI is associated with increased insulin resistance and risk of developing type 2 diabetes and cardiovascular disease. The correlation between abdominal fat and metabolic dysfunction has since been validated in many studies, and waist circumference is now a criterion for the diagnosis of metabolic syndrome. Several mechanisms for this relationship have been postulated; however, we now know that visceral fat is only one of many ectopic fat depots used when the subcutaneous adipose tissue cannot accommodate excess fat because of its limited expandability.

Refeeding meal-fed rats increases lipoprotein lipase activity and deposition of dietary [14C]lipid in white adipose tissue and decreases oxidation to 14CO2. The role of undernutrition.

PubMed Central

Cruz, M L; Williamson, D H

1992-01-01

Meal-fed (3 h) rats had a decreased food intake, body weight and carcass fat compared with rats fed ad libitum. On refeeding a chow meal containing [1-14C]triolein, the production of 14CO2 was lower (45%) and the accumulation of carcass [14C]lipid higher (37%) in the meal-fed rats. There was higher lipoprotein lipase activity and greater accumulation of [14C]lipid in the epididymal and subcutaneous adipose-tissue depots of the meal-fed rats. In contrast, heparin-releasable lipoprotein lipase was not increased in perfused hearts of meal-fed rats on refeeding. Return of meal-fed rats to feeding ad libitum reversed these changes before the restoration of body weight or carcass fat. Evidence is presented that decreased dietary intake rather than meal pattern is an important determinant of the alterations in adipose lipid metabolism in the meal-fed rat in response to a meal. PMID:1497615

Hyperphagia and Increased Fat Accumulation in Two Models of Chronic CNS Glucagon-Like Peptide-1 Loss of Function

PubMed Central

Jones, Kenneth R.; Herman, James P.; D'Alessio, David A.; Woods, Stephen C.; Seeley, Randy J.

2011-01-01

Central administration of glucagon-like peptide-1 (GLP-1) causes a dose-dependent reduction in food intake, but the role of endogenous CNS GLP-1 in the regulation of energy balance remains unclear. Here, we tested the hypothesis that CNS GLP-1 activity is required for normal energy balance by using two independent methods to achieve chronic CNS GLP-1 loss of function in rats. Specifically, lentiviral-mediated expression of RNA interference was used to knock down nucleus of the solitary tract (NTS) preproglucagon (PPG), and chronic intracerebroventricular (ICV) infusion of the GLP-1 receptor (GLP-1r) antagonist exendin (9-39) (Ex9) was used to block CNS GLP-1r. NTS PPG knockdown caused hyperphagia and exacerbated high-fat diet (HFD)-induced fat accumulation and glucose intolerance. Moreover, in control virus-treated rats fed the HFD, NTS PPG expression levels correlated positively with fat mass. Chronic ICV Ex9 also caused hyperphagia; however, increased fat accumulation and glucose intolerance occurred regardless of diet. Collectively, these data provide the strongest evidence to date that CNS GLP-1 plays a physiologic role in the long-term regulation of energy balance. Moreover, they suggest that this role is distinct from that of circulating GLP-1 as a short-term satiation signal. Therefore, it may be possible to tailor GLP-1-based therapies for the prevention and/or treatment of obesity. PMID:21389245

Single and combined effects of body composition phenotypes on carotid intima-media thickness.

PubMed

Melo, X; Santa-Clara, H; Santos, D A; Pimenta, N M; Pinto, R; Minderico, C S; Fernhall, B; Sardinha, L B

2016-08-01

Central fatness might be a more sensitive predictor of atherosclerotic changes in children than are total body fat measures. However, it is unclear whether a total body fat measure coupled with an estimate of a more central pattern of fat accumulation predicts increased carotid intima-media-thickness (cIMT) better than either measure alone. The objective of the study is to identify the ability of a combination of simple anthropometric screening tools or a combination of objective measures of body composition to predict cIMT. cIMT was assessed on the common carotid artery in 349 children aged 11-12 years old (183 girls). Body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR) were dichotomized according to established criteria and indices of total body (TBFI) and abdominal (ABFMI) fat were assessed by dual-energy X-ray absorptiometry and categorized (increased risk ≥85%). Single and combined associations among anthropometric and laboratorial measures with the risk of having increased cIMT (≥85%) and discriminatory performance were tested with logistic regression analysis and Receiver Operator Curve analysis. Children with higher total fatness (BMI and TBFI) or higher central pattern of fat accumulation (WC, WHtR and BFMI) were in higher risk for increased cIMT [odds ratio (OR): 2.08-3.24). The risk for increased cIMT was not higher among children who coupled high total and high central fatness (OR: 2.27-3.10). Combination of total and central measures of fat does not improve the prediction of increased cIMT in children. Simple surrogate measures of fatness can be used to predict increased cIMT urging special attention to those children who exhibit increased abdominal fat. © 2015 World Obesity.

Effects of green tea polyphenol (-)-epigallocatechin-3-gallate on newly developed high-fat/Western-style diet-induced obesity and metabolic syndrome in mice.

PubMed

Chen, Yu-Kuo; Cheung, Connie; Reuhl, Kenneth R; Liu, Anna Ba; Lee, Mao-Jung; Lu, Yao-Ping; Yang, Chung S

2011-11-09

The aim of this study was to investigate the effects of (-)-epigallocatechin-3-gallate (EGCG) on newly developed high-fat/Western-style diet-induced obesity and symptoms of metabolic syndrome. Male C57BL/6J mice were fed a high fat/Western-style (HFW; 60% energy as fat and lower levels of calcium, vitamin D(3), folic acid, choline bitartrate, and fiber) or HFW with EGCG (HFWE; HFW with 0.32% EGCG) diet for 17 wks. As a comparison, two other groups of mice fed a low-fat diet (LF; 10% energy as fat) and high-fat diet (HF; 60% energy as fat) were also included. The HFW group developed more body weight gain and severe symptoms of metabolic syndrome than the HF group. The EGCG treatment significantly reduced body weight gain associated with increased fecal lipids and decreased blood glucose and alanine aminotransferase (ALT) levels compared to those of the HFW group. Fatty liver incidence, liver damage, and liver triglyceride levels were also decreased by the EGCG treatment. Moreover, the EGCG treatment attenuated insulin resistance and levels of plasma cholesterol, monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP), interlukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). Our results demonstrate that the HFW diet produces more severe symptoms of metabolic syndrome than the HF diet and that the EGCG treatment can alleviate these symptoms and body fat accumulation. The beneficial effects of EGCG are associated with decreased lipid absorption and reduced levels of inflammatory cytokines.

High fat diet rescues disturbances to metabolic homeostasis and survival in the Id2 null mouse in a sex-specific manner

PubMed Central

Zhou, Peng; Hummel, Alyssa D.; Pywell, Cameron M.; Dong, X. Charlie; Duffield, Giles E.

2014-01-01

Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated that Id2 null mice have altered expression of circadian genes involved in lipid metabolism, altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue. Here we further characterized the Id2−/− mouse metabolic phenotype in a sex-specific context and under low and high fat diets, and examined metabolic and endocrine parameters associated with lipid and glucose metabolism. Under the low-fat diet Id2−/− mice showed decreased weight gain, reduced gonadal fat mass, and a lower survival rate. Under the high-fat diet, body weight and gonadal fat gain of Id2−/− male mice was comparable to control mice and survival rate improved markedly. Furthermore, the high-fat diet treated Id2−/− male mice lost the enhanced glucose tolerance feature observed in the other Id2−/− groups, and there was a sex-specific difference in white adipose tissue storage of Id2−/− mice. Additionally, a distinct pattern of hepatic lipid accumulation was observed in Id2−/− males: low lipids on the low-fat diet and steatosis on the high-fat diet. In summary, these data provides valuable insights into the impact of Id2 deficiency on metabolic homeostasis of mice in a sex-specific manner. PMID:25108156

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease.

PubMed

Jensen, Thomas; Abdelmalek, Manal F; Sullivan, Shelby; Nadeau, Kristen J; Green, Melanie; Roncal, Carlos; Nakagawa, Takahiko; Kuwabara, Masanari; Sato, Yuka; Kang, Duk-Hee; Tolan, Dean R; Sanchez-Lozada, Laura G; Rosen, Hugo R; Lanaspa, Miguel A; Diehl, Anna Mae; Johnson, Richard J

2018-05-01

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome; its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and a sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high-fructose corn syrup [HFCS]) not only increase the risk of NAFLD, but also non-alcoholic steatohepatitis (NASH). Herein, we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked to the metabolism of fructose by fructokinase C, which results in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations to gut permeability, the microbiome, and associated endotoxemia contribute to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hump on upper back (dorsocervical fat pad)

MedlinePlus

... hump on the upper back between the shoulder blades is an area of fat accumulation on the ... A hump between the shoulder blades by itself is not a sign of a specific condition. The health care provider must consider this along with other symptoms ...

Dietary fat intake promotes the development of hepatic steatosis independently from excess caloric consumption in a murine model.

PubMed

de Meijer, Vincent E; Le, Hau D; Meisel, Jonathan A; Akhavan Sharif, M Reza; Pan, Amy; Nosé, Vânia; Puder, Mark

2010-08-01

Nonalcoholic fatty liver disease results from overconsumption and is a significant and increasing cause of liver failure. The type of diet that is conducive to the development of this disease has not been established, and evidence-based treatment options are currently lacking. We hypothesized that the onset of hepatic steatosis is linked to the consumption of a diet with a high fat content, rather than related to excess caloric intake. In addition, we also hypothesized that fully manifested hepatic steatosis could be reversed by reducing the fat percentage in the diet of obese mice. C57BL/6J male mice were fed either a purified rodent diet containing 10% fat or a diet with 60% of calories derived from fat. A pair-feeding design was used to distinguish the effects of dietary fat content and caloric intake on dietary-induced hepatic lipid accumulation and associated injury. Livers were analyzed by quantitative reverse transcriptase polymerase chain reaction for lipid metabolism-related gene expression. After 9 weeks, mice on the 60%-fat diet exhibited more weight gain, insulin resistance, and hepatic steatosis compared with mice on a 10%-fat diet with equal caloric intake. Furthermore, mice with established metabolic syndrome at 9 weeks showed reversal of hepatic steatosis, insulin resistance, and obesity when switched to a 10%-fat diet for an additional 9 weeks, independent of caloric intake. Quantitative reverse transcriptase polymerase chain reaction revealed that transcripts related to both de novo lipogenesis and increased uptake of free fatty acids were significantly up-regulated in mice pair-fed a 60%-fat diet compared with 10%-fat-fed animals. Dietary fat content, independent from caloric intake, is a crucial factor in the development of hepatic steatosis, obesity, and insulin resistance in the C57BL/6J diet-induced obesity model caused by increased uptake of free fatty acids and de novo lipogenesis. In addition, once established, all these features of the metabolic syndrome can be successfully reversed after switching obese mice to a diet low in fat. Low-fat diets deserve attention in the investigation of a potential treatment of patients with nonalcoholic fatty liver disease. Copyright 2010 Elsevier Inc. All rights reserved.

Pathogenesis and Prevention of Hepatic Steatosis

PubMed Central

Nassir, Fatiha; Rector, R. Scott; Hammoud, Ghassan M.

2015-01-01

Hepatic steatosis is defined as intrahepatic fat of at least 5% of liver weight. Simple accumulation of triacylglycerols in the liver could be hepatoprotective; however, prolonged hepatic lipid storage may lead to liver metabolic dysfunction, inflammation, and advanced forms of nonalcoholic fatty liver disease. Nonalcoholic hepatic steatosis is associated with obesity, type 2 diabetes, and dyslipidemia. Several mechanisms are involved in the accumulation of intrahepatic fat, including increased flux of fatty acids to the liver, increased de novo lipogenesis, and/or reduced clearance through β-oxidation or very-low-density lipoprotein secretion. This article summarizes the mechanisms involved in the accumulation of triacylglycerols in the liver, the clinical implications, and the prevention of hepatic steatosis, with a focus on the role of mitochondrial function and lifestyle modifications. PMID:27099587

Exocrine pancreas ER stress is differentially induced by different fatty acids.

PubMed

Danino, Hila; Ben-Dror, Karin; Birk, Ruth

2015-12-10

Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum (ER), accommodating their high protein production rate. Overload of dietary fat (typical to obesity) is a recognized risk factor in pancreatitis and pancreatic cancer. Dietary fat, especially saturated fat, has been suggested by others and us to induce an acinar lipotoxic effect. The effect of different dietary fatty acids on the ER stress response is unknown. We studied the effect of acute (24h) challenge with different fatty acids (saturated, mono and poly-unsaturated) at different concentrations (between 200 and 500µM, typical to normal and obese states, respectively), testing fat accumulation, ER stress indicators, X-box binding protein 1 (Xbp1) splicing and nuclear translocation, as well as unfolded protein response (UPR) transcripts and protein levels using exocrine pancreas acinar AR42J and primary cells. Acute exposure of AR42J cells to different fatty acids caused increased accumulation of triglycerides, dependent on the type of fat. Different FAs had different effects on ER stress: most notably, saturated palmitic acid significantly affected the UPR response, as demonstrated by altered Xbp1 splicing, elevation in transcript levels of UPR (Xbp, CHOP, Bip) and immune factors (Tnfα, Tgfβ), and enhanced Xbp1 protein levels and Xbp1 time-dependent nuclear translocation. Poly-unsaturated FAs caused milder elevation of ER stress markers, while mono-unsaturated oleic acid attenuated the ER stress response. Thus, various fatty acids differentially affect acinar cell fat accumulation and, apart from oleic acid, induce ER stress. The differential effect of the various fatty acids could have potential nutritional and therapeutic implications. Copyright © 2015 Elsevier Inc. All rights reserved.

Modulation of hepatic steatosis by dietary fatty acids

PubMed Central

Ferramosca, Alessandra; Zara, Vincenzo

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused by fat deposition within liver cells. Liver fat content reflects the equilibrium between several metabolic pathways involved in triglyceride synthesis and disposal, such as lipolysis in adipose tissue and de novo lipogenesis, triglyceride esterification, fatty acid oxidation and very-low-density lipoprotein synthesis/secretion in hepatic tissue. In particular, it has been demonstrated that hepatic de novo lipogenesis plays a significant role in NAFLD pathogenesis. It is widely known that the fatty acid composition of the diet influences hepatic lipogenesis along with other metabolic pathways. Therefore, dietary fat may not only be involved in the pathogenesis of hepatic steatosis, but may also prevent and/or reverse hepatic fat accumulation. In this review, major data from the literature about the role of some dietary fats as a potential cause of hepatic fat accumulation or as a potential treatment for NAFLD are described. Moreover, biochemical mechanisms responsible for an increase or decrease in hepatic lipid content are critically analyzed. It is noteworthy that both quantitative and qualitative aspects of dietary fat influence triglyceride deposition in the liver. A high-fat diet or the dietary administration of conjugated linoleic acids induced hepatic steatosis. In contrast, supplementation of the diet with krill oil or pine nut oil helped in the prevention and/or in the treatment of steatotic liver. Quite interesting is the “case” of olive oil, since several studies have often provided different and⁄or conflicting results in animal models. PMID:24587652

Modulation of hepatic steatosis by dietary fatty acids.

PubMed

Ferramosca, Alessandra; Zara, Vincenzo

2014-02-21

Non-alcoholic fatty liver disease (NAFLD) describes a range of conditions caused by fat deposition within liver cells. Liver fat content reflects the equilibrium between several metabolic pathways involved in triglyceride synthesis and disposal, such as lipolysis in adipose tissue and de novo lipogenesis, triglyceride esterification, fatty acid oxidation and very-low-density lipoprotein synthesis/secretion in hepatic tissue. In particular, it has been demonstrated that hepatic de novo lipogenesis plays a significant role in NAFLD pathogenesis. It is widely known that the fatty acid composition of the diet influences hepatic lipogenesis along with other metabolic pathways. Therefore, dietary fat may not only be involved in the pathogenesis of hepatic steatosis, but may also prevent and/or reverse hepatic fat accumulation. In this review, major data from the literature about the role of some dietary fats as a potential cause of hepatic fat accumulation or as a potential treatment for NAFLD are described. Moreover, biochemical mechanisms responsible for an increase or decrease in hepatic lipid content are critically analyzed. It is noteworthy that both quantitative and qualitative aspects of dietary fat influence triglyceride deposition in the liver. A high-fat diet or the dietary administration of conjugated linoleic acids induced hepatic steatosis. In contrast, supplementation of the diet with krill oil or pine nut oil helped in the prevention and/or in the treatment of steatotic liver. Quite interesting is the "case" of olive oil, since several studies have often provided different and/or conflicting results in animal models.

Production of high levels of 8:0 and 10:0 fatty acids in transgenic canola by overexpression of Ch FatB2, a thioesterase cDNA from Cuphea hookeriana.

PubMed

Dehesh, K; Jones, A; Knutzon, D S; Voelker, T A

1996-02-01

The Mexican shrub Cuphea hookeriana accumulates up to 75% caprylate (8:0) and caprate (10:0) in its seed oil. An acyl-ACP thioesterase cDNA from C. hookeriana, designated Ch FatB2, has been identified, which, when expressed in Escherichia coli, provides thioesterase activity specific for 8:0- and 10:0-ACP substrates. Expression of this clone in seeds of transgenic canola, an oilseed crop that normally does not accumulate any 8:0 and 10:0, resulted in a dramatic increase in the levels of these two fatty acids accompanied by a preferential decrease in the levels of linoleate (18:2) and linolenate (18:3). The Ch FatB2 differs from Ch FatB1, another Cuphea hookeriana thioesterase reported recently, in both substrate specificity and expression pattern. The Ch FatB1 has a broad substrate specificity with strong preference for 16:0-ACP and is expressed throughout the plant; whereas Ch FatB2 is specific for 8:0/10:0-ACP and its expression is confined to the seed. It is proposed that the amplified expression of Ch FatB2 in the embryo provides the hydrolytic enzyme specificity determining the fatty acyl composition of Cuphea hookeriana seed oil.

Saturated and unsaturated fat induce hepatic insulin resistance independently of TLR-4 signaling and ceramide synthesis in vivo.

PubMed

Galbo, Thomas; Perry, Rachel J; Jurczak, Michael J; Camporez, João-Paulo G; Alves, Tiago C; Kahn, Mario; Guigni, Blas A; Serr, Julie; Zhang, Dongyan; Bhanot, Sanjay; Samuel, Varman T; Shulman, Gerald I

2013-07-30

Hepatic insulin resistance is a principal component of type 2 diabetes, but the cellular and molecular mechanisms responsible for its pathogenesis remain unknown. Recent studies have suggested that saturated fatty acids induce hepatic insulin resistance through activation of the toll-like receptor 4 (TLR-4) receptor in the liver, which in turn transcriptionally activates hepatic ceramide synthesis leading to inhibition of insulin signaling. In this study, we demonstrate that TLR-4 receptor signaling is not directly required for saturated or unsaturated fat-induced hepatic insulin resistance in both TLR-4 antisense oligonucleotide treated and TLR-4 knockout mice, and that ceramide accumulation is not dependent on TLR-4 signaling or a primary event in hepatic steatosis and impairment of insulin signaling. Further, we show that both saturated and unsaturated fats lead to hepatic accumulation of diacylglycerols, activation of PKCε, and impairment of insulin-stimulated IRS-2 signaling. These data demonstrate that saturated fat-induced insulin resistance is independent of TLR-4 activation and ceramides.

Review: Animal model and the current understanding of molecule dynamics of adipogenesis.

PubMed

Campos, C F; Duarte, M S; Guimarães, S E F; Verardo, L L; Wei, S; Du, M; Jiang, Z; Bergen, W G; Hausman, G J; Fernyhough-Culver, M; Albrecht, E; Dodson, M V

2016-06-01

Among several potential animal models that can be used for adipogenic studies, Wagyu cattle is the one that presents unique molecular mechanisms underlying the deposit of substantial amounts of intramuscular fat. As such, this review is focused on current knowledge of such mechanisms related to adipose tissue deposition using Wagyu cattle as model. So abundant is the lipid accumulation in the skeletal muscles of these animals that in many cases, the muscle cross-sectional area appears more white (adipose tissue) than red (muscle fibers). This enhanced marbling accumulation is morphologically similar to that seen in numerous skeletal muscle dysfunctions, disease states and myopathies; this might indicate cross-similar mechanisms between such dysfunctions and fat deposition in Wagyu breed. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. This revision underlies some of the complex molecular processes of fat deposition in animals.

Out of the frying pan: dietary saturated fat influences nonalcoholic fatty liver disease.

PubMed

Parks, Elizabeth; Yki-Järvinen, Hannele; Hawkins, Meredith

2017-02-01

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess accumulation of fat in the liver. In some cases, NAFLD is also accompanied by insulin resistance, resulting in metabolic dysfunction. Dietary fat content probably influences both NAFLD and insulin resistance; however, the immediate effects of fat consumption have not been fully explored. In this issue of the JCI, Hernández et al. evaluated hepatic glucose and lipid metabolism in humans and mice following a single oral dose of saturated fat. This one bolus of fat resulted in a measurable increase in insulin resistance, hepatic triglycerides, and gluconeogenesis. In mice, the saturated fat bolus resulted in the induction of several NAFLD-associated genes. Together, the results of this study indicate that saturated fat intake has immediate effects on metabolic function.

Brazilian Green Propolis Promotes Weight Loss and Reduces Fat Accumulation in C57BL/6 Mice Fed A High-Fat Diet.

PubMed

Sakai, Tohru; Ohhata, Miyuki; Fujii, Misaki; Oda, Sayaka; Kusaka, Yasuna; Matsumoto, Miki; Nakamoto, Akiko; Taki, Tomoyo; Nakamoto, Mariko; Shuto, Emi

2017-01-01

Propolis is a bee product with various biological properties. C57BL/6 mice were fed a high-fat diet and treated with propolis for 14 weeks. Body weight in mice treated with 2% propolis was less than that in control mice from 3 weeks after the start of treatment until 14 weeks except for the 7th week. Mice treated with propolis showed significantly lower epididymal fat weight and subcutaneous fat weight. Infiltration of epididymal fat by macrophages and T cells was reduced in the propolis group. Supplementation of propolis increased feces weight and fat content in feces, suggesting that mechanisms of weight reduction by propolis partly include a laxative effect and inhibition of fat absorption.

Visceral fat obesity increases serum DPP-4 levels in men with type 2 diabetes mellitus.

PubMed

Tanaka, Sayuri; Kanazawa, Ippei; Notsu, Masakazu; Sugimoto, Toshitsugu

2016-06-01

The relationship between serum DPP-4 level and visceral fat mass is still unclear in type 2 diabetes mellitus (T2DM). This study thus aimed to examine the association of visceral fat accumulation and metabolic syndrome with serum DPP-4 levels in T2DM. Visceral and subcutaneous fat areas were evaluated by performing computed tomography scan in 135 men with T2DM, who had never taken DPP-4 inhibitors or GLP-1 receptor agonists. We investigated the association between serum DPP-4 levels and visceral fat area as well as the presence of metabolic syndrome. Multiple regression analysis adjusted for age, duration of T2DM, body mass index, serum creatinine, and HbA1c showed that serum DPP-4 levels were positively associated with visceral fat area (β=0.25, p=0.04), but not subcutaneous fat area (β=-0.18, p=0.13). In logistic regression analyses adjusted for the confounding factors described above, serum DPP-4 levels were positively associated with visceral fat obesity and metabolic syndrome [odds ratio (OR)=1.63, 95% confidence interval (CI)=1.00-2.66 per standard deviation (SD) increase, p=0.04; OR=1.77, 95%CI=1.09-2.88 per SD increase, p=0.02, respectively]. The present study showed that serum DPP-4 level was positively and specifically associated with accumulation of visceral fat and the presence of metabolic syndrome in men with T2DM. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in african ancestry men.

PubMed

Kuipers, Allison L; Zmuda, Joseph M; Carr, J Jeffrey; Terry, James G; Nair, Sangeeta; Cvejkus, Ryan; Bunker, Clareann H; Patrick, Alan L; Wassel, Christina L; Miljkovic, Iva

2017-08-01

There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men. Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height. All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC. Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body. Copyright © 2017 Elsevier B.V. All rights reserved.

Adipocyte differentiation-related protein promotes lipid accumulation in goat mammary epithelial cells.

PubMed

Shi, H B; Yu, K; Luo, J; Li, J; Tian, H B; Zhu, J J; Sun, Y T; Yao, D W; Xu, H F; Shi, H P; Loor, J J

2015-10-01

Milk fat originates from the secretion of cytosolic lipid droplets (CLD) synthesized within mammary epithelial cells. Adipocyte differentiation-related protein (ADRP; gene symbol PLIN2) is a CLD-binding protein that is crucial for synthesis of mature CLD. Our hypothesis was that ADRP regulates CLD production and metabolism in goat mammary epithelial cells (GMEC) and thus plays a role in determining milk fat content. To understand the role of ADRP in ruminant milk fat metabolism, ADRP (PLIN2) was overexpressed or knocked down in GMEC using an adenovirus system. Immunocytochemical staining revealed that ADRP localized to the surface of CLD. Supplementation with oleic acid (OA) enhanced its colocalization with CLD surface and enhanced lipid accumulation. Overexpression of ADRP increased lipid accumulation and the concentration of triacylglycerol in GMEC. In contrast, morphological examination revealed that knockdown of ADRP decreased lipid accumulation even when OA was supplemented. This response was confirmed by the reduction in mass of cellular TG when ADRP was knocked down. The fact that knockdown of ADRP did not completely eliminate lipid accumulation at a morphological level in GMEC without OA suggests that some other compensatory factors may also aid in the process of CLD formation. The ADRP reversed the decrease of CLD accumulation induced by adipose triglyceride lipase. This is highly suggestive of ADRP promoting triacylglycerol stability within CLD by preventing access to adipose triglyceride lipase. Collectively, these data provide direct in vitro evidence that ADRP plays a key role in CLD formation and stability in GMEC. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The effect of cocoa supplementation on hepatic steatosis, reactive oxygen species and LFABP in a rat model of NASH

PubMed Central

2011-01-01

Background Non alcoholic steatohepatitis is hypothesised to develop via a mechanism involving fat accumulation and oxidative stress. The current study aimed to investigate if an increase in oxidative stress was associated with changes in the expression of liver fatty acid binding protein in a rat model of non alcoholic steatohepatitis and whether cocoa supplementation attenuated those changes. Methods Female Sprague Dawley rats were fed a high fat control diet, a high fat methionine choline deficient diet, or one of four 12.5% cocoa supplementation regimes in combination with the high fat methionine choline deficient diet. Results Liver fatty acid binding protein mRNA and protein levels were reduced in the liver of animals with fatty liver disease when compared to controls. Increased hepatic fat content was accompanied by higher levels of oxidative stress in animals with fatty liver disease when compared to controls. An inverse association was found between the levels of hepatic liver fatty acid binding protein and the level of hepatic oxidative stress in fatty liver disease. Elevated NADPH oxidase protein levels were detected in the liver of animals with increased severity in inflammation and fibrosis. Cocoa supplementation was associated with partial attenuation of these pathological changes, although the severity of liver disease induced by the methionine choline deficient diet prevented complete reversal of any disease associated changes. Red blood cell glutathione was increased by cocoa supplementation, whereas liver glutathione was reduced by cocoa compared to methionine choline deficient diet fed animals. Conclusion These findings suggest a potential role for liver fatty acid binding protein and NADPH oxidase in the development of non alcoholic steatohepatitis. Furthermore, cocoa supplementation may have be of therapeutic benefit in less sever forms of NASH. PMID:22081873

Deletion of CD73 in mice leads to aortic valve dysfunction.

PubMed

Zukowska, P; Kutryb-Zajac, B; Jasztal, A; Toczek, M; Zabielska, M; Borkowski, T; Khalpey, Z; Smolenski, R T; Slominska, E M

2017-06-01

Aortic stenosis is known to involve inflammation and thrombosis. Changes in activity of extracellular enzyme - ecto-5'-nucleotidase (referred also as CD73) can alter inflammatory and thrombotic responses. This study aimed to evaluate the effect of CD73 deletion in mice on development of aortic valve dysfunction and to compare it to the effect of high-fat diet. Four groups of mice (normal-diet Wild Type (WT), high-fat diet WT, normal diet CD73-/-, high-fat diet CD73-/-) were maintained for 15weeks followed by echocardiographic analysis of aortic valve function, measurement of aortic surface activities of nucleotide catabolism enzymes as well as alkaline phosphatase activity, mineral composition and histology of aortic valve leaflets. CD73-/- knock out led to an increase in peak aortic flow (1.06±0.26m/s) compared to WT (0.79±0.26m/s) indicating obstruction. Highest values of peak aortic flow (1.26±0.31m/s) were observed in high-fat diet CD73-/- mice. Histological analysis showed morphological changes in CD73-/- including thickening and accumulation of dark deposits, proved to be melanin. Concentrations of Ca 2+ , Mg 2+ and PO 4 3- in valve leaflets were elevated in CD73-/- mice. Alkaline phosphatase (ALP) activity was enhanced after ATP treatment and reduced after adenosine treatment in aortas incubated in osteogenic medium. AMP hydrolysis in CD73-/- was below 10% of WT. Activity of ecto-adenosine deaminase (eADA), responsible for adenosine deamination, in the CD73-/- was 40% lower when compared to WT. Deletion of CD73 in mice leads to aortic valve dysfunction similar to that induced by high-fat diet suggesting important role of this surface protein in maintaining heart valve integrity. Copyright © 2017 Elsevier B.V. All rights reserved.

New Advanced Technologies in Stem Cell Therapy

DTIC Science & Technology

2013-09-01

infiltration in skeletal muscle. Ectopic fat accumulation in skeletal muscle can be seen not only in myopathies but also in several disorders...mice; however, the source of the ectopic fat tissue within the skeletal muscle is unknown. In this study, we provide evidence that the RACs, PDGFRα...mesenchymal progenitor cells, are responsible for increased fat cell formation in the skeletal muscle of dKO mice. We observed that dKO-RACs had

Dietary fat intake, supplements, and weight loss

NASA Technical Reports Server (NTRS)

Dyck, D. J.

2000-01-01

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been tested for their effectiveness or safety over prolonged periods of time.

Dietary fat intake, supplements, and weight loss.

PubMed

Dyck, D J

2000-12-01

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been tested for their effectiveness or safety over prolonged periods of time.

Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth.

PubMed

Kanazawa, H; Kawai, M; Niwa, F; Hasegawa, T; Iwanaga, K; Ohata, K; Tamaki, A; Heike, T

2014-06-01

Physical growth in neurologically healthy preterm infants affects motor development. This study investigated the separate relationships between muscle and fat in infancy and later motor development and physical growth. Muscle thickness and subcutaneous fat thickness of the anterior thigh were measured using ultrasound images obtained from neurologically healthy preterm infants at birth, 3, 6, 12 and 18 months' corrected age. We also obtained the Pediatric Evaluation of Disability Inventory and Alberta Infant Motor Scale scores at 18 months' corrected age to assess motor ability and motor delay. Thirty preterm infants completed the study protocol. There was a significant positive correlation between motor ability and increments in subcutaneous fat thickness during the first 3 and 6 months' corrected age (r = 0.48 and 0.40, p < 0.05, respectively), but not between motor ability and muscle thickness growth in any of the periods. A secondary, logistic regression analysis showed that increments in subcutaneous fat thickness during the first 3 months were a protective factor for motor delay. Subcutaneous fat accumulation in early infancy is more strongly associated with motor development and delay than muscle growth. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Specific polyunsaturated fatty acids modulate lipid delivery and oocyte development in C. elegans revealed by molecular-selective label-free imaging

NASA Astrophysics Data System (ADS)

Chen, Wei-Wen; Yi, Yung-Hsiang; Chien, Cheng-Hao; Hsiung, Kuei-Ching; Ma, Tian-Hsiang; Lin, Yi-Chun; Lo, Szecheng J.; Chang, Ta-Chau

2016-08-01

Polyunsaturated fatty acids (PUFAs) exhibit critical functions in biological systems and their importance during animal oocyte maturation has been increasingly recognized. However, the detailed mechanism of lipid transportation for oocyte development remains largely unknown. In this study, the transportation of yolk lipoprotein (lipid carrier) and the rate of lipid delivery into oocytes in live C. elegans were examined for the first time by using coherent anti-Stokes Raman scattering (CARS) microscopy. The accumulation of secreted yolk lipoprotein in the pseudocoelom of live C. elegans can be detected by CARS microscopy at both protein (~1665 cm-1) and lipid (~2845 cm-1) Raman bands. In addition, an image analysis protocol was established to quantitatively measure the levels of secreted yolk lipoprotein aberrantly accumulated in PUFA-deficient fat mutants (fat-1, fat-2, fat-3, fat-4) and PUFA-supplemented fat-2 worms (the PUFA add-back experiments). Our results revealed that the omega-6 PUFAs, not omega-3 PUFAs, play a critical role in modulating lipid/yolk level in the oocytes and regulating reproductive efficiency of C. elegans. This work demonstrates the value of using CARS microscopy as a molecular-selective label-free imaging technique for the study of PUFA regulation and oocyte development in C. elegans.

A novel dual amylin and calcitonin receptor agonist, KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference.

PubMed

Gydesen, Sofie; Hjuler, Sara Toftegaard; Freving, Zenia; Andreassen, Kim Vietz; Sonne, Nina; Hellgren, Lars I; Karsdal, Morten Asser; Henriksen, Kim

2017-04-01

Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities. The effect of the dual amylin and calcitonin receptor agonist (DACRA), KBP-089, on body weight, glucose homeostasis and fatty acid accumulation in liver and muscle tissue and on food preference was investigated. Furthermore, we elucidated weight-independent effects of KBP-089 using a weight-matched group. Rats fed a high-fat diet were treated, s.c., with KBP-089 0.625, 1.25, 2.5 μg·kg -1 or vehicle. KB-089 induced in a dose-dependent and sustained weight loss (~17% by 2.5 μg·kg -1 ). Moreover, KBP-089 reduced fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP-089 improved glucose homeostasis through improved insulin action. To obtain a weight-matched group, significantly less food was offered (9% less than in the KBP-089 group). Weight matching led to improved glucose homeostasis by reducing plasma insulin; however, these effect were inferior compared to those of KBP-089. In the food preference test, rats fed a normal diet obtained 74% of their calories from chocolate. KBP-089 reduced total caloric intake and induced a relative increase in chow consumption while drastically reducing chocolate consumption compared with vehicle. The novel DACRA, KBP-089, induces a sustained weight loss, leading to improved metabolic parameters including food preference, and these are beyond those observed simply by diet-induced weight loss. © 2017 The British Pharmacological Society.

Fatty acid-binding protein 4 regulates fatty infiltration after rotator cuff tear by hypoxia-inducible factor 1 in mice.

PubMed

Lee, Yong-Soo; Kim, Ja-Yeon; Oh, Kyung-Soo; Chung, Seok Won

2017-10-01

Fatty infiltration in skeletal muscle is directly linked to loss of muscle strength and is associated with various adverse physical outcomes such as muscle atrophy, inflammation, insulin resistance, mobility impairments, and even mortality in the elderly. Aging, mechanical unloading, muscle injury, and hormonal imbalance are main causes of muscle fat accumulation, and the fat cells are derived from muscle stem cells via adipogenic differentiation. However, the pathogenesis and molecular mechanisms of fatty infiltration in muscles are still not fully defined. Fatty acid-binding protein 4 (FABP4) is a carrier protein for fatty acids and is involved in fatty acid uptake, transport, and lipid metabolism. Rotator cuff tear (RCT) usually occurs in the elderly and is closely related with fatty infiltration in injured muscle. To investigate potential mechanisms for fatty infiltration other than adipogenic differentiation of muscle stem cells, we examined the role of FABP4 in muscle fatty infiltration in an RCT mouse model. In the RCT model, we evaluated the expression of FABP4 by qRT-PCR, western blotting, and immunohistochemical analyses. Histological changes such as inflammation and fat accumulation in the injured muscles were examined immunohistochemically. To evaluate whether hypoxia induces FABP4 expression, the levels of FABP4 mRNA and protein in C3H10T1/2 cells after hypoxia were examined. Using a transient transfection assay in 293T cells, we assessed the promoter activity of FABP4 by hypoxia-inducible factors (HIFs). Additionally, we evaluated the reduction in FABP4 expression and fat accumulation using specific inhibitors for HIF1 and FABP4, respectively. FABP4 expression was significantly increased after RCT in mice, and its expression was localized in the intramuscular fatty region. Rotator cuff tear-induced FABP4 expression was up-regulated by hypoxia. HIF1α, which is activated by hypoxia, augmented the promoter activity of FABP4, together with HIF1β. Hypoxia-induced FABP4 expression was significantly decreased by HIF1 inhibitor treatment. Furthermore, in RCT model mice, fat accumulation was remarkably reduced by FABP4 inhibitor treatment. This study shows that RCT induces FABP4 expression, leading to fat accumulation in injured muscle. FABP4 transcription is regulated by the direct binding of HIF1 to the FABP4 promoter in the hypoxic condition induced by RCT. Fat accumulation in injured muscle was reduced by the inhibition of FABP4. Ultimately, in the RCT model, we identified a novel mechanism for fatty infiltration by FABP4, which differs from adipogenic differentiation of muscle stem cells, and we found that fatty infiltration might be regulated by inhibition of HIF1 or FABP4. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

A Combination of Flaxseed Oil and Astaxanthin Improves Hepatic Lipid Accumulation and Reduces Oxidative Stress in High Fat-Diet Fed Rats

PubMed Central

Xu, Jiqu; Rong, Shuang; Gao, Hui; Chen, Chang; Yang, Wei; Deng, Qianchun; Huang, Qingde; Xiao, Lingyun; Huang, Fenghong

2017-01-01

Hepatic lipid accumulation and oxidative stress are crucial pathophysiological mechanisms for non-alcoholic fatty liver disease (NAFLD). Thus, we examined the effect of a combination of flaxseed oil (FO) and astaxanthin (ASX) on hepatic lipid accumulation and oxidative stress in rats fed a high-fat diet. ASX was dissolved in flaxseed oil (1 g/kg; FO + ASX). Animals were fed diets containing 20% fat, where the source was lard, or 75% lard and 25% FO + ASX, or 50% lard and 50% FO + ASX, or FO + ASX, for 10 weeks. Substitution of lard with FO + ASX reduced steatosis and reduced hepatic triacylglycerol and cholesterol. The combination of FO and ASX significantly decreased hepatic sterol regulatory element-binding transcription factor 1 and 3-hydroxy-3-methylglutaryl-CoA reductase but increased peroxisome proliferator activated receptor expression. FO + ASX significantly suppressed fatty acid synthase and acetyl CoA carboxylase but induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression. FO + ASX also significantly elevated hepatic SOD, CAT and GPx activity and GSH, and markedly reduced hepatic lipid peroxidation. Thus, FO and ASX may reduce NAFLD by reversing hepatic steatosis and reducing lipid accumulation and oxidative stress. PMID:28335388

The fate of technical-grade chlordane in mice fed a high-fat diet and its roles as a candidate obesogen.

PubMed

Wang, Dezhen; Wang, Xinru; Zhang, Ping; Wang, Yao; Zhang, Renke; Yan, Jin; Zhou, Zhiqiang; Zhu, Wentao

2017-03-01

Epidemiological studies indicate that exposure to persistent organic pollutants is positively associated with the prevalence of obesity. To delineate the potential role of technical-grade chlordane in obesity development, chlordane metabolism and chlordane-induced metabolic changes were investigated in mice fed high-fat diet (HFD) over a 6-week period. Gas chromatography-electron capture detector analysis showed that HFD induced more accumulation of technical chlordane in the liver, muscle and adipose tissue. The enantioselectivities of oxychlordane in selected tissues were also influenced by HFD. 1 H NMR-based liver metabolome indicated that technical chlordane can enhance the metabolic alterations induced by HFD. Compared with the low-fat diet (LFD) group, no differences were observed in the LFD + chlordane group. However, as many as 16 metabolites were significantly different between the HFD group and HFD + chlordane group. Moreover, compared to the LFD + chlordane group, the abundances of 24 metabolites significantly increased or decreased in the HFD + chlordane group. Twenty metabolites were altered in the HFD group compared to the LFD group. Tryptophan profiling suggested that both chlordane and HFD can disturb tryptophan catabolism. These interactions between technical chlordane and HFD suggest that technical chlordane is a candidate obesogen. Copyright © 2016 Elsevier Ltd. All rights reserved.

A microarray analysis of sexual dimorphism of adipose tissues in high-fat-diet-induced obese mice

PubMed Central

Grove, KL; Fried, SK; Greenberg, AS; Xiao, XQ; Clegg, DJ

2013-01-01

Objective A sexual dimorphism exists in body fat distribution; females deposit relatively more fat in subcutaneous/inguinal depots whereas males deposit more fat in the intra-abdominal/gonadal depot. Our objective was to systematically document depot- and sex-related differences in the accumulation of adipose tissue and gene expression, comparing differentially expressed genes in diet-induced obese mice with mice maintained on a chow diet. Research Design and Methods We used a microarray approach to determine whether there are sexual dimorphisms in gene expression in age-matched male, female or ovariectomized female (OVX) C57/BL6 mice maintained on a high-fat (HF) diet. We then compared expression of validated genes between the sexes on a chow diet. Results After exposure to a high fat diet for 12 weeks, females gained less weight than males. The microarray analyses indicate in intra-abdominal/gonadal adipose tissue in females 1642 genes differ by at least twofold between the depots, whereas 706 genes differ in subcutaneous/inguinal adipose tissue when compared with males. Only 138 genes are commonly regulated in both sexes and adipose tissue depots. Inflammatory genes (cytokine–cytokine receptor interactions and acute-phase protein synthesis) are upregulated in males when compared with females, and there is a partial reversal after OVX, where OVX adipose tissue gene expression is more ′male-like′. This pattern is not observed in mice maintained on chow. Histology of male gonadal white adipose tissue (GWAT) shows more crown-like structures than females, indicative of inflammation and adipose tissue remodeling. In addition, genes related to insulin signaling and lipid synthesis are higher in females than males, regardless of dietary exposure. Conclusions These data suggest that male and female adipose tissue differ between the sexes regardless of diet. Moreover, HF diet exposure elicits a much greater inflammatory response in males when compared with females. This data set underscores the importance of analyzing depot-, sex- and steroid-dependent regulation of adipose tissue distribution and function. PMID:20157318

Feminization of the fat distribution pattern of children and adolescents in a recent German population.

PubMed

Scheffler, Christiane; Dammhahn, Melanie

2017-09-10

During the early 1990s, the economic and political situation in eastern Germany changed overnight. Here, we use the rare chance of an experiment-like setting in humans and aim to test whether the rapid change of environmental conditions in eastern Germany in the 1990s led to a change in the sex-specific fat distribution pattern, an endocrine-influenced phenotypic marker. Based on a cross-sectional data set of 6- to 18-year-old girls and boys measured between 1982-1991 and 1997-2012, we calculated a skinfold ratio of triceps to subscapular and percentage of body fat. Using linear regressions, we tested for differences in percentage of body fat and skinfold ratio between these two time periods. We found that the percentage of body fat increased in boys and girls, and they accumulated relatively more fat on extremities than on the trunk in all BMI groups measured after 1997 as compared to those measured between 1982 and 1991. Concurrent with drastic and rapid changes of environmental conditions, the body fat distribution of children and adolescents changed to a more feminized pattern during the early 1990s in an East German population. The changes in this endocrinologically mediated pattern might be associated with the increased exposure of individuals to endocrine-disrupting chemicals which are known to influence the endocrine, reproductive, and immune systems in animals and humans. © 2017 Wiley Periodicals, Inc.

Ablation of PPP1R3G reduces glycogen deposition and mitigates high-fat diet induced obesity.

PubMed

Zhang, Yongxian; Gu, Jin; Wang, Lin; Zhao, Zilong; Pan, Yi; Chen, Yan

2017-01-05

Glycogen and triglyceride are two major forms of energy storage in the body and provide the fuel during different phases of food deprivation. However, how glycogen metabolism is linked to fat deposition in adipose tissue has not been clearly characterized. We generated a mouse model with whole-body deletion of PPP1R3G, a glycogen-targeting subunit of protein phosphatase-1 required for glycogen synthesis. Upon feeding with high-fat diet, the body weight and fat composition are significantly reduced in the PPP1R3G -/- mice compared to the wild type controls. The metabolic rate of the mice as measured by O 2 consumption and CO 2 production is accelerated by PPP1R3G deletion. The high-fat diet-induced liver steatosis is also slightly relieved by PPP1R3G deletion. The glycogen level in adipose tissue is reduced by PPP1R3G deletion. In 3T3L1 cells, overexpression of PPP1R3G leads to increases of both glycogen and triglyceride levels. In conclusion, our study indicates that glycogen is actively involved in fat accumulation in adipose tissue and obesity development upon high-fat diet. Our study also suggests that PPP1R3G is an important player that links glycogen metabolism to lipid metabolism in vivo. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Android Fat Depot Is More Closely Associated with Metabolic Syndrome than Abdominal Visceral Fat in Elderly People

PubMed Central

Kang, Seon Mee; Yoon, Ji Won; Ahn, Hwa Young; Kim, So Yeon; Lee, Kyoung Ho; Shin, Hayley; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo

2011-01-01

Background Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. Methods and Findings As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm2 and 126.9±55.2 cm2 in men (P = 0.045) and 120.0±46.7 cm2 and 211.8±65.9 cm2 in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. Conclusions Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution. PMID:22096613

Android fat depot is more closely associated with metabolic syndrome than abdominal visceral fat in elderly people.

PubMed

Kang, Seon Mee; Yoon, Ji Won; Ahn, Hwa Young; Kim, So Yeon; Lee, Kyoung Ho; Shin, Hayley; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo

2011-01-01

Fat accumulation in android compartments may confer increased metabolic risk. The incremental utility of measuring regional fat deposition in association with metabolic syndrome (MS) has not been well described particularly in an elderly population. As part of the Korean Longitudinal Study on Health and Aging, which is a community-based cohort study of people aged more than 65 years, subjects (287 male, 75.9±8.6 years and 278 female, 76.0±8.8 years) with regional body composition data using Dual energy X-ray absorptiometry for android/gynoid area, computed tomography for visceral/subcutaneous adipose tissue (VAT/SAT), and cardiometabolic markers including adiponectin and high-sensitivity CRP were enrolled. We investigated the relationship between regional body composition and MS in multivariate regression models. Mean VAT and SAT area was 131.4±65.5 cm(2) and 126.9±55.2 cm(2) in men (P = 0.045) and 120.0±46.7 cm(2) and 211.8±65.9 cm(2) in women (P<0.01). Mean android and gynoid fat amount was 1.8±0.8 kg and 2.5±0.8 kg in men and 2.0±0.6 kg and 3.3±0.8 kg in women, respectively (both P<0.01). VAT area and android fat amount was strongly correlated with most metabolic risk factors compared to SAT or gynoid fat. Furthermore, android fat amount was significantly associated with clustering of MS components after adjustment for multiple parameters including age, gender, adiponectin, hsCRP, a surrogate marker of insulin resistance, whole body fat mass and VAT area. Our findings are consistent with the hypothesized role of android fat as a pathogenic fat depot in the MS. Measurement of android fat may provide a more complete understanding of metabolic risk associated with variations in fat distribution.

A Maternal Low-Fiber Diet Predisposes Offspring to Improved Metabolic Phenotypes in Adulthood in an Herbivorous Rodent.

PubMed

Zhang, Xue-Ying; Lou, Mei-Fang; Shen, Wei; Fu, Rong-Shu; Wang, De-Hua

The maternal or paternal dietary composition can have important effects on various aspects of their offspring's physiology. Studies from animal models and humans showed that a maternal high-fiber diet protected offspring against fat accumulation. However, little is known about how a maternal low-fiber diet modifies the metabolism of offspring in herbivorous rodents. We hypothesized that a maternal low-fiber diet would confer long-lasting beneficial effects on offspring metabolic phenotypes in herbivorous Brandt's vole (Lasiopodomys brandtii). Female voles were fed either a control (12.4% fiber) or a low-fiber (3.5% fiber) diet throughout pregnancy and lactation, and all offspring were fed the control diet after weaning till 14 wk old. Offspring were sampled from each litter at 18 d and 14 wk of age. Another subset of adult offspring at 15 wk of age was fed a high-fat diet for 8 wk. We found that there was no difference in litter size, litter mass, or pup mass before weaning between the two maternal diet groups. Offspring from the maternal low-fiber diet increased energy intake, body mass, and lean mass; suppressed fat accumulation; and improved glucose tolerance compared with those from the control diet. Moreover, the maternal low-fiber diet alleviated high-fat diet-induced obesity in the adult offspring. Serum leptin concentration and uncoupling protein 1 content in brown adipose tissue of offspring were not affected by a maternal low-fiber diet. We demonstrate that herbivorous females fed a low-fiber diet during pregnancy and lactation may predispose their offspring to accelerated growth of lean tissue, which may increase the opportunity for survival and reproduction in offspring.

Ethanolic extract of seabuckthorn (Hippophae rhamnoides L) prevents high-fat diet-induced obesity in mice through down-regulation of adipogenic and lipogenic gene expression.

PubMed

Pichiah, P B Tirupathi; Moon, Hye-Jung; Park, Jeong-Eun; Moon, Yeon-Jeong; Cha, Youn-Soo

2012-11-01

Phenolic compounds and flavonoids ameliorate bodyweight, blood glucose, and serum lipid profile. Since seabuckthorn (Hippophae rhamnoides L.) is known as a rich source of isoflavones and flavonoids, we hypothesized that ethanolic extract of seabuckthorn leaves (SL) may have anti-obesity and hypoglycemic effects. To investigate the effect of ethanolic extract of SL, 32 C57BL/6J mice were randomly divided into 4 dietary groups, containing 8 mice in each group: normal diet group; high-fat diet (HD) control group; high-fat diet with SL extract, 500 mg/kg body weight (BW) (SL1) group; and high-fat diet with SL extract, 1000 mg/kg BW (SL2) group. After 13 weeks, it was observed that oral administration of SL extract significantly reduced the energy intake; BW gain; epididymal fat pad weight; hepatic triglyceride, hepatic, and serum total cholesterol levels; and serum leptin levels in the SL groups compared to the HD group. However, differences in serum triglyceride and insulin levels in the SL groups were not significant in comparison to the HD group. The hepatic mRNA expression of peroxisome proliferator-activated receptor (PPAR) α and carnitine palmitoyltransferase 1 along with PPAR-γ were significantly increased in SL groups, whereas the level of acetyl-CoA carboxylase was significantly reduced in SL groups compared to HD group. Our results indicated that SL is effective in preventing BW gain and fat accumulation in the liver; it also reduced adipose tissue mass, hepatic lipid profile, and serum leptin level in the mouse. Together, these observations suggest that SL is a potential agent to study in the management of obesity and related disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Anti-obesity effects of hot water extract from Wasabi (Wasabia japonica Matsum.) leaves in mice fed high-fat diets

PubMed Central

Ogawa, Tetsuro; Wang, Li; Katsube, Takuya; Yamasaki, Yukikazu; Sun, Xufeng; Shiwaku, Kuninori

2013-01-01

The anti-obesity effects of a hot water extract from wasabi (Wasabia japonica Matsum.) leaves (WLE), without its specific pungent constituents, such as allyl-isothiocyanate, were investigated in high fat-diet induced mice. C57J/BL mice were fed a high-fat diet (control group) or a high-fat diet supplemented with 5% WLE (WLE group). Physical parameters and blood profiles were determined. Gene expression associated with lipid metabolism in liver and white adipose tissue were analyzed. After 120 days of feeding, significantly lower body weight gain, liver weight and epididymal white adipose tissue weight was observed in the WLE group compared to the control group. In liver gene expression within the WLE group, PPARα was significantly enhanced and SREBP-1c was significantly suppressed. Subsequent downstream genes controlled by these regulators were significantly suppressed. In epididymal white adipose tissue of the WLE group, expression of leptin, PPARγ, and C/EBPα were significantly suppressed and adiponectin was significantly enhanced. Acox, related to fatty acid oxidization in adipocytes, was also enhanced. Our results demonstrate that the WLE dietary supplement induces mild suppression of obesity in a high-fat diet induced mice, possibly due to suppression of lipid accumulation in liver and white adipose tissue. PMID:23964313

Anti-obesity effects of hot water extract from Wasabi (Wasabia japonica Matsum.) leaves in mice fed high-fat diets.

PubMed

Yamasaki, Masayuki; Ogawa, Tetsuro; Wang, Li; Katsube, Takuya; Yamasaki, Yukikazu; Sun, Xufeng; Shiwaku, Kuninori

2013-08-01

The anti-obesity effects of a hot water extract from wasabi (Wasabia japonica Matsum.) leaves (WLE), without its specific pungent constituents, such as allyl-isothiocyanate, were investigated in high fat-diet induced mice. C57J/BL mice were fed a high-fat diet (control group) or a high-fat diet supplemented with 5% WLE (WLE group). Physical parameters and blood profiles were determined. Gene expression associated with lipid metabolism in liver and white adipose tissue were analyzed. After 120 days of feeding, significantly lower body weight gain, liver weight and epididymal white adipose tissue weight was observed in the WLE group compared to the control group. In liver gene expression within the WLE group, PPARα was significantly enhanced and SREBP-1c was significantly suppressed. Subsequent downstream genes controlled by these regulators were significantly suppressed. In epididymal white adipose tissue of the WLE group, expression of leptin, PPARγ, and C/EBPα were significantly suppressed and adiponectin was significantly enhanced. Acox, related to fatty acid oxidization in adipocytes, was also enhanced. Our results demonstrate that the WLE dietary supplement induces mild suppression of obesity in a high-fat diet induced mice, possibly due to suppression of lipid accumulation in liver and white adipose tissue.

The Role of Storage Lipids in the Relation between Fecundity, Locomotor Activity, and Lifespan of Drosophila melanogaster Longevity-Selected and Control Lines

PubMed Central

Nasiri Moghadam, Neda; Holmstrup, Martin; Manenti, Tommaso; Brandt Mouridsen, Marie; Pertoldi, Cino; Loeschcke, Volker

2015-01-01

The contribution of insect fat body to multiple processes, such as development, metamorphosis, activity, and reproduction results in trade-offs between life history traits. In the present study, age-induced modulation of storage lipid composition in Drosophila melanogaster longevity-selected (L) and non-selected control (C) lines was studied and the correlation between total body fat mass and lifespan assessed. The trade-offs between fecundity, locomotor activity, and lifespan were re-evaluated from a lipid-related metabolic perspective. Fewer storage lipids in the L lines compared to the C lines supports the impact of body fat mass on extended lifespan. The higher rate of fecundity and locomotor activity in the L lines may increase the lipid metabolism and enhance the lipolysis of storage lipids, reducing fat reserves. The correlation between neutral lipid fatty acids and fecundity, as well as locomotor activity, varied across age groups and between the L and C lines. The fatty acids that correlated with egg production were different from the fatty acids that correlated with locomotor activity. The present study suggests that fecundity and locomotor activity may positively affect the lifespan of D. melanogaster through the inhibition of fat accumulation. PMID:26115349

Bisphenol S induces obesogenic effects through deregulating lipid metabolism in zebrafish (Danio rerio) larvae.

PubMed

Wang, Weiwei; Zhang, Xiaona; Wang, Zihao; Qin, Jingyu; Wang, Wei; Tian, Hua; Ru, Shaoguo

2018-05-01

It has been suggested that dramatic increase in obesity may be caused by growing exposure to environmental chemicals. In vitro data has suggested bisphenol S (BPS), a compound widely used in polycarbonate plastic production, can induce lipid accumulation in preadipocytes. However, the mechanisms responsible for BPS-induced obesity in vivo remain unclear. In this study, we used translucent zebrafish (Danio rerio) larvae as a model to investigate the effect of environmentally relevant BPS exposure (1, 10, and 100 μg/L from 2 h to 15 d post fertilization) on lipid accumulation, triacylglycerol (TAG) and lipoproteins content, and mRNA expression of genes involved in the regulation of lipid synthesis, transport, degradation, and storage. We also analyzed activities of two enzymes critical to TAG metabolism: lipoprotein lipase and diglyceride acyltransferase. Overfed, obese larvae were used as positive control. The results indicated that BPS-treated and overfed larvae had much higher TAG levels and visceral fat accumulation compared with control. BPS exhibited obesogenic effects by interfering with lipid metabolism as evidenced by (a) upregulation of the mRNA expression of fasn, acc1, and agpat4 genes encoding enzymes involved in the de novo synthesis of TAG in the liver, (b) downregulation of apolipoprotein expression, which should reduce TAG transport from the liver, and (c) increase in rxrα expression, which should promote visceral fat accumulation. Our study is the first to demonstrate that the obesogenic effects of BPS in zebrafish are related to the disruption of TAG metabolism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Head shape disparity impacts pollutant accumulation in European eel.

PubMed

De Meyer, Jens; Belpaire, Claude; Boeckx, Pascal; Bervoets, Lieven; Covaci, Adrian; Malarvannan, Govindan; De Kegel, Barbara; Adriaens, Dominique

2018-05-08

Several aspects of the life cycle of the critically endangered European eel (Anguilla anguilla) remain poorly understood. One such aspect is the broad-versus narrow-head dimorphism, and how this impacts their overall performance at different stages of their life cycle. At the yellow eel stage, the phenotypes show a trophic divergence. We investigated whether pollutant accumulation is affected by this disparity. We show that broad-headed eels contained higher concentrations of mercury and several lipophilic organic pollutants, compared to narrow-headed ones, irrespective of their fat content. The hereby confirmed link between the phenotypic disparity, its associated feeding ecology and its impact on pollutant accumulation thus raises further concerns about their migratory and reproductive success. Considering that pollution is an important contributor to the European eel's decline, our results demonstrate that broad-headed eels are more vulnerable to detrimental pollutant accumulation. This compromises their successful contribution to their population's reproduction and its restoration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extent of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation and glycated hemoglobin of 5.6–6.4%

PubMed Central

Iwahashi, Hiromi; Noguchi, Midori; Okauchi, Yukiyoshi; Morita, Sachiko; Imagawa, Akihisa; Shimomura, Iichiro

2015-01-01

Aims/Introduction Weight reduction improves glycemic control in obese men with glycated hemoglobin (HbA1c) of 5.6–6.4%, suggesting that it can prevent the development of diabetes in these patients. The aim of the present study was to quantify the amount of weight reduction necessary for minimization of diabetes risk in Japanese men with visceral fat accumulation. Materials and Methods The study participants were 482 men with an estimated visceral fat area of ≥100 cm2, HbA1c of 5.6–6.4%, fasting plasma glucose (FPG) of <126 mg/dL or casual plasma glucose <200 mg/dL. They were divided into two groups based on weight change at the end of the 3-year follow-up period (weight gain and weight loss groups). The weight loss group was classified into quartile subgroups (lowest group, 0 to <1.2%: second lowest group, ≥1.2 to <2.5%: second highest group, ≥2.5 to <4.3%: highest group, ≥4.3% weight loss). The development of diabetes at the end-point represented a rise in HbA1c to ≥6.5% or FPG ≥126 mg/dL, or casual plasma glucose ≥200 mg/dL. Results The cumulative incidence of diabetes at the end of the 3-year follow-up period was 16.2% in the weight gain group and 10.1% in the weight loss group (P not significant). The incidence of diabetes was significantly lower in the highest weight loss group (3.1%), but not in the second highest, the second lowest and the lowest weight loss groups (9.7, 10.1 and 18.3%), compared with the weight gain group. Conclusions Minimization of the risk of diabetes in Japanese men with visceral fat accumulation requires a minimum of 4–5% weight loss in those with HbA1c of 5.6–6.4%. PMID:26417413

Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease

PubMed Central

Catanzaro, Roberto; Cuffari, Biagio; Italia, Angelo; Marotta, Francesco

2016-01-01

After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as “fatty infiltration” or “nonalcoholic fatty pancreas disease” (NAFPD). The term “fatty replacement” describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of “ectopic fat deposition”, which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula. PMID:27678349

Dietary D-psicose reduced visceral fat mass in high-fat diet-induced obese rats.

PubMed

Chung, Young-Mee; Hyun Lee, Joo; Youl Kim, Deuk; Hwang, Se-Hee; Hong, Young-Ho; Kim, Seong-Bo; Jin Lee, Song; Hye Park, Chi

2012-02-01

D-Psicose, a C-3 epimer of D-fructose, has shown promise in reducing body fat accumulation in normal rats and plasma glucose level in genetic diabetic mice. Effects of D-psicose on diet-induced obesity are not clearly elucidated, and we investigated food intake, body weight, and fat accumulation in rats fed high-fat (HF) diet. Sprague-Dawley rats became obese by feeding HF diet for 4 wk, and were assigned either to normal or HF diet supplemented with or without D-psicose, sucrose, or erythritol for 8 wk. Changing HF to normal diet gained less body weight and adipose tissue due to different energy intake. D-psicose-fed rats exhibited lower weight gain, food efficiency ratio, and fat accumulation than erythritol- and sucrose-fed rats. This effect was more prominent in D-psicose-fed rats with normal diet than with HF diet, suggesting combination of psicose and calorie restriction further reduced obesity. There was no difference in serum cholesterol/high-density lipoprotein (HDL)-C and low-density lipoprotein (LDL)-C/HDL-C ratios between D-psicose group and other groups. Liver weight in 5% psicose group with normal diet was higher than in other groups, but histopathological examination did not reveal any psicose-related change. D-Psicose inhibited the differentiation of mesenchymal stem cell (MSC) to adipose tissue in a concentration-dependent manner. These results demonstrate that D-psicose produces a marked decrease, greater than erythritol, in weight gain and visceral fat in an established obesity model by inhibiting MSC differentiation to adipocyte. Thus, D-psicose can be useful in preventing and reducing obesity as a sugar substitute and food ingredient. We can develop D-psicose as a sugar substitute and food ingredient since it can prevent obesity in normal people, but also suppress adiposity as a sugar substitute or food ingredients with antiobesity effect in obese people. D-psicose can be unique functional sweetener because of its function of reducing visceral fat mass and weight gain. © 2012 Institute of Food Technologists®

Dietary creatine supplementation lowers hepatic triacylglycerol by increasing lipoprotein secretion in rats fed high-fat diet.

PubMed

da Silva, Robin P; Leonard, Kelly-Ann; Jacobs, René L

2017-12-01

Recent studies have shown that dietary creatine supplementation can prevent lipid accumulation in the liver. Creatine is a small molecule that plays a large role in energy metabolism, but since the enzyme creatine kinase is not present in the liver, the classical role in energy metabolism does not hold in this tissue. Fat accumulation in the liver can lead to the development of nonalcoholic fatty liver disease (NAFLD), a progressive disease that is prevalent in humans. We have previously reported that creatine can directly influence lipid metabolism in cell culture to promote lipid secretion and oxidation. Our goal in the current study was to determine whether similar mechanisms that occur in cell culture were present in vivo. We also sought to determine whether dietary creatine supplementation could be effective in reversing steatosis. Sprague-Dawley rats were fed a high-fat diet or a high-fat diet supplemented with creatine for 5 weeks. We found that rats supplemented with creatine had significantly improved rates of lipoprotein secretion and alterations in mitochondrial function that were consistent with greater oxidative capacity. We also find that introducing creatine into a high-fat diet halted hepatic lipid accumulation in rats with fatty liver. Our results support our previous report that liver cells in culture with creatine secrete and oxidize more oleic acid, demonstrating that dietary creatine can effectively change hepatic lipid metabolism by increasing lipoprotein secretion and oxidation in vivo. Our data suggest that creatine might be an effective therapy for NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential nongenetic impact of birth weight versus third-trimester growth velocity on glucose metabolism and magnetic resonance imaging abdominal obesity in young healthy twins.

PubMed

Pilgaard, Kasper; Hammershaimb Mosbech, Thomas; Grunnet, Louise; Eiberg, Hans; Van Hall, Gerrit; Fallentin, Eva; Larsen, Torben; Larsen, Rasmus; Poulsen, Pernille; Vaag, Allan

2011-09-01

Low birth weight is associated with type 2 diabetes, which to some extent may be mediated via abdominal adiposity and insulin resistance. Fetal growth velocity is high during the third trimester, constituting a potential critical window for organ programming. Intra-pair differences among monozygotic twins are instrumental in determining nongenetic associations between early environment and adult metabolic phenotype. Our objective was to investigate the relationship between size at birth and third-trimester growth velocity on adult body composition and glucose metabolism using intra-pair differences in young healthy twins. Fifty-eight healthy twins (42 monozygotic/16 dizygotic) aged 18-24 yr participated. Insulin sensitivity was assessed using hyperinsulinemic-euglycemic clamps. Whole-body fat was assessed by dual-energy x-ray absorptiometry scan, whereas abdominal visceral and sc fat (L1-L4) were assessed by magnetic resonance imaging. Third-trimester growth velocity was determined by repeated ultrasound examinations. Size at birth was nongenetically inversely associated with adult visceral and sc fat accumulation but unrelated to adult insulin action. In contrast, fetal growth velocity during third trimester was not associated with adult visceral or sc fat accumulation. Interestingly, third-trimester growth was associated with insulin action in a paradoxical inverse manner. Abdominal adiposity including accumulation of both sc and visceral fat may constitute primary nongenetic factors associated with low birth weight and reduced fetal growth before the third trimester. Reduced fetal growth during vs. before the third trimester may define distinct adult trajectories of metabolic and anthropometric characteristics influencing risk of developing type 2 diabetes.

Inhibition of myostatin protects against diet-induced obesity by enhancing fatty acid oxidation and promoting a brown adipose phenotype in mice.

PubMed

Zhang, C; McFarlane, C; Lokireddy, S; Masuda, S; Ge, X; Gluckman, P D; Sharma, M; Kambadur, R

2012-01-01

Although myostatin-null (Mstn (-/-)) mice fail to accumulate fat in adipose tissue when fed a high-fat diet (HFD), little is known about the molecular mechanism(s) behind this phenomenon. We therefore sought to identify the signalling pathways through which myostatin regulates accumulation and/or utilisation of fat. Wild-type, Mstn (-/-) and wild-type mice treated with soluble activin type IIB receptor (sActRIIB) were fed a control chow diet or an HFD for 12 weeks. Changes in gene expression were measured by microarray and quantitative PCR. Histological changes in white adipose tissue were assessed together with peripheral tissue fatty acid oxidation and changes in circulating hormones following HFD feeding. Our results demonstrate that inactivation of myostatin results in reduced fat accumulation in mice on an HFD. Molecular analysis revealed that metabolic benefits, due to lack of myostatin, are mediated through at least two independent mechanisms. First, lack of myostatin increased fatty acid oxidation in peripheral tissues through induction of enzymes involved in lipolysis and in fatty acid oxidation in mitochondria. Second, inactivation of myostatin also enhanced brown adipose formation in white adipose tissue of Mstn (-/-) mice. Consistent with the above, treatment of HFD-fed wild-type mice with the myostatin antagonist, sActRIIB, reduced the obesity phenotype. We conclude that absence of myostatin results in enhanced peripheral tissue fatty acid oxidation and increased thermogenesis, culminating in increased fat utilisation and reduced adipose tissue mass. Taken together, our data suggest that anti-myostatin therapeutics could be beneficial in alleviating obesity.

[Body fat distribution: anthropometric indicators].

PubMed

Yáñez, M; Albala, C

1995-12-01

There are two types of fat distribution in obese subjects. The abdominal, superior, android or apple shaped and the gluteo-femoral, gynecoid, inferior or pear shaped. In the former, fat is accumulated in the abdomen and in the latter, in the gluteal region. The superior distribution is associated with a higher risk of cardiovascular diseases. Among anthropometric measurements of fat distribution, the ratio between waist circumference measured at the level of the navel and hip circumference, measured at the level of greater trochanters, is the best indicator. Using the cutoff points of 0.8 for women and 1 for men, it has a good correlation with visceral fat.

Ethnic influences on the relations between abdominal subcutaneous and visceral adiposity, liver fat, and cardiometabolic risk profile: the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity.

PubMed

Nazare, Julie-Anne; Smith, Jessica D; Borel, Anne-Laure; Haffner, Steven M; Balkau, Beverley; Ross, Robert; Massien, Christine; Alméras, Natalie; Després, Jean-Pierre

2012-10-01

Ethnic differences in cardiometabolic risk (CMR) may be related to patterns of ethnic-specific body fat distribution. We aimed to identify differences across ethnic groups in interrelations between BMI, abdominal adiposity, liver fat, and CMR profile. In the International Study of Prediction of Intra-Abdominal Adiposity and Its Relationship With Cardiometabolic Risk/Intra-Abdominal Adiposity, 297 physicians recruited 4504 patients (from 29 countries). In the current cross-sectional analyses, 2011 whites, 166 African Caribbean blacks, 381 Hispanics, 1192 East Asians, and 347 Southeast Asians were included. Computed tomography was used to assess abdominal fat distribution and to estimate liver fat content. Anthropometric variables and CMR profile were measured. Higher ranges of BMI were associated with higher levels of visceral [visceral adipose tissue (VAT)] and deep subcutaneous [deep subcutaneous adipose tissue (DSAT)] adiposity, with significant ethnic differences regarding the slope of these relations. Despite lower absolute BMI values, East Asians presented the largest accumulation of VAT but the lowest accumulation of DSAT with increasing adiposity. The association of BMI with liver fat did not differ between ethnic groups. Liver fat and DSAT were positively correlated with VAT with no ethnic variation. All ethnic groups had a similar association between a 1-SD increase in VAT, DSAT, or liver fat with hypertension, type 2 diabetes, hypertriglyceridemia, low HDL-cholesterol concentration, or high C-reactive protein concentration. Ethnicity significantly affects abdominal adiposity and liver fat partitioning, and East Asians have the most deleterious abdominal fat distribution. Irrespective of ethnicity, abdominal and hepatic fat depots are strongly interrelated and increased with obesity. Higher amounts of VAT or liver fat are associated with a more deteriorated CMR profile in all ethnic groups.

Dietary Fat Content and Fiber Type Modulate Hind Gut Microbial Community and Metabolic Markers in the Pig

PubMed Central

Yan, Hui; Potu, Ramesh; Lu, Hang; Vezzoni de Almeida, Vivian; Stewart, Terry; Ragland, Darryl; Armstrong, Arthur; Adeola, Olayiwola; Nakatsu, Cindy H.; Ajuwon, Kolapo M.

2013-01-01

Obesity leads to changes in the gut microbial community which contribute to the metabolic dysregulation in obesity. Dietary fat and fiber affect the caloric density of foods. The impact of dietary fat content and fiber type on the microbial community in the hind gut is unknown. Effect of dietary fat level and fiber type on hindgut microbiota and volatile fatty acid (VFA) profiles was investigated. Expression of metabolic marker genes in the gut, adipose tissue and liver was determined. A 2×2 experiment was conducted in pigs fed at two dietary fat levels (5% or 17.5% swine grease) and two fiber types (4% inulin, fermentable fructo-oligosaccharide or 4% solka floc, non-fermentable cellulose). High fat diets (HFD) resulted in a higher (P<0.05) total body weight gain, feed efficiency and back fat accumulation than the low fat diet. Feeding of inulin, but not solka floc, attenuated (P<0.05) the HFD-induced higher body weight gain and fat mass accumulation. Inulin feeding tended to lead to higher total VFA production in the cecum and resulted in a higher (P<0.05) expression of acyl coA oxidase (ACO), a marker of peroxisomal β-oxidation. Inulin feeding also resulted in lower expression of sterol regulatory element binding protein 1c (SREBP-1c), a marker of lipid anabolism. Bacteria community structure characterized by DGGE analysis of PCR amplified 16S rRNA gene fragments showed that inulin feeding resulted in greater bacterial population richness than solka floc feeding. Cluster analysis of pairwise Dice similarity comparisons of the DGGE profiles showed grouping by fiber type but not the level of dietary fat. Canonical correspondence analysis (CCA) of PCR- DGGE profiles showed that inulin feeding negatively correlated with back fat thickness. This study suggests a strong interplay between dietary fat level and fiber type in determining susceptibility to obesity. PMID:23573202

Brown adipogenesis of mouse embryonic stem cells in alginate microstrands

NASA Astrophysics Data System (ADS)

Unser, Andrea Mannarino

The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders. Employing pluripotent stem cells, with an emphasis on directed differentiation, may overcome many issues currently associated with primary fat cell cultures. However, brown adipocytes are difficult to transplant in vivo due to the instability of fat, in terms of necrosis and neovascularization, once injected. Thus, 3D cell culture systems that have the potential to mimic adipogenic microenvironments are needed, not only to advance brown fat implantation, but also to better understand the role of brown adipocytes in treating obesity. To address this need, we created 3D "Brown-Fat-in-Microstrands" by microfluidic synthesis of alginate hydrogel microstrands that encapsulated cells and directly induced cell differentiation into brown adipocytes, using mouse embryonic stem cells (ESCs) as a model of pluripotent stem cells and brown preadipocytes as a positive control. The effect of hydrogel formation parameters on brown adipogenesis was studied, leading to the establishment of "Brown-Fat-in-Microstrands". Brown adipocyte differentiation within microstrands was confirmed by lipid droplet accumulation, immunocytochemistry and qPCR analysis of gene expression of brown adipocyte marker uncoupling protein 1 (UCP1) in addition to adipocyte marker expression. Compared to a 2D approach, 3D differentiated "Brown-Fat-in-Microstrands" exhibited higher level of brown adipocyte marker expression. The functional analysis of "Brown-Fat-in-Microstrands" was attempted by measuring the mitochondrial activity of ESC-differentiated brown adipocytes in 3D using Seahorse XF24 3 Extracellular Flux Analyzer. The ability to create "Brown-Fat-in-Microstrands" from pluripotent stem cells opens up a new arena to understanding brown adipogenesis and its implications in obesity and metabolic disorders.

FAT10 knock out mice livers fail to develop Mallory-Denk bodies in the DDC mouse model.

PubMed

French, S W; French, B A; Oliva, J; Li, J; Bardag-Gorce, F; Tillman, B; Canaan, A

2012-12-01

Mallory-Denk bodies (MDBs) are aggresomes composed of undigested ubiqutinated short lived proteins which have accumulated because of a decrease in the rate of their degradation by the 26s proteasome. The decrease in the activity of the proteasome is due to a shift in the activity of the 26s proteasome to the immunoproteasome triggered by an increase in expression of the catalytic subunits of the immunoproteasome which replaces the catalytic subunits of the 26s proteasome. This switch in the type of proteasome in liver cells is triggered by the binding of IFNγ to the IFNγ sequence response element (ISRE) located on the FAT10 promoter. To determine if either FAT10 or IFNγ are essential for the formation of MDBs we fed both IFNγ and FAT10 knock out (KO) mice DDC added to the control diet for 10weeks in order to induce MDBs. Mice fed the control diet and Wild type mice fed the DDC or control diet were compared. MDBs were located by immunofluorescent double stains using antibodies to ubiquitin to stain MDBs and FAT10 to localize the increased expression of FAT10 in MDB forming hepatocytes. We found that MDB formation occurred in the IFNγ KO mice but not in the FAT10 KO mice. Western blots showed an increase in the ubiquitin smears and decreases β 5 (chymotrypsin-like 26S proteasome subunit) in the Wild type mice fed DDC but not in the FAT10 KO mice fed DDC. To conclude, we have demonstrated that FAT10 is essential to the induction of MDB formation in the DDC fed mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Comparative omics and feeding manipulations in chicken indicate a shift of the endocrine role of visceral fat towards reproduction.

PubMed

Bornelöv, Susanne; Seroussi, Eyal; Yosefi, Sara; Benjamini, Sharon; Miyara, Shoval; Ruzal, Mark; Grabherr, Manfred; Rafati, Nima; Molin, Anna-Maja; Pendavis, Ken; Burgess, Shane C; Andersson, Leif; Friedman-Einat, Miriam

2018-04-26

The mammalian adipose tissue plays a central role in energy-balance control, whereas the avian visceral fat hardly expresses leptin, the key adipokine in mammals. Therefore, to assess the endocrine role of adipose tissue in birds, we compared the transcriptome and proteome between two metabolically different types of chickens, broilers and layers, bred towards efficient meat and egg production, respectively. Broilers and layer hens, grown up to sexual maturation under free-feeding conditions, differed 4.0-fold in weight and 1.6-fold in ovarian-follicle counts, yet the relative accumulation of visceral fat was comparable. RNA-seq and mass-spectrometry (MS) analyses of visceral fat revealed differentially expressed genes between broilers and layers, 1106 at the mRNA level (FDR ≤ 0.05), and 203 at the protein level (P ≤ 0.05). In broilers, Ingenuity Pathway Analysis revealed activation of the PTEN-pathway, and in layers increased response to external signals. The expression pattern of genes encoding fat-secreted proteins in broilers and layers was characterized in the RNA-seq and MS data, as well as by qPCR on visceral fat under free feeding and 24 h-feed deprivation. This characterization was expanded using available RNA-seq data of tissues from red junglefowl, and of visceral fat from broilers of different types. These comparisons revealed expression of new adipokines and secreted proteins (LCAT, LECT2, SERPINE2, SFTP1, ZP1, ZP3, APOV1, VTG1 and VTG2) at the mRNA and/or protein levels, with dynamic gene expression patterns in the selected chicken lines (except for ZP1; FDR/P ≤ 0.05) and feed deprivation (NAMPT, SFTPA1 and ZP3) (P ≤ 0.05). In contrast, some of the most prominent adipokines in mammals, leptin, TNF, IFNG, and IL6 were expressed at a low level (FPKM/RPKM< 1) and did not show differential mRNA expression neither between broiler and layer lines nor between fed vs. feed-deprived chickens. Our study revealed that RNA and protein expression in visceral fat changes with selective breeding, suggesting endocrine roles of visceral fat in the selected phenotypes. In comparison to gene expression in visceral fat of mammals, our findings points to a more direct cross talk of the chicken visceral fat with the reproductive system and lower involvement in the regulation of appetite, inflammation and insulin resistance.

Saturated- and n-6 polyunsaturated-fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors.

PubMed

Frangioudakis, G; Garrard, J; Raddatz, K; Nadler, J L; Mitchell, T W; Schmitz-Peiffer, C

2010-09-01

Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance.

Folic acid supplementation during high-fat diet feeding restores AMPK activation via an AMP-LKB1-dependent mechanism

PubMed Central

Sid, Victoria; Wu, Nan; Sarna, Lindsei K.; Siow, Yaw L.; House, James D.

2015-01-01

AMPK is an endogenous energy sensor that regulates lipid and carbohydrate metabolism. Nonalcoholic fatty liver disease (NAFLD) is regarded as a hepatic manifestation of metabolic syndrome with impaired lipid and glucose metabolism and increased oxidative stress. Our recent study showed that folic acid supplementation attenuated hepatic oxidative stress and lipid accumulation in high-fat diet-fed mice. The aim of the present study was to investigate the effect of folic acid on hepatic AMPK during high-fat diet feeding and the mechanisms involved. Male C57BL/6J mice were fed a control diet (10% kcal fat), a high-fat diet (60% kcal fat), or a high-fat diet supplemented with folic acid (26 mg/kg diet) for 5 wk. Mice fed a high-fat diet exhibited hyperglycemia, hepatic cholesterol accumulation, and reduced hepatic AMPK phosphorylation. Folic acid supplementation restored AMPK phosphorylation (activation) and reduced blood glucose and hepatic cholesterol levels. Activation of AMPK by folic acid was mediated through an elevation of its allosteric activator AMP and activation of its upstream kinase, namely, liver kinase B1 (LKB1) in the liver. Consistent with in vivo findings, 5-methyltetrahydrofolate (bioactive form of folate) restored phosphorylation (activation) of both AMPK and LKB1 in palmitic acid-treated HepG2 cells. Activation of AMPK by folic acid might be responsible for AMPK-dependent phosphorylation of HMG-CoA reductase, leading to reduced hepatic cholesterol synthesis during high-fat diet feeding. These results suggest that folic acid supplementation may improve cholesterol and glucose metabolism by restoration of AMPK activation in the liver. PMID:26400185

Viscous dietary fiber reduces adiposity and plasma leptin and increases muscle expression of fat oxidation genes in rats.

PubMed

Islam, Ajmila; Civitarese, Anthony E; Hesslink, Robert L; Gallaher, Daniel D

2012-02-01

Dietary interventions that reduce accumulation of body fat are of great interest. Consumption of viscous dietary fibers cause well-known positive metabolic effects, such as reductions in the postprandial glucose and insulin concentrations. However, their effect on body composition and fuel utilization has not been previously studied. To examine this, rats were fed a viscous nonfermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), for 6 weeks. Body composition was measured by dual-energy X-ray absorptiometry (DXA) and fat pad weight. Plasma adipokines, AMP kinase activation, and enzyme and mRNA analysis of key regulators of energetics in liver and soleus muscle were measured. The HPMC diet significantly lowered percent body fat mass and increased percent lean body mass, compared to a cellulose-containing diet (no viscosity). Fasting leptin was reduced 42% and resistin 28% in the HPMC group compared to the cellulose group. Rats fed HPMC had greater activation of AMP kinase in liver and muscle and lower phosphoenolpyruvate carboxykinase (PEPCK) expression in liver. mRNA expression in skeletal muscle was significantly increased for carnitine palmitoyltransferase 1B (CPT-1B), PPARγ coactivator 1α, PPARδ and uncoupling protein 3 (UCP3), as was citrate synthase (CS) activity, in the HPMC group relative to the cellulose group. These results indicate that viscous dietary fiber preserves lean body mass and reduces adiposity, possibly by increasing mitochondrial biogenesis and fatty acid oxidation in skeletal muscle, and thus represents a metabolic effect of viscous fiber not previously described. Thus, viscous dietary fiber may be a useful dietary component to assist in reduction of body fat.

Ω-3 fatty acids prevent hepatic steatosis, independent of PPAR-α activity, in a murine model of parenteral nutrition-associated liver disease.

PubMed

Prince, Esther; Lazare, Farrah B; Treem, William R; Xu, Jiliu; Iqbal, Jahangir; Pan, Xiaoyue; Josekutty, Joby; Walsh, Meghan; Anderson, Virginia; Hussain, M Mahmood; Schwarz, Steven M

2014-07-01

ω-3 Fatty acids (FAs), natural ligands for the peroxisome proliferator-activated receptor-α (PPAR-α), attenuate parenteral nutrition-associated liver disease (PNALD). However, the mechanisms underlying the protective role of ω-3 FAs are still unknown. The aim of this study was to determine the effects of ω-3 FAs on hepatic triglyceride (TG) accumulation in a murine model of PNALD and to investigate the role of PPAR-α and microsomal triglyceride transfer protein (MTP) in this experimental setting. 129S1/SvImJ wild-type or 129S4/SvJaePparatm/Gonz/J PPAR-α knockout mice were fed chow and water (controls); oral, fat-free PN solution only (PN-O); PN-O plus intraperitoneal (IP) ω-6 FA-predominant supplements (PN-ω-6); or PN-O plus IP ω-3 FA (PN-ω-3). Control and PN-O groups received sham IP injections of 0.9% NaCl. Hepatic histology, TG and cholesterol, MTP activity, and PPAR-α messenger RNA were assessed after 19 days. In all experimental groups, PN feeding increased hepatic TG and MTP activity compared with controls. Both PN-O and PN-ω-6 groups accumulated significantly greater amounts of TG when compared with PN-ω-3 mice. Studies in PPAR-α null animals showed that PN feeding increases hepatic TG as in wild-type mice. PPAR-α null mice in the PN-O and PN-ω-6 groups demonstrated variable degrees of hepatic steatosis, whereas no evidence of hepatic fat accumulation was found after 19 days of oral PN plus IP ω-3 FAs. PN induces TG accumulation (steatosis) in wild-type and PPAR-α null mice. In PN-fed wild-type and PPAR-α null mice given IP ω-3 FAs, reduced hepatic TG accumulation and absent steatosis are found. Prevention of steatosis by ω-3 FAs results from PPAR-α-independent pathways. © 2013 American Society for Parenteral and Enteral Nutrition.

The Impact of Fat and Obesity on Bone Microarchitecture and Strength in Children

PubMed Central

Farr, Joshua N.; Dimitri, Paul

2016-01-01

A complex interplay of genetic, environmental, hormonal, and behavioral factors affect skeletal development, several of which are associated with childhood fractures. Given the rise in obesity worldwide, it is of particular concern that excess fat accumulation during childhood appears to be a risk factor for fractures. Plausible explanations for this higher fracture risk include a greater propensity for falls, greater force generation upon fall impact, unhealthy lifestyle habits, and excessive adipose tissue that may have direct or indirect detrimental effects on skeletal development. To date, there remains little resolution or agreement about the impact of obesity and adiposity on skeletal development as well as the mechanisms underpinning these changes. Limitations of imaging modalities, short duration of follow-up in longitudinal studies, and differences among cohorts examined may all contribute to conflicting results. Nonetheless, a linear relationship between increasing adiposity and skeletal development seems unlikely. Fat mass may confer advantages to the developing cortical and trabecular bone compartments, provided that gains in fat mass are not excessive. However, when fat mass accumulation reaches excessive levels, unfavorable metabolic changes may impede skeletal development. Mechanisms underpinning these changes may relate to changes in the hormonal milieu, with adipokines potentially playing a central role, but again findings have been confounding. Changes in the relationship between fat and bone also appear to be age and sex dependent. Clearly, more work is needed to better understand the controversial impact of fat and obesity on skeletal development and fracture risk during childhood. PMID:28013362

The Impact of Fat and Obesity on Bone Microarchitecture and Strength in Children.

PubMed

Farr, Joshua N; Dimitri, Paul

2017-05-01

A complex interplay of genetic, environmental, hormonal, and behavioral factors affect skeletal development, several of which are associated with childhood fractures. Given the rise in obesity worldwide, it is of particular concern that excess fat accumulation during childhood appears to be a risk factor for fractures. Plausible explanations for this higher fracture risk include a greater propensity for falls, greater force generation upon fall impact, unhealthy lifestyle habits, and excessive adipose tissue that may have direct or indirect detrimental effects on skeletal development. To date, there remains little resolution or agreement about the impact of obesity and adiposity on skeletal development as well as the mechanisms underpinning these changes. Limitations of imaging modalities, short duration of follow-up in longitudinal studies, and differences among cohorts examined may all contribute to conflicting results. Nonetheless, a linear relationship between increasing adiposity and skeletal development seems unlikely. Fat mass may confer advantages to the developing cortical and trabecular bone compartments, provided that gains in fat mass are not excessive. However, when fat mass accumulation reaches excessive levels, unfavorable metabolic changes may impede skeletal development. Mechanisms underpinning these changes may relate to changes in the hormonal milieu, with adipokines potentially playing a central role, but again findings have been confounding. Changes in the relationship between fat and bone also appear to be age and sex dependent. Clearly, more work is needed to better understand the controversial impact of fat and obesity on skeletal development and fracture risk during childhood.

Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E.

PubMed

Ni, Yinhua; Nagashimada, Mayumi; Zhuge, Fen; Zhan, Lili; Nagata, Naoto; Tsutsui, Akemi; Nakanuma, Yasuni; Kaneko, Shuichi; Ota, Tsuguhito

2015-11-25

Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese mice. In a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet, astaxanthin alleviated excessive hepatic lipid accumulation and peroxidation, increased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis. Moreover, astaxanthin caused an M2-dominant shift in macrophages/Kupffer cells and a subsequent reduction in CD4(+) and CD8(+) T cell recruitment in the liver, which contributed to improved insulin resistance and hepatic inflammation. Importantly, astaxanthin reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. Overall, astaxanthin was more effective at both preventing and treating NASH compared with vitamin E in mice. Furthermore, astaxanthin improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects. These results suggest that astaxanthin might be a novel and promising treatment for NASH.

Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E

PubMed Central

Ni, Yinhua; Nagashimada, Mayumi; Zhuge, Fen; Zhan, Lili; Nagata, Naoto; Tsutsui, Akemi; Nakanuma, Yasuni; Kaneko, Shuichi; Ota, Tsuguhito

2015-01-01

Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese mice. In a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet, astaxanthin alleviated excessive hepatic lipid accumulation and peroxidation, increased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis. Moreover, astaxanthin caused an M2-dominant shift in macrophages/Kupffer cells and a subsequent reduction in CD4+ and CD8+ T cell recruitment in the liver, which contributed to improved insulin resistance and hepatic inflammation. Importantly, astaxanthin reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. Overall, astaxanthin was more effective at both preventing and treating NASH compared with vitamin E in mice. Furthermore, astaxanthin improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects. These results suggest that astaxanthin might be a novel and promising treatment for NASH. PMID:26603489

Aldose reductase (AKR1B3) regulates the accumulation of advanced glycosylation end products (AGEs) and the expression of AGE receptor (RAGE)

PubMed Central

Baba, Shahid P.; Hellmann, Jason; Srivastava, Sanjay; Bhatnagar, Aruni

2011-01-01

Diabetes results in enhanced chemical modification of proteins by advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) precursors. These modifications have been linked to the development of several secondary diabetic complications. Our previous studies showed that aldose reductase (AR; AKR1B3) catalyzes the reduction of ALEs and AGEs precursors; however, the in vivo significance of this metabolic pathway during diabetes and obesity has not been fully assessed. Therefore we examined the role of AR in regulating ALEs and AGEs formation in murine models of diet-induced obesity and streptozotocin-induced diabetes. In comparison with wild-type (WT) and AR-null mice fed normal chow, mice fed a high-fat (HF) diet (42% kcal fat) showed increased accumulation of AGEs and protein–acrolein adducts in the plasma. AGEs and acrolein adducts were also increased in the epididymal fat of WT and AR-null mice fed a HF diet. Deletion of AR increased the accumulation of 4-hydroxy-trans-2-nonenal (HNE) protein adduct in the plasma and increased the expression of the AGE receptor (RAGE) in HF fed mice. No change in AGEs formation was observed in the kidneys of HF-fed mice. In comparison, renal tissue from AR-null mice treated with streptozotocin showed greater AGE accumulation than streptozotocin-treated WT mice. These data indicated that AR regulated the accumulation of lipid peroxidation derived aldehydes and AGEs under conditions of severe, but not mild, hyperglycemia and that deletion of AR increased RAGE-induction via mechanisms that were independent of AGEs accumulation. PMID:21276777

Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears.

PubMed

Mendias, Christopher L; Roche, Stuart M; Harning, Julie A; Davis, Max E; Lynch, Evan B; Sibilsky Enselman, Elizabeth R; Jacobson, Jon A; Claflin, Dennis R; Calve, Sarah; Bedi, Asheesh

2015-01-01

A persistent atrophy of muscle fibers and an accumulation of fat, collectively referred to as fatty degeneration, commonly occur in patients with chronic rotator cuff tears. The etiology of fatty degeneration and function of the residual rotator cuff musculature have not been well characterized in humans. We hypothesized that muscles from patients with chronic rotator cuff tears have reduced muscle fiber force production, disordered myofibrils, and an accumulation of fat vacuoles. The contractility of muscle fibers from biopsy specimens of supraspinatus muscles of 13 patients with chronic full-thickness posterosuperior rotator cuff tears was measured and compared with data from healthy vastus lateralis muscle fibers. Correlations between muscle fiber contractility, American Shoulder and Elbow Surgeons (ASES) scores, and tear size were analyzed. Histology and electron microscopy were also performed. Torn supraspinatus muscles had a 30% reduction in maximum isometric force production and a 29% reduction in normalized force compared with controls. Normalized supraspinatus fiber force positively correlated with ASES score and negatively correlated with tear size. Disordered sarcomeres were noted, along with an accumulation of lipid-laden macrophages in the extracellular matrix surrounding supraspinatus muscle fibers. Patients with chronic supraspinatus tears have significant reductions in muscle fiber force production. Force production also correlates with ASES scores and tear size. The structural and functional muscle dysfunction of the residual muscle fibers is independent of the additional area taken up by fibrotic tissue. This work may help establish future therapies to restore muscle function after the repair of chronically torn rotator cuff muscles. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Insulin-Stimulated Cardiac Glucose Oxidation Is Increased in High-Fat Diet–Induced Obese Mice Lacking Malonyl CoA Decarboxylase

PubMed Central

Ussher, John R.; Koves, Timothy R.; Jaswal, Jagdip S.; Zhang, Liyan; Ilkayeva, Olga; Dyck, Jason R.B.; Muoio, Deborah M.; Lopaschuk, Gary D.

2009-01-01

OBJECTIVE Whereas an impaired ability to oxidize fatty acids is thought to contribute to intracellular lipid accumulation, insulin resistance, and cardiac dysfunction, high rates of fatty acid oxidation could also impair glucose metabolism and function. We therefore determined the effects of diet-induced obesity (DIO) in wild-type (WT) mice and mice deficient for malonyl CoA decarboxylase (MCD−/−; an enzyme promoting mitochondrial fatty acid oxidation) on insulin-sensitive cardiac glucose oxidation. RESEARCH DESIGN AND METHODS WT and MCD−/− mice were fed a low- or high-fat diet for 12 weeks, and intramyocardial lipid metabolite accumulation was assessed. A parallel feeding study was performed to assess myocardial function and energy metabolism (nanomoles per gram of dry weight per minute) in isolated working hearts (+/– insulin). RESULTS DIO markedly reduced insulin-stimulated glucose oxidation compared with low fat–fed WT mice (167 ± 31 vs. 734 ± 125; P < 0.05). MCD−/− mice subjected to DIO displayed a more robust insulin-stimulated glucose oxidation (554 ± 82 vs. 167 ± 31; P < 0.05) and less incomplete fatty acid oxidation, evidenced by a decrease in long-chain acylcarnitines compared with WT counterparts. MCD−/− mice had long-chain acyl CoAs similar to those of WT mice subjected to DIO but had increased triacylglycerol levels (10.92 ± 3.72 vs. 3.29 ± 0.62 μmol/g wet wt; P < 0.05). CONCLUSIONS DIO does not impair cardiac fatty acid oxidation or function, and there exists disassociation between myocardial lipid accumulation and insulin sensitivity. Our results suggest that MCD deficiency is not detrimental to the heart in obesity. PMID:19478144

Arrhythmia causes lipid accumulation and reduced glucose uptake.

PubMed

Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

2015-01-01

Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways.

Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin.

PubMed

Okere, Isidore C; Chandler, Margaret P; McElfresh, Tracy A; Rennison, Julie H; Sharov, Victor; Sabbah, Hani N; Tserng, Kou-Yi; Hoit, Brian D; Ernsberger, Paul; Young, Martin E; Stanley, William C

2006-07-01

Fatty acids are the primary fuel for the heart and are ligands for peroxisome proliferator-activated receptors (PPARs), which regulate the expression of genes encoding proteins involved in fatty acid metabolism. Saturated fatty acids, particularly palmitate, can be converted to the proapoptotic lipid intermediate ceramide. This study assessed cardiac function, expression of PPAR-regulated genes, and cardiomyocyte apoptosis in rats after 8 wk on either a low-fat diet [normal chow control (NC); 10% fat calories] or high-fat diets composed mainly of either saturated (Sat) or unsaturated fatty acids (Unsat) (60% fat calories) (n = 10/group). The Sat group had lower plasma insulin and leptin concentrations compared with the NC or Unsat groups. Cardiac function and mass and body mass were not different. Cardiac triglyceride content was increased in the Sat and Unsat groups compared with NC (P < 0.05); however, ceramide content was higher in the Sat group compared with the Unsat group (2.9 +/- 0.2 vs. 1.4 +/- 0.2 nmol/g; P < 0.05), whereas the NC group was intermediate (2.3 +/- 0.3 nmol/g). The number of apoptotic myocytes, assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling staining, was higher in the Sat group compared with the Unsat group (0.28 +/- 0.05 vs. 0.17 +/- 0.04 apoptotic cells/1,000 nuclei; P < 0.04) and was positively correlated to ceramide content (P < 0.02). Both high-fat diets increased the myocardial mRNA expression of the PPAR-regulated genes encoding uncoupling protein-3 and pyruvate dehydrogenase kinase-4, but only the Sat diet upregulated medium-chain acyl-CoA dehydrogenase. In conclusion, dietary fatty acid composition affects cardiac ceramide accumulation, cardiomyocyte apoptosis, and expression of PPAR-regulated genes independent of cardiac mass or function.

Intrinsic aerobic capacity impacts susceptibility to acute high-fat diet-induced hepatic steatosis.

PubMed

Morris, E Matthew; Jackman, Matthew R; Johnson, Ginger C; Liu, Tzu-Wen; Lopez, Jordan L; Kearney, Monica L; Fletcher, Justin A; Meers, Grace M E; Koch, Lauren G; Britton, Stephen L; Rector, R Scott; Ibdah, Jamal A; MacLean, Paul S; Thyfault, John P

2014-08-15

Aerobic capacity/fitness significantly impacts susceptibility for fatty liver and diabetes, but the mechanisms remain unknown. Herein, we utilized rats selectively bred for high (HCR) and low (LCR) intrinsic aerobic capacity to examine the mechanisms by which aerobic capacity impacts metabolic vulnerability for fatty liver following a 3-day high-fat diet (HFD). Indirect calorimetry assessment of energy metabolism combined with radiolabeled dietary food was employed to examine systemic metabolism in combination with ex vivo measurements of hepatic lipid oxidation. The LCR, but not HCR, displayed increased hepatic lipid accumulation in response to the HFD despite both groups increasing energy intake. However, LCR rats had a greater increase in energy intake and demonstrated greater daily weight gain and percent body fat due to HFD compared with HCR. Additionally, total energy expenditure was higher in the larger LCR. However, controlling for the difference in body weight, the LCR has lower resting energy expenditure compared with HCR. Importantly, respiratory quotient was significantly higher during the HFD in the LCR compared with HCR, suggesting reduced whole body lipid utilization in the LCR. This was confirmed by the observed lower whole body dietary fatty acid oxidation in LCR compared with HCR. Furthermore, LCR liver homogenate and isolated mitochondria showed lower complete fatty acid oxidation compared with HCR. We conclude that rats bred for low intrinsic aerobic capacity show greater susceptibility for dietary-induced hepatic steatosis, which is associated with a lower energy expenditure and reduced whole body and hepatic mitochondrial lipid oxidation.

Obesity--a disease with many aetiologies disguised in the same oversized phenotype: has the overeating theory failed?

PubMed

Stenvinkel, Peter

2015-10-01

Evolution has led to metabolic thrift in humans--a genetic heritage that, when exposed to the modern 'obesogenic' milieu with energy-dense food and a sedentary lifestyle, predisposes to obesity. The current paradigm that overeating of easily digestible carbohydrates and the resulting imbalance between energy in and out as the cause of overweight has recently been challenged. Indeed, studies suggest that the host response to various nutrients contributes to overeating and fat accumulation. Alterations in neurotransmitter functions, changes in the epigenome, dysbiosis of gut microbiota and effects of specific nutrients (or lack of such nutrients) on mitochondrial function and signalling pathways may promote fat accumulation independent of calories. Whereas nutrients that stimulate generation of uric acid (such as fructose and purine-rich food) cause insulin resistance and fat accumulation, other nutrients (such as antioxidants, plant food, probiotics, nuts, soy and omega-3) counteract the negative effects of a calorie-rich diet by salutary effects on mitochondrial biogenesis. Thus, the specific metabolic effects of different nutrients may be more important than its total energy content. By studying the impact of nutrients on mitochondrial health, as well as the trans-generational impact of nutrients during fetal life, and how specific bacterial species correlate with fat mass accumulation, new dietary targets for obesity management may emerge. Overeating and overshooting of calories could to a large extent represent a symptom rather than a cause of obesity; therefore, hypocaloric diets should probably not be the main, and certainly not the only, focus for treatment of the obese patient. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

[Positive effects of physical exercise on reducing the relationship between subcutaneous abdominal fat and morbility risk].

PubMed

González Calvo, G; Hernández Sánchez, S; Pozo Rosado, P; García López, D

2011-01-01

The consequences related to the accumulation of abdominal fat above healthy levels create a considerable organic damage. Among the physiological consequences we can highlight heart diseases, hypertension, type-2 diabetes, obesity and metabolic syndrome, which drastically reduce life expectancy and quality. Evidence shows that health improvement is correlated to greater levels of physical activity. However, physical exercise can create oxidative damage on organs and muscular tissue, more relevant in subjects with a high percentage of abdominal fat. This piece of work determines which are the fundamental variables of the exercise program in order to optimize its advantages while minimizing oxidative stress. To know the key variables in the accumulation of abdominal fat above healthy levels, and the role of exercise in prevention and improvement of such issue. SPECIFIC PURPOSES: 1) to identify the key variables in an exercise program aimed at reducing abdominal fat; 2) to understand the relationship between abdominal fat, health and exercise; 3) to review the latest research related to physical exercise and its effect on abdominal adipose tissue. A search and identification of original and reviewed articles will be carried out in indexed impact journals within the main databases. Regular physical exercise, most notably aerobic one, reduces body adipose tissue deposits in general, and abdominal ones in particular, both in obese and overweight subjects.

Bilirubin Binding to PPARα Inhibits Lipid Accumulation

PubMed Central

Stec, David E.; John, Kezia; Trabbic, Christopher J.; Luniwal, Amarjit; Hankins, Michael W.; Baum, Justin

2016-01-01

Numerous clinical and population studies have demonstrated that increased serum bilirubin levels protect against cardiovascular and metabolic diseases such as obesity and diabetes. Bilirubin is a potent antioxidant, and the beneficial actions of moderate increases in plasma bilirubin have been thought to be due to the antioxidant effects of this bile pigment. In the present study, we found that bilirubin has a new function as a ligand for PPARα. We show that bilirubin can bind directly to PPARα and increase transcriptional activity. When we compared biliverdin, the precursor to bilirubin, on PPARα transcriptional activation to known PPARα ligands, WY 14,643 and fenofibrate, it showed that fenofibrate and biliverdin have similar activation properties. Treatment of 3T3-L1 adipocytes with biliverdin suppressed lipid accumulation and upregulated PPARα target genes. We treated wild-type and PPARα KO mice on a high fat diet with fenofibrate or bilirubin for seven days and found that both signal through PPARα dependent mechanisms. Furthermore, the effect of bilirubin on lowering glucose and reducing body fat percentage was blunted in PPARα KO mice. These data demonstrate a new function for bilirubin as an agonist of PPARα, which mediates the protection from adiposity afforded by moderate increases in bilirubin. PMID:27071062

Role of innate immune receptors TLR2 and TLR4 as mediators of the inflammatory reaction in human visceral adipose tissue.

PubMed

Fusaru, Ana Marina; Stănciulescu, Camelia Elena; Surlin, V; Taisescu, C; Bold, Adriana; Pop, O T; Baniţă, Ileana Monica; Crăiţoiu, Stefania; Pisoschi, Cătălina Gabriela

2012-01-01

White adipose tissue from different locations is characterized by significant differences in the structure of adipocyte "secretoma". Fat accumulation in the central-visceral depots is usually associated with a chronic inflammatory state, which is complicated by the metabolic syndrome. Recently, the adipose tissue was emerged to have an essential role in the innate immunity, adipocytes being considered effector cells due to the presence of the Toll-like receptors (TLRs). In this study, we compared the expression of TNF-α, TLR2 and TLR4 in peripheral-subcutaneous and central-peritoneal adipose depots in three different conditions - lean, obese and obese diabetic - using immunohistochemistry. Our results suggest a correlation between the incidence of the stromal vascular cells and adipocytes TNF-α and TLR4 in the visceral depots in strong correlation with adipose tissue expansion. TLR2 positive cells were seen in the peripheral depots from all groups without any association with fat accumulation. These results focus on the existence of a new pathogenic pathway, the activation of TLR4, for the involvement of visceral adipose tissue in the activation and maintenance of the inflammatory cascade in obesity.

Background diet and fat type alters plasma lipoprotein response but not aortic cholesterol accumulation in F1B golden syrian hamsters

USDA-ARS?s Scientific Manuscript database

Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat typ...

Regulation of fat specific protein 27 by isoproterenol and TNF-alpha to control lipolysis in murine adipocytes

USDA-ARS?s Scientific Manuscript database

The lipid droplet-associated fat specific protein 27 (FSP27) suppresses lipolysis and thereby enhances triglyceride accumulation in adipocytes. We and others have recently found FSP27 to be a remarkably short-lived protein (half-life, 15 min) due to its rapid ubiquitination and proteasomal degradati...

Saturated and unsaturated fat induce hepatic insulin resistance independently of TLR-4 signaling and ceramide synthesis in vivo

PubMed Central

Galbo, Thomas; Perry, Rachel J.; Jurczak, Michael J.; Camporez‎, João-Paulo G.; Alves, Tiago C.; Kahn, Mario; Guigni, Blas A.; Serr, Julie; Zhang, Dongyan; Bhanot, Sanjay; Samuel, Varman T.; Shulman, Gerald I.

2013-01-01

Hepatic insulin resistance is a principal component of type 2 diabetes, but the cellular and molecular mechanisms responsible for its pathogenesis remain unknown. Recent studies have suggested that saturated fatty acids induce hepatic insulin resistance through activation of the toll-like receptor 4 (TLR-4) receptor in the liver, which in turn transcriptionally activates hepatic ceramide synthesis leading to inhibition of insulin signaling. In this study, we demonstrate that TLR-4 receptor signaling is not directly required for saturated or unsaturated fat-induced hepatic insulin resistance in both TLR-4 antisense oligonucleotide treated and TLR-4 knockout mice, and that ceramide accumulation is not dependent on TLR-4 signaling or a primary event in hepatic steatosis and impairment of insulin signaling. Further, we show that both saturated and unsaturated fats lead to hepatic accumulation of diacylglycerols, activation of PKCε, and impairment of insulin-stimulated IRS-2 signaling. These data demonstrate that saturated fat-induced insulin resistance is independent of TLR-4 activation and ceramides. PMID:23840067

Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

PubMed

Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

2018-01-15

Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice.

PubMed

Hollander, K S; Tempel Brami, C; Konikoff, F M; Fainaru, M; Leikin-Frenkel, A

2014-07-01

Our objective was to test the contribution of dietary enrichment in essential or saturated fatty acids, in normocaloric diets, on the lipid accumulation and insulin resistance in the adult offspring in a C57Bl6/J mice model. Pregnant mothers were fed normocaloric diets containing 6% fat enriched in essential fatty acids (EFA): alpha-linolenic (ALA-18:3, n-3), linoleic (LA-18:2, n-6), or saturated fatty acids (SFA). After a washing-out period with regular diet, the offspring received a high-fat diet before euthanization. Adult mice fed maternal ALA showed lower body weight gain and lower liver fat accumulation, lower HOMA index and lower stearoyl-CoA desaturase (SCD1) activity than those fed maternal SFA. The results observed using this novel model suggest that ALA in maternal diet may have the potential to inhibit insulin resistance in adult offspring.

Comparison of Lipid Accumulation Product Index with Body Mass Index and Waist Circumference as a Predictor of Metabolic Syndrome in Indian Population.

PubMed

Ray, Lopamudra; Ravichandran, Kandasamy; Nanda, Sunil Kumar

2018-06-01

Metabolic syndrome (MetS), which confers a high risk for cardiovascular diseases, needs early diagnosis and treatment to reduce morbidity and mortality. Lipid accumulation product index has been reported to be an inexpensive marker of visceral fat and metabolic syndrome. This study aimed to evaluate lipid accumulation product index as a marker for metabolic syndrome in the Indian population where the prevalence of the condition is steadily increasing. A hospital-based, case-control study was conducted with 72 diagnosed cases of metabolic syndrome and 79 control subjects. In all the participants, body mass index (BMI) and lipid accumulation product index were calculated. The difference between cases and controls in BMI, waist circumference (WC), and lipid accumulation product index was assessed by Mann-Whitney U test/unpaired t-test. Associations of BMI, WC, and lipid accumulation product index with metabolic syndrome were compared by multiple logistic regression analysis and receiver operating characteristic analysis. BMI, WC, and lipid accumulation product index were significantly higher in metabolic syndrome (P < 0.05). Although all were independently associated with metabolic syndrome, lipid accumulation product index had the highest prediction accuracy. The parameter also had a high area under curve of 0.901 (95% confidence interval 0.85-0.95) and a high sensitivity (76.4%), specificity (91.1%), positive predictive value (88.7%), and negative predictive value (80.9%) for detection of metabolic syndrome. In the Indian population, lipid accumulation product index is a better predictor of metabolic syndrome compared to BMI and WC and should be incorporated in laboratory reports as early, accurate, and inexpensive indicator of metabolic syndrome.

Sugar versus fat: elimination of glycogen storage improves lipid accumulation in Yarrowia lipolytica.

PubMed

Bhutada, Govindprasad; Kavšcek, Martin; Ledesma-Amaro, Rodrigo; Thomas, Stéphane; Rechberger, Gerald N; Nicaud, Jean-Marc; Natter, Klaus

2017-05-01

Triacylglycerol (TAG) and glycogen are the two major metabolites for carbon storage in most eukaryotic organisms. We investigated the glycogen metabolism of the oleaginous Yarrowia lipolytica and found that this yeast accumulates up to 16% glycogen in its biomass. Assuming that elimination of glycogen synthesis would result in an improvement of lipid accumulation, we characterized and deleted the single gene coding for glycogen synthase, YlGSY1. The mutant was grown under lipogenic conditions with glucose and glycerol as substrates and we obtained up to 60% improvement in TAG accumulation compared to the wild-type strain. Additionally, YlGSY1 was deleted in a background that was already engineered for high lipid accumulation. In this obese background, TAG accumulation was also further increased. The highest lipid content of 52% was found after 3 days of cultivation in nitrogen-limited glycerol medium. Furthermore, we constructed mutants of Y. lipolytica and Saccharomyces cerevisiae that are deleted for both glycogen and TAG synthesis, demonstrating that the ability to store carbon is not essential. Overall, this work showed that glycogen synthesis is a competing pathway for TAG accumulation in oleaginous yeasts and that deletion of the glycogen synthase has beneficial effects on neutral lipid storage. © FEMS 2017.

Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation

PubMed Central

Bartels, Emil D.; Nielsen, Jan M.; Hellgren, Lars I.; Ploug, Thorkil; Nielsen, Lars B.

2009-01-01

Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease. PMID:19390571

Role of Choline Deficiency in the Fatty Liver Phenotype of Mice Fed a Low Protein, Very Low Carbohydrate Ketogenic Diet

PubMed Central

Schugar, Rebecca C.; Huang, Xiaojing; Moll, Ashley R.; Brunt, Elizabeth M.; Crawford, Peter A.

2013-01-01

Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet – weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction – were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation. PMID:24009777

Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity.

PubMed

de Melo, T S; Lima, P R; Carvalho, K M M B; Fontenele, T M; Solon, F R N; Tomé, A R; de Lemos, T L G; da Cruz Fonseca, S G; Santos, F A; Rao, V S; de Queiroz, M G R

2017-01-05

Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20-25 g (n=6-8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.

Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet.

PubMed

Schugar, Rebecca C; Huang, Xiaojing; Moll, Ashley R; Brunt, Elizabeth M; Crawford, Peter A

2013-01-01

Though widely employed for clinical intervention in obesity, metabolic syndrome, seizure disorders and other neurodegenerative diseases, the mechanisms through which low carbohydrate ketogenic diets exert their ameliorative effects still remain to be elucidated. Rodent models have been used to identify the metabolic and physiologic alterations provoked by ketogenic diets. A commonly used rodent ketogenic diet (Bio-Serv F3666) that is very high in fat (~94% kcal), very low in carbohydrate (~1% kcal), low in protein (~5% kcal), and choline restricted (~300 mg/kg) provokes robust ketosis and weight loss in mice, but through unknown mechanisms, also causes significant hepatic steatosis, inflammation, and cellular injury. To understand the independent and synergistic roles of protein restriction and choline deficiency on the pleiotropic effects of rodent ketogenic diets, we studied four custom diets that differ only in protein (5% kcal vs. 10% kcal) and choline contents (300 mg/kg vs. 5 g/kg). C57BL/6J mice maintained on the two 5% kcal protein diets induced the most significant ketoses, which was only partially diminished by choline replacement. Choline restriction in the setting of 10% kcal protein also caused moderate ketosis and hepatic fat accumulation, which were again attenuated when choline was replete. Key effects of the 5% kcal protein diet - weight loss, hepatic fat accumulation, and mitochondrial ultrastructural disarray and bioenergetic dysfunction - were mitigated by choline repletion. These studies indicate that synergistic effects of protein restriction and choline deficiency influence integrated metabolism and hepatic pathology in mice when nutritional fat content is very high, and support the consideration of dietary choline content in ketogenic diet studies in rodents to limit hepatic mitochondrial dysfunction and fat accumulation.

Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity

PubMed Central

de Melo, T.S.; Lima, P.R.; Carvalho, K.M.M.B.; Fontenele, T.M.; Solon, F.R.N.; Tomé, A.R.; de Lemos, T.L.G.; da Cruz Fonseca, S.G.; Santos, F.A.; Rao, V.S.; de Queiroz, M.G.R.

2017-01-01

Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20–25 g (n=6–8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses. PMID:28076453

Quantitative characterization of fatty liver disease using x-ray scattering

NASA Astrophysics Data System (ADS)

Elsharkawy, Wafaa B.; Elshemey, Wael M.

2013-11-01

Nonalcoholic fatty liver disease (NAFLD) is a dynamic condition in which fat abnormally accumulates within the hepatocytes. It is believed to be a marker of risk of later chronic liver diseases, such as liver cirrhosis and carcinoma. The fat content in liver biopsies determines its validity for liver transplantation. Transplantation of livers with severe NAFLD is associated with a high risk of primary non-function. Moreover, NAFLD is recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection. Unfortunately, there is a lack in a precise, reliable and reproducible method for quantification of NAFLD. This work suggests a method for the quantification of NAFLD. The method is based on the fact that fatty liver tissue would have a characteristic x-ray scattering profile with a relatively intense fat peak at a momentum transfer value of 1.1 nm-1 compared to a soft tissue peak at 1.6 nm-1. The fat content in normal and fatty liver is plotted against three profile characterization parameters (ratio of peak intensities, ratio of area under peaks and ratio of area under fat peak to total profile area) for measured and Monte Carlo simulated x-ray scattering profiles. Results show a high linear dependence (R2>0.9) of the characterization parameters on the liver fat content with a reported high correlation coefficient (>0.9) between measured and simulated data. These results indicate that the current method probably offers reliable quantification of fatty liver disease.

The effects of the aqueous extract and residue of Matcha on the antioxidant status and lipid and glucose levels in mice fed a high-fat diet.

PubMed

Xu, Ping; Ying, Le; Hong, Gaojie; Wang, Yuefei

2016-01-01

Matcha is a kind of powdered green tea produced by grinding with a stone mill. In the present study, the preventive effects of the aqueous extract (water-soluble) and residue (water-insoluble) of Matcha on the antioxidant status and lipid and glucose levels in mice fed a high-fat diet were investigated. Mice were fed seven different experimental diets for 4 weeks: a normal diet control (NC), a high-fat diet (HF), a high-fat diet with 0.025% Matcha (MLD), a high-fat diet with 0.05% Matcha (MMD), a high-fat diet with 0.075% Matcha (MHD), a high-fat diet with 0.05% Matcha aqueous extracts (ME), and a high-fat diet with 0.05% Matcha residues (MR). It was found that serum total cholesterol (TC) and triglyceride (TG) levels of the MHD group were significantly decreased compared to those of the HF group. Furthermore, in the MHD group, the level of high-density lipoprotein-cholesterol (HDL-C) was elevated, on the contrary the level of low-density lipoprotein-cholesterol (LDL-C) was suppressed. Moreover, Matcha could significantly lower the blood glucose levels, and improve the superoxide dismutase (SOD) activity and malondialdehyde (MAD) contents both in serum and liver; besides, the serum GSH-Px activity indicated that the oxidative stress caused by HF could be reversed by administration of Matcha. These findings suggest that Matcha has beneficial effects through the suppression of the blood glucose (BG) accumulation and promotion of the lipid metabolism and antioxidant activities. Moreover, the water-insoluble part of Matcha is suggested to play an important role in the suppression of diet-induced high levels of lipid and glucose.

Moderate alcohol consumption aggravates high-fat diet induced steatohepatitis in rats.

PubMed

Wang, Yan; Seitz, Helmut K; Wang, Xiang-Dong

2010-03-01

Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. Sprague-Dawley rats were first fed ad libitum with Lieber-DeCarli high-fat diet (71% energy from fat) for 6 weeks to induce NASH, as demonstrated previously. Afterwards, these rats were continuously fed with high-fat diet (HFD, 55% total energy from fat) or high fat plus alcohol diet (HFA, 55% energy from fat and 16% energy from alcohol) for an additional 4 weeks. Pathological lesions including fat accumulation and inflammatory foci in liver were examined and graded. Lipid peroxidation and apoptotic hepatocytes in the liver were assessed. The mRNA expressions of tumor necrosis factor-alpha (TNFalpha) and TNF receptor 1 (TNF-R1), Fas death receptor (Fas) and Fas ligant (FasL), IL-1beta and IL-12 were determined by real-time PCR. Protein levels of total and cleaved caspase-3, CYP2E1, Bax, and Bcl-2 were measured by western blotting. The number of hepatic inflammatory foci and apoptotic hepatocytes were significantly increased in rats fed with HFA as compared with those in HFD-fed rats. The aggravated inflammatory response and cellular apoptosis mediated by HFA were associated with elevated mRNA expression of Fas/FasL and cleaved caspase-3 protein. Although no significant differences were observed between HFD and HFA groups, the levels of lipid peroxidation, Bax and Bcl-2 protein concentration, and mRNA levels of other inflammatory cytokines were significantly higher in these 2 groups than those in the control group. These data suggest that even moderate alcohol consumption can cause more hepatic inflammation and cellular apoptosis in a pre-existing NASH condition.

[Evaluation of influence of diet content and its supplementation with chosen group of B vitamins on lipids and lipoprtoteins concentration in female rat serum].

PubMed

Friedrich, Mariola; Goluch-Koniuszy, Zuzanna

2009-01-01

The influence of diet content and its supplementation with chosen group of B vitamins on the intake of feeding stuff increase, changes of body mass, accumulation of fat tissue, lipids and lipoproteins concentration in the blood of female rats were under research. The animals, aged 5 months, were divided into three groups (8 persons each) and fed ad libitum with granulated Labofeed B type mix. Group I with the basic mix containing among other things whole grain, Group II with a modified mix, where whole grain was replaced by wheat flour and saccharose and Group III with modified mix supplemented in excess with chosen vitamins of B group. This experiment took 6 weeks during which the amount of consumed feed was currently evaluated, and the body mass was controlled weekly. After finishing the experiment in the obtained serum the concentration of triacylglycerols, complete cholesterol with enzyme method and the content of cholesterol fractions with electrophoretic separation method were determined. Analysis of fat content in muscles and livers was conducted and the amount of round the bodily organ fat was determined. It was ascertained that change of the content of the feed and its supplementation with the chosen B group vitamins did not influence in a substantial way its intake and the increase of body mass, however it had influenced substantially, in animals fed with the modified feed the accumulation of round the organ fat and in supplemented the intramuscular fat. Analysis of the results enabled the ascertainment that the diet supplementation with chosen ingredients of the B group vitamins corrects the negative effect of accumulation of the visceral fat tissue as a result of the change of its contents, caused substantial increase in the concentration of triacylglycerols, complete cholesterol and its fractions VLDL- and LDL- with simultaneous decrease of the concentration of cholesterol HDL- fractions.

Corticosterone administration and high-energy feed results in enhanced fat accumulation and insulin resistance in broiler chickens.

PubMed

Yuan, L; Lin, H; Jiang, K J; Jiao, H C; Song, Z G

2008-07-01

1. Two experiments were conducted to investigate the effects of exogenous corticosterone administration (30 mg/kg diet) and dietary energy level on feed or energy intake and fat deposition in broiler chickens of 1 and 4 weeks of age. 2. Corticosterone treatment significantly suppressed body weight (BW) gain and reduced feed and caloric efficiencies. The retarded growth may conceal the stimulatory effect of corticosterone on feed consumption or metabolisable energy (ME) intake. A high-energy diet may increase energy intake and partially alleviate the suppressing effect of corticosterone on growth of broilers. 3. Corticosterone administration promoted the conservation of energy stores as fat at both abdominal and subcutaneous sites and this process occurred regardless of dietary energy level in ad libitum feeding status. A high-energy diet increased fat accumulation and showed no significant interaction with corticosterone treatment. 4. The suppressed development of breast and thigh muscles by corticosterone treatment was observed only in 1-week-old chickens fed on the low-energy diet. In contrast, the yield of breast muscle but not thigh muscle was significantly decreased by corticosterone in 4-week-old chickens, suggesting that the tissue specificity to corticosterone challenge is age dependent. 5. Plasma concentrations of glucose, insulin, triglyceride, non-esterified fatty acids (NEFA) and very low density lipoprotein were increased by corticosterone treatment regardless of diet treatment. A high-energy diet increased plasma levels of NEFA and resulted in hyperinsulinism in 4-week-old chickens but not in 1-week-old chickens. 6. Lipoprotein lipase (LPL) activities in adipose tissues may have been up-regulated by corticosterone treatment and showed tissue specificity. The increased LPL activities at ad libitum feeding status were not necessarily linked with the increased fat accumulation in corticosterone challenged chickens. 7. Corticosterone resulted in augmented energy consumption and altered energy redistribution toward lipid deposition. The induced insulin resistance and enhanced hepatic de novo lipogenesis by corticosterone are likely to be responsible for the increased fat deposition.

Drinking water boosts food intake rate, body mass increase and fat accumulation in migratory blackcaps (Sylvia atricapilla).

PubMed

Tsurim, Ido; Sapir, Nir; Belmaker, Jonathan; Shanni, Itai; Izhaki, Ido; Wojciechowski, Michał S; Karasov, William H; Pinshow, Berry

2008-05-01

Fat accumulation by blackcaps (Sylvia atricapilla) is a prerequisite for successful migratory flight in the autumn and has recently been determined to be constrained by availability of drinking water. Birds staging in a fruit-rich Pistacia atlantica plantation that had access to water increased their body mass and fat reserves both faster and to a greater extent than birds deprived of water. We conducted a series of laboratory experiments on birds captured during the autumn migration period in which we tested the hypotheses that drinking water increases food use by easing limitations on the birds' dietary choices and, consequently, feeding and food processing rates, and that the availability of drinking water leads to improved digestion and, therefore, to higher apparent metabolizable energy. Blackcaps were trapped in autumn in the Northern Negev Desert, Israel and transferred to individual cages in the laboratory. Birds were provided with P. atlantica fruit and mealworms, and had either free access to water (controls) or were water-deprived. In experiment 1, in which mealworm availability was restricted, water-deprived birds had a fourfold lower fruit and energy intake rates and, consequently, gained less fat and total mass than control birds. Water availability did not affect food metabolizability. In experiment 2, in which mealworms were provided ad libitum, water availability influenced the birds' diet: water-restricted birds ate more mealworms, while control birds consumed mainly P. atlantica fruit. Further, in experiment 2, fat and mass gain did not differ between the two treatment groups. We conclude that water availability may have important consequences for fat accumulation in migrating birds while they fatten at stopover sites, especially when water-rich food is scarce. Restricted water availability may also impede the blackcap's dietary shift from insectivory to frugivory, a shift probably necessary for successful pre-migratory fattening.

The R148.3 Gene Modulates Caenorhabditis elegans Lifespan and Fat Metabolism

PubMed Central

Roy-Bellavance, Catherine; Grants, Jennifer M.; Miard, Stéphanie; Lee, Kayoung; Rondeau, Évelyne; Guillemette, Chantal; Simard, Martin J.; Taubert, Stefan; Picard, Frédéric

2017-01-01

Despite many advances, the molecular links between energy metabolism and longevity are not well understood. Here, we have used the nematode model Caenorhabditis elegans to study the role of the yet-uncharacterized gene R148.3 in fat accumulation and lifespan. In wild-type worms, a R148.3p::GFP reporter showed enhanced expression throughout life in the pharynx, in neurons, and in muscles. Functionally, a protein fusing a predicted 22 amino acid N-terminal signal sequence (SS) of R148.3 to mCherry displayed robust accumulation in coelomyocytes, indicating that R148.3 is a secreted protein. Systematic depletion of R148.3 by RNA interference (RNAi) at L1 but not at young-adult stage enhanced triglyceride accumulation, which was associated with increased food uptake and lower expression of genes involved in lipid oxidation. However, RNAi of R148.3 at both L1 and young-adult stages robustly diminished mean and maximal lifespan of wild-type worms, and also abolished the long-lived phenotypes of eat-2 and daf-2/InsR mutants. Based on these data, we propose that R148.3 is an SS that modulates fat mass and longevity in an independent manner. PMID:28620088

Low-carbohydrate diets reduce lipid accumulation and arterial inflammation in guinea pigs fed a high-cholesterol diet.

PubMed

Leite, Jose O; DeOgburn, Ryan; Ratliff, Joseph; Su, Randy; Smyth, Joan A; Volek, Jeff S; McGrane, Mary M; Dardik, Alan; Fernandez, Maria Luz

2010-04-01

Low-carbohydrate diets (LCD) efficiently induce weight loss and favorably affect plasma lipids, however, the effect of LCD on atherosclerosis is still argued. To evaluate the effect of LCD on the prevention of atherosclerosis. Twenty guinea pigs were fed either a LCD or a low-fat diet (LFD) in combination with high-cholesterol (0.25g/100g) for 12 weeks. The percentage energy of macronutrient distribution was 10:65:25 for carbohydrate:fat:protein for the LCD, and 55:20:25 for the LFD. Plasma lipids were measured using colorimetric assays. Plasma and aortic oxidized (oxLDL) were quantified using ELISA methods. Inflammatory cytokines were measured in aortic homogenates using an immunoassay. H&E stained sections of aortic sinus and Schultz stained sections of carotid arteries were examined. LDL cholesterol was lower in the LCD compared to the LFD group (71.9+/-34.8 vs. 81.7+/-26.9mg/dL; p=0.039). Aortic cholesterol was also lower in the LCD (4.98+/-1.3mg/g) compared to the LFD group (6.68+/-2.0mg/g); p<0.05. The Schultz staining method confirmed less aortic cholesterol accumulation in the LCD group. Plasma oxLDL did not differ between groups, however, aortic oxLDL was 61% lower in the LCD compared to the LFD group (p=0.045). There was a positive correlation (r=0.63, p=0.03) between oxLDL and cholesterol concentration in the aorta of LFD group, which was not observed in LCD group (r=-0.05, p=0.96). Inflammatory markers were reduced in guinea pigs from the LCD group (p<0.05) and they were correlated with the decreases in oxLDL in aorta. These results suggest that LCD not only decreases lipid deposition, but also prevents the accumulation of oxLDL and reduces inflammatory cytokines within the arterial wall and may prevent atherosclerosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

The effects of chronic testosterone administration on body weight, food intake, and fat weight were age-dependent.

PubMed

Iwasa, Takeshi; Matsuzaki, Toshiya; Yiliyasi, Mayila; Yano, Kiyohito; Irahara, Minoru

2017-11-01

Previously, we showed that chronic testosterone administration increased body weight (BW) and food intake (FI), but did not alter fat weight, in young female rats. To examine our hypothesis that the effects of androgens on BW, FI and body composition might be age-dependent, the effects of chronic testosterone administration were evaluated in rats of different ages; i.e., young and middle-aged rats. Although chronic testosterone administration increased BW gain, FI, and feed efficiency in both young and middle-aged rats, it increased visceral fat weight in middle-aged rats, but not in young rats. Therefore, it is possible that testosterone promotes the conversion of energy to adipose tissue and exacerbates fat accumulation in older individuals. In addition, although the administration of testosterone increased the serum leptin level, it did not alter hypothalamic neuropeptide Y mRNA expression in middle-aged rats. On the contrary, the administration of testosterone did not affect the serum leptin levels of young rats. Thus, testosterone might induce hypothalamic leptin resistance, which could lead to fat accumulation in older individuals. Testosterone might disrupt the mechanisms that protect against adiposity and hyperphagia and represent a risk factor for excessive body weight and obesity, especially in older females. Copyright © 2017 Elsevier Inc. All rights reserved.

Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

PubMed

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

2012-03-01

The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities. Copyright © 2010 Elsevier GmbH. All rights reserved.

Zanthoxylum piperitum DC ethanol extract suppresses fat accumulation in adipocytes and high fat diet-induced obese mice by regulating adipogenesis.

PubMed

Gwon, So Young; Ahn, Ji Yun; Kim, Tae Wan; Ha, Tae Youl

2012-01-01

This study was conducted to determine the anti-obesity effects of Zanthoxylum piperitum DC fruit ethanol extract (ZPE) in 3T3-L1 adipocytes and obese mice fed a high-fat diet. We evaluated the influence of the addition of ZPE to a high-fat diet on body weight, adipose tissue weight, serum and hepatic lipids in C57BL/6 mice. In addition, adipogenic gene expression was determined by Western blot and real-time reverse transcription-PCR analysis. We assessed the effect of ZPE on 3T3-L1 preadipocyte differentiation. ZPE reduced weight gain, white adipose tissue mass, and serum triglyceride and cholesterol levels (p<0.05) in high-fat diet-fed C57BL/6 mice. ZPE decreased lipid accumulation and PPARγ, C/EBPα, SREBP-1, and FAS protein and mRNA levels in the liver. ZPE inhibited in vitro adipocyte differentiation in a dose-dependent manner and significantly attenuated adipogenic transcription factors, such as PPARγ, C/EBPα, and SREBP-1 in 3T3L1 cells. These findings suggest that Z. piperitum DC exerts an anti-obesity effect by inhibiting adipogenesis through the downregulation of genes involved in the adipogenesis pathway.

Enterobacter cloacae administration induces hepatic damage and subcutaneous fat accumulation in high-fat diet fed mice.

PubMed

Keskitalo, Anniina; Munukka, Eveliina; Toivonen, Raine; Hollmén, Maija; Kainulainen, Heikki; Huovinen, Pentti; Jalkanen, Sirpa; Pekkala, Satu

2018-01-01

Accumulating evidence indicates that gut microbiota plays a significant role in obesity, insulin resistance and associated liver disorders. Family Enterobacteriaceae and especially Enterobacter cloacae strain B29 have been previously linked to obesity and hepatic damage. The underlying mechanisms, however, remain unclear. Therefore, we comprehensively examined the effects of E. cloacae subsp. cloacae (ATCC® 13047™) administration on host metabolism of mice fed with high-fat diet (HFD). C57BL/6N mice were randomly divided into HFD control, chow control, and E. cloacae treatment groups. The E. cloacae treatment group received live bacterial cells in PBS intragastrically twice a week, every other week for 13 weeks. Both control groups received PBS intragastrically. After the 13-week treatment period, the mice were sacrificed for gene and protein expression and functional analyses. Our results show that E. cloacae administration increased subcutaneous fat mass and the relative proportion of hypertrophic adipocytes. Both subcutaneous and visceral fat had signs of decreased insulin signaling and elevated lipolysis that was reflected in higher serum glycerol levels. In addition, E. cloacae -treated mice had significantly higher hepatic AST and AST/ALT ratio, and their liver histology indicated fibrosis, demonstrating that E. cloacae subsp. cloacae administration promotes hepatic damage in HFD fed mice.

Retraining Attentional Bias to Unhealthy Food Cues

DTIC Science & Technology

2013-06-26

Obesity ’Overweight’ and ’Obese’ describe levels of body fat (i.e., adiposity) that exceed ranges of weight that are considered healthy for a given...to an accumulation of excess body fat . Obesity is further divided into Class I (30.0 - 34.9 kg/m2) and Class II obesity (35.0 - 39.9 kg/m2) and Class...weight gain through excessive consumption of palatable foods that contain large amounts of fat and sugar. Processed foods such as those from fast food

Chromium downregulates the expression of Acetyl CoA Carboxylase 1 gene in lipogenic tissues of domestic goats: a potential strategy for meat quality improvement.

PubMed

Najafpanah, Mohammad Javad; Sadeghi, Mostafa; Zali, Abolfazl; Moradi-Shahrebabak, Hossein; Mousapour, Hojatollah

2014-06-15

Acetyl CoA Carboxylase 1 (ACC1) is a biotin-dependent enzyme that catalyzes the carboxylation of Acetyl CoA to form Malonyl CoA, the key intermediate metabolite in fatty acid synthesis. In this study, the mRNA expression of the ACC1 gene was evaluated in four different tissues (liver, visceral fat, subcutaneous fat, and longissimus muscle) of the domestic goat (Capra hircus) kids feeding on four different levels of trivalent chromium (0, 0.5, 1, and 1.5mg/day) as food supplementation. RT-qPCR technique was used for expression analyses and heat shock protein 90 gene (HSP-90) was considered as reference gene for data normalization. Our results revealed that 1.5mg/day chromium significantly reduced the expression of the ACC1 gene in liver, visceral fat, and subcutaneous fat tissues, but not in longissimus muscles (P<0.05). We measured some phenotypic traits of kid's carcasses to detect their probable correlations with chromium-mediated downregulation of ACC1 expression. Interestingly, changes in ACC1 expression were accompanied with decreased accumulation of fats in adipose tissues such that the subcutaneous fat thickness and heart fat percentage decreased in kids feeding on chromium. By contrast, chromium supplemented kids showed higher percentage of muscles despite the fact that their total body weight did not differ from that of non-supplemented kids. Our study suggests that trivalent chromium alters the direction of energy accumulation towards muscles rather than fats and provides insights into application of chromium supplementation as a useful strategy for improvement of meat quality in domestic animals. Copyright © 2014 Elsevier B.V. All rights reserved.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

PubMed

Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

2017-09-30

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Long-term dietary effects on substrate selection and muscle fiber type in very-long-chain acyl-CoA dehydrogenase deficient (VLCAD(-/-)) mice.

PubMed

Tucci, Sara; Pearson, Sonja; Herebian, Diran; Spiekerkoetter, Ute

2013-04-01

Dietary fat restriction and increased carbohydrate intake are part of treatment in very-long-chain acyl-CoA dehydrogenase (VLCAD)-deficiency, the most common defect of long-chain fatty acid oxidation. The long-term impact of these interventions is unknown. We characterized here the effects of a fat-reduced, carbohydrate-enriched diet and an increased fat intake on energy metabolism in a mouse model of VLCAD-deficiency. Wild-type and VLCAD(-/-) mice were fed one year either with a normal (5.1%), a high fat (10.6%) or a low-fat, carbohydrate-enriched (2.6%) diet. Dietary effects on genes involved in lipogenesis, energy homeostasis and substrate selection were quantified by real-time-PCR. Acylcarnitines as sign of impaired energy production were determined in dried blood spots and tissues. White skeletal muscle was analyzed for muscle fiber type as well as for glycogen and triglyceride content. Both dietary modifications induced enhanced triacylglyceride accumulation in skeletal muscle and inhibition of glucose oxidation. This was accompanied by an up-regulation of genes coding for oxidative muscle fiber type I and a marked accumulation of acylcarnitines, especially prominent in the heart (164±2.8 in VLCAD(-/-) vs. 82.3±2.1 in WT μmol/mg) under a low-fat, carbohydrate-enriched diet. We demonstrate here that both dietary interventions with respect to the fat content of the diet reverse endogenous compensatory mechanisms in muscle that have evolved in VLCAD(-/-) mice resulting in pronounced energy deficiency. In particular, the low-fat carbohydrate-enriched diet was not effective in the long term. Further experiments are necessary to define the optimal energy provision for fatty acid oxidation defects. Copyright © 2013 Elsevier B.V. All rights reserved.

Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

PubMed

Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

2018-02-01

The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

Effects of Polysaccharide Elicitors from Endophytic Fusarium oxysporum Fat9 on the Growth, Flavonoid Accumulation and Antioxidant Property of Fagopyrum tataricum Sprout Cultures.

PubMed

Zhong, Lingyun; Niu, Bei; Tang, Lin; Chen, Fang; Zhao, Gang; Zhao, Jianglin

2016-11-25

The purpose of this study was to evaluate the effects of four different fungal polysaccharides, named water-extracted mycelia polysaccharide (WPS), sodium hydroxide-extracted mycelia polysaccharide (SPS), hydrochloric-extracted mycelia polysaccharide (APS), and exo-polysaccharide (EPS) obtained from the endophytic Fusarium oxysporum Fat9 on the sprout growth, flavonoid accumulation, and antioxidant capacity of tartary buckwheat. Without visible changes in the appearance of the sprouts, the exogenous polysaccharide elicitors strongly stimulated sprout growth and flavonoid production, and the stimulation effect was closely related with the polysaccharide (PS) species and its treatment dosage. With application of 200 mg/L of EPS, 200 mg/L of APS, 150 mg/L of WPS, or 100 mg/L of SPS, the total rutin and quercetin yields of buckwheat sprouts were significantly increased to 41.70 mg/(100 sprouts), 41.52 mg/(100 sprouts), 35.88 mg/(100 sprouts), and 32.95 mg/(100 sprouts), respectively. This was about 1.11 to 1.40-fold compared to the control culture of 31.40 mg/(100 sprouts). Moreover, the antioxidant capacity of tartary buckwheat sprouts was also enhanced after treatment with the four PS elicitors. Furthermore, the present study revealed the polysaccharide elicitation that caused the accumulation of functional flavonoid by stimulating the phenylpropanoid pathway. The application of beneficial fungal polysaccharide elicitors may be an effective approach to improve the nutritional and functional characteristics of tartary buckwheat sprouts.

Maturation of Acorns of Cherrybark, Water, and Willow Oaks

Treesearch

F. T. Bonner

1974-01-01

Acorns of cherrybark, water, and willow oaks grew slowly but steadily in July and August and reached maximum size in September, when fats and carbohydrates, the major storage foods, accumulated rapidly. At physiological maturity in late October or early November, crude fat levels were 15 to 20 percent of seed dry weight and carbohydrates totaled 25 percent.

Mouse fat storage-inducing transmembrane protein 2 (FIT2) promotes lipid droplet accumulation in plants

USDA-ARS?s Scientific Manuscript database

Fat Storage-Inducing Transmembrane protein 2 (FIT2) is an endoplasmic reticulum (ER)-localized protein that plays an important role in lipid droplet (LD) formation in animal cells. However, no obvious homologue of FIT2 is found in plants. Here, we tested the function of FIT2 in plant cells by ectopi...

Effects of Endogenous Androgens and Abdominal Fat Distribution on the Interrelationship Between Insulin and Non-Insulin-Mediated Glucose Uptake in Females

PubMed Central

Ezeh, Uche; Pall, Marita; Mathur, Ruchi; Dey, Damini; Berman, Daniel; Chen, Ida Y.; Dumesic, Daniel A.

2013-01-01

Background: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance. Glucose disposal occurs via noninsulin-mediated glucose uptake (NIMGU) and insulin-mediated glucose uptake (IMGU). It is unknown whether in PCOS NIMGU increases to compensate for declining IMGU and whether androgens and fat distribution influence this relationship. Objectives: The objective of the study was to compare in women with PCOS and controls the interrelationship between NIMGU [ie, glucose effectiveness (Sg)] and IMGU [ie, the insulin sensitivity index (Si)] and the role of androgens and fat distribution. Participants: Twenty-eight PCOS (by National Institutes of Health 1990 criteria) and 28 control (age, race, and body mass index matched) women were prospectively studied. A subset of 16 PCOS subjects and 16 matched controls also underwent abdominal computed tomography. Main Outcome Measures: Glucose disposal (by a frequently sampled iv glucose tolerance test), circulating androgens, and abdominal fat distribution [by waist to hip ratio and visceral (VAT) and sc (SAT) adipose tissue content] were measured. Results: PCOS women had lower mean Si and similar Sg and abdominal fat distribution compared with controls. PCOS women with Si below the PCOS median (more insulin resistant) had a lower mean Sg than controls with Si above the control median (more insulin sensitive). In PCOS only, body mass index, free T, modified Ferriman-Gallwey score, and waist to hip ratio independently predicted Sg, whereas Si did not. In PCOS, VAT and SAT independently and negatively predicted Si and Sg, respectively. Conclusion: The decreased IMGU in PCOS is not accompanied by a compensatory increase in NIMGU or associated with excessive VAT accumulation. Increased general obesity, SAT, and hyperandrogenism are primary predictors of the deterioration of NIMGU in PCOS. PMID:23450052

Anti-Obesity Effects of Aster spathulifolius Extract in High-Fat Diet-Induced Obese Rats.

PubMed

Kim, Sa-Jic; Bang, Chae-Young; Guo, Yuan-Ri; Choung, Se-Young

2016-04-01

The aim of this study was to investigate the anti-obesity and antihyperlipidemic efficacy and molecular mechanisms of Aster spathulifolius Maxim extract (ASE) in rats with high-fat diet (HFD)-induced obesity. Rats were separately fed a normal diet or a HFD for 8 weeks, then they were treated with ASE (62.5, 125, or 250 mg/kg) for another 4.5 weeks. The ASE supplementation significantly lowered body weight gain, visceral fat pad weights, serum lipid levels, as well as hepatic lipid levels in HFD-induced obese rats. Histological analysis showed that the ASE-treated group showed lowered numbers of lipid droplets and smaller size of adipocytes compared to the HFD group. To understand the mechanism of action of ASE, the expression of genes and proteins involved in obesity were measured in liver and skeletal muscle. The expression of fatty acid oxidation and thermogenesis-related genes (e.g., PPAR-α, ACO, CPT1, UCP2, and UCP3) of HFD-induced obese rats were increased by ASE treatment. On the other hand, ASE treatment resulted in decreased expression of fat intake-related gene ACC2 and lipogenesis-related genes (e.g., SREBP-1c, ACC1, FAS, SCD1, GPATR, AGPAT, and DGAT). Furthermore, ASE treatment increased the level of phosphorylated AMPKα in obese rats. Similarly, the level of phosphorylated ACC, a target protein of AMPKα in ASE groups, was increased by ASE treatment compared with the HFD group. These results suggest that ASE attenuated visceral fat accumulation and improved hyperlipidemia in HFD-induced obese rats by increasing lipid metabolism through the regulation of AMPK activity and the expression of genes and proteins involved in lipolysis and lipogenesis.

Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats.

PubMed

Shidfar, Farzad; Faghihi, Amirhosein; Amiri, Hamid Lorvand; Mousavi, Seyedeh Neda

2018-01-01

Studies have shown that zinc and selenium deficiency is common in nonalcoholic fatty liver disease (NAFLD). However, the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD are not clear enough. The aim of this study was to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on NAFLD prognosis. Forty male Sprague-Dawley rats (197±4 g) were randomly assigned to 4 dietary groups: normal-fat diet (NFD; receiving 9% of calories as fat), high-fat diet (HFD; receiving 82% of calories as fat), supplementation before disease progression (S+HFD), and supplementation after disease progression (HFD+S). The diets were implemented over a 20-week period in all the groups. Biochemical and histologic parameters were compared between the 4 groups, and between-group comparisons were also carried out. There were significant differences in the average food dietary intake (P<0.001), weight (P<0.001), fasting blood sugar (P=0.005), triglyceride (P<0.001), total cholesterol (P<0.001), low-density lipoprotein cholesterol (P=0.002), high-density lipoprotein cholesterol (P=0.001), alanine aminotransferase (P<0.001), and aspartate aminotransferase (P<0.001) between the 4 dietary groups. Serum triglyceride and total cholesterol were significantly lower in the HFD+S Group than in the S+HFD Group (P<0.001 and P=0.003, respectively). Fat accumulation was significantly reduced in the HFD+S Group (P<0.001). Zinc and selenium co-supplementation after disease progression improved biochemical and histologic parameters in an experimental model of NAFLD.

Evaluation of safety and efficacy of 980-nm diode laser-assisted lipolysis versus traditional liposuction for submental rejuvenation: A randomized clinical trial.

PubMed

Valizadeh, Neda; Jalaly, Niloofar Y; Zarghampour, Manijeh; Barikbin, Behrooz; Haghighatkhah, Hamid Reza

2016-01-01

Submental fat accumulation and skin laxity is a frequent concern of cosmetic patients. The aim of this randomized prospective controlled clinical trial was to compare the efficacy and safety of laser-assisted lipolysis and liposuction in the submental rejuvenation. Thirty-six female adults were enrolled in this clinical trial and were categorized into two groups: group 1 underwent 980-nm diode laser with the power of 6-8 W and group 2 underwent traditional liposuction. Patients were evaluated with ultrasonography 2 weeks and 2 months after the procedures. Ultrasonographic evaluation reported the significant reduction of fat thickness in each group compared with the baseline (p value < 0.001). At the 2 weeks and 2 months follow-up visit, fat thickness reduction was significantly higher in the lipolysis group (p value < 0.05). Overall patients' satisfaction in lipolysis group was higher than liposuction with 11 (61%) of lipolysis patients being very satisfied in contrast to 10 (55.5%) of liposuction patients reporting "dissatisfied or neutral" results. Laser-assisted lipolysis using 980-nm diode is approved to be safe and effective for skin tightening and rejuvenation of the submental area and seems to be a better option than traditional techniques for treatment of this cosmetic problem.

Parkin is a lipid-responsive regulator of fat uptake in mice and mutant human cells

PubMed Central

Kim, Kye-Young; Stevens, Mark V.; Akter, M. Hasina; Rusk, Sarah E.; Huang, Robert J.; Cohen, Alexandra; Noguchi, Audrey; Springer, Danielle; Bocharov, Alexander V.; Eggerman, Tomas L.; Suen, Der-Fen; Youle, Richard J.; Amar, Marcelo; Remaley, Alan T.; Sack, Michael N.

2011-01-01

It has long been hypothesized that abnormalities in lipid biology contribute to degenerative brain diseases. Consistent with this, emerging epidemiologic evidence links lipid alterations with Parkinson disease (PD), and disruption of lipid metabolism has been found to predispose to α-synuclein toxicity. We therefore investigated whether Parkin, an E3 ubiquitin ligase found to be defective in patients with early onset PD, regulates systemic lipid metabolism. We perturbed lipid levels by exposing Parkin+/+ and Parkin–/– mice to a high-fat and -cholesterol diet (HFD). Parkin–/– mice resisted weight gain, steatohepatitis, and insulin resistance. In wild-type mice, the HFD markedly increased hepatic Parkin levels in parallel with lipid transport proteins, including CD36, Sr-B1, and FABP. These lipid transport proteins were not induced in Parkin–/– mice. The role of Parkin in fat uptake was confirmed by increased oleate accumulation in hepatocytes overexpressing Parkin and decreased uptake in Parkin–/– mouse embryonic fibroblasts and patient cells harboring complex heterozygous mutations in the Parkin-encoding gene PARK2. Parkin conferred this effect, in part, via ubiquitin-mediated stabilization of the lipid transporter CD36. Reconstitution of Parkin restored hepatic fat uptake and CD36 levels in Parkin–/– mice, and Parkin augmented fat accumulation during adipocyte differentiation. These results demonstrate that Parkin is regulated in a lipid-dependent manner and modulates systemic fat uptake via ubiquitin ligase–dependent effects. Whether this metabolic regulation contributes to premature Parkinsonism warrants investigation. PMID:21865652

C. elegans Major Fats Are Stored in Vesicles Distinct from Lysosome-Related Organelles

PubMed Central

O’Rourke, Eyleen J.; Soukas, Alexander A.; Carr, Christopher E.; Ruvkun, Gary

2010-01-01

SUMMARY Genetic conservation allows ancient features of fat storage endocrine pathways to be explored in C. elegans. Multiple studies have used Nile red or BODIPY-labeled fatty acids to identify regulators of fat mass. When mixed with their food, E. coli bacteria, Nile red, and BODIPY-labeled fatty acids stain multiple spherical cellular structures in the C. elegans major fat storage organ, the intestine. However, here we demonstrate that, in the conditions previously reported, the lysosome-related organelles stained by Nile red and BODIPY-labeled fatty acids are not the C. elegans major fat storage compartment. We show that the major fat stores are contained in a distinct cellular compartment that is not stained by Nile red. Using biochemical assays, we validate oil red O staining as a method to assess major fat stores in C. elegans, allowing for efficient and accurate genetic and functional genomic screens for genes that control fat accumulation at the organismal level. PMID:19883620

Transcript levels of genes implicated in steroidogenesis in the testes and fat tissue in relation to androstenone accumulation in fat of pubertal pigs.

PubMed

Robic, A; Feve, K; Riquet, J; Prunier, A

2016-10-01

The present study was performed to measure messenger RNA levels of steroidogenic enzymes in testes and fat tissue and determine whether they are related to fat androstenone level. Real-time polymerase chain reaction experiments were performed on 26 testes and 12 adipose tissue samples from pubertal boars using 21 genes. The absence of significant correlations between fat androstenone and the transcriptional activity of the SRD5A2 and SRD5A3 genes but the high correlation coefficient with that of the SRD5A1 gene (r = 0.62, P < 0.05) suggests that the enzyme coded by SRD5A1 is mainly responsible for the last step of androstenone synthesis. The testicular transcriptional activities of CYP17, CYP11A1, CYP19A, AKR1C-pig6, SRD5A1, LHCGR, and AR were significantly correlated. Only transcriptional levels of CYP17, CYP11A1, CYP19A, SRD5A1, and AKR1C-pig6 were correlated with the fat concentration of androstenone (0.57 < r < 0.70, P < 0.05) confirming that the amount of androstenone stored in fat is related to the production in testes of androstenone and more generally to all sex steroids. Altogether, our data are in favor of a preponderant role of AKR1C-pig6 instead of HSD17B3 for testicular synthesis of steroids. Concerning fat tissue, our data do not support a significant de novo biosynthesis of steroids in porcine adipose tissues. The presence of transcripts coding for steroid enzymes, especially those of AKR1C-pig6, suggests that steroids can be transformed. None of transcript abundance was related to androstenone accumulation (P > 0.1). Therefore, steroids synthesized elsewhere can be transformed in fat tissue but synthesis of androstenone is unlikely. Copyright © 2016 Elsevier Inc. All rights reserved.

Decursin, an active compound isolated from Angelica gigas, inhibits fat accumulation, reduces adipocytokine secretion and improves glucose tolerance in mice fed a high-fat diet.

PubMed

Hwang, Jin-Taek; Kim, Sung Hee; Hur, Haeng Jeon; Kim, Hyun Jin; Park, Jae Ho; Sung, Mi Jeong; Yang, Hye Jeong; Ryu, Shi Yong; Kim, Young Sup; Cha, Mi Ran; Kim, Myung Sunny; Kwon, Dae Young

2012-05-01

Decursin (De), an active component of Angelica gigas, is known to exert anticancer and neuroprotective effects. However, its antiobesity and antidiabetic potential has not yet been investigated. This study evaluated the antiobesity effect of decursin, particularly focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. Decursin treatment resulted in the inhibition of adipocyte differentiation and the expression of fatty acid synthase. The study further investigated these antiobesity effects using mice fed a normal diet (ND), a high-fat diet (HFD) and a HFD plus decursin 200 mg/kg diet (HFD + De) for 7 weeks. Mice administered HFD plus decursin showed a drastic decrease in weight gain, triglyceride content, total cholesterol content and fat size compared with those that received the HFD alone; this was observed despite similar quantities of total food intake. Furthermore, decursin improved glucose tolerance in mice fed a HFD. Finally, administration of decursin along with the HFD significantly reduced the secretion of HFD-induced adipocytokines such as leptin, resistin, IL-6 and MCP-1. These results suggest that decursin might be useful for the treatment of obesity and diabetes. Copyright © 2011 John Wiley & Sons, Ltd.

Transcriptome analysis revealed anti-obesity effects of the Sodium Alginate in high-fat diet -induced obese mice.

PubMed

Wang, Xiong; Liu, Fang; Gao, Yuan; Xue, Chang-Hu; Li, Robert W; Tang, Qing-Juan

2018-04-10

Human obesity and overweight, caused by accumulated of fat, is the most commonly phenomenon from all over the world, especially in Western countries and Chinese mainland during the past three decades. Sodium Alginate, a polysaccharide extracted from brown seaweeds, has been proved its strong ability on body weight loss and anti-inflammatory response. However, no studies have been explored the effects of Sodium Alginate on colonic transcriptome, especially in obese individuals. Therefore, the current study was designed to detect whether Sodium Alginate could remit obesity and ease chronic metabolism disease through strengthening the bio-functionality of the lower intestine, particularly in colon. The data showed after Sodium Alginate gavaged for four weeks, the body weight, fat accumulation, triglyceride and total cholesterol were ameliorated in high fat diet induced obese mice. Sodium Alginate also improved the blood glucose level and lipopolysaccharides in serum. Furthermore, data from RNA sequence indicated that there were significantly changes in several genes, which involved in lipid metabolism and carbohydrate metabolism. In conclusion, these results suggested that Sodium Alginate could effectively suppress obesity and obesity related metabolic syndromes, due to the colonic transcriptome changes. Copyright © 2018. Published by Elsevier B.V.

Excess weight, arterial pressure and physical activity in commuting to school: correlations.

PubMed

Silva, Kelly S; Lopes, Adair S

2008-08-01

The prevalence of obesity and elevated arterial pressure (AP) has increased in children and adolescents, whereas physical activity has decreased. To identify and correlate excess weight, body fat and elevated AP among active and passive students with the way they commute to school. One thousand five hundred and seventy students aged 7 to 12 years participated in the study conducted in João Pessoa, state of Paraíba. Students completed a questionnaire about the way they commuted to school (active = walking/biking or passive = by car/motorcycle/bus) and the time spent traveling to school. Excess weight was determined by BMI > or =25 kg/m(2), excess body fat as > or =85th percentile for tricipital fold measurement, and high AP as > or =90th percentile. Chi-square test and Poisson's regression were used for the analysis. Active commuting was associated with a lower prevalence of excess weight and body fat as compared to passive commuting (p<0.05). The prevalence ratio (PR) of excess weight was associated with excess body fat (Male: PR= 6.45 95%CI= 4.55-9.14; Female: PR= 4.10 95%CI= 3.09-5.45), elevated SAP [Systolic Arterial Pressure] (Male: PR= 1.99 95%CI= 1.30-3.06; Female: PR= 2.09 95%CI= 1.45-3.01), and elevated DAP [Diastolic Arterial Pressure] in girls (PR = 1.96 95%CI= 1.41-2.75). No association with active commuting was observed (p>0.05) Passive commuting to school showed a correlation with excess weight and body fat but not with elevated AP. Excess weight was associated with excessive body fat and elevated AP. Excess weight should be prevented as a way to avoid fat accumulation and AP elevation.

Modification of the fatty acid composition of an obesogenic diet improves the maternal and placental metabolic environment in obese pregnant mice.

PubMed

Gimpfl, Martina; Rozman, Jan; Dahlhoff, Maik; Kübeck, Raphaela; Blutke, Andreas; Rathkolb, Birgit; Klingenspor, Martin; Hrabě de Angelis, Martin; Öner-Sieben, Soner; Seibt, Annette; Roscher, Adelbert A; Wolf, Eckhard; Ensenauer, Regina

2017-06-01

Peri-conceptional exposure to maternal obesogenic nutrition is associated with in utero programming of later-life overweight and metabolic disease in the offspring. We aimed to investigate whether dietary intervention with a modified fatty acid quality in an obesogenic high-calorie (HC) diet during the preconception and gestational phases can improve unfavourable effects of an adipogenic maternal environment. In NMRI mice, peri-conceptional and gestational obesity was induced by feeding a HC diet (controls), and they were compared with dams on a fat-modified (Fat-mod) HC diet of the same energy content but enriched with medium-chain fatty acids (MCFAs) and adjusted to a decreased ratio of n-6 to n-3 long-chain polyunsaturated fatty acids (LC-PUFAs). Effects on maternal and placental outcomes at delivery (day 17.5 post coitum) were investigated. Despite comparable energy assimilation between the two groups of dams, the altered fatty acid composition of the Fat-mod HC diet induced lower maternal body weight, weights of fat depots, adipocyte size, and hepatic fat accumulation compared to the unmodified HC diet group. Further, there was a trend towards lower fasting glucose, insulin and leptin concentrations in dams fed the Fat-mod HC diet. Phenotypic changes were accompanied by inhibition of transcript and protein expression of genes involved in hepatic de novo lipogenesis comprising PPARG2 and its target genes Fasn, Acaca, and Fabp4, whereas regulation of other lipogenic factors (Srebf1, Nr1h3, Abca1) appeared to be more complex. The modified diet led to a sex-specific placental response by upregulating PPARG-dependent fatty acid transport gene expression in female versus male placentae. Qualitative modification of the fatty acid spectrum of a high-energy maternal diet, using a combination of both MCFAs and n-3 LC-PUFAs, seems to be a promising interventional approach to ameliorate the adipogenic milieu of mice before and during gestation. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation

PubMed Central

Mansor, Latt S.; Sousa Fialho, Maria da Luz; Yea, Georgina; Coumans, Will A.; West, James A.; Kerr, Matthew; Carr, Carolyn A.; Luiken, Joost J.F.P.; Glatz, Jan F.C.; Evans, Rhys D.; Griffin, Julian L.; Tyler, Damian J.; Clarke, Kieran

2017-01-01

Aims The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress. Methods and results Hearts from type 2 diabetic and control male Wistar rats were perfused in normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N-succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial triglyceride concentration by 48% compared with untreated diabetic hearts, restoring fatty acid metabolism to control levels following hypoxia-reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and decreased lactate efflux rate by 56% compared with untreated diabetic hearts during reoxygenation. In addition, SSO treatment of diabetic hearts increased intermediates within the second span of the Krebs cycle, namely fumarate, oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts following decreased oxygen availability was prevented by SSO-infusion prior to the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure product by 60% during hypoxia and by 32% following reoxygenation, restoring function to control levels. Conclusions Diabetic hearts have limited metabolic flexibility and cardiac dysfunction when stressed, which can be rapidly rectified by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel therapeutic approach not only reduces fat oxidation but also lipotoxicity, by targeting the primary step in the fatty acid metabolism pathway. PMID:28419197

Diet Affects Muscle Quality and Growth Traits of Grass Carp (Ctenopharyngodon idellus): A Comparison Between Grass and Artificial Feed

PubMed Central

Zhao, Honghao; Xia, Jianguo; Zhang, Xi; He, Xugang; Li, Li; Tang, Rong; Chi, Wei; Li, Dapeng

2018-01-01

Fish muscle, the main edible parts with high protein level and low fat level, is consumed worldwide. Diet contributes greatly to fish growth performance and muscle quality. In order to elucidate the correlation between diet and muscle quality, the same batch of juvenile grass carp (Ctenopharyngodon idellus) were divided into two groups and fed with either grass (Lolium perenne, Euphrasia pectinata and Sorghum sudanense) or artificial feed, respectively. However, the different two diets didn't result in significant differences in all the detected water quality parameters (e.g., Tm, pH, DO, NH3/NH4+-N, NO3--N, NO2-, TN, TP, and TOC) between the two experimental groups. After a 4-month culture period, various indexes and expression of myogenic regulatory factor (MRFs) and their related genes were tested. The weight gain of the fish fed with artificial feed (AFG) was nearly 40% higher than the fish fed with grass (GFG). Significantly higher alkaline phosphatase, total cholestrol, high density cholestrol and total protein were detected in GFG as compared to AFG. GFG also showed increased hardness, resilience and shear force in texture profile analysis, with significantly bigger and compact muscle fibers in histologic slices. The fat accumulation was most serious in the abdomen muscle of AFG. Additionally, the expression levels of MyoG, MyoD, IGF-1, and MSTNs were higher, whereas Myf-5, MRF4, and IGF-2 were lower in most positional muscles of GFG as compared to AFG. Overall, these results suggested that feeding grass could promote muscle growth and development by stimulating muscle fiber hypertrophy, as well as significantly enhance the expression of CoL1As. Feeding C. idellus with grass could also improve flesh quality by improving muscle characteristics, enhancing the production of collagen, meanthile, reducing fat accumulation and moisture in muscle, but at the cost of a slower growth. PMID:29632496

Relationship between soluble receptor for advanced glycation end products (sRAGE), body composition and fat distribution in healthy women.

PubMed

Dozio, Elena; Briganti, Silvia; Delnevo, Alessandra; Vianello, Elena; Ermetici, Federica; Secchi, Francesco; Sardanelli, Francesco; Morricone, Lelio; Malavazos, Alexis E; Corsi Romanelli, Massimiliano M

2017-12-01

Soluble receptor for advanced glycation end products (sRAGE) is a decoy receptor which sequesters RAGE ligands and acts as a cytoprotective agent. To date, it is unclear whether the lower sRAGE levels observed in obesity are a marker of increased overall adiposity or reflect increases in particular fat depots. Therefore, we evaluated in healthy women the relationship among sRAGE and indicators of adiposity, including abdominal visceral (VAT) and epicardial visceral (EAT) adipose tissues, to explore the potential role of sRAGE as an earlier biomarker of cardiometabolic risk. Plasma sRAGE levels were quantified by an enzyme-linked immunosorbent assay in 47 healthy women. Total fat mass (FM) and fat-free mass were estimated with bioimpedance analysis. Anthropometric measures and biochemical data were recorded. Subcutaneous adipose tissue, VAT and EAT volumes were measured by magnetic resonance imaging. Obese women had lower sRAGE levels compared to normal-weight women. sRAGE levels were also lower in women with a waist circumference (WC) larger than 80 cm. Correlation analyses indicated an inverse association of sRAGE with body mass index and FM. Concerning adipose tissue distribution, sRAGE inversely correlated with WC, EAT and VAT depots. In a multiple stepwise regression analysis, performed to emphasize the role of fat distribution, EAT volume was the only predictor of sRAGE. Lower sRAGE levels reflect accumulation of visceral fat mainly at the epicardial level and are present in advance of metabolic complications in adult women. sRAGE quantification might be an early marker of cardiometabolic risk.

Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity.

PubMed

López-Lluch, Guillermo

2017-03-01

Mitochondria play an essential role in ageing and longevity. During ageing, a general deregulation of metabolism occurs, affecting molecular, cellular and physiological activities in the organism. Dysfunction of mitochondria has been associated with ageing and age-related diseases indicating their importance in the maintenance of cell homeostasis. Three major nutritional sensors, mTOR, AMPK and Sirtuins are involved in the control of mitochondrial physiology. These nutritional sensors control mitochondrial biogenesis, dynamics by regulating fusion and fission processes, and turnover through mito- and autophagy. Apart of the known factors involved in fusion, OPA1 and mitofusins, and fission, DRP1 and FIS1, emerging factors such as prohibitins and sestrins can play important functions in mitochondrial dynamics regulation. Mitochondria is also affected by sexual hormones that suffer drastic changes during ageing. The recent literature demonstrates the complex interaction between nutritional sensors and mitochondrial homeostasis in the physiology of adipose tissue and in the accumulation of fat in other organs such as muscle and liver. In this article, the role of mitochondrial homeostasis in ageing and age-dependent fat accumulation is revised. This review highlights the importance of mitochondria in the accumulation of fat during ageing and related diseases such as obesity, metabolic syndrome or type 2 diabetes mellitus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The expression of the Cuphea palustris thioesterase CpFatB2 in Yarrowia lipolytica triggers oleic acid accumulation.

PubMed

Stefan, Alessandra; Hochkoeppler, Alejandro; Ugolini, Luisa; Lazzeri, Luca; Conte, Emanuele

2016-01-01

The conversion of industrial by-products into high-value added compounds is a challenging issue. Crude glycerol, a by-product of the biodiesel production chain, could represent an alternative carbon source for the cultivation of oleaginous yeasts. Here, we developed five minimal synthetic glycerol-based media, with different C/N ratios, and we analyzed the production of biomass and fatty acids by Yarrowia lipolytica Po1g strain. We identified two media at the expense of which Y. lipolytica was able to accumulate ∼5 g L(-1) of biomass and 0.8 g L(-1) of fatty acids (0.16 g of fatty acids per g of dry weight). These optimized media contained 0.5 g L(-1) of urea or ammonium sulfate and 20 g L(-1) of glycerol, and were devoid of yeast extract. Moreover, Y. lipolytica was engineered by inserting the FatB2 gene, coding for the CpFatB2 thioesterase from Cuphea palustris, in order to modify the fatty acid composition towards the accumulation of medium-chain fatty acids. Contrary to the expected, the expression of the heterologous gene increased the production of oleic acid, and concomitantly decreased the level of saturated fatty acids. © 2015 American Institute of Chemical Engineers.

New haystacks reveal new needles: using Caenorhabditis elegans to identify novel targets for ameliorating body composition changes during human aging.

PubMed

Wolkow, Catherine A

2010-01-01

Dramatic changes in body composition accompany aging in humans, particularly with respect to adiposity and the musculature. People accumulate fat as they age and lose muscle mass and strength. Caenorhabditis elegans nematodes are small, hermaphroditic soil nematodes that offer a flexible model for studying genetic pathways regulating body composition in humans. While there are significant physiological differences between worms and people, many of the genetic pathways relevant to human lipid and muscle homeostasis are present in worms. Initial studies indicate that adiposity increases in C. elegans during aging, as occurs in humans. Furthermore, substantial evidence demonstrates age-related loss of muscle mass in worms. Possible mechanisms for these changes in C. elegans are presented. Recent studies have highlighted neuroendocrine and environmental signals regulating C. elegans fat metabolism. Potential dysfunction of these pathways during aging could affect overall fat accumulation. By contrast, muscle decline in aging worms results from accumulated damage and 'wear-and-tear' over life span. However, neuroendocrine pathways also regulate muscle mass in response to food availability. Such pathways might provide useful therapeutic approaches for combating muscle loss during aging. From this chapter, readers will develop a deeper understanding of the ways that C.elegans can be used for mechanistic gerontological studies. Copyright © 2010 S. Karger AG, Basel.

Paradoxical dissociation between hepatic fat content and de novo lipogenesis due to PNPLA3 sequence variant.

PubMed

Mancina, Rosellina M; Matikainen, Niina; Maglio, Cristina; Söderlund, Sanni; Lundbom, Nina; Hakkarainen, Antti; Rametta, Raffaela; Mozzi, Enrico; Fargion, Silvia; Valenti, Luca; Romeo, Stefano; Taskinen, Marja-Riitta; Borén, Jan

2015-05-01

Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic disease characterized by increased hepatic fat, due to an imbalance between synthesis and removal of hepatic lipids. In particular, increased hepatic de novo lipogenesis (DNL) is a key feature associated with NAFLD. The genetic variations I148M in PNPLA3 and E167K in TM6SF2 confer susceptibility to NAFLD. Here we aimed to investigate the contribution of DNL to liver fat accumulation in the PNPLA3 I148M or TM6SF2 E167K genetic determinants of NAFLD. The PNPLA3 I148M and TM6SF2 E167K were genotyped in two well-characterized cohorts of Europeans. In the first cohort (Helsinki cohort; n = 88), we directly quantified hepatic DNL using deuterated water. In the second cohort (Milan cohort; n = 63), we quantified the hepatic expression of SREBP1c that we have found previously associated with increased fat content. Liver fat was measured by magnetic resonance proton spectroscopy in the Helsinki cohort, and by histological assessment of liver biopsies in the Milan cohort. PNPLA3 148M was associated with lower DNL and expression of the lipogenic transcription factor SREBP1c despite substantial increased hepatic fat content. Our data show a paradoxical dissociation between hepatic DNL and hepatic fat content due to the PNPLA3 148M allele indicating that increased DNL is not a key feature in all individuals with hepatic steatosis, and reinforces the contribution of decreased mobilization of hepatic triglycerides for hepatic lipid accumulation in subject with the PNPLA3 148M allele.

Genetic modification of human mesenchymal stem cells helps to reduce adiposity and improve glucose tolerance in an obese diabetic mouse model.

PubMed

Sen, Sabyasachi; Domingues, Cleyton C; Rouphael, Carol; Chou, Cyril; Kim, Chul; Yadava, Nagendra

2015-12-09

Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible. We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene expression. HG increased reactive superoxide (ROS) accumulation noted by day 7 both in cytosol and mitochondria. The OCR between the NG and HG exposed groups however did not change until 10 days at which point OCR of HG exposed cells were reduced significantly. We noted that HG exposure upregulated mRNA expression of adipogenic (PPARG, FABP-4, CREBP alpha and beta), inflammatory (IL-6 and TNF alpha) and antioxidant (SOD2 and Catalase) genes. Next, we used AdSOD2 to upregulate SOD2 prior to HG exposure and thereby noted reduction in superoxide generation. SOD2 upregulation helped reduce mRNA over-expression of PPARG, FABP-4, IL-6 and TNFα. In a series of separate experiments, we delivered the eGFP and SOD2 upregulated MSCs (5 days post ex-vivo transduction) and saline intra-peritoneally (IP) to obese diabetic (db/db) mice. We confirmed homing-in of eGFP labeled MSCs, delivered IP, to different inflamed fat pockets, particularly omental fat. Mice receiving SOD2-MSCs showed progressive reduction in body weight and improved glucose tolerance (GTT) at 4 weeks, post MSCs transplantation compared to the GFP-MSC group (control). High glucose evokes superoxide generation, OCR reduction and adipogenic differentiation. Mitochondrial superoxide dismutase upregulation quenches excess superoxide and reduces adipocyte inflammation. Delivery of superoxide dismutase (SOD2) using MSCs as a gene delivery vehicle reduces inflammation and improves glucose tolerance in vivo. Suppression of superoxide production and adipocyte inflammation using mitochondrial superoxide dismutase may be a novel and safe therapeutic tool to combat hyperglycemia mediated effects.

Effect of dietary betaine on growth performance, antioxidant capacity and lipid metabolism in blunt snout bream fed a high-fat diet.

PubMed

Adjoumani, Jean-Jacques Yao; Wang, Kaizhou; Zhou, Man; Liu, Wenbin; Zhang, Dingdong

2017-12-01

An 8-week feeding experiment was conducted to determine the effect of dietary betaine levels on the growth performance, antioxidant capacity, and lipid metabolism in high-fat diet-fed blunt snout bream (Megalobrama amblycephala) with initial body weight 4.3 ± 0.1 g [mean ± SEM]. Five practical diets were formulated to contain normal-fat diet (NFD), high-fat diet (HFD), and high-fat diet with betaine addition (HFB) at difference levels (0.6, 1.2, 1.8%), respectively. The results showed that the highest final body weight (FBW), weight gain ratio (WGR), specific growth rate (SGR), condition factor (CF), and feed intake (FI) (P < 0.05) were obtained in fish fed 1.2% betaine supplementation, whereas feed conversion ratio (FCR) was significantly lower in the same group compared to others. Hepatosomatic index (HSI) and abdominal fat rate (AFR) were significantly high in fat group compared to the lowest in NDF and 1.2% betaine supplementation, while VSI and survival rate (SR) were not affected by dietary betaine supplementation. Significantly higher (P < 0.05), plasma total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), aspartate transaminase (AST), alanine transaminase (ALT), cortisol, and lower high-density lipoprotein (HDL) content were observed in HFD but were improved when supplemented with 1.2% betaine. In addition, increase in superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in 1.2% betaine inclusion could reverse the increasing malondialdehyde (MDA) level induced by HFD. Based on the second-order polynomial analysis, the optimum growth of blunt snout bream was observed in fish fed HFD supplemented with 1.2% betaine. HFD upregulated fatty acid synthase messenger RNA (mRNA) expression and downregulated carnitine palmitoyltransferase 1, peroxisome proliferator-activated receptor α, and microsomal triglyceride transfer protein mRNA expression; nevertheless, 1.2% betaine supplementation significantly reversed these HFD-induced effects, implying suppression of fatty acid synthesis, β-oxidation, and lipid transport. This present study indicated that inclusion of betaine (1.2%) can significantly improve growth performance and antioxidant defenses, as well as reduce fatty acid synthesis and enhance mitochondrial β-oxidation and lipid transportation in high-fat diet-fed blunt snout bream, thus effectively alleviating fat accumulation in the liver by changing lipid metabolism.

Suppression of murine preadipocyte differentiation and reduction of visceral fat accumulation by a Petasites japonicus ethanol extract in mice fed a high-fat diet.

PubMed

Watanabe, Takayuki; Hata, Keishi; Hiwatashi, Kazuyuki; Hori, Kazuyuki; Suzuki, Nao; Itoh, Hideaki

2010-01-01

We investigated in this study the anti-obesity effect of an extract of Petasites japonicus (a culinary vegetable from Eastern Asia) on a murine adipocyte cell line (3T3-L1) and on diet-induced obesity-prone mice. An ethanol extract of P. japonicus. (PJET) suppressed 3T3-L1 preadipocyte differentiation; however, a hot water extract of P. japonicus (PJHW) exhibited no effect on cell differentiation. PJET significantly attenuated three adipogenetic transcription factors, peroxisome proliferator-activated receptor gamma2, CCAAT/enhancer-binding protein and sterol regulatory element-binding protein 1C, at the mRNA level and suppressed the gene expression of fatty acid synthetase. An experiment with diet-induced obesity-prone C57BL/6J mice showed that PJET lowered the body weight gain and visceral fat tissue accumulation, and ameliorated the plasma cholesterol concentration. These findings suggest that P. japonicus might be an effective food against obesity.

Effects of feeding outer bran fraction of rice on lipid accumulation and fecal excretion in rats.

PubMed

Ijiri, Daichi; Nojima, Tsutomu; Kawaguchi, Mana; Yamauchi, Yoko; Fujita, Yoshikazu; Ijiri, Satoru; Ohtsuka, Akira

2015-01-01

Outer bran fraction of rice (OBFR) contains higher concentrations of crude fiber, γ-oryzanol, and phytic acid compared to whole rice bran (WRB). In this study, we examined the effects of feeding OBFR on lipid accumulation and fecal excretion in rats. Twenty-one male rats at seven-week-old were divided into a control group and two treatment groups. The control group was fed a control diet, and the treatment groups were fed OBFR- or WRB-containing diet for 21 days. There was no significant difference in growth performance. Feeding OBFR diet increased fecal number and weight accompanied by increased fecal lipid content, while it did not affect mRNA expressions encoding lipid metabolism-related protein in liver. In addition, feeding OBFR-diet decreased the abdominal fat tissue weight and improved plasma lipid profiles, while WRB-containing diet did not affect them. These results suggested that feeding OBFR-diet might prevent lipid accumulation via enhancing fecal lipid excretion in rats.

Colloidal transport phenomena of milk components during convective droplet drying.

PubMed

Fu, Nan; Woo, Meng Wai; Chen, Xiao Dong

2011-10-15

Material segregation has been reported for industrial spray-dried milk powders, which indicates potential material migration during drying process. The relevant colloidal transport phenomenon and the underlying mechanism are still under debate. This study extended the glass-filament single droplet drying technique to observe not only the drying behaviour but also the dissolution behaviour of the correspondingly dried single particle. At progressively longer drying stage, a solvent droplet (water or ethanol) was attached to the semi-dried milk particle and the interaction between the solvent and the particle was video-recorded. Based on the different dissolution and wetting behaviours observed, material migration during milk drying was studied. Fresh skim milk and fresh whole milk were investigated using water and ethanol as solvents. Fat started to accumulate on the surface as soon as drying was started. At the initial stage of drying, the fat layer remained thin and the solubility of the semi-dried milk particle was much affected by lactose and protein present underneath the fat layer. Fat kept accumulating at the surface as drying progressed and the accumulation was completed by the middle stage of drying. The results from drying of model milk materials (pure sodium caseinate solution and lactose/sodium caseinate mixed solution) supported the colloidal transport phenomena observed for the milk drying. When mixed with lactose, sodium caseinate did not form an apparent solvent-resistant protein shell during drying. The extended technique of glass-filament single droplet approach provides a powerful tool in examining the solubility of individual particle after drying. Copyright © 2011 Elsevier B.V. All rights reserved.

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.

PubMed

Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

2017-03-01

Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437-446; http://dx.doi.org/10.1289/EHP360.

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice

PubMed Central

Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

2016-01-01

Background: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. Objectives: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. Methods: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Results: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. Conclusions: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437–446; http://dx.doi.org/10.1289/EHP360 PMID:27634282

Chemical and biochemical composition of caviar from different sturgeon species and origins.

PubMed

Wirth, M; Kirschbaum, F; Gessner, J; Krüger, A; Patriche, N; Billard, R

2000-08-01

The chemical and biochemical composition of caviar in 22 specimens of wild caught and of 2 farmed animals were measured. The results include grain size, protein and fat content, fatty acid composition of triglycerides and phospholipids, as well as the concentrations of relevant heavy metals and chlorinated hydrocarbons. The average protein content varied between 26.2 and 31.1% (wet weight) and fat from 10.9 to 19.4% (wet weight) with lowest values for caviar from farmed sturgeon. The triglycerides and phospholipids contained more n-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid than n-6 fatty acids. The copper and zinc concentrations varied between 1.20 and 1.69 and 10.3 and 12.4 mg/kg (wet weight), respectively. These values reflect the elevated requirement of sturgeons for these components. Lead content varied between 0.06 and 0.15 mg/kg (wet weight). The cadmium concentrations were less than 5 micrograms/kg (wet weight) leading to the conclusion that no accumulation took place in the eggs. The concentrations of sigma DDT and sigma PCB were extremely high in caviar from Huso huso compared to the samples of the other species thus reflecting the different food habits leading to increased bio-accumulation.

Evaluation of abdominal fat index by ultrasonography and its relationship with psoriasis and metabolic syndrome.

PubMed

Gönül, Müzeyyen; Tatar, İdil; Canpolat, Filiz; Işıl Kurmus, Gökçe; Ergin, Can; Hekimoğlu, Baki

2017-10-01

Accumulating evidence indicates that psoriasis is associated with obesity and metabolic syndrome. Psoriasis and obesity share similar inflammatory mediators, and obesity may potentiate some inflammatory cytokines seen in psoriasis. Body fat distribution, particularly visceral adipose tissue (VAT), is an important factor in metabolic syndrome and atherosclerotic diseases. An association has been demonstrated between psoriasis and abdominal VAT measured by computed tomography (CT). To measure abdominal VAT noninvasively by ultrasonography (USG) in patients with psoriasis and investigated its relation to psoriasis and metabolic syndrome. The study population consisted of 41 psoriasis patients and 41 control subjects matched for age, sex, and body mass index. The maximal preperitoneal fat thickness (Pmax) at the anterior surface of the liver and the minimal subcutaneous fat thickness (Smin) of the abdomen were measured by USG. The abdominal fat index (AFI = Pmax/Smin ratio) was calculated and the results were compared between groups. The rate of metabolic syndrome was significantly higher in psoriasis patients ( p = 0.0018). The mean AFI was similar in both groups. AFI was not associated with psoriasis in subjects with metabolic syndrome ( p = 0.495) or with Psoriasis Area and Severity Index ( r = 0.123, p = 0.443). This is the first study to evaluate abdominal VAT by USG. Computed tomography may be more reliable than USG, but its high cost and radiation exposure are major disadvantages. Further studies are required to determine the relationships between psoriasis and VAT.

Dietary protein content alters energy expenditure and composition of the mass gain in grizzly bears (Ursus arctos horribilis).

PubMed

Felicetti, Laura A; Robbins, Charles T; Shipley, Lisa A

2003-01-01

Many fruits contain high levels of available energy but very low levels of protein and other nutrients. The discrepancy between available energy and protein creates a physiological paradox for many animals consuming high-fruit diets, as they will be protein deficient if they eat to meet their minimum energy requirement. We fed young grizzly bears both high-energy pelleted and fruit diets containing from 1.6% to 15.4% protein to examine the role of diet-induced thermogenesis and fat synthesis in dealing with high-energy-low-protein diets. Digestible energy intake at mass maintenance increased 2.1 times, and composition of the gain changed from primarily lean mass to entirely fat when the protein content of the diet decreased from 15.4% to 1.6%. Daily fat gain was up to three times higher in bears fed low-protein diets ad lib., compared with bears consuming the higher-protein diet and gaining mass at the same rate. Thus, bears eating fruit can either consume other foods to increase dietary protein content and reduce energy expenditure, intake, and potentially foraging time or overeat high-fruit diets and use diet-induced thermogenesis and fat synthesis to deal with their skewed energy-to-protein ratio. These are not discrete options but a continuum that creates numerous solutions for balancing energy expenditure, intake, foraging time, fat accumulation, and ultimately fitness, depending on food availability, foraging efficiency, bear size, and body condition.

Conjugated linoleic acid reduces body weight gain in ovariectomized female C57BL/6J mice.

PubMed

Kanaya, Noriko; Chen, Shiuan

2010-10-01

Estrogen is an important protective factor against obesity in females. Therefore, postmenopausal women have a higher rate of obesity than premenopausal women, which is associated with age-related loss of ovary function. It has been reported that a diet containing conjugated linoleic acid (CLA) reduced body weight and body fat mass in the animal model as well as in human trials. We hypothesized that ingestion of CLA would reduce body weight gain in ovariectomized (OVX) female C57BL/6J mice that is a model for postmenopausal women. We further hypothesized that body weight reduction may improve obesity-related complication. To test this hypothesis, the OVX mice were fed with a high-fat diet containing CLA for 3 months. Mice had significantly reduced body weight gain compared with OVX mice fed with a high-fat diet without CLA. Although CLA was effective in slowing down body weight gain of both sham and OVX mice, analysis of adipocyte size and number suggested different mechanisms for loss of fat tissue in these 2 groups of mice. Treatment with CLA did not increase liver weight and accumulation of fat in the livers of OVX mice. Furthermore, CLA intake did not change insulin resistance. Our results indicate that CLA is functional as an antiobesity supplement in the mouse model for postmenopausal women and that the antiobesity effect of CLA is not estrogen related. Copyright © 2010 Elsevier Inc. All rights reserved.

Reduced mitochondrial mass and function add to age-related susceptibility toward diet-induced fatty liver in C57BL/6J mice.

PubMed

Lohr, Kerstin; Pachl, Fiona; Moghaddas Gholami, Amin; Geillinger, Kerstin E; Daniel, Hannelore; Kuster, Bernhard; Klingenspor, Martin

2016-10-01

Nonalcoholic fatty liver disease (NAFLD) is a major health burden in the aging society with an urging medical need for a better understanding of the underlying mechanisms. Mitochondrial fatty acid oxidation and mitochondrial-derived reactive oxygen species (ROS) are considered critical in the development of hepatic steatosis, the hallmark of NAFLD. Our study addressed in C57BL/6J mice the effect of high fat diet feeding and age on liver mitochondria at an early stage of NAFLD development. We therefore analyzed functional characteristics of hepatic mitochondria and associated alterations in the mitochondrial proteome in response to high fat feeding in adolescent, young adult, and middle-aged mice. Susceptibility to diet-induced obesity increased with age. Young adult and middle-aged mice developed fatty liver, but not adolescent mice. Fat accumulation was negatively correlated with an age-related reduction in mitochondrial mass and aggravated by a reduced capacity of fatty acid oxidation in high fat-fed mice. Irrespective of age, high fat diet increased ROS production in hepatic mitochondria associated with a balanced nuclear factor erythroid-derived 2 like 2 (NFE2L2) dependent antioxidative response, most likely triggered by reduced tethering of NFE2L2 to mitochondrial phosphoglycerate mutase 5. Age indirectly influenced mitochondrial function by reducing mitochondrial mass, thus exacerbating diet-induced fat accumulation. Therefore, consideration of age in metabolic studies must be emphasized. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

PubMed Central

Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

2011-01-01

The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

High fat diet feeding exaggerates perfluorooctanoic acid-induced liver injury in mice via modulating multiple metabolic pathways.

PubMed

Tan, Xiaobing; Xie, Guoxiang; Sun, Xiuhua; Li, Qiong; Zhong, Wei; Qiao, Peter; Sun, Xinguo; Jia, Wei; Zhou, Zhanxiang

2013-01-01

High fat diet (HFD) is closely linked to a variety of health issues including fatty liver. Exposure to perfluorooctanoic acid (PFOA), a synthetic perfluorinated carboxylic acid, also causes liver injury. The present study investigated the possible interactions between high fat diet and PFOA in induction of liver injury. Mice were pair-fed a high-fat diet (HFD) or low fat control with or without PFOA administration at 5 mg/kg/day for 3 weeks. Exposure to PFOA alone caused elevated plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels and increased liver weight along with reduced body weight and adipose tissue mass. HFD alone did not cause liver damage, but exaggerated PFOA-induced hepatotoxicity as indicated by higher plasma ALT and AST levels, and more severe pathological changes including hepatocyte hypertrophy, lipid droplet accumulation and necrosis as well as inflammatory cell infiltration. These additive effects of HFD on PFOA-induced hepatotoxicity correlated with metabolic disturbance in liver and blood as well as up-regulation of hepatic proinflammatory cytokine genes. Metabolomic analysis demonstrated that both serum and hepatic metabolite profiles of PFOA, HFD, or HFD-PFOA group were clearly differentiated from that of controls. PFOA affected more hepatic metabolites than HFD, but HFD showed positive interaction with PFOA on fatty acid metabolites including long chain fatty acids and acylcarnitines. Taken together, dietary high fat potentiates PFOA-induced hepatic lipid accumulation, inflammation and necrotic cell death by disturbing hepatic metabolism and inducing inflammation. This study demonstrated, for the first time, that HFD increases the risk of PFOA in induction of hepatotoxicity.

Microbial community adaptation influences long-chain fatty acid conversion during anaerobic codigestion of fats, oils, and grease with municipal sludge.

PubMed

Ziels, Ryan M; Karlsson, Anna; Beck, David A C; Ejlertsson, Jörgen; Yekta, Sepehr Shakeri; Bjorn, Annika; Stensel, H David; Svensson, Bo H

2016-10-15

Codigesting fats, oils, and greases with municipal wastewater sludge can greatly improve biomethane recovery at wastewater treatment facilities. Process loading rates of fats, oils, and greases have been previously tested with little knowledge of the digester microbial community structure, and high transient fat loadings have led to long chain fatty acid (LCFA) accumulation and digester upsets. This study utilized recently-developed quantitative PCR assays for syntrophic LCFA-degrading bacteria along with 16S amplicon sequencing to relate changes in microbial community structure to LCFA accumulation during transient loading increases to an anaerobic codigester receiving waste restaurant oil and municipal wastewater sludge. The 16S rRNA gene concentration of the syntrophic β-oxidizing genus Syntrophomonas increased to ∼15% of the Bacteria community in the codigester, but stayed below 3% in the control digester that was fed only wastewater sludge. Methanosaeta and Methanospirillum were the dominant methanogenic genera enriched in the codigester, and together comprised over 80% of the Archaea community by the end of the experimental period. Constrained ordination showed that changes in the codigester Bacteria and Archaea community structures were related to measures of digester performance. Notably, the effluent LCFA concentration in the codigester was positively correlated to the specific loading rate of waste oil normalized to the Syntrophomonas 16S rRNA concentration. Specific loading rates of 0-1.5 × 10(-12) g VS oil/16S gene copies-day resulted in LCFA concentrations below 30 mg/g TS, whereas LCFA accumulated up to 104 mg/g TS at higher transient loading rates. Based on the community-dependent loading limitations found, enhanced biomethane production from high loadings of fats, oils and greases can be achieved by promoting a higher biomass of slow-growing syntrophic consortia, such as with longer digester solids retention times. This work also demonstrates the potential for controlling the loading rate of fats, oils, and greases based on the analysis of the codigester community structure, such as with quantitative PCR measurements of syntrophic LCFA-degrading bacteria abundance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI

PubMed Central

Zhang, Yue; Udayakumar, Durga; Cai, Ling; Hu, Zeping; Kapur, Payal; Kho, Eun-Young; Pavía-Jiménez, Andrea; Fulkerson, Michael; de Leon, Alberto Diaz; Yuan, Qing; Dimitrov, Ivan E.; Ye, Jin; Mitsche, Matthew A.; Kim, Hyeonwoo; McDonald, Jeffrey G.; Madhuranthakam, Ananth J.; Dwivedi, Durgesh K.; Lenkinski, Robert E.; Cadeddu, Jeffrey A.; Margulis, Vitaly; Brugarolas, James; DeBerardinis, Ralph J.

2017-01-01

BACKGROUND. Dysregulated lipid and glucose metabolism in clear cell renal cell carcinoma (ccRCC) has been implicated in disease progression, and whole tumor tissue–based assessment of these changes is challenged by the tumor heterogeneity. We studied a noninvasive quantitative MRI method that predicts metabolic alterations in the whole tumor. METHODS. We applied Dixon-based MRI for in vivo quantification of lipid accumulation (fat fraction [FF]) in targeted regions of interest of 45 primary ccRCCs and correlated these MRI measures to mass spectrometry–based lipidomics and metabolomics of anatomically colocalized tissue samples isolated from the same tumor after surgery. RESULTS. In vivo tumor FF showed statistically significant (P < 0.0001) positive correlation with histologic fat content (Spearman correlation coefficient, ρ = 0.79), spectrometric triglycerides (ρ = 0.56) and cholesterol (ρ = 0.47); it showed negative correlation with free fatty acids (ρ = –0.44) and phospholipids (ρ = –0.65). We observed both inter- and intratumoral heterogeneity in lipid accumulation within the same tumor grade, whereas most aggressive tumors (International Society of Urological Pathology [ISUP] grade 4) exhibited reduced lipid accumulation. Cellular metabolites in tumors were altered compared with adjacent renal parenchyma. CONCLUSION. Our results support the use of noninvasive quantitative Dixon-based MRI as a biomarker of reprogrammed lipid metabolism in ccRCC, which may serve as a predictor of tumor aggressiveness before surgical intervention. FUNDING. NIH R01CA154475 (YZ, MF, PK, IP), NIH P50CA196516 (IP, JB, RJD, JAC, PK), Welch Foundation I-1832 (JY), and NIH P01HL020948 (JGM). PMID:28768909

Dietary fats, cerebrovasculature integrity and Alzheimer's disease risk.

PubMed

Takechi, R; Galloway, S; Pallebage-Gamarallage, M M S; Lam, V; Mamo, J C L

2010-04-01

An emerging body of evidence is consistent with the hypothesis that dietary fats influence Alzheimer's disease (AD) risk, but less clear is the mechanisms by which this occurs. Alzheimer's is an inflammatory disorder, many consider in response to fibrillar formation and extracellular deposition of amyloid-beta (Abeta). Alternatively, amyloidosis could notionally be a secondary phenomenon to inflammation, because some studies suggest that cerebrovascular disturbances precede amyloid plaque formation. Hence, dietary fats may influence AD risk by either modulating Abeta metabolism, or via Abeta independent pathways. This review explores these two possibilities taking into consideration; (i) the substantial affinity of Abeta for lipids and its ordinary metabolism as an apolipoprotein; (ii) evidence that Abeta has potent vasoactive properties and (iii) studies which show that dietary fats modulate Abeta biogenesis and secretion. We discuss accumulating evidence that dietary fats significantly influence cerebrovascular integrity and as a consequence altered Abeta kinetics across the blood-brain barrier (BBB). Specifically, chronic ingestion of saturated fats or cholesterol appears to results in BBB dysfunction and exaggerated delivery from blood-to-brain of peripheral Abeta associated with lipoproteins of intestinal and hepatic origin. Interestingly, the pattern of saturated fat/cholesterol induced cerebrovascular disturbances in otherwise normal wild-type animal strains is analogous to established models of AD genetically modified to overproduce Abeta, consistent with a causal association. Saturated fats and cholesterol may exacerbate Abeta induced cerebrovascular disturbances by enhancing exposure of vessels of circulating Abeta. However, presently there is no evidence to support this contention. Rather, SFA and cholesterol appear to more broadly compromise BBB integrity with the consequence of plasma protein leakage into brain, including lipoprotein associated Abeta. The latter findings are consistent with the concept that AD is a dietary-fat induced phenotype of vascular dementia, reflecting the extraordinary entrapment of peripherally derived lipoproteins endogenously enriched in Abeta. Rather than being the initiating trigger for inflammation in AD, accumulation of extracellular lipoprotein-Abeta may be a secondary amplifier of dietary induced inflammation, or possibly, simply be consequential. Clearly, delineating the mechanisms by which dietary fats increase AD risk may be informative in developing new strategies for prevention and treatment of AD. Copyright 2009 Elsevier Ltd. All rights reserved.

Analysis of Fat Intake Based on the US Department of ...

EPA Pesticide Factsheets

EPA released the final report, Analysis of Fat Intake Based on USDA’s 1994-1996, 1998 Continuing Survey of Food Intakes by Individuals (CSFII, Final Report). For this report, the EPA conducted an analysis of fat consumption across the U.S. population based on data derived from the U.S. Department of Agriculture's 1994-96, 1998 Continuing Survey of Food Intakes by Individuals (CSFII) and EPA's Food Commodity Intake Database (FCID). Percentiles of fat consumption were calculated on the basis of total mass and on a per-unit body-weight basis for 12 food categories and 98 demographic cohorts. In addition, dietary breakdown and fat intake percentiles were calculated for a subset of the sample population whose consumption of animal fats exceeded the 90th percentile within its age group. Many chemicals found in the environment tend to accumulate in fatty tissue. Assessing risks from these chemicals requires knowledge of dietary habits and the amount of fat present in various types of foods.

Nutritional Factors Affecting Abdominal Fat Deposition in Poultry: A Review

PubMed Central

Fouad, A. M.; El-Senousey, H. K.

2014-01-01

The major goals of the poultry industry are to increase the carcass yield and to reduce carcass fatness, mainly the abdominal fat pad. The increase in poultry meat consumption has guided the selection process toward fast-growing broilers with a reduced feed conversion ratio. Intensive selection has led to great improvements in economic traits such as body weight gain, feed efficiency, and breast yield to meet the demands of consumers, but modern commercial chickens exhibit excessive fat accumulation in the abdomen area. However, dietary composition and feeding strategies may offer practical and efficient solutions for reducing body fat deposition in modern poultry strains. Thus, the regulation of lipid metabolism to reduce the abdominal fat content based on dietary composition and feeding strategy, as well as elucidating their effects on the key enzymes associated with lipid metabolism, could facilitate the production of lean meat and help to understand the fat-lowering effects of diet and different feeding strategies. PMID:25050050

Nordihydroguaiaretic acid protects against high-fat diet-induced fatty liver by activating AMP-activated protein kinase in obese mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Myoung-Su; Kim, Daeyoung; Jo, Keunae

Research highlights: {yields} NDGA decreases high-fat diet-induced body weight gain and adiposity. {yields} NDGA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} NDGA improves lipid storage in vitro through altering lipid regulatory proteins. {yields} Inhibition of lipid storage in vivo and in vitro is mediated by AMPK activation. -- Abstract: Nonalcoholic fatty liver disease, one of the most common causes of chronic liver disease, is strongly associated with metabolic syndrome. Nordihydroguaiaretic acid (NDGA) has been reported to inhibit lipoprotein lipase; however, the effect of NDGA on hepatic lipid metabolism remains unclear. We evaluated body weight, adiposity, liver histology, and hepaticmore » triglyceride content in high-fat diet (HFD)-fed C57BL/6J mice treated with NDGA. In addition, we characterized the underlying mechanism of NDGA's effects in HepG2 hepatocytes by Western blot and RT-PCR analysis. NDGA (100 or 200 mg/kg/day) reduced weight gain, fat pad mass, and hepatic triglyceride accumulation, and improved serum lipid parameters in mice fed a HFD for 8 weeks. NDGA significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the liver and in HepG2 hepatocytes. NDGA downregulated the level of mature SREBP-1 and its target genes (acetyl-CoA carboxylase and fatty acid synthase), but, it upregulated expression of genes involved in fatty acid oxidation, such as peroxisome proliferator-activated receptor (PPAR){alpha}, PPAR{gamma} coactivator-1, carnitine palmitoyl transferase-1, and uncoupling protein-2. The specific AMPK inhibitor compound C attenuated the effects of NDGA on expression of lipid metabolism-related proteins in HepG2 hepatocytes. The beneficial effects of NDGA on HFD-induced hepatic triglyceride accumulation are mediated through AMPK signaling pathways, suggesting a potential target for preventing NAFLD.« less

Silk and silkworm pupa peptides suppress adipogenesis in preadipocytes and fat accumulation in rats fed a high-fat diet.

PubMed

Lee, Sun Hee; Park, Dongsun; Yang, Goeun; Bae, Dae-Kwon; Yang, Yun-Hui; Kim, Tae Kyun; Kim, Dajeong; Kyung, Jangbeen; Yeon, Sungho; Koo, Kyo Chul; Lee, Jeong-Yong; Hwang, Seock-Yeon; Joo, Seong Soo; Kim, Yun-Bae

2012-12-01

The objective was to confirm the anti-obesity activity of a silk peptide (SP) and a silkworm pupa peptide (SPP) in rats fed a high-fat diet (HFD) and to elucidate their action mechanism(s) in a preadipocyte culture system. In an in vitro mechanistic study, the differentiation and maturation of 3T3-L1 preadipocytes were stimulated with insulin (5 μg/mL), and effects of SP and SPP on the adipogenesis of mature adipocytes were assessed. In an in vivo anti-obesity study, male C57BL/6 mice were fed an HFD containing SP or SPP (0.3, 1.0, or 3.0%) for 8 weeks, and blood and tissue parameters of obesity were analyzed. Hormonal stimulation of preadipocytes led to a 50-70% increase in adipogenesis. Polymerase chain reaction and Western blot analyses revealed increases in adipogenesis-specific genes (leptin and Acrp30) and proteins (peroxisome proliferator-activated receptor-γ and Acrp30). The hormone-induced adipogenesis and activated gene expression was substantially inhibited by treatment with SP and SPP (1-50 μg/mL). The HFD markedly increased body weight gain by increasing the weight of epididymal and mesenteric fat. Body and fat weights were significantly reduced by SP and SPP, in which decreases in the area of abdominal adipose tissue and the size of epididymal adipocytes were confirmed by magnetic resonance imaging and microscopic examination, respectively. Long-term HFD caused hepatic lipid accumulation and increased blood triglycerides and cholesterol, in addition to their regulatory factors Acrp30 and leptin. However, SP and SPP recovered the concentrations of Acrp30 and leptin, and attenuated steatosis. SP and SPP inhibit the differentiation of preadipocytes and adipogenesis by modulating signal transduction pathways and improve HFD-induced obesity by reducing lipid accumulation and the size of adipocytes.

Assessment of body fat in the pony: part II. Validation of the deuterium oxide dilution technique for the measurement of body fat.

PubMed

Dugdale, A H A; Curtis, G C; Milne, E; Harris, P A; Argo, C Mc

2011-09-01

Excessive accumulations or depletions of body fat have been associated with increased morbidity and mortality in horses and ponies. An objective, minimally-invasive method to accurately quantify body fat in living animals is required to aid nutritional management and define welfare/performance limits. To compare deuterium oxide (D(2) O) dilution-derived estimates of total body water (TBW) and body fat with values obtained by 'gold standard' proximate analysis and cadaver dissection. D(2) O dilution offers a valid method for the determination of TBW and body fat in equids. Seven mature (mean ± s.e. 13 ± 3 years, 212 ± 14 kg, body condition scores 1.25-7/9), healthy, Welsh Mountain pony mares, destined for euthanasia (for nonresearch purposes) were used. Blood samples were collected before and 4 h after D(2) O (0.11-0.13 g/kg bwt, 99.8 atom percent excess) administration. Plasma was analysed by gas isotope ratio mass spectrometry following filtration and zinc reduction. After euthanasia, white adipose tissue (WAT) mass was recorded before all body tissues were analysed by proximate chemical analyses. D(2) O-derived estimates of TBW and body fat were strongly associated with proximate analysis- and dissection-derived values (all r(2) >0.97, P≤0.0001). Bland-Altman analyses demonstrated good agreements between methods. D(2) O dilution slightly overestimated TBW (0.79%, limits of agreement (LoA) -3.75-2.17%) and underestimated total body lipid (1.78%, LoA -0.59-4.15%) and dissected WAT (0.72%, LoA -2.77-4.21%). This study provides the first validation of the D(2) O dilution method for the minimally-invasive, accurate, repeatable and objective measurement of body water and fat in living equids. © 2011 EVJ Ltd.

Hibernation-associated changes in persistent organic pollutant (POP) levels and patterns in British Columbia grizzly bears (ursus arctos horribilis).

PubMed

Christensen, Jennie R; MacDuffee, Misty; Yunker, Mark B; Ross, Peter S

2007-03-15

We hypothesized that depleted fat reserves in grizzly bears (Ursus arctos horribilis) following annual hibernation would reveal increases in persistent organic pollutant (POP) concentrations compared to those present in the fall. We obtained fat and hair from British Columbia grizzly bears in early spring 2004 to compare with those collected in fall 2003, with the two tissue types providing contaminant and dietary information, respectively. By correcting for the individual feeding habits of grizzlies using a stable isotope-based approach, we found that polychlorinated biphenyls (sigmaPCBs) increased by 2.21x, polybrominated diphenylethers (sigmaPBDEs) increased by 1.58x, and chlordanes (sigmaCHL) by 1.49x in fat following hibernation. Interestingly, individual POPs elicited a wide range of hibernation-associated concentration effects (e.g., CB-153, 2.25x vs CB-169, 0.00x), resulting in POP pattern convergence in a PCA model of two distinct fall feeding groups (salmon-eating vs non-salmon-eating) into a single spring (post-hibernation) group. Our results suggest that diet dictates contaminant patterns during a feeding phase, while metabolism drives patterns during a fasting phase. This work suggests a duality of POP-associated health risks to hibernating grizzly bears: (1) increased concentrations of some POPs during hibernation; and (2) a potentially prolonged accumulation of water-soluble, highly reactive POP metabolites, since grizzly bears do not excrete during hibernation.

Adipose tissue dysregulation and metabolic consequences in childhood and adolescent obesity: potential impact of dietary fat quality.

PubMed

McMorrow, Aoibheann M; Connaughton, Ruth M; Lithander, Fiona E; Roche, Helen M

2015-02-01

Evidence suggests that at a population level, childhood and adolescent obesity increase the long-term risk of chronic diseases such as type 2 diabetes and CVD. At an individual level, however, the metabolic consequences of obesity in youth vary immensely. Despite comparable BMI, some adolescents develop impaired glucose tolerance while others maintain normal glucose homeostasis. It has been proposed that the variation in the capacity to store lipid in the subcutaneous adipose tissue (SAT) may partially discriminate metabolically healthy from unhealthy obesity. In positive energy balance, a decreased capacity to expand SAT may drive lipid accumulation to visceral adipose tissue, liver and skeletal muscle. This state of lipotoxicity is associated with chronic low-grade inflammation, insulin resistance and dyslipidaemia. The present review examines the differential adipose tissue development and function in children and adolescents who exhibit metabolic dysregulation compared with those who are protected. Additionally, the role of manipulating dietary fat quality to potentially prevent and treat metabolic dysfunction in obesity will be discussed. The findings of the present review highlight the need for further randomised controlled trials to establish the effect of dietary n-3 PUFA on the metabolic phenotype of obese children and adolescents. Furthermore, using a personalised nutrition approach to target interventions to those at risk of, or those with established metabolic dysregulation may optimise the efficacy of modifying dietary fat quality.

Accumulation and elimination of polychlorinated dibenzo-p-dioxins and dibenzofurans in mule ducks.

PubMed

Wu, Ting-Wei; Lee, Jai-Wei; Liu, Hsueh-Yen; Lin, Wei-Hsiao; Chu, Chun-Yen; Lin, Sheng-Lun; Chang-Chien, Guo Ping; Yu, Chi

2014-11-01

In Taiwan, a food safety crisis involving a presence of high concentrations of dioxin residues in duck eggs occurred in 2004. The dioxin content in duck meat sampled from supermarkets was also reported to be substantially higher than in products from other farm animals. Despite increased awareness of the potential for contamination and exposure to dioxins, the accumulation and elimination of dioxins in ducks have not been well characterized. In the present study, mule ducks were fed capsules containing polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) for 14 days and the trial was continued for another 28 days without PCDD/Fs supplementation. Ducks were sacrificed on the 14th, 28th, and 42nd days from the beginning of administration and samples of abdominal fat, breast, and liver tissue were obtained. The concentrations of PCDD/Fs were analyzed in the samples to investigate their distribution and elimination in various duck tissues. The bioaccumulation of PCDD/Fs in ducks was found to be tissue-dependent. In the abdominal fat, the bioconcentration factor was negatively correlated with the degree of chlorination. Conversely, more chlorinated PCDD/Fs (hexa- or hepta-congeners) were associated with higher bioconcentration in the liver and breast tissue. In terms of the efficiency of PCDD/Fs elimination, the liver was found to be the fastest, followed by the breast and the abdominal fat. The clearance rate positively correlated with the degree of chlorination, as determined by comparing the apparent elimination rate constant (k) of PCDD/Fs in various tissues. Overall, lower k values observed in this study imply that mule ducks have a reduced clearance of PCDD/Fs in comparison with layer and broiler chickens. Copyright © 2014 Elsevier B.V. All rights reserved.

Liver Fatty Acid Composition and Inflammation in Mice Fed with High-Carbohydrate Diet or High-Fat Diet.

PubMed

da Silva-Santi, Lorena Gimenez; Antunes, Marina Masetto; Caparroz-Assef, Silvana Martins; Carbonera, Fabiana; Masi, Laureane Nunes; Curi, Rui; Visentainer, Jesuí Vergílio; Bazotte, Roberto Barbosa

2016-10-29

Both high-carbohydrate diet (HCD) and high-fat diet (HFD) modulate liver fat accumulation and inflammation, however, there is a lack of data on the potential contribution of carbohydrates and lipids separately. For this reason, the changes in liver fatty acid (FA) composition in male Swiss mice fed with HCD or HFD were compared, at the time points 0 (before starting the diets), and after 7, 14, 28 or 56 days. Activities of stearoyl-CoA desaturase-1 (SCD-1), ∆-6 desaturase (D6D), elongases and de novo lipogenesis (DNL) were estimated. Liver mRNA expression of acetyl-CoA carboxylase 1 (ACC1) was evaluated as an additional indicator of the de novo lipogenesis. Myeloperoxidase activity, nitric oxide (NO) production, and mRNA expressions of F4/80, type I collagen, interleukin (IL)-6, IL-1β, IL-10, and tumor necrosis factor-α (TNF-α) were measured as indication of the liver inflammatory state. The HCD group had more intense lipid deposition, particularly of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). This group also showed higher DNL, SCD-1, and D6D activities associated with increased NO concentration, as well as myeloperoxidase activity. Livers from the HFD group showed higher elongase activity, stored more polyunsaturated fatty acids (PUFAs) and had a lower omega-6/omega-3 fatty acid ( n -6/ n -3) ratio. In conclusion, liver lipid accumulation, fatty acids (FA) composition and inflammation were modulated by the dietary composition of lipids and carbohydrates. The HCD group had more potent lipogenic and inflammatory effects in comparison with HFD.

Comparison of Dorsocervical With Abdominal Subcutaneous Adipose Tissue in Patients With and Without Antiretroviral Therapy–Associated Lipodystrophy

PubMed Central

Sevastianova, Ksenia; Sutinen, Jussi; Greco, Dario; Sievers, Meline; Salmenkivi, Kaisa; Perttilä, Julia; Olkkonen, Vesa M.; Wågsäter, Dick; Lidell, Martin E.; Enerbäck, Sven; Eriksson, Per; Walker, Ulrich A.; Auvinen, Petri; Ristola, Matti; Yki-Järvinen, Hannele

2011-01-01

OBJECTIVE Combination antiretroviral therapy (cART) is associated with lipodystrophy, i.e., loss of subcutaneous adipose tissue in the abdomen, limbs, and face and its accumulation intra-abdominally. No fat is lost dorsocervically and it can even accumulate in this region (buffalo hump). It is unknown how preserved dorsocervical fat differs from abdominal subcutaneous fat in HIV-1–infected cART-treated patients with (cART+LD+) and without (cART+LD−) lipodystrophy. RESEARCH DESIGN AND METHODS We used histology, microarray, PCR, and magnetic resonance imaging to compare dorsocervical and abdominal subcutaneous adipose tissue in cART+LD+ (n = 21) and cART+LD− (n = 11). RESULTS Albeit dorsocervical adipose tissue in cART+LD+ seems spared from lipoatrophy, its mitochondrial DNA (mtDNA; copies/cell) content was significantly lower (by 62%) than that of the corresponding tissue in cART+LD−. Expression of CD68 mRNA, a marker of macrophages, and numerous inflammatory genes in microarray were significantly lower in dorsocervical versus abdominal subcutaneous adipose tissue. Genes with the greatest difference in expression between the two depots were those involved in regulation of transcription and regionalization (homeobox genes), irrespective of lipodystrophy status. There was negligible mRNA expression of uncoupling protein 1, a gene characteristic of brown adipose tissue, in either depot. CONCLUSIONS Because mtDNA is depleted even in the nonatrophic dorsocervical adipose tissue, it is unlikely that the cause of lipoatrophy is loss of mtDNA. Dorsocervical adipose tissue is less inflamed than lipoatrophic adipose tissue. It does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal subcutaneous adipose tissue is in expression of homeobox genes. PMID:21602514

Apo-10'-lycopenoic acid, a lycopene 1 metabolite, increases sirtuin 1 mRNA and protein levels and decreases hepatic fat accumulation in ob/ob mice

USDA-ARS?s Scientific Manuscript database

Lycopene has been shown to be beneficial in protecting against high-fat diet-induced fatty liver. The recent demonstration that lycopene can be converted by carotene 99,10’-oxygenase into a biologically active metabolite, ALA, led us to propose that the function of lycopene can be mediated by ALA. I...

The Definition and Prevalence of Obesity and Metabolic Syndrome.

PubMed

Engin, Atilla

2017-01-01

Increase in prevalence of obesity has become a worldwide major health problem in adults, as well as among children and adolescents. Furthermore, total adiposity and truncal subcutaneous fat accumulation during adolescence are positively and independently associated with atherosclerosis at adult ages. Centrally accumulation of body fat is associated with insulin resistance, whereas distribution of body fat in a peripheral pattern is metabolically less important. Obesity is associated with a large decrease in life expectancy. The effect of extreme obesity on mortality is greater among younger than older adults. In this respect, obesity is also associated with increased risk of several cancer types. However, up to 30% of obese patients are metabolically healthy with insulin sensitivity similar to healthy normal weight individuals, lower visceral fat content, and lower intima media thickness of the carotid artery than the majority of metabolically "unhealthy" obese patients.Abdominal obesity is the most frequently observed component of metabolic syndrome. The metabolic syndrome; clustering of abdominal obesity, dyslipidemia, hyperglycemia and hypertension, is a major public health challenge. The average prevalence of metabolic syndrome is 31%, and is associated with a two-fold increase in the risk of coronary heart disease, cerebrovascular disease, and a 1.5-fold increase in the risk of all-cause mortality.

Anti-obesity and anti-diabetic effects of ethanol extract of Artemisia princeps in C57BL/6 mice fed a high-fat diet.

PubMed

Yamamoto, Norio; Kanemoto, Yuki; Ueda, Manabu; Kawasaki, Kengo; Fukuda, Itsuko; Ashida, Hitoshi

2011-01-01

Artemisia princeps is commonly used as a food ingredient and in traditional Asian medicine. In this study, we examined the effects of long-term administration of an ethanol extract of A. princeps (APE) on body weight, white adipose tissue, blood glucose, insulin, plasma and hepatic lipids, and adipocytokines in C57BL/6 mice fed a high-fat diet. Daily feeding of a 1% APE diet for 14 weeks normalized elevated body weight, white adipose tissue, and plasma glucose and insulin levels, and delayed impaired glucose tolerance in mice a fed high-fat diet. These events were not observed in mice fed a control diet containing 1% APE. Liver triglyceride and cholesterol levels were similar in mice fed a 1% APE-diet and those fed a control diet. In the high-fat diet groups, APE inhibited hepatic fatty acid synthase (FAS) and suppressed the elevation of plasma leptin, but had no effect on adiponectin levels. These findings suggest that the regulation of leptin secretion by APE may inhibit FAS activity with subsequent suppression of triglyceride accumulation in the liver and adipose tissues. Inhibition of lipid accumulation can, in turn, lead to improvements in impaired glucose tolerance.

Deficiency of NPGPx, an oxidative stress sensor, leads to obesity in mice and human

PubMed Central

Chang, Yi-Cheng; Yu, Yu-Hsiang; Shew, Jin-Yuh; Lee, Wei-Jei; Hwang, Juey-Jen; Chen, Yen-Hui; Chen, Yet-Ran; Wei, Pei-Chi; Chuang, Lee-Ming; Lee, Wen-Hwa

2013-01-01

Elevated oxidative stress is closely associated with obesity. Emerging evidence shows that instead of being a consequence of obesity, oxidative stress may also contribute to fat formation. Nonselenocysteine-containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) is a conserved oxidative stress sensor/transducer and deficiency of NPGPx causes accumulation of reactive oxygen species (ROS). In this communication, we show that NPGPx was highly expressed in preadipocytes of adipose tissue. Deficiency of NPGPx promoted preadipocytes to differentiate to adipocytes via ROS-dependent dimerization of protein kinase A regulatory subunits and activation of CCAAT/enhancer-binding protein beta (C/EBPβ). This enhanced adipogenesis was alleviated by antioxidant N-acetylcysteine (NAC). Consistently, NPGPx-deficient mice exhibited markedly increased fat mass and adipocyte hypertrophy, while treatment with NAC ablated these phenotypes. Furthermore, single nucleotide polymorphisms (SNPs) in human NPGPx gene, which correlated with lower NPGPx expression level in adipose tissue, were associated with higher body mass index (BMI) in several independent human populations. These results indicate that NPGPx protects against fat accumulation in mice and human via modulating ROS, and highlight the importance of targeting redox homeostasis in obesity management. Deficiency of the glutathione peroxidase NPGPx increases ROS levels in preadipocytes and promotes adipocyte differentiation via increasing oxidative stress and consequent increased fat mass and adipocyte hypertrophy. PMID:23828861

Dolichos lablab Protects Against Nonalcoholic Fatty Liver Disease in Mice Fed High-Fat Diets.

PubMed

Im, A-Rang; Kim, Yun Hee; Kim, Young Hwa; Yang, Won-Kyung; Kim, Seung Hyung; Song, Kwang Hoon

2017-12-01

Hyacinth bean, Dolichos lablab or Lablab purpureus, has been used for centuries in India and China as an edible pod and animal forage, as well as to treat diarrhea and other gastrointestinal disease in traditional Korean medicine. Recently, we have demonstrated that D. lablab extract (DLL-Ex) prevented free fatty acid-induced lipid accumulation in an in vitro cellular nonalcoholic fatty liver disease (NAFLD) model. In this study, we, thus, aimed at clarifying the hepatoprotective effects of DLL-Ex in a high-fat diet-induced in vivo animal NAFLD model, as well as at elucidating underlying mechanisms of identified effects. Sixty, 6-week-old, male C57BL/6J mice were randomly divided into six groups: a control group fed a low-fat diet, four high-fat diet (HFD) groups, three receiving daily oral supplementation of DLL-Ex (25, 50, and 100 mg/kg/day), and one HFD group receiving daily oral supplementation of MILK (100 mg/kg/day). Effects of DLL-Ex supplementation were evaluated by histopathological and histochemical assessments. DLL-Ex supplementation inhibited HFD-induced increases in body weight and body fat mass and ameliorated increases in body weight, manifested as decreased liver function tests, lower serum triglycerides and cholesterol levels, and increased serum adiponectin levels. The expression of hepatic genes involved in lipid droplet accumulation and in fatty acid uptake was also decreased. We provide evidence of a protective effect of DLL-Ex against HFD-induced fatty liver disease in an animal model.

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children.

PubMed

Knøsgaard, L; Kazankov, K; Birkebæk, N H; Holland-Fischer, P; Lange, A; Solvig, J; Hørlyck, A; Kristensen, K; Rittig, S; Vilstrup, H; Grønbæk, H; Handberg, A

2016-09-01

Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications.

Improvement of metabolic disorders by an EP2 receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.

PubMed

Tsuji, Takao; Yamaguchi, Kazuhiro; Kikuchi, Ryota; Nakamura, Hiroyuki; Misaka, Ryoichi; Nagai, Atsushi; Aoshiba, Kazutetsu

2017-05-01

Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhancement of Muscle Mitochondrial Oxidative Capacity and Alterations in Insulin Action Are Lipid Species Dependent

PubMed Central

Turner, Nigel; Hariharan, Krit; TidAng, Jennifer; Frangioudakis, Georgia; Beale, Susan M.; Wright, Lauren E.; Zeng, Xiao Yi; Leslie, Simon J.; Li, Jing-Ya; Kraegen, Edward W.; Cooney, Gregory J.; Ye, Ji-Ming

2009-01-01

OBJECTIVE Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action. RESEARCH DESIGN AND METHODS C57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4–5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured. RESULTS Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P < 0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20–50%, P < 0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet–fed controls; however; the increase in oxidative capacity was substantially greater in MCFA-fed animals (50–140% versus low-fat–fed controls, P < 0.01). The MCFA diet induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic enzymes. In rats, isocaloric feeding of MCFA or LCFA high-fat diets induced hepatic insulin resistance to a similar degree; however, insulin action was preserved at the level of low-fat diet–fed controls in muscle and adipose from MCFA-fed animals. CONCLUSIONS MCFAs reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance in the liver. Dietary supplementation with MCFAs may therefore be beneficial for preventing obesity and peripheral insulin resistance. PMID:19720794

AAV-Mediated Administration of Myostatin Pro-Peptide Mutant in Adult Ldlr Null Mice Reduces Diet-Induced Hepatosteatosis and Arteriosclerosis

PubMed Central

Guo, Wen; Wong, Siu; Bhasin, Shalender

2013-01-01

Genetic disruption of myostatin or its related signaling is known to cause strong protection against diet-induced metabolic disorders. The translational value of these prior findings, however, is dependent on whether such metabolically favorable phenotype can be reproduced when myostatin blockade begins at an adult age. Here, we reported that AAV-mediated delivery of a myostatin pro-peptide D76A mutant in adult mice attenuates the development of hepatic steatosis and arteriosclerosis, two common diet-induced metabolic diseases. A single dose of AAV-D76A in adult Ldlr null mice resulted in sustained expression of myostatin pro-peptide in the liver. Compared to vehicle-treated mice, D76A-treated mice gained similar amount of lean and fat mass when fed a high fat diet. However, D76A-treated mice displayed significantly reduced aortic lesions and liver fat, in association with a reduction in hepatic expression of lipogenic genes and improvement in liver insulin sensitivity. This suggests that muscle and fat may not be the primary targets of treatment under our experimental condition. In support to this argument, we show that myostatin directly up-regulated lipogenic genes and increased fat accumulation in cultured liver cells. We also show that both myostatin and its receptor were abundantly expressed in mouse aorta. Cultured aortic endothelial cells responded to myostatin with a reduction in eNOS phosphorylation and an increase in ICAM-1 and VCAM-1 expression. Conclusions: AAV-mediated expression of myostatin pro-peptide D76A mutant in adult Ldlr null mice sustained metabolic protection without remarkable impacts on body lean and fat mass. Further investigations are needed to determine whether direct impact of myostatin on liver and aortic endothelium may contribute to the related metabolic phenotypes. PMID:23936482

1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents.

PubMed

Fonvig, Cilius Esmann; Chabanova, Elizaveta; Andersson, Ehm Astrid; Ohrt, Johanne Dam; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

2015-01-01

This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children. Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years. In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol. Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.

Alleviative effects of deep-seawater drinking water on hepatic lipid accumulation and oxidation induced by a high-fat diet.

PubMed

Chen, I-Shu; Chang, Yuan-Yen; Hsu, Chin-Lin; Lin, Hui-Wen; Chang, Ming-Hsu; Chen, Jr-Wei; Chen, Sheng-Shih; Chen, Yi-Chen

2013-02-01

Hepatic steatosis is defined as excessive amounts of triglyceride and other fats inside liver cells and has become an emergent liver disease in developed and developing countries. Deep seawater (DSW)300, DSW900, and DSW1500 drinking waters were formulated via a combination of reverse osmosis and electrodialysis. Hamsters on a high-fat diet were assigned to drink the following solutions: (1) normal distilled water, (2) DSW300, (3) DSW900, or (4) DSW1500. Serum, liver, and fecal biochemical values, expression of hepatic genes related to fatty-acid homeostasis, as well as liver antioxidative levels were measured after a 6-week feeding period. Additionally, hematoxylin and eosin staining was used to investigate the liver histopathology. Serum/liver lipids, liver sizes, liver malondialdehyde content, and serum aspartate aminotransferase and alanine aminotransferase of high-fat diet hamsters were reduced (p < 0.05) by drinking DSW, while daily fecal lipid and bile acid outputs were increased (p < 0.05). DSW drinking water maintained (p < 0.05) higher liver glutathione and Trolox equivalent antioxidant capacity levels. Although hepatic sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and malic enzyme gene expression were not (p > 0.05) altered, DSW drinking water upregulated (p < 0.05) hepatic peroxisome proliferator-activated receptor-alpha, retinoid X receptor alpha, and uncoupling protein-2 gene expression in high-fat diet hamsters. The lipid droplets in livers were also reduced in DSW-drinking-water groups as compared to those only drinking distilled water. DSW shows a preventive effect on development of hepatosteatosis induced by a high-fat diet. Copyright © 2012. Published by Elsevier B.V.

Dietary α-cyclodextrin modifies gut microbiota and reduces fat accumulation in high-fat-diet-fed obese mice.

PubMed

Nihei, Nanako; Okamoto, Hinako; Furune, Takahiro; Ikuta, Naoko; Sasaki, Kengo; Rimbach, Gerald; Yoshikawa, Yutaka; Terao, Keiji

2018-05-07

We investigated the effect of α-cyclodextrin (α-CD) on the bacterial populations of gut microbiota, production of organic acids, and short-chain fatty acids (SCFAs), and lipid metabolism in obese mice induced by feeding a high-fat diet (HFD). Male C57BL/6J mice were assigned to three diet groups: normal diet (ND) (5% [w/w] fat), HFD (35% [w/w] fat), and HFD (35% [w/w] fat) + 5.5% (w/w) α-CD for 16 weeks. Increases in body and epididymal adipose tissue weights were observed in the HFD group compared with the ND group, which were attenuated in the HFD+α-CD group. The supplementation of α-CD increased the total number of bacteria, Bacteroides, Bifidobacterium, and Lactobacillus that were decreased in gut microbiota of mice by feeding the HFD. Importantly, α-CD administration increased the concentrations of lactic acid and SCFAs, such as acetic, propionic, and butyric acids, and decreased glucose concentrations in cecal contents. Furthermore, supplementation of α-CD upregulated the gene expression of peroxisome proliferator-activated receptor (PPAR)γ involved in adipocyte differentiation and PPARα involved in energy expenditure and downregulated that of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase involved in fatty acid and triglyceride synthesis in adipose tissue. This study revealed that the alteration in gut microbiota and increased production of lactic acid and SCFAs by supplementation of α-CD have beneficial antiobesity effects via modulating the expression of genes related to lipid metabolism, indicating a prebiotic property of α-CD. © 2018 BioFactors, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Carnosic acid as a major bioactive component in rosemary extract ameliorates high-fat-diet-induced obesity and metabolic syndrome in mice.

PubMed

Zhao, Yantao; Sedighi, Rashin; Wang, Pei; Chen, Huadong; Zhu, Yingdong; Sang, Shengmin

2015-05-20

In this study, we investigated the preventive effects of carnosic acid (CA) as a major bioactive component in rosemary extract (RE) on high-fat-diet-induced obesity and metabolic syndrome in mice. The mice were given a low-fat diet, a high-fat diet or a high-fat diet supplemented with either 0.14% or 0.28% (w/w) CA-enriched RE (containing 80% CA, RE#1L and RE#1H), or 0.5% (w/w) RE (containing 45% CA, RE#2), for a period of 16 weeks. There was the same CA content in the RE#1H and RE#2 diets and half of this amount in the RE#1L diet. The dietary RE supplementation significantly reduced body weight gain, percent of fat, plasma ALT, AST, glucose, insulin levels, liver weight, liver triglyceride, and free fatty acid levels in comparison with the mice fed with a HF diet without RE treatment. RE administration also decreased the levels of plasma and liver malondialdehyde, advanced glycation end products (AGEs), and the liver expression of receptor for AGE (RAGE) in comparison with those for mice of the HF group. Histological analyses of liver samples showed decreased lipid accumulation in hepatocytes in mice administrated with RE in comparison with that of HF-diet-fed mice. Meanwhile, RE administration enhanced fecal lipid excretion to inhibit lipid absorption and increased the liver GSH/GSSG ratio to perform antioxidant activity compared with HF group. Our results demonstrate that rosemary is a promising dietary agent to reduce the risk of obesity and metabolic syndrome.

Quantitative monitoring of lipid accumulation over time in cultured adipocytes as function of culture conditions: toward controlled adipose tissue engineering.

PubMed

Or-Tzadikario, Shira; Sopher, Ran; Gefen, Amit

2010-10-01

Adipose tissue engineering is investigated for native fat substitutes and wound healing model systems. Research and clinical applications of bioartificial fat require a quantitative and objective method to continuously measure adipogenesis in living cultures as opposed to currently used culture-destructive techniques that stain lipid droplet (LD) accumulation. To allow standardization, automatic quantification of LD size is further needed, but currently LD size is measured mostly manually. We developed an image processing-based method that does not require staining to monitor adipose cell maturation in vitro nondestructively using optical micrographs taken consecutively during culturing. We employed our method to monitor LD accumulation in 3T3-L1 and mesenchymal stem cells over 37 days. For each cell type, percentage of lipid area, number of droplets per cell, and droplet diameter were obtained every 2-3 days. In 3T3-L1 cultures, high insulin concentration (10 microg/mL) yielded a significantly different (p < 0.01) time course of all three outcome measures. In mesenchymal stem cell cultures, high fetal bovine serum concentration (12.5%) produced significantly more lipid area (p < 0.01). Our method was able to successfully characterize time courses and extents of adipogenesis and is useful for a wide range of applications testing the effects of biochemical, mechanical, and thermal stimulations in tissue engineering of bioartificial fat constructs.

Mitochondrial-Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation.

PubMed

Lee, Hui-Young; Lee, Jae Sung; Alves, Tiago; Ladiges, Warren; Rabinovitch, Peter S; Jurczak, Michael J; Choi, Cheol Soo; Shulman, Gerald I; Samuel, Varman T

2017-08-01

We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute infusion of a lipid emulsion. RC-fed MCAT mice were similar to littermate wild-type (WT) mice. However, HFD-fed MCAT mice were protected from diet-induced insulin resistance. In contrast, an acute lipid infusion caused muscle insulin resistance in both MCAT and WT mice. ROS production was decreased in both HFD-fed and lipid-infused MCAT mice and cannot explain the divergent response in insulin action. MCAT mice had subtly increased energy expenditure and muscle fat oxidation with decreased intramuscular diacylglycerol (DAG) accumulation, protein kinase C-θ (PKCθ) activation, and impaired insulin signaling with HFD. In contrast, the insulin resistance with the acute lipid infusion was associated with increased muscle DAG content in both WT and MCAT mice. These studies suggest that altering muscle mitochondrial ROS production does not directly alter the development of lipid-induced insulin resistance. However, the altered energy balance in HFD-fed MCAT mice protected them from DAG accumulation, PKCθ activation, and impaired muscle insulin signaling. © 2017 by the American Diabetes Association.

The fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms improves insulin resistance and hepatic lipid accumulation by modulation of liver adenosine monophosphate-activated protein kinase activity and lipogenic gene expression in high-fat diet-fed obese mice.

PubMed

Saito, Tetsuo; Nishida, Miyako; Saito, Masafumi; Tanabe, Akari; Eitsuka, Takahiro; Yuan, Shi-Hua; Ikekawa, Nobuo; Nishida, Hiroshi

2016-10-01

Obesity-associated insulin resistance is a major risk factor for most metabolic diseases, including dyslipidemia and type 2 diabetes. Acanthopanax senticosus (Rupr. et Maxim.) Harms (Goka) root has been used in traditional Chinese medicine for treatment of diabetes and other conditions; however, little is known about the effects of Goka fruit (GF). Goka fruit is rich in anthocyanin, which has beneficial effects on obesity and insulin resistance via activation of adenosine monophosphate-activated protein kinase (AMPK). We hypothesized that GF can improve obesity-associated insulin resistance. The aim of the present study was to investigate whether GF improves insulin resistance in high-fat diet (HFD)-induced obese mice. High-fat diet mice treated with GF (500 and 1000 mg/kg) for 12 weeks showed an improved glucose tolerance and insulin sensitivity, as well as reduced plasma insulin and liver lipid accumulation. Moreover, GF administration to HFD mice resulted in down-regulation of fatty acid synthase expression and up-regulation of cholesterol 7-alpha-hydroxylase expression in the liver. Notably, AMPK phosphorylation in the liver increased after GF administration. In summary, GF supplementation improved obesity-associated insulin resistance and hepatic lipid accumulation through modulation of AMPK activity and lipid metabolism-associated gene expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Pre-hibernation energy reserves in a temperate anuran, Rana chensinensis, along a relatively fine elevational gradient

USGS Publications Warehouse

Lu, X.; Li, B.; Li, Y.; Ma, X.; Fellers, G.M.

2008-01-01

Temperate anurans have energy substrates in the liver, fat bodies, carcass and gonads; these stores provide support for metabolism and egg production during hibernation, and for breeding activities in spring. This paper compares the energy budget shortly before hibernation among Rana chensinensis populations at elevations of 1400, 1700 and 2000 m along a river in northern China. The larger frogs, regardless of elevation, had relatively heavy storage organs and the masses of nearly all these organs were positively correlated with each other. After controlling for the effect of body size, we found no significant difference in energetic organ mass among different age classes for each of the three populations. There were sexual differences in energy strategy. Males in all populations accumulated greater reserves in liver, fat bodies and carcass than did females. In contrast, females put more energy into their ovaries and oviducts. Frogs from higher elevations tended to have heavier organs than those from lower elevations; however, the pattern did not vary systematically along fine environmental gradients. Mid-elevation R. chensinensis built up significantly more reserves than low-elevation individuals, but were similar to their highland conspecifics. Males from higher elevations tended to have heavier liver and fat bodies; females were similar in liver and ovary mass across all elevations, but formed heavier fat bodies, oviducts and somatic tissue at higher elevation sites.

A mouse model for a partially inactive obesity-associated human MC3R variant

PubMed Central

Lee, Bonggi; Koo, Jashin; Yun Jun, Joo; Gavrilova, Oksana; Lee, Yongjun; Seo, Arnold Y.; Taylor-Douglas, Dezmond C.; Adler-Wailes, Diane C.; Chen, Faye; Gardner, Ryan; Koutzoumis, Dimitri; Sherafat Kazemzadeh, Roya; Roberson, Robin B.; Yanovski, Jack A.

2016-01-01

We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3RhWT/hWT) and double-mutant (C17A+G241A) human (MC3RhDM/hDM) MC3R, that MC3RhDM/hDM have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3RhWT/hWT. MC3RhDM/hDM mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3RhDM/hDM mice and MC3RhDM/hDM human subjects. MC3RhDM/hDM bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3RhWT/hWT MSCs. MC3RhDM/hDM impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development. PMID:26818770

Propolis prevents diet-induced hyperlipidemia and mitigates weight gain in diet-induced obesity in mice.

PubMed

Koya-Miyata, Satomi; Arai, Norie; Mizote, Akiko; Taniguchi, Yoshifumi; Ushio, Shimpei; Iwaki, Kanso; Fukuda, Shigeharu

2009-12-01

We examined the hypolipidemic effect of propolis in a mouse obesity model induced by a high fat-diet. C57BL/6N mice were fed a high-fat diet ad libitum and given propolis extract intragastrically at 0 mg/kg (control), 5 mg/kg or 50 mg/kg twice daily for 10 d. Compared with mice in the control group, mice in the propolis extract-administrated groups displayed a reduction in all of the following parameters: body weight gain, weight of visceral adipose tissue, liver and serum triglycerides, cholesterol, and non-esterified fatty acids. Real-time polymerase chain reaction analysis of the liver showed down-regulation of mRNA expression associated with fatty acid biosynthesis, including fatty acid synthase, acetyl-CoA carboxylase alpha, and sterol regulatory element binding protein in the propolis-administrated mice. Subsequently, obese C57BL/6N mice that had been administered a high-fat diet were given propolis extract at 0 mg/kg (control), 2.5 mg/kg or 25 mg/kg for 4 weeks. The propolis extract treated mice showed a decrease in weight gain, a reduction of serum non-esterified fatty acids, and lipid accumulation in the liver. These results suggest that propolis extract prevented and mitigated high-fat diet-induced hyperlipidemia by down-regulating the expression of genes associated with lipid metabolism.

Fiber type- and fatty acid composition-dependent effects of high-fat diets on rat muscle triacylglyceride and fatty acid transporter protein-1 content.

PubMed

Marotta, Mario; Ferrer-Martnez, Andreu; Parnau, Josep; Turini, Marco; Macé, Katherine; Gómez Foix, Anna M

2004-08-01

Intramuscular triacylglyceride (TAG) is considered an independent marker of insulin resistance in humans. Here, we examined the effect of high-fat diets, based on distinct fatty acid compositions (saturated, monounsaturated or n-6 polyunsaturated), on TAG levels and fatty acid transporter protein (FATP-1) expression in 2 rat muscles that differ in their fiber type, soleus, and gastrocnemius; the relationship to whole body glucose intolerance was also studied. Compared with carbohydrate-fed rats, the groups subjected to any one of the high-fat diets consistently exhibited enhanced body weight gain and adiposity, elevated plasma free fatty acids and TAG in the fed condition, hyperinsulinemia, and glucose intolerance. TAG content was consistently higher in soleus than in gastrocnemius, but was only significantly elevated by the n-6 polyunsaturated-based diet. FATP-1 levels in soleus were double those in gastrocnemius muscle in carbohydrate-fed animals. High-fat diets caused an elevation in FATP-1 protein content in soleus, but a reduction in gastrocnemius. In conclusion, the hyperinsulinemic hyperlipidemic condition upregulates FATP-1 expression in soleus and downregulates that of gastrocnemius. Hypercaloric saturated, monounsaturated, or n-6 polyunsaturated lipid diets cause equivalent whole body insulin resistance in rats, but only an n-6 polyunsaturated acid-based diet triggers intramuscular TAG accumulation. Copyright 2004 Elsevier Inc.

Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease

PubMed Central

Wang, Zhigang; Yao, Tong; Pini, Maria; Zhou, Zhanxiang; Fantuzzi, Giamila

2010-01-01

Adipose tissue dysfunction, featured by insulin resistance and/or dysregulated adipokine production, plays a central role not only in disease initiation but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Promising beneficial effects of betaine supplementation on nonalcoholic fatty liver disease (NAFLD) have been reported in both clinical investigations and experimental studies; however, data related to betaine therapy in NAFLD are still limited. In this study, we examined the effects of betaine supplementation on hepatic fat accumulation and injury in mice fed a high-fat diet and evaluated mechanisms underlying its hepatoprotective effects. Male C57BL/6 mice weighing 25 ± 0.5 (SE) g were divided into four groups (8 mice/group) and started on one of four treatments: control diet, control diet supplemented with betaine, high-fat diet, and high-fat diet supplemented with betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Our results showed that long-term high-fat feeding caused NAFLD in mice, which was manifested by excessive neutral fat accumulation in the liver and elevated plasma alanine aminotransferase levels. Betaine supplementation alleviated hepatic pathological changes, which were concomitant with attenuated insulin resistance as shown by improved homeostasis model assessment of basal insulin resistance values and glucose tolerance test, and corrected abnormal adipokine (adiponectin, resistin, and leptin) productions. Specifically, betaine supplementation enhanced insulin sensitivity in adipose tissue as shown by improved extracellular signal-regulated kinases 1/2 and protein kinase B activations. In adipocytes freshly isolated from mice fed a high-fat diet, pretreatment of betaine enhanced the insulin signaling pathway and improved adipokine productions. Further investigation using whole liver tissues revealed that betaine supplementation alleviated the high-fat diet-induced endoplasmic reticulum stress response in adipose tissue as shown by attenuated glucose-regulated protein 78/C/EBP homologous protein (CHOP) protein abundance and c-Jun NH2-terminal kinase activation. Our findings suggest that betaine might serve as a safe and efficacious therapeutic tool for NAFLD by improving adipose tissue function. PMID:20203061

Accumulation of (18)F-FDG in the liver in hepatic steatosis.

PubMed

Keramida, Georgia; Potts, Jonathan; Bush, Jan; Verma, Sumita; Dizdarevic, Sabina; Peters, Adrien M

2014-09-01

Nonalcoholic fatty liver disease is associated with hepatic inflammation. An emerging technique to image inflammation is PET using the glucose tracer, (18)F-FDG. The purpose of this study was to determine whether in hepatic steatosis the liver accumulates FDG in excess of FDG physiologically exchanging between blood and hepatocyte. Hepatic FDG uptake, as SUV = [voxel counts / administered activity] × body weight), and CT density were measured in a liver region in images obtained 60 minutes after injection of FDG in 304 patients referred for routine PET/CT. Maximum SUV (region voxel with the highest count rate, SUVmax) and average SUV ( SUVave) were measured. Blood FDG concentration was measured as the maximum SUV over the left ventricular cavity (SUVLV). SUVave was adjusted for hepatic fat using a formula equating percentage fat to CT density. Patients were divided in subgroups on the basis of blood glucose (< 4, 4 to < 5, 5 to < 6, 6 to < 8, 8 to < 10, and > 10 mmol/L). Hepatic steatosis was defined as CT density less than 40 HU (n = 71). The percentage of hepatic fat increased exponentially with blood glucose. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV but not SUVave / SUVLV correlated with blood glucose. Fat-adjusted SUVave was higher in patients with hepatic steatosis (p < 0.001) by ~0.4 in all blood glucose groups. There was a similar difference (~0.3) in SUVmax (p < 0.005) but no difference in SUVave. SUVmax / SUVLV and fat-adjusted SUVave / SUVLV correlated with blood glucose in patients with hepatic steatosis but not in those without. SUVave / SUVLV correlated with blood glucose in neither group. FDG uptake is increased in hepatic steatosis, probably resulting from irreversible uptake in inflammatory cells superimposed on reversible hepatocyte uptake.

An advanced glycation endproduct (AGE)-rich diet promotes accumulation of AGEs in Achilles tendon.

PubMed

Skovgaard, Dorthe; Svensson, Rene B; Scheijen, Jean; Eliasson, Pernilla; Mogensen, Pernille; Hag, Anne Mette F; Kjær, Michael; Schalkwijk, Casper G; Schjerling, Peter; Magnusson, Stig P; Couppé, Christian

2017-03-01

Advanced Glycation Endproducts (AGEs) accumulate in long-lived tissue proteins like collagen in bone and tendon causing modification of the biomechanical properties. This has been hypothesized to raise the risk of orthopedic injury such as bone fractures and tendon ruptures. We evaluated the relationship between AGE content in the diet and accumulation of AGEs in weight-bearing animal Achilles tendon. Two groups of mice (C57BL/6Ntac) were fed with either high-fat diet low in AGEs high-fat diet (HFD) ( n  = 14) or normal diet high in AGEs (ND) ( n  = 11). AGE content in ND was six to 50-fold higher than HFD The mice were sacrificed at week 40 and Achilles and tail tendons were carefully excised to compare weight and nonweight-bearing tendons. The amount of the AGEs carboxymethyllysine (CML), methylglyoxal-derived hydroimidazolone (MG-H1) and carboxyethyllysine (CEL) in Achilles and tail tendon was measured using ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and pentosidine with high-pressure liquid chromatography (HPLC) with fluorescent detection. AGEs in Achilles tendon were higher than in tail tendon for CML ( P  < 0.0001), CEL ( P  < 0.0001), MG-H1 and pentosidine (for both ND and HFD) ( P  < 0.0001). The AGE-rich diet (ND) resulted in an increase in CML ( P  < 0.0001), MG-H1 ( P  < 0.001) and pentosidine ( P  < 0.0001) but not CEL, in Achilles and tail tendon. This is the first study to provide evidence for AGE accumulation in injury-prone, weight-bearing Achilles tendon associated with intake of an AGE-rich diet. This indicates that food-derived AGEs may alter tendon properties and the development of tendon injuries. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Ganoderic Acid A improves high fat diet-induced obesity, lipid accumulation and insulin sensitivity through regulating SREBP pathway.

PubMed

Zhu, Jing; Jin, Jie; Ding, Jiexia; Li, Siying; Cen, Panpan; Wang, Keyi; Wang, Hai; Xia, Junbo

2018-06-25

Obesity and its major co-morbidity, type 2 diabetes, have been an alarming epidemic prevalence without an effective treatment available. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. Therefore, inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Here, we identify a small molecule, Ganoderic Acid A (GAA), inhibits the SREBP expression and decreases the cellular levels of cholesterol and fatty acid in vitro. GAA also ameliorates body weight gain and fat accumulation in liver or adipose tissues, and improves serum lipid levels and insulin sensitivity in high fat diet (HFD)-induced obese mice. Consistently, GAA regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Taken together, GAA could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance. Copyright © 2018. Published by Elsevier B.V.

Elevated fat skatole levels in immunocastrated, surgically castrated and entire male pigs with acute dysentery.

PubMed

Skrlep, Martin; Batorek, Nina; Bonneau, Michel; Fazarinc, Gregor; Segula, Blaž; Candek-Potokar, Marjeta

2012-12-01

Boar taint is due to androstenone and skatole (3-methyl-indole) accumulation in fat tissues. During a study to investigate the effect of immunocastration on fattening pigs, an outbreak of acute dysentery occurred caused by Lawsonia intracellularis and Brachyspira hyodysenteriae and resulted in cachexia and high mortality. Low androstenone levels in the immunocastrates (0.25 ± 0.04 μg/g liquid fat) suggested that the immunocastration had been effective, but unusually high skatole concentrations in fat tissues were found not only in entire males, but also in surgical castrates and immunocastrates (0.22 ± 0.15, 0.14 ± 0.08 and 0.18 ± 0.14 μg/g liquid fat, respectively). The findings suggest that boar taint can arise in cases of intestinal infections, even in castrated pigs. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Prevention of Pediatric Obesity During Pregnancy: A Pilot Study

DTIC Science & Technology

2012-09-24

years (Sievers, et al., 2002). Formula and breast milk also have been shown to have different protein levels (Koletzko et al., 2005). Most formulas...fiber intake. Also, enough servings of meat, poultry, low- fat dairy, and/or legumes will help make sure that women are meeting their protein needs...prevent overweight and obesity, clear definitions of the conditions must exist. Obesity is defined as the accumulation of excess body fat to the

Feasibility Study of a Novel Diet-Based Intervention for Prostate Cancer

DTIC Science & Technology

2013-11-01

of nutritional practice ( 40 -42). Carotenoids, which are fat- soluble pigments found almost exclusively in vegetables and fruits , accumulate in blood...flashes who had higher vegetable , fruit and fiber and lower fat intakes (70). These data tentatively support the notion that diet change may alter the...period. 4.2.2 Patients consuming ≥ 6 servings per day of fruits and vegetables (not including juices ), as measured by a food frequency questionnaire

Berberine attenuates oxidative stress and hepatocytes apoptosis via protecting mitochondria in blunt snout bream Megalobrama amblycephala fed high-fat diets.

PubMed

Lu, Kang-Le; Wang, Li-Na; Zhang, Ding-Dong; Liu, Wen-Bin; Xu, Wei-Na

2017-02-01

High-fat diets may have favorable effects on growth and cost, but high-fat diets often induce excessive fat deposition, resulting in liver damage. This study aimed to identify the hepatoprotective of a Chinese herb (berberine) for blunt snout bream (Megalobrama amblycephala). Fish were fed with a normal diet (LFD, 5 % fat), high-fat diet (HFD, 15 % fat) or berberine-supplemented diets (BSD, 15 % fat with berberine 50 or 100 mg/kg level) for 8 weeks. After the feeding, histology, oxidative status and mitochondrial function of liver were assessed. The results showed that HFD caused fat accumulation, oxidative stress and apoptosis in hepatocytes of fish. Hepatocytes in HFD group appeared to be hypertrophied, with larger liver cells diameter than these of LFD group. Berberine-supplemented diets could attenuate oxidative stress and hepatocytes apoptosis. HFD induced the decreasing mitochondrial complexes activities and bulk density and surface area density. Berberine improved function of mitochondrial respiratory chain via increasing the complex activities. Moreover, the histological results showed that berberine has the potential to repair mitochondrial ultrastructural damage and elevate the density in cells. In conclusion, our study demonstrated that berberine has attenuated liver damage induced by the high fat mainly via the protection for mitochondria.

Intermuscular and perimuscular fat expansion in obesity correlates with skeletal muscle T cell and macrophage infiltration and insulin resistance

PubMed Central

Khan, Ilvira M.; Dai Perrard, Xiao-Yuan; Brunner, Gerd; Lui, Hua; Sparks, Lauren M.; Smith, Steven R.; Wang, Xukui; Shi, Zheng-Zheng; Lewis, Dorothy E.; Wu, Huaizhu; Ballantyne, Christie M.

2015-01-01

Background/Objectives Limited numbers of studies demonstrated obesity-induced macrophage infiltration in skeletal muscle (SM), but dynamics of immune cell accumulation and contribution of T cells to SM insulin resistance are understudied. Subjects/Methods T cells and macrophage markers were examined in SM of obese humans by RT-PCR. Mice were fed high-fat diet (HFD) for 2–24 weeks, and time course of macrophage and T cell accumulation was assessed by flow cytometry and quantitative RT-PCR. Extramyocellular adipose tissue (EMAT) was quantified by high-resolution micro-CT, and correlation to T cell number in SM was examined. CD11a−/− mice and C57BL/6 mice were treated with CD11a-neutralizing antibody to determine the role of CD11a in T cell accumulation in SM. To investigate the involvement JAK/STAT, the major pathway for T helper I (TH1) cytokine IFNγ? in SM and adipose tissue inflammation and insulin resistance, mice were treated with a JAK1/JAK2 inhibitor, baricitinib. Results Macrophage and T cells markers were upregulated in SM of obese compared with lean humans. SM of obese mice had higher expression of inflammatory cytokines, with macrophages increasing by 2 weeks on HFD and T cells increasing by 8 weeks. The immune cells were localized in EMAT. Micro-CT revealed that EMAT expansion in obese mice correlated with T cell infiltration and insulin resistance. Deficiency or neutralization of CD11a reduced T cell accumulation in SM of obese mice. T cells polarized into a proinflammatory TH1 phenotype, with increased STAT1 phosphorylation in SM of obese mice. In vivo inhibition of JAK/STAT pathway with baricitinib reduced T cell numbers and activation markers in SM and adipose tissue and improved insulin resistance in obese mice. Conclusions Obesity-induced expansion of EMAT in SM was associated with accumulation and proinflammatory polarization of T cells, which may regulate SM metabolic functions through paracrine mechanisms. Obesity-associated SM “adiposopathy” may thus play an important role in development of insulin resistance and inflammation. PMID:26041698

DASH diet, insulin resistance, and serum hs-CRP in polycystic ovary syndrome: a randomized controlled clinical trial.

PubMed

Asemi, Z; Esmaillzadeh, A

2015-03-01

This study was designed to assess the effects of Dietary Approaches to Stop Hypertension (DASH) eating plan on insulin resistance and serum hs-CRP in overweight and obese women with PCOS. This randomized controlled clinical trial was done on 48 women diagnosed with PCOS. Subjects were randomly assigned to consume either the control (n=24) or the DASH eating pattern (n=24) for 8 weeks. The DASH diet consisted of 52% carbohydrates, 18% proteins, and 30% total fats. It was designed to be rich in fruits, vegetables, whole grains, and low-fat dairy products and low in saturated fats, cholesterol, refined grains, and sweets. Sodium content of the DASH diet was designed to be less than 2 400 mg/day. The control diet was also designed to contain 52% carbohydrates, 18% protein, and 30% total fat. Fasting blood samples were taken at baseline and after 8 weeks intervention to measure -insulin resistance and serum hs-CRP levels. -Adherence to the DASH eating pattern, compared to the -control diet, resulted in a significant reduction of serum insulin levels (-1.88 vs. 2.89 μIU/ml, p=0.03), HOMA-IR score (-0.45 vs. 0.80; p=0.01), and serum hs-CRP levels (-763.29 vs. 665.95 ng/ml, p=0.009). Additionally, a significant reduction in waist (-5.2 vs. -2.1 cm; p=0.003) and hip circumference (-5.9 vs. -1 cm; p<0.0001) was also seen in the DASH group compared with the control group. In conclusion, consumption of the DASH eating pattern for 8 weeks in overweight and obese women with PCOS resulted in the improvement of insulin resistance, serum hs-CRP levels, and abdominal fat accumulation. www.irct.ir: IRCT201304235623N6. © Georg Thieme Verlag KG Stuttgart · New York.

Accretion of visceral fat and hepatic insulin resistance in pregnant rats.

PubMed

Einstein, Francine H; Fishman, Sigal; Muzumdar, Radhika H; Yang, Xiao Man; Atzmon, Gil; Barzilai, Nir

2008-02-01

Insulin resistance (IR) is a hallmark of pregnancy. Because increased visceral fat (VF) is associated with IR in nonpregnant states, we reasoned that fat accretion might be important in the development of IR during pregnancy. To determine whether VF depots increase in pregnancy and whether VF contributes to IR, we studied three groups of 6-mo-old female Sprague-Dawley rats: 1) nonpregnant sham-operated rats (Nonpreg; n = 6), 2) pregnant sham-operated rats (Preg; n = 6), and 3) pregnant rats in which VF was surgically removed 1 mo before mating (PVF-; n = 6). VF doubled by day 19 of pregnancy (Nonpreg 5.1 +/- 0.3, Preg 10.0 +/- 1.0 g, P < 0.01), and PVF- had similar amounts of VF compared with Nonpreg (PVF- 4.6 +/- 0.8 g). Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp in late gestation in chronically catheterized unstressed rats. Glucose IR (mg.kg(-1).min(-1)) was highest in Nonpreg (19.4 +/- 2.0), lowest in Preg (11.1 +/- 1.4), and intermediate in PVF- (14.7 +/- 0.6; P < 0.001 between all groups). During the clamp, Nonpreg had greater hepatic insulin sensitivity than Preg [hepatic glucose production (HGP): Nonpreg 4.5 +/- 1.3, Preg 9.3 +/- 0.5 mg.kg(-1).min(-1); P < 0.001]. With decreased VF, hepatic insulin sensitivity was similar to nonpregnant levels in PVF- (HGP 4.9 +/- 0.8 mg.kg(-1).min(-1)). Both pregnant groups had lower peripheral glucose uptake compared with Nonpreg. In parallel with hepatic insulin sensitivity, hepatic triglyceride content was increased in pregnancy (Nonpreg 1.9 +/- 0.4 vs. Preg 3.2 +/- 0.3 mg/g) and decreased with removal of VF (PVF- 1.3 +/- 0.4 mg/g; P < 0.05). Accretion of visceral fat is an important component in the development of hepatic IR in pregnancy, and accumulation of hepatic triglycerides is a mechanism by which visceral fat may modulate insulin action in pregnancy.

High hydrostatic pressure extract of garlic increases the HDL cholesterol level via up-regulation of apolipoprotein A-I gene expression in rats fed a high-fat diet.

PubMed

Lee, Seohyun; Joo, Hyunjin; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

2012-06-19

Cardiovascular disease (CVD) is the number one cause of mortality worldwide and a low high-density lipoprotein cholesterol (HDL-C) level is an important marker of CVD risk. Garlic (Allium sativum) has been widely used in the clinic for treatment of CVD and regulation of lipid metabolism. This study investigated the effects of a high hydrostatic pressure extract of garlic (HEG) on HDL-C level and regulation of hepatic apolipoprotein A-I (apoA-I) gene expression. Male Sprague-Dawley rats were divided into two groups and maintained on a high-fat control diet (CON) or high-fat control diet supplemented with high hydrostatic pressure extract of garlic (HEG) for 5 weeks. Changes in the expression of genes related to HDL-C metabolism were analyzed in liver, together with biometric and blood parameters. In the HEG group, the plasma triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased in comparison with the CON group (P < 0.05). Dietary HEG also lowered the hepatic TG and total cholesterol (TC) levels compared to the CON group. While the plasma HDL-C level and mRNA level of hepatic apoA-I, which is one of primarily proteins of HDL-C particle, were significantly increased in the HEG group compared to the CON group (P < 0.05). The gene expression of ATP-binding cassette transporter A1 (ABCA1) and lecithin:cholesterol acyltransferase (LCAT), importantly involved in the biogenesis in HDL, were also up-regulated by dietary HEG. These results suggest that HEG ameliorates plasma lipid profiles and attenuates hepatic lipid accumulation in the high-fat fed rats. Our findings provides that the effects of HEG on the increase of the plasma HDL-C level was at least partially mediated by up-regulation of hepatic genes expression such as apoA-I, ABCA1, and LCAT in rats fed a high-fat diet.

Increased bioactive lipids content in human subcutaneous and epicardial fat tissue correlates with insulin resistance.

PubMed

Błachnio-Zabielska, Agnieszka U; Baranowski, Marcin; Hirnle, Tomasz; Zabielski, Piotr; Lewczuk, Anna; Dmitruk, Iwona; Górski, Jan

2012-12-01

Obesity is a risk factor for metabolic diseases. Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. These lipids are probably implicated in obesity-associated insulin resistance not only in skeletal muscle but also in fat tissue. Only few data are available about ceramide content in human subcutaneous adipose tissue. However, there are no data on DAG and LCACoA content in adipose tissue. The aim of our study was to measure the lipids content in human SAT and epicardial adipose tissue we sought to determine the bioactive lipids content by LC/MS/MS in fat tissue from lean non-diabetic, obese non-diabetic, and obese diabetic subjects and test whether the lipids correlate with HOMA-IR. We found, that total content of measured lipids was markedly higher in OND and OD subjects in both types of fat tissue (for all p < 0.001) as compared to LND group. In SAT we found positive correlation between HOMA-IR and C16:0-Cer (r = 0.79, p < 0.001) and between HOMA-IR and C16:0/18:2 DAG (r = 0.56, p < 0.001). In EAT we found a strong correlation between C16:0-CoA content and HOMA-IR (r = 0.73, p < 0.001). The study showed that in obese and obese diabetic patients, bioactive lipids content is greater in subcutaneous and epicardial fat tissue and the particular lipids content positively correlates with HOMA-IR.

Exercise training prevents the development of cardiac dysfunction in the low-dose streptozotocin diabetic rats fed a high-fat diet.

PubMed

Epp, Riley A; Susser, Shanel E; Morissette, Marc P; Kehler, D Scott; Jassal, Davinder S; Duhamel, Todd A

2013-01-01

This study tested the hypothesis that exercise training would prevent the development of diabetes-induced cardiac dysfunction and altered expression of sarcoplasmic reticulum Ca(2 +)-transport proteins in the low-dose streptozotocin-induced diabetic rats fed a high-fat diet (HFD+STZ). Male Sprague-Dawley rats (4 weeks old; 125-150 g) were made diabetic using a high-fat diet (40% fat, w/w) and a low-dose of streptozotocin (35 mg·(kg body mass)(-1)) by intravenous injection. Diabetic animals were divided among a sedentary group (Sed+HFD+STZ) or an exercise-trained group (Ex+HFD+STZ) that accumulated 3554 ± 338 m·day(-1) of voluntary wheel running (mean ± SE). Sedentary animals fed a low-fat diet served as the control (Sed+LFD). Oral glucose tolerance was impaired in the sedentary diabetic group (1179 ± 29; area under the curve (a.u.c.)) compared with that in the sedentary control animals (1447 ± 42 a.u.c.). Although left ventricular systolic function was unchanged by diabetes, impaired E/A ratios (i.e., diastolic function) and rates of pressure decay (-dP/dt) indicated the presence of diastolic dysfunction. Diabetes also reduced SERCA2a protein content and maximal SERCA2a activity (V(max)) by 21% and 32%, respectively. In contrast, the change in each parameter was attenuated by exercise training. Based on these data, it appears that exercise training prevented the development of diabetic cardiomyopathy and the dysregulation of sarcoplasmic reticulum protein content in an inducible animal model of type 2 diabetes.

Fabp1 gene ablation inhibits high-fat diet-induced increase in brain endocannabinoids.

PubMed

Martin, Gregory G; Landrock, Danilo; Chung, Sarah; Dangott, Lawrence J; Seeger, Drew R; Murphy, Eric J; Golovko, Mikhail Y; Kier, Ann B; Schroeder, Friedhelm

2017-01-01

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high-fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high-fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid-derived arachidonoylethanolamide in males correlated with increased brain-free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain-free and total arachidonic acid in males. In females, brain-free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice. © 2016 International Society for Neurochemistry.

Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis.

PubMed

Alsanea, Sary; Gao, Mingming; Liu, Dexi

2017-05-01

Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.

Anti-Obesity Effect of the Above-Ground Part of Valeriana dageletiana Nakai ex F. Maek Extract in High-Fat Diet-Induced Obese C57BL/6N Mice

PubMed Central

Wang, Zhiqiang; Hwang, Seung Hwan; Kim, Ju Hee; Lim, Soon Sung

2017-01-01

Valeriana dageletiana Nakai ex F. Maek (VD) has been used as traditional medicine for the treatment of restlessness and sleeping disorders. However, it is still unclear whether obesity in mice can be altered by diet supplementation with VD. In this study, we first investigated the influences of VD on the accumulation of lipid content in 3T3-L1 cells; and the results showed that the above-ground VD extracts (VDAE) suppressed the differentiation of 3T3-L1 preadipocytes in a concentration-dependent manner without cytotoxicity. Thus, the effects of VDAE on preventing obesity were then studied in the C57BL/6N mice for 10 weeks (n = 6): normal-fat diet, high-fat diet (HFD), HFD supplemented with 1% (10 g/kg) Garcinia combogia extract (positive control), and HFD supplemented with 1% (10 g/kg) VDAE. The results showed that VDAE reduced food efficiency ratio, body weight, epididymal adipose and hepatic tissue weight, hepatic lipid metabolites, and triacylglycerol and cholesterol serum levels compared to the high-fat diet group. Moreover, VD significantly inhibited the expression of adipogenic genes, such as PPAR-γ, C/EBP-α, and aP2, and lipogenic genes, such as SREBP-1c, FAS, SCD-1, and CD36, in epididymal adipose tissue and hepatic tissue. These findings indicate anti-adipogenic and anti-lipogenic effects of VDAE and suggest that it could be a potent functional food ingredient for the prevention of high-fat diet-induced obesity. PMID:28671595

Nitric oxide, can it be only good? Increasing the antioxidant properties of nitric oxide in hepatocytes by YC-1 compound.

PubMed

Aharoni-Simon, Michal; Anavi, Sarit; Beifuss, Uwe; Madar, Zecharia; Tirosh, Oren

2012-12-01

The aim of the study was to evaluate the effect of Nitric oxide (NO) on redox changes and fat accumulation in hepatocytes. AML-12 hepatocytes were exposed to the NO donor Diethylenetriamine-NONOate (DETA-NO). DETA-NO led to a dose- and time-dependent increase in lipid accumulation in the cells, measured by Nile red fluorescence. Exposure of the cells to 1mM DETA-NO for 24h increased reactive oxygen species production, mainly peroxides. At the same time, NO induced elevation of reduced glutathione (GSH) and a mild activation of the antioxidant transcription factors Hypoxia-inducible factor 1α (HIF1α) and NF-E2 related factor 2 (Nrf-2). We used 100 μM YC-1 to inhibit HIF1α activity and induce activation of soluble Guanylate Cyclase (sGC). YC-1 alone did not affect fat accumulation, and only moderately increased the expression of Nrf-2-targeted genes Heme oxygenase 1 (Hmox1), NAD(P)H dehydrogenase (quinone 1) (Nqo1) and Glutathione S-transferase α1 (Gstα1). However, YC-1 abolished the negative effect of NO on fat accumulation when administered together. Strikingly, YC-1 potentiated the effect of NO on Nrf-2 activation, thus increasing dramatically the antioxidant properties of NO. Moreover, YC-1 intensified the effect of NO on the expression of peroxisome-proliferator-activated receptor-gamma co-activator 1α (PGC1α) and mitochondrial biogenesis markers. This study suggests that YC-1 may shift the deleterious effects of NO into the beneficial ones, and may improve the antioxidant properties of NO. 2012 Elsevier Inc. All rights reserved

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years.

PubMed

Kocarnik, Beverly M; Boyko, Edward J; Matsumoto, Alvin M; Fujimoto, Wilfred Y; Hayashi, Tomoshige; Leonetti, Donna L; Page, Stephanie T

The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. This is a longitudinal observational study in community-dwelling Japanese-American men (n=215, mean age 52 years, BMI 25.4kg/m 2 ). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r=-0.05 for both time points, p=0.45 and p=0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p=0.52 and p=0.55, respectively). Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. Copyright © 2015 Asia Oceania Association for the Study of Obesity. All rights reserved.

Baseline estradiol concentration in community-dwelling Japanese American men is not associated with intra-abdominal fat accumulation over 10 years

PubMed Central

Kocarnik, Beverly M.; Boyko, Edward J.; Matsumoto, Alvin M.; Fujimoto, Wilfred Y.; Hayashi, Tomoshige; Leonetti, Donna L.; Page, Stephanie T.

2016-01-01

Summary Problem The role of plasma estradiol in the accumulation of intra-abdominal fat (IAF) in men is uncertain. Cross-sectional studies using imaging of IAF have shown either a positive or no association. In contrast, a randomised controlled trial using an aromatase inhibitor to suppress estradiol production found an association between oestrogen deficiency and short-term IAF accumulation. No longitudinal study has been conducted to examine the relationship between plasma estradiol concentration and the change in IAF area measured using direct imaging. Methods This is a longitudinal observational study in community-dwelling Japanese-American men (n = 215, mean age 52 years, BMI 25.4 kg/m2). IAF and subcutaneous fat areas were assessed using computerized tomography (CT) at baseline, 5 and 10 years. Baseline plasma estradiol concentrations were measured using liquid chromatography-tandem mass spectrometry. Results Univariate analysis found no association between baseline estradiol concentration and baseline IAF, or 5- or 10-year changes in IAF area (r = −0.05 for both time points, p = 0.45 and p = 0.43, respectively). Multivariate linear regression analysis of the change in IAF area by baseline estradiol concentration adjusted for age, baseline IAF area, and weight change found no association with either the 5- or 10-year IAF area change (p = 0.52 and p = 0.55, respectively). Conclusions Plasma estradiol concentration was not associated with baseline IAF nor with change in IAF area over 5 or 10 years based on serial CT scans in community-dwelling Japanese-American men. These results do not support a role for oestrogen deficiency in IAF accumulation in men. PMID:26747209

Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue.

PubMed

Harford, Karen A; Reynolds, Clare M; McGillicuddy, Fiona C; Roche, Helen M

2011-11-01

High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.

Differential roles of breakfast only (one meal per day) and a bigger breakfast with a small dinner (two meals per day) in mice fed a high-fat diet with regard to induced obesity and lipid metabolism

PubMed Central

2012-01-01

Background Recent studies on humans and rodents have suggested that the timing of food intake plays an important role in circadian regulation and metabolic health. Consumption of high-fat foods during the inactive period or at the end of the awake period results in weight gain and metabolic syndrome in rodents. However, the distinct effects of breakfast size and the breakfast/dinner size ratio on metabolic health have not yet been fully examined in mice. Methods We examined whether the parameters of metabolic syndrome were differentially affected in mice that consumed a large meal at the beginning of the awake period (breakfast; one meal group) and a relatively smaller meal at end of the awake period (dinner; two meals group). The mice of each group were provided equal food volume per day. Results Mice on one meal exhibited an increase in body weight gain, hyperinsulinemia, hyperleptinemia, and a decrease of gene expression associated with β-oxidation in adipose tissue and liver compared with those on two meals. The circadian expression pattern of the Clock gene in mice on one meal was disturbed compared with those on two meals. Conclusions In conclusion, a bigger breakfast with a smaller dinner (two meals per day) but not breakfast only (one meal per day) helps control body weight and fat accumulation in mice on a high-fat meals schedule. The findings of this study suggest that dietary recommendations for weight reduction and/or maintenance should include information on the timing and quantity of dietary intake. PMID:22587351

Non-alcoholic fatty liver disease and subclinical atherosclerosis: A comparison of metabolically- versus genetically-driven excess fat hepatic storage.

PubMed

Di Costanzo, Alessia; D'Erasmo, Laura; Polimeni, Licia; Baratta, Francesco; Coletta, Paola; Di Martino, Michele; Loffredo, Lorenzo; Perri, Ludovica; Ceci, Fabrizio; Montali, Anna; Girelli, Gabriella; De Masi, Bruna; Angeloni, Antonio; Catalano, Carlo; Maranghi, Marianna; Del Ben, Maria; Angelico, Francesco; Arca, Marcello

2017-02-01

Non-alcoholic fatty liver disease (NAFLD) is frequently associated with atherosclerosis. However, it is unclear whether this association is related to excess fat liver storage per se or to metabolic abnormalities that typically accompany NAFLD. To investigate this, we compared individuals with hepatic steatosis driven by metabolic disturbances to those with hepatic steatosis associated with the rs738409 GG genotype in the patatin-like phospholipase domain-containing 3 gene (PNPLA3). Carotid intima-media thickness (CIMT), as a surrogate marker of subclinical atherosclerosis, was measured in 83 blood donors with the mutant GG genotype (group G), 100 patients with features of metabolic syndrome (MetS) but the wildtype CC genotype (group M), and 74 blood donors with the wildtype CC genotype (controls). Fatty liver was evaluated by ultrasonography and hepatic fat fraction (HFF) was measured using magnetic resonance (MRS/MRI) in 157 subjects. Compared with group G and controls, group M subjects were older and had increased adiposity indices, dyslipidemia, insulin resistance and elevated transaminase levels (all p < 0.05). They also had a more fatty liver on both ultrasonography and MRS/MRI. After adjustment for confounders (including severity of hepatic steatosis), the median CIMT in group M (0.84 [0.70-0.95] mm) was significantly greater than that in group G (0.66 [0.55-0.74] mm; p < 0.001), which was similar to that in controls (0.70 [0.64-0.81] mm). Results were similar in the subgroup evaluated using MRS/MRI. Excess liver fat accumulation appeared to increase the burden of subclinical atherosclerosis only when it is associated with metabolic abnormalities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cranberry (Vaccinium macrocarpon) extract treatment improves triglyceridemia, liver cholesterol, liver steatosis, oxidative damage and corticosteronemia in rats rendered obese by high fat diet.

PubMed

Peixoto, Thamara C; Moura, Egberto G; de Oliveira, Elaine; Soares, Patrícia N; Guarda, Deysla S; Bernardino, Dayse N; Ai, Xu Xue; Rodrigues, Vanessa da S T; de Souza, Gabriela Rodrigues; da Silva, Antonio Jorge Ribeiro; Figueiredo, Mariana S; Manhães, Alex C; Lisboa, Patrícia C

2017-05-13

Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed. HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.

Synergistic effects of Artemisia iwayomogi and Curcuma longa radix on high-fat diet-induced hyperlipidemia in a mouse model.

PubMed

Han, Jong-Min; Lee, Jin-Seok; Kim, Hyeong-Geug; Seol, In-Chan; Im, Hwi-Jin; Cho, Jung-Hyo; Son, Chang-Gue

2015-09-15

The medicinal plants Artemisia iwayomogi and Curcuma longa radix are both used to treat hyperlipidemia in traditional Korean and Chinese medicine. To evaluate the anti-hyperlipidemic effects of the 30% ethanol extracts of A. iwayomogi (AI), C. longa (CL), and the mixture of A. iwayomogi and C. longa (ACE), using a high-fat diet-induced hyperlipidemia model. Six of seven groups of C57BL/6N male mice (i.e., not including the naïve group) were fed a high-fat diet freely for 10 weeks. Of these six groups, five (i.e., not including the control group) were administered a high-fat diet supplemented with AI (100mg/kg), CL (100mg/kg), ACE (50 or 100mg/kg), or Lipitor (20mg/kg). Serum lipid profiles, obesity-related markers, hepatic steatosis, hepatic gene expression, and oxidative stress markers were analyzed. AI, CL, and ACE were associated with significant effects on serum lipid profiles (total cholesterol [TC] and triglyceride), body, liver and peritoneal adipose tissue weights, hepatic lipid accumulation, and oxidative stress biomarkers. ACE at 100mg/kg was associated with significantly greater improvements in serum TC and triglyceride, hepatic triglyceride, epididymal adipocyte size, and oxidative stress biomarkers, compared with AI and CL. AI, CL and ACE normalized lipid synthesis-associated gene expression (peroxisome proliferator-activated receptor gamma, fatty acid synthase, sterol regulatory element-binding transcription factor-1c, and peroxisome proliferator-activated receptor alpha). ACE exhibits anti-hyperlipidemia properties and is associated with partially synergistic effects compared with AI or CL alone. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dietary Mung Bean Protein Reduces Hepatic Steatosis, Fibrosis, and Inflammation in Male Mice with Diet-Induced, Nonalcoholic Fatty Liver Disease.

PubMed

Watanabe, Hitoshi; Inaba, Yuka; Kimura, Kumi; Asahara, Shun-Ichiro; Kido, Yoshiaki; Matsumoto, Michihiro; Motoyama, Takayasu; Tachibana, Nobuhiko; Kaneko, Shuichi; Kohno, Mitsutaka; Inoue, Hiroshi

2017-01-01

As the prevalence of nonalcoholic fatty liver disease (NAFLD), including steatosis and nonalcoholic steatohepatitis, is increasing, novel dietary approaches are required for the prevention and treatment of NAFLD. We evaluated the potential of mung bean protein isolate (MuPI) to prevent NAFLD progression. In Expts. 1 and 2, the hepatic triglyceride (TG) concentration was compared between 8-wk-old male mice fed a high-fat diet (61% of energy from fat) containing casein, MuPI, and soy protein isolate and an MuPI-constituent amino acid mixture as a source of amino acids (18% of energy) for 4 wk. In Expt. 3, hepatic fatty acid synthase (Fasn) expression was evaluated in 8-wk-old male Fasn-promoter-reporter mice fed a casein- or MuPI-containing high-fat diet for 20 wk. In Expt. 4, hepatic fibrosis was examined in 8-wk-old male mice fed an atherogenic diet (61% of energy from fat, containing 1.3 g cholesterol/100 g diet) containing casein or MuPI (18% of energy) as a protein source for 20 wk. In the high fat-diet mice, the hepatic TG concentration in the MuPI group decreased by 66% and 47% in Expt. 1 compared with the casein group (P < 0.001) and the soy protein isolate group (P = 0.001), respectively, and decreased by 56% in Expt. 2 compared with the casein group (P = 0.011). However, there was no difference between the MuPI-constituent amino acid mixture and casein groups in Expt. 2. In Expt. 3, Fasn-promoter-reporter activity and hepatic TG concentration were lower in the MuPI group than in those fed casein (P < 0.05). In Expt. 4, in mice fed an atherogenic diet, hepatic fibrosis was not induced in the MuPI group, whereas it developed overtly in the casein group. MuPI potently reduced hepatic lipid accumulation in mice and may be a potential foodstuff to prevent NAFLD onset and progression. © 2017 American Society for Nutrition.

High-Glucose or -Fructose Diet Cause Changes of the Gut Microbiota and Metabolic Disorders in Mice without Body Weight Change.

PubMed

Do, Moon Ho; Lee, Eunjung; Oh, Mi-Jin; Kim, Yoonsook; Park, Ho-Young

2018-06-13

High fat diet-induced changes in gut microbiota have been linked to intestinal permeability and metabolic endotoxemia, which is related to metabolic disorders. However, the influence of a high-glucose (HGD) or high-fructose (HFrD) diet on gut microbiota is largely unknown. We performed changes of gut microbiota in HGD- or HFrD-fed C57BL/6J mice by 16S rRNA analysis. Gut microbiota-derived endotoxin-induced metabolic disorders were evaluated by glucose and insulin tolerance test, gut permeability, Western blot and histological analysis. We found that the HGD and HFrD groups had comparatively higher blood glucose and endotoxin levels, fat mass, dyslipidemia, and glucose intolerance without changes in bodyweight. The HGD- and HFrD-fed mice lost gut microbial diversity, characterized by a lower proportion of Bacteroidetes and a markedly increased proportion of Proteobacteria. Moreover, the HGD and HFrD groups had increased gut permeability due to alterations to the tight junction proteins caused by gut inflammation. Hepatic inflammation and lipid accumulation were also markedly increased in the HGD and HFrD groups. High levels of glucose or fructose in the diet regulate the gut microbiota and increase intestinal permeability, which precedes the development of metabolic endotoxemia, inflammation, and lipid accumulation, ultimately leading to hepatic steatosis and normal-weight obesity.

The Influence of Abdominal and Ectopic Fat Accumulation on Carotid Intima-Media Thickness: A Chongqing Study.

PubMed

Yi, Xu; Liu, Yu-Hui; Zhou, Xin-Fu; Wang, Yan-Jiang; Deng, Juan; Liu, Juan; He, Hong-Bo; Xu, Zhi-Qiang

2018-04-16

To investigate the effects of abdominal obesity (AO) and nonalcoholic fatty liver disease (NAFLD) with or without AO on carotid arteries by determining carotid intima-media thickness (CIMT). A total of 2745 Chinese Han adults (aged between 40 and 50 years old) were recruited and divided into 4 groups: (1) NW-no NAFL group: the normal body weight without NAFLD (n = 1888); (2) AO-no NAFL group: AO without NAFLD (n = 259); (3) NW-with NAFL group: NAFLD without AO (n = 93); and (4) AO-with NAFL group: AO with NAFLD (n = 505). The CIMT rate of each group was compared among 4 groups and the regression analysis was further used to correct confounders. We found that the NW-with NAFL group had a significantly higher CIMT rate than the AO-no NAFL group ([.87 ± .31] versus [.72 ± .29] P < .01) and the AO-with NAFL group ([.87 ± .31] versus [.79 ± .26], P < .01). The ectopic liver fat accumulation may increase the risk of atherosclerosis. Therefore, screening NAFLD in the population with normal weight may be beneficial for the prevention of atherosclerosis at an early stage. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Contribution of a membrane estrogen receptor to the estrogenic regulation of body temperature and energy homeostasis.

PubMed

Roepke, Troy A; Bosch, Martha A; Rick, Elizabeth A; Lee, Benjamin; Wagner, Edward J; Seidlova-Wuttke, Dana; Wuttke, Wolfgang; Scanlan, Thomas S; Rønnekleiv, Oline K; Kelly, Martin J

2010-10-01

The hypothalamus is a key region of the central nervous system involved in the control of homeostasis, including energy and core body temperature (Tc). 17β-Estradiol (E2) regulates Tc, in part, via actions in the basal hypothalamus and preoptic area. E2 primarily controls hypothalamic functions via the nuclear steroid receptors, estrogen receptor α/β. However, we have previously described an E2-responsive, Gq-coupled membrane receptor that reduces the postsynaptic inhibitory γ-aminobutyric acid-ergic tone and attenuates postovariectomy body weight gain in female guinea pigs through the administration of a selective Gq-mER ligand, STX. To determine the role of Gq-mER in regulating Tc, energy and bone homeostasis, ovariectomized female guinea pigs, implanted ip with temperature probes, were treated with STX or E2 for 7-8 wk. Tc was recorded for 4 wk, whereas food intake and body weight were monitored daily. Bone density and fat accumulation were determined postmortem. Both E2 and STX significantly reduced Tc in the females compared with controls. STX, similar to E2, reduced food intake and fat accumulation and increased tibial bone density. Therefore, a Gq-mER-coupled signaling pathway appears to be involved in maintaining homeostatic functions and may constitute a novel therapeutic target for treatment of hypoestrogenic symptoms.

A rich medium-chain triacylglycerol diet benefits adiposity but has adverse effects on the markers of hepatic lipogenesis and beta-oxidation.

PubMed

Chamma, Carolina Maria de Oliveira; Bargut, Thereza Cristina Lonzetti; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

2017-02-22

We investigated the increasing amounts of medium-chain triacylglycerol (MCT) in the diet on hepatic lipid metabolism. Mature C57BL/6 male mice were randomly divided into five groups (n = 10/group). The animals received their diet for 12 weeks, as a control (C group, 10% of energy from lipids); high-fat lard (HF group, isoenergetic diet, 50% of energy from lipids with lard); a mixture of lard and MCT oil (with a gradual replacement of lard by MCT: HF-MCT25%, HF-MCT75%, and HF-MCT100% groups). At euthanasia, we collected blood and dissected the liver for analyses (glucose, insulin, HOMA-IR, QUICK index, and triacylglycerol, light microscopy, western blotting, and RT-qPCR). The HF diet groups showed a greater body mass gain compared to the C group, but the HF-MCT100% group showed diminished adiposity and amelioration of insulin resistance. All the HF groups also showed a clear increase in hepatic lipid accumulation, increased lipogenesis and decreased PPAR-alpha expression, although HF-MCT groups showed improved local insulin signaling. Lastly, the HF-MCT100% group had raised markers of beta-oxidation (UCP3 and MCAD) and mitochondrial biogenesis (PGC1-alpha and NRF1). In conclusion, the findings demonstrated that a high amount of MCT (HF-MCT100% group) added to an HF diet reduces the body fat accumulation and insulin resistance. However, the lipid accumulation as well as the lipid metabolism is altered in the liver of animals fed with a very high MCT diet, indicating that higher doses of MCT may be harmful in a long-term.

Nutritional status and physical inactivity in moderated asthmatics: A pilot study.

PubMed

Bruno, Andreina; Uasuf, Carina Gabriela; Insalaco, Giuseppe; Barazzoni, Rocco; Ballacchino, Antonella; Gjomarkaj, Mark; Pace, Elisabetta

2016-08-01

Preservation of nutritional status and of fat-free mass (FFM) and/or preventing of fat mass (FM) accumulation have a positive impact on well-being and prognosis in asthma patients. Physical inactivity is identified by World Health Organization as the fourth leading risk factor for global mortality. Physical activity (PA) may contribute to limit FM accumulation, but little information is available on the interactions between habitual PA and body composition and their association with disease severity in asthma severity.Associations between habitual PA, FM, FFM, and pulmonary function were investigated in 42 subjects (24 patients with mild-moderate asthma and 18 matched control subjects). Sensewear Armband was used to measure PA and metabolic equivalent of tasks (METs) continuously over 4 days, while body composition was measured by bioelectrical impedance analysis. Respiratory functions were also assessed in all study participants.FM and FFM were comparable in mild-moderate asthmatics and controls, but PA was lower in asthmatics and it was negatively correlated with FM and positively with the FFM marker body cell mass in all study subjects (P < 0.05). Among asthmatics, treated moderate asthmatics (ICS, n = 12) had higher FM and lower PA, METs, steps number/die, and forced expiratory volume in the 1st second (FEV1)/forced vital capacity (FVC) than in untreated intermittent asthmatics (UA, n = 12).This pilot study assesses that in mild-moderate asthma patients, lower PA is associated with higher FM and higher disease severity. The current results support enhancement of habitual PA as a potential tool to limit FM accumulation and potentially contribute to preserve pulmonary function in moderate asthma, considering the physical inactivity a strong risk factor for asthma worsening.

Low-Dose Physiological Growth Hormone in Patients With HIV and Abdominal Fat Accumulation

PubMed Central

Lo, Janet; You, Sung Min; Canavan, Bridget; Liebau, James; Beltrani, Greg; Koutkia, Polyxeni; Hemphill, Linda; Lee, Hang; Grinspoon, Steven

2008-01-01

Context Antiretroviral therapy can be associated with visceral adiposity and metabolic complications, increasing cardiovascular risk, and reduced growth hormone (GH) secretion may be a contributing factor. Objective To investigate the effects of low-dose physiological GH administration on body composition, glucose, and cardiovascular parameters in patients with human immunodeficiency virus (HIV) having abdominal fat accumulation and relative GH deficiency. Design, Setting, and Patients A randomized, double-blind, placebo-controlled trial of 56 patients with HIV, abdominal fat accumulation, and reduced GH secretion (peak GH <7.5 ng/mL) conducted at a US academic medical center between November 2003 and October 2007. Intervention Patients were randomly assigned to receive either subcutaneous GH or matching placebo titrated to the upper quartile of normal insulinlike growth factor 1 (IGF-1) range for 18 months. Starting dose was 2 μg/kg/d and increased to maximum dose of 6 μg/kg/d (average dose, 0.33 mg/d). Main Outcome Measures Change in body composition assessed by computed tomographic scan and dual-energy x-ray absorptiometry. Secondary outcomes included glucose, IGF-1, blood pressure (BP), and lipids. Treatment effect was the difference in the change between GH and placebo groups, using all available data. Results Fifty-five patients (26 with GH and 29 with placebo) were included in the safety analyses and 52 patients (25 with GH and 27 with placebo) were included in the efficacy analyses. Visceral adipose tissue area (treatment effect [last-value-carried-forward analysis {n=56}, -19 cm2; 95% confidence interval {CI}, -37 to -0.3 cm2], -19 cm2; 95% CI, -38 to -0.5 cm2; P=.049); trunk fat (-0.8 kg; 95% CI, -1.5 to -0.04 kg; P=.04); diastolic BP (-7 mm Hg; 95% CI, -11 to -2 mm Hg; P=.006); and triglycerides (-7 mg/dL, P=.002) improved but 2-hour glucose levels on glucose tolerance testing increased in the GH group vs the placebo group (treatment effect, 22 mg/dL; 95% CI, 6-37 mg/dL; P=.009). The IGF-1 levels increased (treatment effect, 129 ng/mL; 95% CI, 95-164 ng/mL; P<.001). Adverse events were not increased for GH vs placebo (23%; 95% CI, 9%-44% vs 28%; 95% CI, 13%-47%; P=.70). Conclusions In HIV-associated abdominal fat accumulation and relative GH deficiency, low-dose GH received for 18 months resulted in significantly reduced visceral fat and truncal obesity, triglycerides, and diastolic BP, but 2-hour glucose levels on glucose tolerance testing were increased. PMID:18677023

[Fast food promotes weight gain].

PubMed

Stender, Steen; Dyerberg, Jørn; Astrup, Arne V

2007-05-07

The total amounts of fat in a fast food menu consisting of French fries and fried Chicken Nuggets from McDonald's and KFC, respectively, bought in 35 different countries vary from 41 to 71 gram. In most countries the menu contained unacceptably high amounts of industrially-produced trans fat which contributes to an increased risk of ischaemic heart disease, weight gain, abdominal fat accumulation and type 2 diabetes. The quality of the ingredients in fast food ought to be better and the size of the portions smaller and less energy-dense so that frequent fast food meals do not increase the risk of obesity and diseases among customers.

The effect of diet and litter size on the elimination of 2,4,5,2 prime ,4 prime ,5 prime -( sup 14 C)hexachlorobiphenyl from lactating mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ring, B.J.; Seitz, K.R.; Gallenberg, L.A.

It was shown that 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) administered to adult female mice accumulated in their nursing offspring more rapidly than a dose administered to weanling mice when treated animals were bred at equivalent ages. This suggested that the PCB was eliminated from the maternal animal relative to its time of sequestration into storage depots. Using a model which more closely approximates conditions during human lactation, the influence of a high-fat diet and decreased litter size on this phenomenon was examined. Female ICR mice were treated with 4 mg/kg (14C)-6-CB as 13-g weanlings (dW) at 3 weeks of age or as adultsmore » (dA) at 11 weeks of age. All animals were mated at 11 weeks of age. On Day 1 of pregnancy, mice were placed on a low-fat (11.5% of the total calories) or high-fat (43.8% of total calories) diet. At parturition, litters were adjusted to either two or eight within each diet group. Elimination of maternal 6-CB was determined by assessing radioactivity in offspring carcasses on Day 15 of gestation or Day 1, 3, 5, 10, or 15 postpartum. Consumption of a high-fat diet significantly extended the t1/2 of elimination of 6-CB from mothers nursing a litter of two in the dW group (low fat = 7.3 days; high fat = 12.4 days) and in both the dW and dA groups nursing litters of eight (dW: low fat = 4.6 days; high fat = 6.8 days; and dA: low fat = 1.8 days; high fat = 3.0 days). Within diet and group, reducing litter size to two also significantly decreased the rate of elimination of 6-CB from maternal animals. 6-CB was eliminated to offspring more rapidly from the dA group when compared to the dW group regardless of diet in animals nursing litters of eight. This relationship was not observed in maternal animals nursing litters of two. In general, exposure to a high-fat diet increased the t1/2 of elimination of 6-CB from maternal animals.« less

The rising prevalence of obesity: part A: impact on public health.

PubMed

Agha, Maliha; Agha, Riaz

2017-08-01

Excessive fat accumulation in the body may impair health leading to a significant long-term health consequences including the development of diabetes, coronary heart disease, and osteoarthritis as well as increasing the risk of developing certain cancers and influencing their outcomes. England has some of the worst figures and trends in obesity compared with the rest of the Europe. In the majority of European countries the trend has increased from 10% to 40% in the last 10 years, whereas in England prevalence has more than doubled. This article outlines the public health impact of rising obesity levels.

Accumulation of oxidized LDL in the tendon tissues of C57BL/6 or apolipoprotein E knock-out mice that consume a high fat diet: potential impact on tendon health.

PubMed

Grewal, Navdeep; Thornton, Gail M; Behzad, Hayedeh; Sharma, Aishwariya; Lu, Alex; Zhang, Peng; Reid, W Darlene; Granville Alex Scott, David J

2014-01-01

Clinical studies have suggested an association between dyslipidemia and tendon injuries or chronic tendon pain; the mechanisms underlying this association are not yet known. The objectives of this study were (1) to evaluate the impact of a high fat diet on the function of load-bearing tendons and on the distribution in tendons of oxidized low density lipoprotein (oxLDL), and (2) to examine the effect of oxLDL on tendon fibroblast proliferation and gene expression. Gene expression (Mmp2, Tgfb1, Col1a1, Col3a1), fat content (Oil Red O staining), oxLDL levels (immunohistochemistry) and tendon biomechanical properties were examined in mice (C57Bl/6 or ApoE -/-) receiving a standard or a high fat diet. Human tendon fibroblast proliferation and gene expression (COL1A1, COL3A1, MMP2) were examined following oxLDL exposure. In both types of mice (C57Bl/6 or ApoE -/-), consumption of a high fat diet led to a marked increase in oxLDL deposition in the load-bearing extracellular matrix of the tendon. The consumption of a high fat diet also reduced the failure stress and load of the patellar tendon in both mouse types, and increased Mmp2 expression. ApoE -/- mice exhibited more pronounced reductions in tendon function than wild-type mice, and decreased expression of Col1a1 compared to wild type mice. Human tendon fibroblasts responded to oxLDL by increasing their proliferation and their mRNA levels of MMP2, while decreasing their mRNA levels for COL1A1 and COL3A1. The consumption of a high fat diet resulted in deleterious changes in tendon function, and these changes may be explained in part by the effects of oxLDL, which induced a proliferative, matrix-degrading phenotype in human tenocytes.

Citrus flavanones prevent systemic inflammation and ameliorate oxidative stress in C57BL/6J mice fed high-fat diet.

PubMed

Ferreira, Paula S; Spolidorio, Luis C; Manthey, John A; Cesar, Thais B

2016-06-15

The flavanones hesperidin, eriocitrin and eriodictyol were investigated for their prevention of the oxidative stress and systemic inflammation caused by high-fat diet in C57BL/6J mice. The mice received a standard diet (9.5% kcal from fat), high-fat diet (45% kcal from fat) or high-fat diet supplemented with hesperidin, eriocitrin or eriodictyol for a period of four weeks. Hesperidin, eriocitrin and eriodictyol increased the serum total antioxidant capacity, and restrained the elevation of interleukin-6 (IL-6), macrophage chemoattractant protein-1 (MCP-1), and C-reactive protein (hs-CRP). In addition, the liver TBARS levels and spleen mass (g per kg body weight) were lower for the flavanone-treated mice than in the unsupplemented mice. Eriocitrin and eriodictyol reduced TBARS levels in the blood serum, and hesperidin and eriodictyol also reduced fat accumulation and liver damage. The results showed that hesperidin, eriocitrin and eriodictyol had protective effects against inflammation and oxidative stress caused by high-fat diet in mice, and may therefore prevent metabolic alterations associated with the development of cardiovascular diseases in other animals.

[Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol].

PubMed

Robaczyk, Maciej G

2002-01-01

The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk when compared to OTY subjects. Absolute LEP levels were correlated with trunk BF in CUS patients whereas in KON and AD groups these levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM-corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP levels were lower than in controls. No correlation was found between plasma levels of F and LEP in CUS and AD groups. This correlation was negative in KON (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups demonstrated a negative correlation between plasma ACTH and LEP levels. CUS patients showed positive, BFM-independent correlations between LEP levels, FIRI and G values, and a positive, BFM-dependent correlation between IRI and LEP levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI and LEP levels. In these and in AD patients, a positive, BFM-independent correlation between IRI and LEP levels was found. Moreover, a negative, BFM-dependent correlation between GH and LEP levels was found in OTY patients. In this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in the AD group, a midnight increase in leptin levels was observed. In conclusion, upregulation of leptin levels in relation to body fat in Cushing's syndrome is independent of the source of hypercortisolism. Apparently, it results from insulin resistance and hyperglycaemia and contributes to coexisting metabolic abnormalities. In Addison's disease, downregulation of leptin may reflect an adaptation mechanism to cortisol deficiency and result from low insulin and extremely high adrenocorticotrophin levels. In women with normal cortisol levels, irrespectively of nutritional status; leptin levels reflect body fat content. In obese subjects, leptin levels may be influenced by cortisol levels, high levels of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone. Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not directly influence diurnal variation in plasma leptin levels. In Cushing's syndrome, visceral fat may be a predominant source of leptin, whereas in women with normal or low cortisol levels peripherally accumulated fat may determine leptin secretion.

The Portal Theory Supported by Venous Drainage–Selective Fat Transplantation

PubMed Central

Rytka, Julia M.; Wueest, Stephan; Schoenle, Eugen J.; Konrad, Daniel

2011-01-01

OBJECTIVE The “portal hypothesis” proposes that the liver is directly exposed to free fatty acids and cytokines increasingly released from visceral fat tissue into the portal vein of obese subjects, thus rendering visceral fat accumulation particularly hazardous for the development of hepatic insulin resistance and type 2 diabetes. In the present study, we used a fat transplantation paradigm to (artificially) increase intra-abdominal fat mass to test the hypothesis that venous drainage of fat tissue determines its impact on glucose homeostasis. RESEARCH DESIGN AND METHODS Epididymal fat pads of C57Bl6/J donor mice were transplanted into littermates, either to the parietal peritoneum (caval/systemic venous drainage) or, by using a novel approach, to the mesenterium, which confers portal venous drainage. RESULTS Only mice receiving the portal drained fat transplant developed impaired glucose tolerance and hepatic insulin resistance. mRNA expression of proinflammatory cytokines was increased in both portally and systemically transplanted fat pads. However, portal vein (but not systemic) plasma levels of interleukin (IL)-6 were elevated only in mice receiving a portal fat transplant. Intriguingly, mice receiving portal drained transplants from IL-6 knockout mice showed normal glucose tolerance. CONCLUSIONS These results demonstrate that the metabolic fate of intra-abdominal fat tissue transplantation is determined by the delivery of inflammatory cytokines to the liver specifically via the portal system, providing direct evidence in support of the portal hypothesis. PMID:20956499

Effects of a 15-week accumulated brisk walking programme on the body composition of primary school children.

PubMed

Ford, Paul A; Perkins, Gill; Swaine, Ian

2013-01-01

The purpose of this study was to establish whether an accumulated brisk walking programme, performed during the school day, is effective in changing body composition in primary school children aged 5-11 years. Altogether, 152 participants (79 boys and 73 girls) took part in this repeated-measures intervention study, divided into groups of walkers and controls. The walkers took part in the intervention during school time, which involved brisk walking around the school grounds for 15 min in the morning and afternoon, at least three times a week for 15 weeks. This represented an additional 90 min of moderate physical activity per week. The controls undertook their usual school day activities. Pre- and post-intervention anthropometric and body composition measures were taken. Body fat (-1.95 ± 2.6%) and fat mass (-0.49 ± 1.0 kg) were significantly reduced in the walkers after the intervention, whereas the controls showed no significant changes in these measures. Our results show that regular accumulated bouts of brisk walking during the school day can positively affect body composition in primary school children.

Effects of dietary fat on the saturated and monounsaturated fatty acid metabolism in growing pigs.

PubMed

Raj, Stanisława; Skiba, Grzegorz; Sobol, Monika; Pastuszewska, Barbara

2017-08-01

The effect of dietary fats differing in fatty acid (FA) composition on the metabolism of saturated FA (SFA) and monounsaturated FA (MUFA) in growing pigs was investigated. The deposition of FA in the body and the fate of individual dietary FA were assessed after slaughter. Gilts with an initial body weight (BW) of 60 kg were used as experimental animals. Six pigs were slaughtered at 60 kg BW, while further 18 pigs received three isoenergetic and isonitrogen experimental diets containing linseed oil, rapeseed oil or beef tallow at 50 g/kg diet until they reached 105 kg (six pigs per group). The chemical composition and the content of FA in the whole body were determined and compared across groups. Regardless of dietary treatment, the whole body contained similar amounts of protein, fat and total FA. The total accumulation (percentage of net intake and de novo production) of SFA and MUFA was similar in all groups, but the processes of elongation and desaturation of SFA and MUFA depended upon the type of FA added to the diet. A high dietary content and intake of MUFA inhibits desaturation compared to SFA- and PUFA-rich diets, whereas a high SFA content and intake lowers elongation rate. The increasing net intake of total SFA and MUFA was associated with a lower total de novo production of these FA in the whole body of pigs.

Effects of castration on expression of lipid metabolism genes in the liver of korean cattle.

PubMed

Baik, Myunggi; Nguyen, Trang Hoa; Jeong, Jin Young; Piao, Min Yu; Kang, Hyeok Joong

2015-01-01

Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001) hepatic lipids contents and higher (p<0.01) mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration.

Adiposity indices in German children and adolescents with genetically confirmed Prader-Willi syndrome (PWS).

PubMed

Hauffa, B P; Schlippe, G; Gillessen-Kaesbach, G

2001-05-01

Morbid obesity develops as a result of hyperphagia and compulsive eating behavior in patients with Prader-Willi syndrome (PWS), if caloric intake is not rigorously controlled. PWS-specific centile curves for adiposity indices constructed in the past were based on clinically diagnosed patients. With the advent of molecular genetic methods, allowing for an unequivocal diagnosis, new PWS curves based exclusively on molecularly diagnosed patients are becoming available, eliminating a potential diagnostic bias. To compare fat distribution in molecularly confirmed German PWS patients to that of clinically diagnosed American PWS patients and a healthy reference population. Cross-sectional anthropometric study. One hundred German patients (49 F) with molecularly confirmed PWS (age: <30 y). Triceps (subscapular) skinfold thickness, waist and hip circumference. Skinfold thickness was massively elevated in the majority of the molecularly confirmed German PWS patients compared to a healthy reference population. Whereas triceps skinfold thickness was in good agreement with American PWS patients, subscapular skinfold thickness in German girls rose earlier than in American PWS girls, indicating possible differences between caloric intake or the proportion of patients entering puberty spontaneously. Waist circumference and waist-hip ratio (n=89) were elevated in a relative small proportion of patients only and did not reflect lower abdominal fat. This may be due to the peculiar shape of many patients with a typical fat accumulation around the buttocks. In addition to body mass index, use of skinfold thickness is recommended for follow-up of dietary interventions in PWS.

Understanding the spatial formation and accumulation of fats, oils and grease deposits in the sewer collection system.

PubMed

Dominic, Christopher Cyril Sandeep; Szakasits, Megan; Dean, Lisa O; Ducoste, Joel J

2013-01-01

Sanitary sewer overflows are caused by the accumulation of insoluble calcium salts of fatty acids, which are formed by the reaction between fats, oils and grease (FOG) and calcium found in wastewaters. Different sewer structural configurations (i.e., manholes, pipes, wet wells), which vary spatially, along with other obstructions (roots intrusion) and pipe deformations (pipe sags), may influence the detrimental buildup of FOG deposits. The purpose of this study was to quantify the spatial variation in FOG deposit formation and accumulation in a pilot-scale sewer collection system. The pilot system contained straight pipes, manholes, roots intrusion, and a pipe sag. Calcium and oil were injected into the system and operated at alkaline (pH = 10) and neutral (pH = 7) pH conditions. Results showed that solid accumulations were slightly higher at neutral pH. Fourier transform infrared (FTIR) analysis on the solids samples confirmed that the solids were indeed calcium-based fatty acid salts. However, the fatty acid profiles of the solids deviated from the profile found from FOG deposits in sewer systems, which were primarily saturated fatty acids. These results confirm the work done previously by researchers and suggest an alternative fate of unsaturated fatty acids that does not lead to their incorporation in FOG deposits in full-scale sewer systems.

Dietary fat intake predicts 1-year change in body fat in adolescent girls with type 1 diabetes.

PubMed

Särnblad, Stefan; Ekelund, Ulf; Aman, Jan

2006-06-01

The purpose of this study was to determine whether objectively measured physical activity and dietary macronutrient intake differentially predict body fat in adolescent girls with type 1 diabetes and control girls. This study comprised 23 girls (12-19 years) with type 1 diabetes and 19 age-matched healthy control girls. At baseline, physical activity and energy intake were assessed for 7 consecutive days by accelerometry and a structured food diary, respectively. Body composition was measured by dual-energy X-ray absorptiometry at baseline and after 1 year. Fat intake was positively related to a 1-year change in percentage body fat (P = 0.006), after adjustment for total energy intake. No significant interaction was observed (case-control group x main exposure), indicating that the association between fat intake and gain in body fat was similar in both groups. Physical activity did not predict gain in body fat; however, total physical activity was positively associated with a gain in lean body mass (P < 0.01). Girls treated with six daily dosages of insulin increased their percentage of body fat significantly more than those treated with four daily injections (P < 0.05). In this prospective case-control study, we found that fat intake predicted gain in percentage of body fat in both adolescent girls with type 1 diabetes and healthy control girls. The number of daily insulin injections seems to influence the accumulation of body fat in girls with type 1 diabetes.

Quantitative Assessment of Liver Fat with Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Reeder, Scott B.; Cruite, Irene; Hamilton, Gavin; Sirlin, Claude B.

2011-01-01

Hepatic steatosis is characterized by abnormal and excessive accumulation of lipids within hepatocytes. It is an important feature of diffuse liver disease, and the histological hallmark of non-alcoholic fatty liver disease (NAFLD). Other conditions associated with steatosis include alcoholic liver disease, viral hepatitis, HIV and genetic lipodystrophies, cystic fibrosis liver disease, and hepatotoxicity from various therapeutic agents. Liver biopsy, the current clinical gold standard for assessment of liver fat, is invasive and has sampling errors, and is not optimal for screening, monitoring, clinical decision making, or well-suited for many types of research studies. Non-invasive methods that accurately and objectively quantify liver fat are needed. Ultrasound (US) and computed tomography (CT) can be used to assess liver fat but have limited accuracy as well as other limitations. Magnetic resonance (MR) techniques can decompose the liver signal into its fat and water signal components and therefore assess liver fat more directly than CT or US. Most magnetic resonance (MR) techniques measure the signal fat-fraction (the fraction of the liver MR signal attributable to liver fat), which may be confounded by numerous technical and biological factors and may not reliably reflect fat content. By addressing the factors that confound the signal fat-fraction, advanced MR techniques measure the proton density fat-fraction (the fraction of the liver proton density attributable to liver fat), which is a fundamental tissue property and a direct measure of liver fat content. These advanced techniques show promise for accurate fat quantification and are likely to be commercially available soon. PMID:22025886

HDL subclasses are heterogeneous in their associations with body fat, as measured by dual-energy X-ray absorptiometry: the Kitakata Kids Health Study.

PubMed

Kouda, Katsuyasu; Nakamura, Harunobu; Fujita, Yuki; Hamada, Masami; Kajita, Etsuko; Nakatani, Yoshimi; Sato, Yuho; Uenishi, Kazuhiro; Iki, Masayuki

2015-04-15

Obesity, defined as the excessive accumulation of body fat, is frequently associated with low concentrations of high-density lipoprotein (HDL) cholesterol. However, HDL particles are heterogeneous in size and composition. HDL subclasses may be differentially associated with body fat. This study investigated associations between the cholesterol concentrations of HDL subclasses, as determined by high-performance liquid chromatography, and body fat variables, as measured by dual-energy X-ray absorptiometry. The source population was all ninth grade students who attended Shiokawa Junior High School in Japan. Cross-sectional data on body fat and serum HDL subclasses were obtained for 87 students (72.5% of the source population). The cholesterol concentration of the large HDL subclass showed a significant (P<0.05) inverse relationship with whole body fat and trunk fat (r=-0.24 and -0.30), whereas the concentration of the small HDL subclass showed a significant positive relationship with these body fat variables (r=0.25 and 0.31). After adjusting for potential confounding factors, the mean concentration of small HDL significantly increased from the lowest to highest tertiles of trunk fat mass index. These results indicate that HDL subclasses are heterogeneous in their associations with body fat variables that were accurately measured by dual-energy X-ray absorptiometry among Japanese students. Copyright © 2015 Elsevier B.V. All rights reserved.

Antioxidant Properties of Proanthocyanidins Attenuate Carbon Tetrachloride (CCl4)–Induced Steatosis and Liver Injury in Rats via CYP2E1 Regulation

PubMed Central

Zou, Yuan; Zhu, Lei; Wang, Hui-Fang; Dai, Mu-Gen

2014-01-01

Abstract Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical–generating CYP2E1 enzyme. PMID:24712752

Antioxidant properties of proanthocyanidins attenuate carbon tetrachloride (CCl4)-induced steatosis and liver injury in rats via CYP2E1 regulation.

PubMed

Dai, Ning; Zou, Yuan; Zhu, Lei; Wang, Hui-Fang; Dai, Mu-Gen

2014-06-01

Liver steatosis is characterized by lipid dysregulation and fat accumulation in the liver and can lead to oxidative stress in liver. Since proanthocyanidins are present in plant-based foods and have powerful antioxidant properties, we investigated whether proanthocyanidins can prevent oxidative stress and subsequent liver injury. Carbon tetrachloride (CCl4) treatment can cause steatosis in rats that models both alcoholic and non-alcoholic fatty liver disease in humans. We pre-treated rats by oral administration of proanthocyanidins extracted from grape seeds 7 days prior to intragastrically administering CCl4. Proanthocyanidin treatment continued for an additional 2 weeks, after which time liver and serum were harvested, and mediators of liver injury, oxidative stress, and histological features were evaluated. CCl4-treated rats exhibited significant increases in the following parameters as compared to non-treated rats: fat droplets in the liver, liver injury (ALT, AST), and DNA damage (8-OHdG). Additionally, CCl4 treatment decreased antioxidant enzymes SOD, GSH, GPX, and CAT in the liver due to their rapid depletion after battling against oxidative stress. Compared to CCl4-treated rats, treatment with proanthocyanidins effectively suppressed lipid accumulation, liver injury, DNA damage, as well as restored antioxidant enzyme levels. Further investigation revealed that proanthocyanidins treatment also inhibited expression of CYP2E1 in liver, which prevented the initial step of generating free radicals from CCl4. The data presented here show that treatment with orally administered proanthocyanidins prevented liver injury in the CCl4-induced steatosis model, likely through exerting antioxidant actions to suppress oxidative stress and inhibiting the free radical-generating CYP2E1 enzyme.

Mice deficient in mitochondrial glycerol-3-phosphate acyltransferase-1 have diminished myocardial triacylglycerol accumulation during lipogenic diet and altered phospholipid fatty acid composition

PubMed Central

Lewin, Tal M.; de Jong, Hendrik; Schwerbrock, Nicole J. M.; Hammond, Linda E.; Watkins, Steven M.; Combs, Terry P.; Coleman, Rosalind A.

2008-01-01

Glycerol-3-phosphate acyltransferase-1 (GPAT1), which is located on the outer mitochondrial membrane comprises up to 30% of total GPAT activity in the heart. It is one of at least four mammalian GPAT isoforms known to catalyze the initial, committed, and rate limiting step of glycerolipid synthesis. Because excess triacylglycerol (TAG) accumulates in cardiomyocytes in obesity and type 2 diabetes, we determined whether lack of GPAT1 would alter the synthesis of heart TAG and phospholipids after a 2-week high sucrose diet or a 3-month high fat diet. Even in the absence of hypertriglyceridemia, TAG increased 2-fold with both diets in hearts from wildtype mice. In contrast, hearts from Gpat1−/− mice contained 20–80% less TAG than the wildtype controls. In addition, hearts from Gpat1−/− mice fed the high-sucrose diet incorporate 60% less [14C]palmitate into heart TAG as compared to wildtype mice. Because GPAT1 prefers 16:0-CoA to other long chain acyl-CoA substrates, we determined the fatty acid composition of heart phospholipids. Compared to wildtype littermate controls, hearts from Gpat1−/− mice contained a lower amount of 16:0 in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine/phosphatidylinositol and significantly more C20:4n6. Phosphatidylcholine and phosphatidylethanolamine from Gpat1−/− hearts also contained higher amounts of 18:0 and 18:1. Although at least three other GPAT isoforms are expressed in the heart, our data suggest that GPAT1 contributes significantly to cardiomyocyte TAG synthesis during lipogenic or high fat diets and influences the incorporation of 20:4n6 into heart phospholipids. PMID:18522808

Genetics Home Reference: cryptogenic cirrhosis

MedlinePlus

... likely result from a condition called non-alcoholic fatty liver disease (NAFLD). In NAFLD, fat accumulates in the ... Information & Resources MedlinePlus (5 links) Encyclopedia: Cirrhosis Encyclopedia: Fatty Liver--Nonalcoholic Encyclopedia: Liver Cancer--Hepatocellular Carcinoma Health Topic: ...

Fat tissue after lipolysis of lipomas: a histopathological and immunohistochemical study.

PubMed

Bechara, Falk G; Sand, Michael; Hoffmann, Klaus; Sand, Daniel; Altmeyer, Peter; Stücker, Markus

2007-07-01

Injections with Lipostabil, a phosphatidylcholine (PDC) containing substance, have become a popular technique to treat localized fat accumulation and lipomas for aesthetic reasons. Despite its frequent use, the mechanism of action of PDC and histological changes of treated fat tissue still remain unclear. To investigate the histological changes of lipomas after treatment with PDC. In all, fourteen lipomas (n = 14) in five patients presenting with multiple lipomas were treated with intralesional injections of PDC (Lipostabil, Nettermann, Germany). Histological changes with immunohistochemical analysis of the inflammatory process were evaluated 4, 10, 24, 48 h, 10 days, 30 days and 60 days after lipolysis. Between 4 and 48 h after injection, histology shows a lobular neutrophilic infiltrate with partially destroyed fat cells. At day 10 the inflammatory process is accompanied by an infiltration of T-lymphocytes. After 60 days formation of macrophages with foam cells are visible, accompanied by thickened septa and capsula. Lipolysis with PDC results in a distinct inflammatory reaction of affected fat tissue, similar to factitial panniculitis. Early destruction of fat cells may suggest the involvement of detergent or osmotic mechanisms in the process.

Supplementation of chitosan alleviates high-fat diet-enhanced lipogenesis in rats via adenosine monophosphate (AMP)-activated protein kinase activation and inhibition of lipogenesis-associated genes.

PubMed

Chiu, Chen-Yuan; Chan, Im-Lam; Yang, Tsung-Han; Liu, Shing-Hwa; Chiang, Meng-Tsan

2015-03-25

This study investigated the role of chitosan in lipogenesis in high-fat diet-induced obese rats. The lipogenesis-associated genes and their upstream regulatory proteins were explored. Diet supplementation of chitosan efficiently decreased the increased weights in body, livers, and adipose tissues in high-fat diet-fed rats. Chitosan supplementation significantly raised the lipolysis rate; attenuated the adipocyte hypertrophy, triglyceride accumulation, and lipoprotein lipase activity in epididymal adipose tissues; and decreased hepatic enzyme activities of lipid biosynthesis. Chitosan supplementation significantly activated adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and attenuated high-fat diet-induced protein expressions of lipogenic transcription factors (PPAR-γ and SREBP1c) in livers and adipose tissues. Moreover, chitosan supplementation significantly inhibited the expressions of downstream lipogenic genes (FAS, HMGCR, FATP1, and FABP4) in livers and adipose tissues of high-fat diet-fed rats. These results demonstrate for the first time that chitosan supplementation alleviates high-fat diet-enhanced lipogenesis in rats via AMPK activation and lipogenesis-associated gene inhibition.

High fat diet exacerbates dextran sulfate sodium induced colitis through disturbing mucosal dendritic cell homeostasis.

PubMed

Cheng, Lu; Jin, Huimin; Qiang, Yetao; Wu, Shuiyun; Yan, Cheng; Han, Mutian; Xiao, Tengfei; Yan, Nannan; An, Huazhang; Zhou, Xiaoming; Shao, Qixiang; Xia, Sheng

2016-11-01

Epidemiological studies have shown that fat rich western diet contributes to the high incidence of inflammatory bowel disease (IBD). Moreover, accumulated data indicated that fat dietary factor might promote the change of the composition and metabolism in commensal flora. But, the exact mechanisms for fatty diet in gut inflammation are not well demonstrated. In this study, we found that high fat diet (HFD) promoted inflammation and exacerbated the disease severity of dextran sulfate sodium (DSS) induced colitis in mice. Compared with low fat diet (LFD)/DSS mice, shorter colon length, more epithelial loss and crypt destruction and more Gr-1 + myeloid inflammatory cells infiltration in colons were observed in HFD/DSS cohorts. Interestingly, such HFD mediated inflammation accompanied with the dys-regulation of hematopoiesis, and more hematopoiesis stem and progenitor cells were detected in colon and spleen. We further analyzed the effects of HFD and DSS treatment on mucosal DC subsets, and found that DSS treatment in LFD mice mainly dramatically increased the percentage of CD11c + CD103 - CD11b + DCs in lamina propria (LP). While, in HFD/DSS mice, HFD pre-treatment not only increased the percentage of CD11c + CD103 - CD11b + DCs, but also decreased CD11c + CD103 + CD11b + in both LP and mesenteric lymph nodes (MLN) in mice with colitis. This disequilibrium of mucosal dendritic cells in HFD/DSS mice may depend on the reduced levels of buytrate and retinoic acid. Thus, this study declared the effects of HFD on gut microenviroment, and further indicated its potential role in the development of DSS induced colitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Valproic acid reduces insulin-resistance, fat deposition and FOXO1-mediated gluconeogenesis in type-2 diabetic rat.

PubMed

Khan, Sabbir; Kumar, Sandeep; Jena, Gopabandhu

2016-06-01

Recent evidences highlighted the role of histone deacetylases (HDACs) in insulin-resistance, gluconeogenesis and islet function. HDACs can modulate the expression of various genes, which directly or indirectly affect glucose metabolism. This study was aimed to evaluate the role of valproic acid (VPA) on fat deposition, insulin-resistance and gluconeogenesis in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet and low dose streptozotocin. VPA at the doses of 150 and 300 mg/kg/day and metformin (positive control) 150 mg/kg twice daily for 10 weeks were administered by oral gavage. Insulin-resistance, dyslipidemia and glycemia were evaluated by biochemical estimations, while fat accumulation and structural alteration were assessed by histopathology. Protein expression and insulin signaling were evaluated by western blot and immunohistochemistry. VPA treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, fat deposition in brown adipose tissue, white adipose tissue and liver, which are comparable to metformin treatment. Further, VPA inhibited the gluconeogenesis and glucagon expression as well as restored the histopathological alterations in pancreas and liver. Our findings provide new insights on the anti-diabetic role of VPA in type-2 diabetes mellitus by the modulation of insulin signaling and forkhead box protein O1 (FOXO1)-mediated gluconeogenesis. Since VPA is a well established clinical drug, the detailed molecular mechanisms of the present findings can be further investigated for possible clinical use. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Oral administration of Bifidobacterium breve B-3 modifies metabolic functions in adults with obese tendencies in a randomised controlled trial.

PubMed

Minami, Jun-Ichi; Kondo, Shizuki; Yanagisawa, Naotake; Odamaki, Toshitaka; Xiao, Jin-Zhong; Abe, Fumiaki; Nakajima, Shigeru; Hamamoto, Yukie; Saitoh, Sanae; Shimoda, Taeko

2015-01-01

Accumulating evidence suggests an association between gut microbiota and the development of obesity, raising the possibility of probiotic administration as a therapeutic approach. Bifidobacterium breve B-3 was found to exhibit an anti-obesity effect on high-fat diet-induced obesity mice. In the present study, a randomised, double-blind, placebo-controlled trial was conducted to evaluate the effect of the consumption of B. breve B-3 on body compositions and blood parameters in adults with a tendency for obesity. After a 4-week run-in period, the participants were randomised to receive either placebo or a B-3 capsule (approximately 5 × 10(10) colony-forming units of B-3/d) daily for 12 weeks. A significantly lowered fat mass was observed in the B-3 group compared with the placebo group at week 12. Improvements were observed for some blood parameters related to liver functions and inflammation, such as γ-glutamyltranspeptidase and high-sensitivity C-reactive protein. Significant correlations were found between the changed values of some blood parameters and the changed fat mass in the B-3 group. These results suggest the beneficial potential of B. breve B-3 in improving metabolic disorders.

The l-α-Lysophosphatidylinositol/GPR55 System and Its Potential Role in Human Obesity

PubMed Central

Moreno-Navarrete, José María; Catalán, Victoria; Whyte, Lauren; Díaz-Arteaga, Adenis; Vázquez-Martínez, Rafael; Rotellar, Fernando; Guzmán, Rocío; Gómez-Ambrosi, Javier; Pulido, Marina R.; Russell, Wendy R.; Imbernón, Mónica; Ross, Ruth A.; Malagón, María M.; Dieguez, Carlos; Fernández-Real, José Manuel; Frühbeck, Gema; Nogueiras, Ruben

2012-01-01

GPR55 is a putative cannabinoid receptor, and l-α-lysophosphatidylinositol (LPI) is its only known endogenous ligand. We investigated 1) whether GPR55 is expressed in fat and liver; 2) the correlation of both GPR55 and LPI with several metabolic parameters; and 3) the actions of LPI on human adipocytes. We analyzed CB1, CB2, and GPR55 gene expression and circulating LPI levels in two independent cohorts of obese and lean subjects, with both normal or impaired glucose tolerance and type 2 diabetes. Ex vivo experiments were used to measure intracellular calcium and lipid accumulation. GPR55 levels were augmented in the adipose tissue of obese subjects and further so in obese patients with type 2 diabetes when compared with nonobese subjects. Visceral adipose tissue GPR55 correlated positively with weight, BMI, and percent fat mass, particularly in women. Hepatic GPR55 gene expression was similar in obese and type 2 diabetic subjects. Circulating LPI levels were increased in obese patients and correlated with fat percentage and BMI in women. LPI increased the expression of lipogenic genes in visceral adipose tissue explants and intracellular calcium in differentiated visceral adipocytes. These findings indicate that the LPI/GPR55 system is positively associated with obesity in humans. PMID:22179809

Physiologicomathematical model for studying human exposure to organic solvents: kinetics of blood/tissue n-hexane concentrations and of 2,5-hexanedione in urine.

PubMed Central

Perbellini, L; Mozzo, P; Brugnone, F; Zedde, A

1986-01-01

The physiologicomathematical model with eight compartments described allows the simulation of the absorbtion, distribution, biotransformation, excretion of an organic solvent, and the kinetics of its metabolites. The usual compartments of the human organism (vessel rich group, muscle group, and fat group) are integrated with the lungs, the metabolising tissues, and three other compartments dealing with the metabolic kinetics (biotransformation, water, and urinary compartments). The findings obtained by mathematical simulation of exposure to n-hexane were compared with data previously reported. The concentrations of n-hexane in alveolar air and in venous blood described both in experimental and occupational exposures provided a substantial validation for the data obtained by mathematical simulation. The results of the urinary excretion of 2,5-hexanedione given by the model were in good agreement with data already reported. The simulation of an exposure to n-hexane repeated five days a week suggested that the solvent accumulates in the fat tissue. The half life of n-hexane in fat tissue equalled 64 hours. The kinetics of 2,5-hexanedione resulting from the model suggest that occupational exposure results in the presence of large amounts of 2,5-hexanedione in the body for the whole working week. PMID:3790456

Transcriptome Analyses Reveal Lipid Metabolic Process in Liver Related to the Difference of Carcass Fat Content in Rainbow Trout (Oncorhynchus mykiss)

PubMed Central

Hu, Guo; Gu, Wei; Sun, Peng; Bai, Qingli

2016-01-01

Excessive accumulation of carcass fat in farm animals, including fish, has a significant impact on meat quality and on the cost of feeding. Similar to farmed animals and humans, the liver can be considered one of the most important organs involved in lipid metabolism in rainbow trout (Oncorhynchus mykiss). RNA-seq based whole transcriptome sequencing was performed to liver tissue of rainbow trout with high and low carcass fat content in this study. In total 1,694 differentially expressed transcripts were identified, including many genes involved in lipid metabolism, such as L-FABP, adiponectin, PPAR-α, PPAR-β, and IGFBP1a. Evidence presented in this study indicated that lipid metabolic process in liver may be related to the difference of carcass fat content. The relevance of PPAR-α and PPAR-β as molecular markers for fat storage in liver should be worthy of further investigation. PMID:27652256

Liver fat: a relevant target for dietary intervention? Summary of a Unilever workshop.

PubMed

Peters, Harry P F; Schrauwen, Patrick; Verhoef, Petra; Byrne, Christopher D; Mela, David J; Pfeiffer, Andreas F H; Risérus, Ulf; Rosendaal, Frits R; Schrauwen-Hinderling, Vera

2017-01-01

Currently it is estimated that about 1 billion people globally have non-alcoholic fatty liver disease (NAFLD), a condition in which liver fat exceeds 5 % of liver weight in the absence of significant alcohol intake. Due to the central role of the liver in metabolism, the prevalence of NAFLD is increasing in parallel with the prevalence of obesity, insulin resistance and other risk factors of metabolic diseases. However, the contribution of liver fat to the risk of type 2 diabetes mellitus and CVD, relative to other ectopic fat depots and to other risk markers, is unclear. Various studies have suggested that the accumulation of liver fat can be reduced or prevented via dietary changes. However, the amount of liver fat reduction that would be physiologically relevant, and the timeframes and dose-effect relationships for achieving this through different diet-based approaches, are unclear. Also, it is still uncertain whether the changes in liver fat per se or the associated metabolic changes are relevant. Furthermore, the methods available to measure liver fat, or even individual fatty acids, differ in sensitivity and reliability. The present report summarises key messages of presentations from different experts and related discussions from a workshop intended to capture current views and research gaps relating to the points above.

Evaluation of Beneficial Metabolic Effects of Berries in High-Fat Fed C57BL/6J Mice

PubMed Central

Blanco, Narda; Sterner, Olov; Holm, Cecilia

2014-01-01

Objective. The aim of the study was to screen eight species of berries for their ability to prevent obesity and metabolic abnormalities associated with type 2 diabetes. Methods. C57BL/6J mice were assigned the following diets for 13 weeks: low-fat diet, high-fat diet or high-fat diet supplemented (20%) with lingonberry, blackcurrant, bilberry, raspberry, açai, crowberry, prune or blackberry. Results. The groups receiving a high-fat diet supplemented with lingonberries, blackcurrants, raspberries or bilberries gained less weight and had lower fasting insulin levels than the control group receiving high-fat diet without berries. Lingonberries, and also blackcurrants and bilberries, significantly decreased body fat content, hepatic lipid accumulation, and plasma levels of the inflammatory marker PAI-1, as well as mediated positive effects on glucose homeostasis. The group receiving açai displayed increased weight gain and developed large, steatotic livers. Quercetin glycosides were detected in the lingonberry and the blackcurrant diets. Conclusion. Lingonberries were shown to fully or partially prevent the detrimental metabolic effects induced by high-fat diet. Blackcurrants and bilberries had similar properties, but to a lower degree. We propose that the beneficial metabolic effects of lingonberries could be useful in preventing obesity and related disorders. PMID:24669315

Adzuki bean ameliorates hepatic lipogenesis and proinflammatory mediator expression in mice fed a high-cholesterol and high-fat diet to induce nonalcoholic fatty liver disease.

PubMed

Kim, Sera; Hong, Jihye; Jeon, Raok; Kim, Hyun-Sook

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) is a simple steatosis, in which fat accumulates more than 5% in the liver, and regarded as most common liver diseases worldwide. Because NAFLD can be developed to severe liver disease and correlated with metabolic disease, its importance is currently emphasized. Occurrence of NAFLD is strongly related to dietary patterns and lifestyles; therefore, the suggestion of physiologically beneficial food is essential. Based on these, adzuki beans containing anthocyanin, catechin, and adzukisaponin are suggested as a health-beneficial food. Moreover, the effects of adzuki beans on metabolic improvement are not well established through the in vivo studies. Therefore, this study hypothesized that adzuki beans can alleviate lipid accumulation and oxidative stress-mediated inflammation in high-cholesterol and high-fat diet-induced NALFD mice. To demonstrate its effects, 6-week-old C57BL/6 male mice were allocated into 4 groups and fed a normal diet (ND), a high-cholesterol and high-fat diet (HCD), and HCD with 10% and 20% adzuki bean for 10 weeks. The result shows that fasting blood glucose, serum and hepatic triglyceride and cholesterol levels, and antioxidative enzyme activity ameliorated in the adzuki bean groups (P < .05). The transcriptional factors of hepatic lipogenesis, such as adiponectin, AMP-activated protein kinase α, sterol regulatory element-binding protein 1c, fatty acid synthase, carnitine palmitoyltransferase 1, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and apolipoprotein B, as well as proinflammatory mediators, such as tumor necrosis factor α, nuclear factor κB, and caspase-3, improved in both experimental groups (P < .05). These results suggested that adzuki beans attenuate lipid accumulation and oxidative stress-induced inflammation by suppressing hepatic messenger RNA expression of lipogenic and inflammatory mediators in NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

Comprehensive Endocrine-Metabolic Evaluation of Patients with Alström Syndrome Compared to BMI-Matched Controls.

PubMed

Han, Joan C; Reyes-Capo, Daniela P; Liu, Chia-Ying; Reynolds, James C; Turkbey, Evrim; Turkbey, Ismail Baris; Bryant, Joy; Marshall, Jan D; Naggert, Jürgen K; Gahl, William A; Yanovski, Jack A; Gunay-Aygun, Meral

2018-04-27

Alström syndrome (AS), a monogenic form of obesity, is caused by recessive mutations in the centrosome- and basal body-associated gene, ALMS1. AS is characterized by retinal dystrophy, sensory hearing loss, cardiomyopathy, childhood obesity, and metabolic derangements. We sought to characterize the endocrine and metabolic features of AS while accounting for obesity as a confounder by comparing patients with AS to BMI-matched controls. We evaluated 38 patients with AS (age 2-38y) who were matched with 76 controls (age 2-48y) by age, sex, race, and BMI. Fasting biochemistries, mixed meal test (MMT), indirect calorimetry, DEXA, and MRI/MRS were performed. Frequent abnormalities in AS included 76% obesity, 37% type 2 diabetes (T2DM), 29% hypothyroidism (1/3-central, 2/3-primary), 3% central adrenal insufficiency, 57% adult hypogonadism (1/3-central, 2/3-primary), and 25% female hyperandrogenism. AS and controls had similar BMI-Z, body fat, waist circumference, abdominal visceral fat, muscle fat, resting energy expenditure (adjusted for lean mass), free fatty acids, glucagon, prolactin, ACTH, and cortisol. Compared to controls, AS were shorter and had lower IGF1 concentrations (p's≤0.001). AS had significantly greater fasting and MMT insulin resistance indices, higher MMT glucose, insulin, and C-peptide values, higher hemoglobin A1c, and higher prevalence of T2DM (p's<0.001). AS had significantly higher triglycerides, lower HDL-cholesterol, and a 10-fold greater prevalence of metabolic syndrome (p's<0.001). AS demonstrated significantly greater liver triglyceride accumulation and higher transaminases (p's<0.001). Severe insulin resistance and T2DM are the hallmarks of AS. However, patients with AS may present with multiple other endocrinopathies affecting growth and development.

Beneficial effects of Plantago albicans on high-fat diet-induced obesity in rats.

PubMed

Samout, Noura; Ettaya, Amani; Bouzenna, Hafsia; Ncib, Sana; Elfeki, Abdelfattah; Hfaiedh, Najla

2016-12-01

Obesity is a one of the main global public health problems associated with chronic diseases such as coronary heart disease, diabetes and cancer. As a solution to obesity, we suggest Plantago albicans, which is a medicinal plant with several biological effects. This study assesses the possible anti-obesity protective properties of Plantago albicans in high fat diet-fed rats. 28 male Wistar rats were divided into 4 groups; a group which received normal diet (C), the second group was fed HDF diet (HDF), the third group was given normal diet supplemented with Plantago albicans (P.AL), and the fourth group received HDF supplemented with Plantago albicans (HDF+P.AL) (30mg/kg/day) for 7 weeks. Our results showed an increase in body weight of HDF rats by ∼16% as compared to the control group with an increase in the levels of total cholesterol (TC) as well as LDL-cholesterol, triglycerides (TG) in serum. Also, the concentration of TBARS increased in the liver and heart of HDF-fed rats as compared to the control group. The oral gavage of Plantago albicans extract to obese rats induced a reduction in their body weight, lipid accumulation in liver and heart tissue, compared to the high-fat diet control rats. The obtained results proved that the antioxidant potency of Plantago albicans extracts was correlated with their phenolic and flavonoid contents. The antioxidant capacity of the extract was evaluated by DPPH test (as EC50=250±2.12μg/mL) and FRAP tests (as EC50=27.77±0.14μg/mL). These results confirm the phytochemical and antioxidant impact of Plantago albicans extracts. Plantago albicans content was determined using validated HPLC methodology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver disease in rats

PubMed Central

Hussein, Osamah; Grosovski, Masha; Lasri, Etti; Svalb, Sergio; Ravid, Uzi; Assy, Nimer

2007-01-01

AIM: To evaluate the effects of different types of dietary fats on the hepatic lipid content and oxidative stress parameters in rat liver with experimental non-alcoholic fatty liver disease (NAFLD). METHODS: A total of 32 Sprague-Dawley rats were randomly divided into five groups. The rats in the control group (n = 8) were on chow diet (Group 1), rats (n = 6) on methionine choline-deficient diet (MCDD) (Group 2), rats (n = 6) on MCDD enriched with olive oil (Group 3), rats (n = 6) on MCDD with fish oil (Group 4) and rats (n = 6) on MCDD with butter fat (Group 5). After 2 mo, blood and liver sections were examined for lipids composition and oxidative stress parameters. RESULTS: The liver weight/rat weight ratio increased in all treatment groups as compared with the control group. Severe fatty liver was seen in MCDD + fish oil and in MCDD + butter fat groups, but not in MCDD and MCDD + olive oil groups. The increase in hepatic triglycerides (TG) levels was blunted by 30% in MCDD + olive oil group (0.59 ± 0.09) compared with MCDD group (0.85 ± 0.04, p < 0.004), by 37% compared with MCDD + fish oil group (0.95 ± 0.07, p < 0.001), and by 33% compared with MCDD + butter group (0.09 ± 0.1, p < 0.01). The increase in serum TG was lowered by 10% in MCDD + olive oil group (0.9 ± 0.07) compared with MCDD group (1.05 ± 0.06). Hepatic cholesterol increased by 15-fold in MCDD group [(0.08 ± 0.02, this increment was blunted by 21% in MCDD + fish oil group (0.09 ± 0.02)]. In comparison with the control group, ratio of long-chain polyunsaturated fatty acids omega-6/omega-3 increased in MCDD + olive oil, MCDD + fish oil and MCDD + butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD group (1.58 ± 0.08), hepatic MDA contents in MCDD + olive oil (3.3 ± 0.6), MCDD + fish oil (3.0 ± 0.4), and MCDD + butter group (2.9 ± 0.36) were increased by 108%, 91% and 87%, respectively (p < 0.004). Hepatic paraoxonase activity decreased significantly in all treatment groups, mostly with MCDD + olive oil group (-68%). CONCLUSION: Olive oil decreases the accumulation of triglyceride in the liver of rats with NAFLD, but does not provide the greatest antioxidant activity. PMID:17230603

Emodin ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

PubMed

Cao, Yanni; Chang, Shufang; Dong, Jie; Zhu, Shenyin; Zheng, Xiaoying; Li, Juan; Long, Rui; Zhou, Yuanda; Cui, Jianyu; Zhang, Ye

2016-06-05

Emodin, an anthraquinone derivative isolated from root and rhizome of Rheum palmatum, has been reported to have promising anti-diabetic activity. The present study was to explore the possible mechanism of emodin to ameliorate insulin resistance. Insulin resistance was induced by feeding a high fat diet to Sprague-Dawley rats. The blood glucose and lipid profiles in serum were measured by an enzymatic method, and a hyperinsulinaemic-euglycaemic clamp was used to evaluate insulin resistance. L6 cells were cultured and treated with palmitic acid and emodin. The lipid content was assayed in the soleus muscle and L6 cells by Oil Red O staining. Western blot, qRT-PCR, and immunohistochemical staining were used to detect the following in the rat soleus muscle and L6 cells: protein levels, mRNA levels of FATP1, FATP4, transporter fatty acid translocase (FAT/CD36), and plasma membrane-associated fatty acid protein (FABPpm). We found that blood glucose, triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the emodin group. Oil Red O staining and the level of TG in skeletal muscle and L6 cells confirmed that lipid deposition decreased after treatment with emodin. Furthermore, the protein levels and mRNA levels of FATP1 in skeletal muscle and in L6 cells of rats were significantly decreased, yet the protein levels and mRNA levels of FATP4, FAT/CD36 and FABPpm did not drop off significantly. The study suggest that emodin ameliorates insulin resistance by reducing FATP1-mediated skeletal muscle lipid accumulation in rats fed a high fat diet. Copyright © 2016 Elsevier B.V. All rights reserved.

Loss of P2X7 receptor function dampens whole body energy expenditure and fatty acid oxidation.

PubMed

Giacovazzo, Giacomo; Apolloni, Savina; Coccurello, Roberto

2018-05-12

The established role of ATP-responsive P2X7 receptor in inflammatory, neurodegenerative, and immune diseases is now expanding to include several aspects of metabolic dysregulation. Indeed, P2X7 receptors are involved in β cell function, insulin secretion, and liability to diabetes, and loss of P2X7 function may increase the risk of hepatic steatosis and disrupt adipogenesis. Recently, body weight gain, abnormal lipid accumulation, adipocyte hyperplasia, increased fat mass, and ectopic fat distribution have been found in P2X7 KO mice. Here, we hypothesized that such clinical picture of dysregulated lipid metabolism might be the result of altered in vivo energy metabolism. By indirect calorimetry, we assessed 24 h of energy expenditure (EE) and respiratory exchange ratio (RER) as quotient of carbohydrate to fat oxidation in P2X7 KO mice. Moreover, we assessed the same parameters in aged-matched WT counterparts that underwent a 7-day treatment with the P2X7 antagonist A804598. We found that loss of P2X7 function elicits a severe decrease of EE that was less pronounced in A804598-treated mice. In parallel, P2X7KO mice show a drastic increase of RER, thus indicating the occurrence of a greater ratio of carbohydrate to fat oxidation. Decreased EE and fat oxidation is predictive of body weight gain, which was here confirmed. Taken together, our data provide evidence that P2X7 loss of function produces defective energy homeostasis that, together with disrupted adipogenesis, might help to explain accumulation of adipose tissue and contribute to disclose the potential role of P2X7 in metabolic diseases.

Pharmacokinetics of Venetoclax, a Novel BCL-2 Inhibitor, in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Non-Hodgkin Lymphoma.

PubMed

Salem, Ahmed Hamed; Agarwal, Suresh K; Dunbar, Martin; Enschede, Sari L Heitner; Humerickhouse, Rod A; Wong, Shekman L

2017-04-01

Venetoclax is a selective BCL-2 inhibitor that is approved in the United States for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least 1 prior therapy. The aim of this analysis was to characterize venetoclax pharmacokinetics in the plasma and urine of patients with hematological malignancies and evaluate the effect of dose proportionality, accumulation, weak and moderate CYP3A inhibitors, as well as low- and high-fat meals on venetoclax pharmacokinetics. Patients received a once-daily venetoclax dose of 20 to 1200 mg. Pharmacokinetic parameters were estimated using noncompartmental methods. Venetoclax peak exposures were achieved at 5 to 8 hours under low-fat conditions, and the mean terminal-phase elimination half-life ranged between 14.1 and 18.2 hours at different doses. Venetoclax steady-state exposures showed minimal accumulation and increased proportionally over the dose range of 300 to 900 mg. Low-fat and high-fat meals increased venetoclax exposures by approximately 4-fold relative to the fasting state. Moderate CYP3A inhibitors increased venetoclax exposures by 40% to 60%, whereas weak CYP3A inhibitors had no effect. A negligible amount of venetoclax was excreted in the urine. In summary, venetoclax exhibits a pharmacokinetic profile that is compatible with once-daily dosing with food regardless of fat content. Concomitant use of venetoclax with moderate CYP3A inhibitors should be avoided or venetoclax dose should be reduced during the venetoclax initiation and ramp-up phase in CLL patients. Renal excretion plays a minimal role in the elimination of venetoclax. © 2016, The American College of Clinical Pharmacology.

External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals.

PubMed

Cuthbertson, Daniel J; Weickert, Martin O; Lythgoe, Daniel; Sprung, Victoria S; Dobson, Rebecca; Shoajee-Moradie, Fariba; Umpleby, Margot; Pfeiffer, Andreas F H; Thomas, E Louise; Bell, Jimmy D; Jones, Helen; Kemp, Graham J

2014-11-01

Simple clinical algorithms including the fatty liver index (FLI) and lipid accumulation product (LAP) have been developed as surrogate markers for non-alcoholic fatty liver disease (NAFLD), constructed using (semi-quantitative) ultrasonography. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as determined quantitatively by proton magnetic resonance spectroscopy (1H-MRS). Data were collected from 168 patients with NAFLD and 168 controls who had undergone clinical, biochemical and anthropometric assessment. Values of FLI and LAP were determined and assessed both as predictors of the presence of hepatic steatosis (liver fat>5.5%) and of actual liver fat content, as measured by 1H-MRS. The discriminative ability of FLI and LAP was estimated using the area under the receiver operator characteristic curve (AUROC). As FLI can also be interpreted as a predictive probability of hepatic steatosis, we assessed how well calibrated it was in our cohort. Linear regression with prediction intervals was used to assess the ability of FLI and LAP to predict liver fat content. Further validation was provided in 54 patients with type 2 diabetes mellitus. FLI, LAP and alanine transferase discriminated between patients with and without steatosis with an AUROC of 0.79 (IQR=0.74, 0.84), 0.78 (IQR=0.72, 0.83) and 0.83 (IQR=0.79, 0.88) respectively although could not quantitatively predict liver fat. Additionally, the algorithms accurately matched the observed percentages of patients with hepatic steatosis in our cohort. FLI and LAP may be used to identify patients with hepatic steatosis clinically or for research purposes but could not predict liver fat content. © 2014 European Society of Endocrinology.

The effect of peripheral chronic salsolinol administration on fat pad adipocytes morphological parameters.

PubMed

Aleksandrovych, Veronika; Kurnik, Magdalena; Białas, Magdalena; Bugajski, Andrzej; Thor, Piotr; Gil, Krzysztof

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is thought to regulate dopaminergic neurons and to act as a mediator in the neuroendocrine system. We have previously reported that exogenous salsolinol evokes enteric neuronal cell death, leading to the impairment of myenteric neurons density and abnormal intestinal transit in rats. We also observed significant reduction of body weight, related to the disrupted gastrointestinal homeostasis. e aim of current study was to evaluate the influence of prolonged salsolinol administration body weight, food intake, adipose tissue accumulation and fad pad adipocyte morphological parameters assessed by image analysis. Male Wistar rats were subjected to continuous intraperitoneal low dosing of salsolinol - 200 mg/kg in total with ALZET osmotic mini-pumps (Durtec, USA) for 2 or 4 weeks with either normal or high-fat diet. Appropriate groups served as the controls. Food intake, body weight were measured each morning. Both epididymal fat pads were dissected, weighted and processed for routine hematoxylin and eosin staining. e following parameters: cell area, perimeter, long and short axis, aspect ratio and circularity factor were assessed in stained specimens with the image analysis system (Multiscan, Poland). Salsolinol administration significantly reduced total body mass with no differences in total food intake between the groups. The epididymal fat pad weight over final body mass ratio was lower in salsolinol treated rats on high fat diet in comparison with the control groups. e area, perimeter, short and long axis of the fad pad adipocytes were significantly decreased in salsolinol treated animals in comparison with relevant controls. Salsolinol targets some regulatory mechanisms concerned with the basic rat metabolism. Prolonged peripheral salsolinol administration in rats significantly decreases the adipocyte size, and such effect is related to the weight loss and reduced adipose tissue accumulation.

Dehydroepiandrosterone reduces accumulation of lipid droplets in primary chicken hepatocytes by biotransformation mediated via the cAMP/PKA-ERK1/2 signaling pathway.

PubMed

Li, Longlong; Ge, Chongyang; Wang, Dian; Yu, Lei; Zhao, Jinlong; Ma, Haitian

2018-06-01

Dehydroepiandrosterone (DHEA) is commonly used as a nutritional supplement to control fat deposition, but the mechanism of this action is poorly understood. In this study, we demonstrated that DHEA increased phosphorylation of AMP-activated protein kinase (p-AMPK). Elevated p-AMPK levels resulted in reduced expression of sterol regulatory element binding protein-1c, acetyl CoA carboxylase, fatty acid synthase and enhanced expression of peroxisome proliferators-activated receptor α and carnitine palmitoyl transferase-I, ultimately leading to the reduction of lipid droplet accumulation in primary chicken hepatocytes. We found that DHEA activates the cyclic adenosine 3', 5'-monophosphate/protein kinase A - extracellular signal-regulated kinase 1/2 (cAMP/PKA-ERK1/2) signaling pathway, which regulates the conversion of DHEA into testosterone and estradiol by increasing the 17β-hydroxysteroid dehydrogenase and aromatase protein expression. Importantly, the fat-reducing effects of DHEA are more closely associated with the conversion of DHEA into estradiol than with the action of DHEA itself as an active biomolecule, or to its alternative metabolite, testosterone. Taken together, our results indicate that DHEA is converted into active hormones through activation of the cAMP/PKA-ERK1/2 signaling pathway; the fat-reducing effects of DHEA are achieved through its conversion into estradiol, not testosterone, and not through direct action of DHEA itself, which led to the activation of the p-AMPK in primary chicken hepatocytes. These data provide novel insight into the mechanisms underlying the action of DHEA in preventing fat deposition, and suggest potential applications for DHEA treatment to control fat deposition or as an agent to treat disorders related to lipid metabolism in animals and humans. Copyright © 2018 Elsevier B.V. All rights reserved.

Genetics Home Reference: Farber lipogranulomatosis

MedlinePlus

... breakdown and use of fats in the body (lipid metabolism). In affected individuals, lipids accumulate abnormally in cells and tissues throughout the ... health problems beginning in infancy due to massive lipid deposits in the liver, spleen, lungs, and immune ...

Intermittent cold exposure enhances fat accumulation in mice.

PubMed

Yoo, Hyung Sun; Qiao, Liping; Bosco, Chris; Leong, Lok-Hei; Lytle, Nikki; Feng, Gen-Sheng; Chi, Nai-Wen; Shao, Jianhua

2014-01-01

Due to its high energy consuming characteristics, brown adipose tissue (BAT) has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE), unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis.

Intermittent Cold Exposure Enhances Fat Accumulation in Mice

PubMed Central

Yoo, Hyung sun; Qiao, Liping; Bosco, Chris; Leong, Lok-Hei; Lytle, Nikki; Feng, Gen-Sheng; Chi, Nai-Wen; Shao, Jianhua

2014-01-01

Due to its high energy consuming characteristics, brown adipose tissue (BAT) has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE), unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis. PMID:24789228

Abdominal fat analyzed by DEXA scan reflects visceral body fat and improves the phenotype description and the assessment of metabolic risk in mice

PubMed Central

Chen, Weiyi; Wilson, Jenny L.; Khaksari, Mohammad; Cowley, Michael A.

2012-01-01

Clinical studies have demonstrated a strong relationship between visceral fat content and metabolic diseases, such as type 2 diabetes and liver steatosis. Obese mouse models are an excellent tool to study metabolic diseases; however, there are limited methods for the noninvasive measurement of fat distribution in mice. Although micromagnetic resonance imaging and microcomputed tomography are the “gold standards” in the measurement of fat distribution, more economical and accessible methods are required. Dual energy X-ray absorptiometry (DEXA) is an effective method in characterizing fat content; however, it cannot discriminate between visceral and subcutaneous fat depots. We demonstrate that an evaluation of abdominal fat content measured by DEXA through the selection of one localized abdominal area strongly correlates with visceral fat content in C57BL/6J mice. We found that DEXA is able to measure fat pad volume ex vivo with high accuracy; however, the measurement of visceral fat in vivo shows an overestimation caused by subcutaneous tissue interference. The overestimation is almost constant for a wide range of values, and thus it is possible to correct the data for a more accurate estimation of visceral fat content. We demonstrate the utility of this technique in characterizing phenotypes of several obese mouse models (ob/ob, db/db, MC4R-KO, and DIO) and evaluating the effect of treatments on visceral fat content in longitudinal studies. Additionally, we also establish abdominal obesity as a potential biomarker for metabolic abnormalities (liver fat accumulation, insulin resistance/diabetes) in mice, similar to that described in humans. PMID:22761161

High intake of saturated fat, but not polyunsaturated fat, improves survival in heart failure despite persistent mitochondrial defects.

PubMed

Galvao, Tatiana F; Brown, Bethany H; Hecker, Peter A; O'Connell, Kelly A; O'Shea, Karen M; Sabbah, Hani N; Rastogi, Sharad; Daneault, Caroline; Des Rosiers, Christine; Stanley, William C

2012-01-01

The impact of a high-fat diet on the failing heart is unclear, and the differences between polyunsaturated fatty acids (PUFA) and saturated fat have not been assessed. Here, we compared a standard low-fat diet to high-fat diets enriched with either saturated fat (palmitate and stearate) or PUFA (linoleic and α-linolenic acids) in hamsters with genetic cardiomyopathy. Male δ-sarcoglycan null Bio TO2 hamsters were fed a standard low-fat diet (12% energy from fat), or high-fat diets (45% fat) comprised of either saturated fat or PUFA. The median survival was increased by the high saturated fat diet (P< 0.01; 278 days with standard diet and 361 days with high saturated fat)), but not with high PUFA (260 days) (n = 30-35/group). Body mass was modestly elevated (∼10%) in both high fat groups. Subgroups evaluated after 24 weeks had similar left ventricular chamber size, function, and mass. Mitochondrial oxidative enzyme activity and the yield of interfibrillar mitochondria (IFM) were decreased to a similar extent in all TO2 groups compared with normal F1B hamsters. Ca(2+)-induced mitochondrial permeability transition pore opening was enhanced in IFM in all TO2 groups compared with F1B hamsters, but to a significantly greater extent in those fed the high PUFA diet compared with the standard or high saturated fat diet. These results show that a high intake of saturated fat improves survival in heart failure compared with a high PUFA diet or low-fat diet, despite persistent mitochondrial defects.

Two candidate genes (FTO and INSIG2) for fat accumulation in four canids: chromosome mapping, gene polymorphisms and association studies of body and skin weight of red foxes.

PubMed

Grzes, M; Szczerbal, I; Fijak-Nowak, H; Szydlowski, M; Switonski, M

2011-01-01

Fat accumulation is a polygenic trait which has a significant impact on human health and animal production. Obesity is also an increasingly serious problem in dog breeding. The FTO and INSIG2 are considered as candidate genes associated with predisposition for human obesity. In this report we present a comparative genomic analysis of these 2 genes in 4 species belonging to the family Canidae - the dog and 3 species which are kept in captivity for fur production, i.e. red fox, arctic fox and Chinese raccoon dog. We cytogenetically mapped these 2 loci by FISH and compared the entire coding sequence of INSIG2 and a fragment of the coding sequence of FTO. The FTO gene was assigned to the following chromosomes: CFA2q25 (dog), VVU2q21 (red fox), ALA8q25 (arctic fox) and NPP10q24-25 (Chinese raccoon dog), while the INSIG2 was mapped to CFA19q17, VVU5p14, ALA24q15 and NPP9q22, respectively. Altogether, 29 SNPs were identified (16 in INSIG2 and 13 in FTO) and among them 2 were missense substitutions in the dog (23C/T, Thr>Met in the FTO gene and 40C/A, Arg>Ser in INSIG2). The distribution of these 2 SNPs was studied in 14 dog breeds. Two synonymous SNPs, one in the FTO gene (-28T>C in the 5'-flanking region) and one in the INSIG2 (10175C>T in intron 2), were used for the association studies in red foxes (n = 390) and suggestive evidence was observed for their association with body weight (FTO, p < 0.08) and weight of raw skin (INSIG2, p < 0.05). These associations indicate that both genes are potential candidates for growth or adipose tissue accumulation in canids. We also suggest that the 2 missense substitutions found in dogs should be studied in terms of genetic predisposition to obesity. Copyright © 2011 S. Karger AG, Basel.

Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients.

PubMed

Jaganjac, Morana; Almuraikhy, Shamma; Al-Khelaifi, Fatima; Al-Jaber, Mashael; Bashah, Moataz; Mazloum, Nayef A; Zarkovic, Kamelija; Zarkovic, Neven; Waeg, Georg; Kafienah, Wael; Elrayess, Mohamed A

2017-08-01

Obesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype. OM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery. Levels of 4-HNE protein adducts, adipocyte size and number of macrophages were determined within these tissues by immunohistochemistry. Adipogenic capacity and gene expression profiles were assessed in preadipocytes derived from these tissues in relation to insulin resistance and in response to 4-HNE, metformin or combined metformin and insulin treatment. Preadipocytes isolated from insulin resistant (IR) and T2DM individuals exhibited lower adipogenesis, marked by upregulation of anti-adipogenic genes, compared to preadipocytes derived from insulin sensitive (IS) individuals. Impaired adipogenesis was also associated with increased 4-HNE levels, smaller adipocytes and greater macrophage presence in the adipose tissues. Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues. Treatment of preadipocytes in vitro with 4-HNE reduced their adipogenesis and increased proliferation, even in the presence of metformin, which was partially rescued by the presence of insulin. This study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic action of insulin and metformin. Further studies are needed to evaluate involvement of 4-HNE in metabolically impaired abdominal adipogenesis and to confirm benefits of combined metformin-insulin therapy in T2DM patients. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Accumulation of Polychlorinated Biphenyls in Adipocytes: Selective Targeting to Lipid Droplets and Role of Caveolin-1

PubMed Central

Bourez, Sophie; Le Lay, Soazig; Van den Daelen, Carine; Louis, Caroline; Larondelle, Yvan; Thomé, Jean-Pierre; Schneider, Yves-Jacques; Dugail, Isabelle; Debier, Cathy

2012-01-01

Background Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that preferentially accumulate in lipid-rich tissues of contaminated organisms. Although the adipose tissue constitutes a major intern reservoir of PCBs and recent epidemiological studies associate PCBs to the development of obesity and its related disorders, little is known about the mechanisms involved in their uptake by the adipose tissue and their intracellular localization in fat cells. Methodology/Principal Findings We have examined the intracellular distribution of PCBs in mouse cultured adipocytes and tested the potential involvement of caveolin-1, an abundant adipocyte membrane protein, in the uptake of these compounds by fat cells. We show that 2,4,4′-trichlorobiphenyl (PCB-28), 2,3′,4,4′,5-pentachlorobiphenyl (PCB-118) and 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB-153) congeners rapidly and extensively accumulate in 3T3-L1 or mouse embryonic fibroblast (MEF) derived cultured adipocytes. The dynamics of accumulation differed between the 3 congeners tested. By subcellular fractionation of primary adipocytes, we demonstrate that these pollutants were almost exclusively recovered within the lipid droplet fraction and practically not associated to cell membranes. The absence of caveolin-1 expression in primary adipocytes from cav-1 deficient mice did not modify lipid droplet selective targeting of PCBs. In cav-1 KO MEF differentiated adipocytes, PCB accumulation was decreased, which correlated with reduced cell triglyceride content. Conversely, adenoviral mediated cav-1 overexpressing in 3T3-L1 cells, which had no impact on total cell lipid content, did not change PCB accumulation. Conclusion/Significance Our data indicate that caveolin-1 per se is not required for selective PCB accumulation, but rather point out a primary dependence on adipocyte triglyceride content. If the crucial role of lipid droplets in energy homeostasis is considered, the almost exclusive accumulation of PCBs in these organelles warrants future attention as the impairment of their function could be linked to the worldwide obesity epidemic. PMID:22363745

Waking and sleeping in the rat made obese through a high-fat hypercaloric diet.

PubMed

Luppi, Marco; Cerri, Matteo; Martelli, Davide; Tupone, Domenico; Del Vecchio, Flavia; Di Cristoforo, Alessia; Perez, Emanuele; Zamboni, Giovanni; Amici, Roberto

2014-01-01

Sleep restriction leads to metabolism dysregulation and to weight gain, which is apparently the consequence of an excessive caloric intake. On the other hand, obesity is associated with excessive daytime sleepiness in humans and promotes sleep in different rodent models of obesity. Since no consistent data on the wake-sleep (WS) pattern in diet-induced obesity rats are available, in the present study the effects on the WS cycle of the prolonged delivery of a high-fat hypercaloric (HC) diet leading to obesity were studied in Sprague-Dawley rats. The main findings are that animals kept under a HC diet for either four or eight weeks showed an overall decrease of time spent in wakefulness (Wake) and a clear Wake fragmentation when compared to animals kept under a normocaloric diet. The development of obesity was also accompanied with the occurrence of a larger daily amount of REM sleep (REMS). However, the capacity of HC animals to respond to a "Continuous darkness" exposure condition (obtained by extending the Dark period of the Light-Dark cycle to the following Light period) with an increase of Sequential REMS was dampened. The results of the present study indicate that if, on one hand, sleep curtailment promotes an excess of energy accumulation; on the other hand an over-exceeding energy accumulation depresses Wake. Thus, processes underlying energy homeostasis possibly interact with those underlying WS behavior, in order to optimize energy storage. Copyright © 2013 Elsevier B.V. All rights reserved.

IMM-H007, a new therapeutic candidate for nonalcoholic fatty liver disease, improves hepatic steatosis in hamsters fed a high-fat diet.

PubMed

Shi, Huijie; Wang, Qingchun; Yang, Liu; Xie, Shouxia; Zhu, Haibo

2017-09-01

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease in humans, is characterized by the accumulation of triacylglycerols (TGs) in hepatocytes. We tested whether 2',3',5'-tri-acetyl-N6-(3-hydroxylaniline) adenosine (IMM-H007) can eliminate hepatic steatosis in hamsters fed a high-fat diet (HFD), as a model of NAFLD. Compared with HFD-only controls, IMM-H007 treatment significantly lowered serum levels of TG, total cholesterol, and free fatty acids (FFAs) in hamsters fed the HFD, with a prominent decrease in levels of serum transaminases and fasting insulin, without affecting fasting glucose levels. Moreover, 1 H-MRI and histopathological analyses revealed that hepatic lipid accumulation and fibrosis were improved by IMM-H007 treatment. These changes were accompanied by improvement of insulin resistance and oxidative stress, and attenuation of inflammation. IMM-H007 reduced expression of proteins involved in uptake of hepatic fatty acids and lipogenesis, and increased very low density lipoprotein secretion and expression of proteins responsible for fatty acid oxidation and autophagy. In studies in vivo , IMM-H007 inhibited fatty acid import into hepatocytes and liver lipogenesis, and concomitantly stimulated fatty acid oxidation, autophagy, and export of hepatic lipids. These data suggest that IMM-H007 resolves hepatic steatosis in HFD-fed hamsters by the regulation of lipid metabolism. Thus, IMM-H007 has therapeutic potential for NAFLD.

Fermented Moringa oleifera Decreases Hepatic Adiposity and Ameliorates Glucose Intolerance in High-Fat Diet-Induced Obese Mice.

PubMed

Joung, Hyunchae; Kim, Bobae; Park, Hyunjoon; Lee, Kyuyeon; Kim, Hee-Hoon; Sim, Ho-Cheol; Do, Hyun-Jin; Hyun, Chang-Kee; Do, Myoung-Sool

2017-05-01

Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver disease (NAFLD), are primary risk factors for life-threatening conditions such as diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and anticancer effects. Fermentation can further improve the safety and nutritional value of certain foods. We investigated the efficacy of fermented M. oleifera extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic lipid accumulation and investigated the underlying mechanisms by analyzing expression of proteins and genes involved in glucose and lipid regulation. C57BL/6 mice were fed with normal chow diet (ND) or HFD supplemented with distilled water (DW, control), nonfermented M. oleifera extract (NFM), or FM for 10 weeks. Although body weights were similar among HFD-fed treatment groups, liver weight was decreased, and glucose tolerance test (GTT) results improved in the FM group compared with DW and NFM groups. Hepatic lipid accumulation was also lower in the FM group, and expressions of genes involved in liver lipid metabolism were upregulated. In addition, HFD-induced endoplasmic reticulum (ER) stress, oxidative stress, and lipotoxicity in quadriceps muscles were decreased by FM. Finally, proinflammatory cytokine mRNA expression was decreased by FM in the liver, epididymal adipose tissue, and quadriceps of HFD-fed mice. FMs may decrease glucose intolerance and NAFLD under HFD-induced obesity by decreasing ER stress, oxidative stress, and inflammation.

Advanced Hemophilic Arthropathy: Sensitivity of Soft Tissue Discrimination With Musculoskeletal Ultrasound.

PubMed

von Drygalski, Annette; Moore, Randy E; Nguyen, Sonha; Barnes, Richard F W; Volland, Lena M; Hughes, Tudor H; Du, Jiang; Chang, Eric Y

2018-01-24

Point-of-care musculoskeletal ultrasound (US) is increasingly used by hemophilia providers to guide management; however, pathologic tissue differentiation with US is uncertain. We sought to determine the extent to which point-of-care musculoskeletal US can identify and discriminate pathologic soft tissue changes in hemophilic arthropathy. Thirty-six adult patients with hemophilia A/B were prospectively enrolled. Point-of-care musculoskeletal US examinations were performed on arthropathic joints (16 knees, 10 ankles, and 10 elbows) using standard views by a musculoskeletal US-trained and certified hematologist, who recorded abnormal intra-articular soft tissue accumulation. Within 3 days, magnetic resonance imaging was performed using conventional and multiecho ultrashort echo time sequences. Soft tissue identification (synovial proliferation with or without hemosiderin, fat, and/or blood products) was performed by a musculoskeletal radiologist. Findings obtained with both imaging modalities were compared and correlated in a blinded fashion. There was perfect agreement between the modalities on the presence of abnormal soft tissue (34 of 36 cases). However, musculoskeletal US was unable to discriminate between coagulated blood, synovium, intrasynovial or extrasynovial fat tissue, or hemosiderin deposits because of wide variations in echogenicity. Musculoskeletal US is valuable for point-of-care imaging to determine the presence of soft tissue accumulation in discrete areas. However, because of limitations of musculoskeletal US in discriminating the nature of pathologic soft tissues and detecting hemosiderin, magnetic resonance imaging will be required if such discrimination is clinically important. © 2018 by the American Institute of Ultrasound in Medicine.

Effect of Regular Exercise on the Histochemical Changes of d-Galactose-Induced Oxidative Renal Injury in High-Fat Diet-Fed Rats

PubMed Central

Park, Sok; Kim, Chan-Sik; Lee, Jin; Suk Kim, Jung; Kim, Junghyun

2013-01-01

Renal lipid accumulation exhibits slowly developing chronic kidney disease and is associated with increased oxidative stress. The impact of exercise on the obese- and oxidative stress-related renal disease is not well understood. The purpose of this study was to investigate whether a high-fat diet (HFD) would accelerate d-galactose-induced aging process in rat kidney and to examine the preventive effect of regular exercise on the obese- and oxidative stress-related renal disease. Oxidative stress was induced by an administration of d-galactose (100 mg/kg intraperitoneally injected) for 9 weeks, and d-galactose-treated rats were also fed with a high-fat diet (60% kcal as fat) for 9 weeks to induce obesity. We investigated the efficacy of regular exercise in reducing renal injury by analyzing Nε-carboxymethyllysine (CML), 8-hydroxygluanine (8-OHdG) and apoptosis. When rats were fed with a HFD for 9 weeks in d-galactose-treated rats, an increased CML accumulation, oxidative DNA damage and renal podocyte loss were observed in renal glomerular cells and tubular epithelial cells. However, the regular exercise restored all these renal changes in HFD plus d-galactose-treated rats. Our data suggested that long-term HFD may accelerate the deposition of lipoxidation adducts and oxidative renal injury in d-galactose-treated rats. The regular exercise protects against obese- and oxidative stress-related renal injury by inhibiting this lipoxidation burden. PMID:24023395

High fat diet-induced oxidative stress blocks hepatocyte nuclear factor 4α and leads to hepatic steatosis in mice.

PubMed

Yu, Dongsheng; Chen, Gang; Pan, Minglin; Zhang, Jia; He, Wenping; Liu, Yang; Nian, Xue; Sheng, Liang; Xu, Bin

2018-06-01

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease with manifestation of over-accumulation of fat in liver. Increasing evidences indicate that NAFLD may be in part caused by malfunction of very low density lipoprotein (VLDL) secretion. Hepatocyte nuclear factor 4α (HNF4α), a nuclear receptor protein, plays an important role in sustain hepatic lipid homeostasis via transcriptional regulation of genes involved in secretion of VLDL, such as apolipoprotein B (ApoB). However, the exact functional change of HNF4α in NAFLD remains to be elucidated. In the present study, we found that high fat diet (HFD) induced cytoplasmic retention of HNF4α in hepatocytes, which led to down-regulation of hepatic ApoB expression and its protein level in serum, as well as reduced secretion of VLDL. We further revealed that oxidative stress, elevated in fatty liver, was the key factor inducing the cytoplasmic retention of HNF4α in hepatocytes by activating protein kinase C (PKC)-mediated phosphorylation in HNF4α. Thus, our findings reveal a novel mechanism underlying HFD-induced fatty liver that oxidative stress impairs function of HNF4α on ApoB expression and VLDL secretion via PKC activation, eventually promoting fat accumulation in the liver. Therefore, oxidative stress/PKC/HNF4α pathway may be a novel target to treat diet-induced fatty liver. © 2017 Wiley Periodicals, Inc.

Food consumption and the actual statistics of cardiovascular diseases: an epidemiological comparison of 42 European countries

PubMed Central

Grasgruber, Pavel; Sebera, Martin; Hrazdira, Eduard; Hrebickova, Sylva; Cacek, Jan

2016-01-01

Background The aim of this ecological study was to identify the main nutritional factors related to the prevalence of cardiovascular diseases (CVDs) in Europe, based on a comparison of international statistics. Design The mean consumption of 62 food items from the FAOSTAT database (1993–2008) was compared with the actual statistics of five CVD indicators in 42 European countries. Several other exogenous factors (health expenditure, smoking, body mass index) and the historical stability of results were also examined. Results We found exceptionally strong relationships between some of the examined factors, the highest being a correlation between raised cholesterol in men and the combined consumption of animal fat and animal protein (r=0.92, p<0.001). The most significant dietary correlate of low CVD risk was high total fat and animal protein consumption. Additional statistical analyses further highlighted citrus fruits, high-fat dairy (cheese) and tree nuts. Among other non-dietary factors, health expenditure showed by far the highest correlation coefficients. The major correlate of high CVD risk was the proportion of energy from carbohydrates and alcohol, or from potato and cereal carbohydrates. Similar patterns were observed between food consumption and CVD statistics from the period 1980–2000, which shows that these relationships are stable over time. However, we found striking discrepancies in men's CVD statistics from 1980 and 1990, which can probably explain the origin of the ‘saturated fat hypothesis’ that influenced public health policies in the following decades. Conclusion Our results do not support the association between CVDs and saturated fat, which is still contained in official dietary guidelines. Instead, they agree with data accumulated from recent studies that link CVD risk with the high glycaemic index/load of carbohydrate-based diets. In the absence of any scientific evidence connecting saturated fat with CVDs, these findings show that current dietary recommendations regarding CVDs should be seriously reconsidered. PMID:27680091

Metabolomics Reveals that the Type of Protein in a High-Fat Meal Modulates Postprandial Mitochondrial Overload and Incomplete Substrate Oxidation in Healthy Overweight Men.

PubMed

Pujos-Guillot, Estelle; Brandolini-Bunlon, Marion; Fouillet, Hélène; Joly, Charlotte; Martin, Jean-François; Huneau, Jean-François; Dardevet, Dominique; Mariotti, François

2018-06-01

A meal rich in saturated fatty acids induces a postprandial metabolic challenge. The type of dietary protein may modulate postprandial metabolism. We studied the effect of dietary protein type on postprandial changes in the metabolome after a high-fat meal. In a 3-period, crossover, postprandial study, 10 healthy overweight men with an elevated waist circumference (>94 cm) ingested high-fat meals made up of cream fat (70% of energy), sucrose (15% energy), and protein (15% energy) from either casein (CAS), whey protein (WHE), or α-lactalbumin-enriched whey protein (LAC). Urine collected immediately before and 2, 4, and 6 h after the meal was analyzed for metabolomics, a secondary outcome of the clinical study. We used mixed-effect models, partial least-square regression, and pathway enrichment analysis. At 4 and 6 h after the meal, the postprandial metabolome was found to be fully discriminated according to protein type. We identified 17 metabolites that significantly explained the effect of protein type on postprandial metabolomic changes (protein-time interaction). Among this signature, acylcarnitines and other acylated metabolites related to fatty acid or amino acid oxidation were the main discriminant features. The difference in metabolic profiles was mainly explained by urinary acylcarnitines and some other acylated products (protein type, Ps < 0.0001), with a dramatically greater increase (100- to 1000-fold) after WHE, and to a lesser extent after LAC, as compared with CAS. Pathway enrichment analysis confirmed that the type of protein had modified fatty acid oxidation (P < 0.05). Taken together, our results indicate that, in healthy overweight men, the type of protein in a high-fat meal interplays with fatty acid oxidation with a differential accumulation of incomplete oxidation products. A high-fat meal containing WHE, but not CAS, resulted in this outpacing of the tricarboxylic acid cycle. This study was registered at clinicaltrials.gov as NCT00931151.

Korean Curcuma longa L. induces lipolysis and regulates leptin in adipocyte cells and rats

PubMed Central

Song, Won-Yeong

2016-01-01

BACKGROUND/OBJECTIVES Turmeric (Curcuma longa L.) has been reported to have many biological functions including anti-obesity. Leptin, peptide hormone produced by adipocytes and its concentration is increased in proportion to the amount of the adipocytes. In the present study, we examined the effects of Korean turmeric on the regulation of adiposity and leptin levels in 3T3-L1 adipocytes and rats fed a high-fat and high-cholesterol diet. MATERIALS/METHODS Leptin secretion, free fatty acid and glycerol contents in 3T3-L1 adipocytes were measured after incubation of cells with turmeric for 24 hours. Rats were divided into four experimental groups: a normal diet group (N), a high-fat and high-cholesterol diet group (HF), a high-fat and high-cholesterol diet group supplemented with 2.5% turmeric extracts (TPA group) and a high-fat and high-cholesterol diet group supplemented with 5% turmeric extracts (TPB group). Serum samples were used for the measurement of leptin concentration. RESULTS Contents of free fatty acid and glycerol showed concentration dependent increase in response to turmeric extracts. Effects of turmeric extracts on reduction of lipid accumulation in 3T3-L1 cells were examined by Oil Red O staining. Treatment with turmeric extracts resulted in increased expression levels of adipose triglyceride lipase and hormone-sensitive lipase mRNA. The concentration of leptin from 3T3-L1 adipocytes was significantly decreased by turmeric. Proportional abdominal and epididymal fats weights of the turmeric 5% supplemented group, TPB has significantly decreased compared to the HF group. The serum levels of leptin in the TPA and TPB groups were significantly lower than those of the HF group. CONCLUSIONS Based on these results, we suggested that Korean turmeric may contribute to the decreasing of body fat and regulating leptin secretion. PMID:27698955

The Body Fat-Cognition Relationship in Healthy Older Individuals: Does Gynoid vs Android Distribution Matter?

PubMed

Forte, R; Pesce, C; De Vito, G; Boreham, C A G

2017-01-01

To examine the relationship between regional and whole body fat accumulation and core cognitive executive functions. Cross-sectional study. 78 healthy men and women aged between 65 and 75 years recruited through consumer's database. DXA measured percentage total body fat, android, gynoid distribution and android/gynoid ratio; inhibition and working memory updating through Random Number Generation test and cognitive flexibility by Trail Making test. First-order partial correlations between regional body fat and cognitive executive function were computed partialling out the effects of whole body fat. Moderation analysis was performed to verify the effect of gender on the body fat-cognition relationship. Results showed a differentiated pattern of fat-cognition relationship depending on fat localization and type of cognitive function. Statistically significant relationships were observed between working memory updating and: android fat (r = -0.232; p = 0.042), gynoid fat (r = 0.333; p = 0.003) and android/gynoid ratio (r = -0.272; p = 0.017). Separating genders, the only significant relationship was observed in females between working memory updating and gynoid fat (r = 0.280; p = 0.045). In spite of gender differences in both working memory updating and gynoid body fat levels, moderation analysis did not show an effect of gender on the relationship between gynoid fat and working memory updating. Results suggest a protective effect of gynoid body fat and a deleterious effect of android body fat. Although excessive body fat increases the risk of developing CDV, metabolic and cognitive problems, maintaining a certain proportion of gynoid fat may help prevent cognitive decline, particularly in older women. Guidelines for optimal body composition maintenance for the elderly should not target indiscriminate weight loss, but weight maintenance through body fat/lean mass control based on non-pharmacological tools such as physical exercise, known to have protective effects against CVD risk factors and age-related cognitive deterioration.

Metallothioneins regulate the adipogenic differentiation of 3T3-L1 cells via the insulin signaling pathway

PubMed Central

Toriuchi, Yuriko; Aki, Yuka; Mizuno, Yuto; Kawakami, Takashige; Nakaya, Tomoko; Sato, Masao; Suzuki, Shinya

2017-01-01

Knockout of metallothionein (MT) genes contributes to a heavier body weight in early life and the potential to become obese through the intake of a high fat diet (HFD) in mice. It has thus been suggested that MT genes regulate the formation of adipose tissue, which would become the base for later HFD-induced obesity. We evaluated the fat pads of mice during the lactation stage. The fat mass and adipocyte size of MT1 and MT2 knockout mice were greater than those of wild type mice. Next, we assayed the ability of small interfering RNA (siRNA) to silence MT genes in the 3T3-L1 cell line. The expressions of MT1 and MT2 genes were transiently upregulated during adipocyte differentiation, and the siRNA pretreatment led to the suppression of the expression of both MT mRNAs and proteins. The MT siRNA promoted lipid accumulation in adipocytes and caused proliferation of post-confluent preadipocytes; these effects were suppressed by an inhibitor of phosphatidylinositol 3-kinase (LY294002). In addition, MT siRNA promoted insulin-stimulated phosphorylation of Akt, a downstream kinase of the insulin signaling pathway. Enhanced lipid accumulation in 3T3-L1 cells resulting from MT-gene silencing was inhibited by pretreatment with an antioxidant, N-acetylcysteine, used as a substitute for antioxidant protein MTs. These results suggest that interference in MT expression enhanced the activation of the insulin signaling pathway, resulting in higher lipid accumulation in 3T3-L1 adipocytes. PMID:28426713

Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation.

PubMed

Axelsen, Lene N; Lademann, Jacob B; Petersen, Jørgen S; Holstein-Rathlou, Niels-Henrik; Ploug, Thorkil; Prats, Clara; Pedersen, Henrik D; Kjølbye, Anne Louise

2010-06-01

Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model of metabolic syndrome. Sprague-Dawley rats were fed a 60 kcal/100 kcal fat diet with 10% fructose in the drinking water. After 6, 12, 18, 24, 36, and 48 wk of feeding, blood pressure, glucose tolerance, plasma insulin, glucose, and lipid levels were measured. Cardiac function was examined by in vivo pressure volume measurements, and intramyocardial lipid accumulation was analyzed by confocal microscopy. Cardiac AMP-activated kinase (AMPK) and hepatic phosphoenolpyruvate carboxykinase (PEPCK) levels were measured by Western blotting. Finally, an ischemia-reperfusion study was performed after 56 wk of feeding. FFFRs developed severe obesity, decreased glucose tolerance, increased serum insulin and triglyceride levels, and an initial increased fasting glucose, which returned to control levels after 24 wk of feeding. The diet had no effect on blood pressure but decreased hepatic PEPCK levels. FFFRs showed significant intramyocardial lipid accumulation, and cardiac hypertrophy became pronounced between 24 and 36 wk of feeding. FFFRs showed no signs of cardiac dysfunction during unstressed conditions, but their hearts were much more vulnerable to ischemia-reperfusion and had a decreased level of phosphorylated AMPK at 6 wk of feeding. This study characterizes a new animal model of the metabolic syndrome that could be beneficial in future studies of metabolic syndrome and cardiac complications.

Agmatine ameliorates type 2 diabetes induced-Alzheimer's disease-like alterations in high-fat diet-fed mice via reactivation of blunted insulin signalling.

PubMed

Kang, Somang; Kim, Chul-Hoon; Jung, Hosung; Kim, Eosu; Song, Ho-Taek; Lee, Jong Eun

2017-02-01

The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, p-Akt, and p-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lipolysis stimulating peptides of potato protein hydrolysate effectively suppresses high-fat-diet-induced hepatocyte apoptosis and fibrosis in aging rats.

PubMed

Chiang, Wen-Dee; Huang, Chih Yang; Paul, Catherine Reena; Lee, Zong-Yan; Lin, Wan-Teng

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most common outcomes of obesity and is characterized by the accumulation of triglycerides, increased tissue apoptosis, and fibrosis. NAFLD is more common among elderly than in younger age groups, and it causes serious hepatic complications. In this study, alcalase treatment derived potato protein hydrolysate (APPH) with lipolysis-stimulating property has been evaluated for its efficiency to provide hepato-protection in a high-fat-diet (HFD)-fed aging rats. Twenty-four-month-old SD rats were randomly divided into six groups (n=8): aged rats fed with standard chow, HFD-induced aged obese rats, HFD with low-dose (15 mg/kg/day) APPH treatment, HFD with moderate (45 mg/kg/day) APPH treatment, HFD with high (75 mg/kg/day) APPH treatment, and HFD with probucol. APPH was found to reduce the NAFLD-related effects in rat livers induced by HFD and all of the HFD-fed rats exhibited heavier body weight than those with control chow diet. However, the HFD-induced hepatic fat accumulation was effectively attenuated in rats administered with low (15 mg/kg/day), moderate (45 mg/kg/day), and high (75 mg/kg/day) doses of APPH. APPH oral administration also suppressed the hepatic apoptosis- and fibrosis-related proteins induced by HFD. Our results thus indicate that APPH potentially attenuates hepatic lipid accumulation and anti-apoptosis and fibrosis effects in HFD-induced rats. APPH may have therapeutic potential in the amelioration of NAFLD liver damage.

Regulation of lipid deposition in farm animals: Parallels between agriculture and human physiology

PubMed Central

Brandebourg, Terry D

2016-01-01

For many years, clinically oriented scientists and animal scientists have focused on lipid metabolism and fat deposition in various fat depots. While dealing with a common biology across species, the goals of biomedical and food animals lipid metabolism research differ in emphasis. In humans, mechanisms and regulation of fat synthesis, accumulation of fat in regional fat depots, lipid metabolism and dysmetabolism in adipose, liver and cardiac tissues have been investigated. Further, energy balance and weight control have also been extensively explored in humans. Finally, obesity and associated maladies including high cholesterol and atherosclerosis, cardiovascular disease, insulin resistance, hypertension, metabolic syndrome and health outcomes have been widely studied. In food animals, the emphasis has been on regulation of fatty acid synthesis and lipid deposition in fat depots and deposition of intramuscular fat. For humans, understanding the regulation of energy balance and body weight and of prevention or treatment of obesity and associated maladies have been important clinical outcomes. In production of food animals lowering fat content in muscle foods while enhancing intramuscular fat (marbling) have been major targets. In this review, we summarize how our laboratories have addressed the goal of providing lean but yet tasty and juicy muscle food products to consumers. In addition, we here describe efforts in the development of a new porcine model to study regulation of fat metabolism and obesity. Commonalities and differences in regulation of lipid metabolism between humans, rodents and food animals are emphasized throughout this review. PMID:27302175

Honokiol activates the LKB1–AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seo, Min Suk; Kim, Jung Hwan; Kim, Hye Jung

Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1 h, and then exposed to 1 mM free fatty acid (FFA) for 24 h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28 days, and honokiol (10 mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated proteinmore » kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1–AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. - Highlights: • Honokiol attenuates lipid accumulation induced by free fatty acid in hepatocyte. • Honokiol inhibits the increase in lipogenic enzyme levels induced by free fatty acid. • Honokiol induces the phosphorylation of AMPK and ACC and inhibits SREBP-1c maturation. • LKB1–AMPK signaling pathway mediates anti-lipogenic effect of honokiol in hepatocyte. • Honokiol activates LKB1 and AMPK and inhibits nonalcoholic steatosis in HFD-fed mice.« less

Change in Intra-Abdominal Fat Predicts the Risk of Hypertension in Japanese Americans.

PubMed

Sullivan, Catherine A; Kahn, Steven E; Fujimoto, Wilfred Y; Hayashi, Tomoshige; Leonetti, Donna L; Boyko, Edward J

2015-07-01

In Japanese Americans, intra-abdominal fat area measured by computed tomography is positively associated with the prevalence and incidence of hypertension. Evidence in other populations suggests that other fat areas may be protective. We sought to determine whether a change in specific fat depots predicts the development of hypertension. We prospectively followed up 286 subjects (mean age, 49.5 years; 50.4% men) from the Japanese American Community Diabetes Study for 10 years. At baseline, subjects did not have hypertension (defined as blood pressure ≥140/90 mm Hg) and were not taking blood pressure or glucose-lowering medications. Mid-thigh subcutaneous fat area, abdominal subcutaneous fat area, and intra-abdominal fat area were directly measured by computed tomography at baseline and 5 years. Logistic regression was used to estimate odds of incident hypertension over 10 years in relation to a 5-year change in fat area. The relative odds of developing hypertension for a 5-year increase in intra-abdominal fat was 1.74 (95% confidence interval, 1.28-2.37), after adjusting for age, sex, body mass index, baseline intra-abdominal fat, alcohol use, smoking status, and weekly exercise energy expenditure. This relationship remained significant when adjusted for baseline fasting insulin and 2-hour glucose levels or for diabetes mellitus and pre-diabetes mellitus classification. There were no significant associations between baseline and change in thigh or abdominal subcutaneous fat areas and incident hypertension. In conclusion, in this cohort of Japanese Americans, the risk of developing hypertension is related to the accumulation of intra-abdominal fat rather than the accrual of subcutaneous fat in either the thigh or the abdominal areas. © 2015 American Heart Association, Inc.

Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

PubMed

Yang, Ping; Xiao, Yayun; Luo, Xuan; Zhao, Yunfei; Zhao, Lei; Wang, Yan; Wu, Tingting; Wei, Li; Chen, Yaxi

2017-07-01

Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

The animal fat paradox and meat quality.

PubMed

Webb, E C; O'Neill, H A

2008-09-01

The purpose of this paper is to address some of the paradoxical issues and perceptions regarding animal fats and the related effects on meat quality and consumer perceptions. Meat scientists have been studying carcass characteristics for many years and although the factors that influence the accumulation, distribution and composition of carcass fat in livestock have been extensively researched, the role, value and perceptions of animal fats in meat quality differ significantly in importance between producers, abattoirs, butchers, retailers and consumers. Fat and long-chain fatty acids, whether in adipose tissue or muscle, contribute to important aspects of meat quality and are central to the nutritional and sensory values of meat. In this review the nutritional value of fat, as well as the importance of fat in terms of carcass and meat quality will be highlighted. The 'quality' of meat depends greatly on the socio-demographic backgrounds of the consumer. The aim is to focus on the global importance of fat in the carcass to the producer, processor and consumer. There is currently no clear cut definition for fat quality because the acceptability and perceived quality of fat varies significantly in terms of quantity, colour, consistency and chemical composition in different species of livestock around the world. The association between animal fats and human health is critical and recommendations by health professionals range from excluding fats altogether to a moderate consumption of fats due to their essential role in the body. Recently the emphasis has shifted away from fat quantity to fat quality. Despite these recommendations and years of bad publicity in terms of the adverse affects of animal fats in human health, the livestock industry seems reluctant to shift its focus to fat quality rather than quantity. This approach may adversely affect future meat consumption by consumers who are becoming increasingly critical about the food they eat.

GLUT2 Accumulation in Enterocyte Apical and Intracellular Membranes

PubMed Central

Ait-Omar, Amal; Monteiro-Sepulveda, Milena; Poitou, Christine; Le Gall, Maude; Cotillard, Aurélie; Gilet, Jules; Garbin, Kevin; Houllier, Anne; Château, Danièle; Lacombe, Amélie; Veyrie, Nicolas; Hugol, Danielle; Tordjman, Joan; Magnan, Christophe; Serradas, Patricia; Clément, Karine; Leturque, Armelle; Brot-Laroche, Edith

2011-01-01

OBJECTIVE In healthy rodents, intestinal sugar absorption in response to sugar-rich meals and insulin is regulated by GLUT2 in enterocyte plasma membranes. Loss of insulin action maintains apical GLUT2 location. In human enterocytes, apical GLUT2 location has not been reported but may be revealed under conditions of insulin resistance. RESEARCH DESIGN AND METHODS Subcellular location of GLUT2 in jejunal enterocytes was analyzed by confocal and electron microscopy imaging and Western blot in 62 well-phenotyped morbidly obese subjects and 7 lean human subjects. GLUT2 locations were assayed in ob/ob and ob/+ mice receiving oral metformin or in high-fat low-carbohydrate diet–fed C57Bl/6 mice. Glucose absorption and secretion were respectively estimated by oral glucose tolerance test and secretion of [U-14C]-3-O-methyl glucose into lumen. RESULTS In human enterocytes, GLUT2 was consistently located in basolateral membranes. Apical GLUT2 location was absent in lean subjects but was observed in 76% of obese subjects and correlated with insulin resistance and glycemia. In addition, intracellular accumulation of GLUT2 with early endosome antigen 1 (EEA1) was associated with reduced MGAT4a activity (glycosylation) in 39% of obese subjects on a low-carbohydrate/high-fat diet. Mice on a low-carbohydrate/high-fat diet for 12 months also exhibited endosomal GLUT2 accumulation and reduced glucose absorption. In ob/ob mice, metformin promoted apical GLUT2 and improved glucose homeostasis. Apical GLUT2 in fasting hyperglycemic ob/ob mice tripled glucose release into intestinal lumen. CONCLUSIONS In morbidly obese insulin-resistant subjects, GLUT2 was accumulated in apical and/or endosomal membranes of enterocytes. Functionally, apical GLUT2 favored and endosomal GLUT2 reduced glucose transepithelial exchanges. Thus, altered GLUT2 locations in enterocytes are a sign of intestinal adaptations to human metabolic pathology. PMID:21852673

Utilization of Solid Waste as a Substrate for Production of Oil from Oleaginous Microorganisms.

PubMed

Laker, Fortunate; Agaba, Arnold; Akatukunda, Andrew; Gazet, Robert; Barasa, Joshua; Nanyonga, Sarah; Wendiro, Deborah; Wacoo, Alex Paul

2018-01-01

The overwhelming demand of oil and fats to meet the ever increasing needs for biofuel, cosmetics production, and other industrial purposes has enhanced a number of innovations in this industry. One such innovation is the use of microorganisms as alternative sources of oil and fats. Organic solid waste that is causing a big challenge of disposal worldwide is biodegradable and can be utilized as substrate for alternative oil production. The study evaluated the potential of isolated yeast-like colonies to grow and accumulate oil by using organic solid waste as substrate. Of the 25 yeast-like colonies isolated from the soil samples collected from three different suburbs in Kampala district, Uganda, 20 were screened positive for accumulation of lipid but only 2 were oleaginous. The NHC isolate with the best oil accumulation potential of 48.8% was used in the central composite design (CCD) experiments. The CCD experimental results revealed a maximum oil yield of 61.5% from 1.25 g/L cell biomass at 10 g/L of solid waste and temperature of 25°C. The study revealed that organic solid waste could be used as a substrate for microbial oil production.

Comparing the effects of sucrose and high-fructose corn syrup on lipid metabolism and the risk of cardiovascular disease in male rats.

PubMed

Sadowska, Joanna; Bruszkowska, Magda

2017-01-01

The objective of this study was to compare, in an animal model, the effect of different sugar types (sucrose vs. high-fructose corn syrup 55%) consumed as 10% by weight of the diet (11.6% of daily caloric intake) on the amount of food consumed, body weight, fatty tissue deposits, concentrations of selected lipids, and atherogenic indices of blood plasma. Material and method. The experiment was carried out on 30 5-month-old Wistar male rats, fed three differ- ent diets, containing, amongst other foods, (1) ground unrefined cereal grains, (2) sucrose, (3) high-fructose corn syrup. Results. Weight gains in animals on sucrose or high-fructose corn syrup diets were higher than those con- suming basic feed, but the effect was not associated with perivisceral fat accumulation. It has been found that all the atherogenic indices (Castelli’s Risk Index I, Castelli’s Risk Index II, Atherogenic Index of Plasma, Atherogenic Coefficient) were statistically significantly higher in animals on a high-fructose corn syrup diet compared to both the control group and those on a sucrose diet. Conclusion. The effect of the 55% high-fructose corn syrup on the tested parameters of lipid metabolism was not equivalent to that of sucrose. Using HFCS-55 instead of sucrose has an adverse effect on blood lipid parameters, while weight gains and peri-organ fat deposits are comparable. Moreover, the obtained results confirm that tested animals were susceptible to the adverse effects of sugars added to their diet, even in small amounts. This emphasises the need to precisely control the amount of added sugars in. nd. The objective of this study was to compare, in an animal model, the effect of different sugar types (sucrose vs. high-fructose corn syrup 55%) consumed as 10% by weight of the diet (11.6% of daily caloric intake) on the amount of food consumed, body weight, fatty tissue deposits, concentrations of selected lipids, and atherogenic indices of blood plasma. Material and method. The experiment was carried out on 30 5-month-old Wistar male rats, fed three differ- ent diets, containing, amongst other foods, (1) ground unrefined cereal grains, (2) sucrose, (3) high-fructose corn syrup. Weight gains in animals on sucrose or high-fructose corn syrup diets were higher than those con- suming basic feed, but the effect was not associated with perivisceral fat accumulation. It has been found that all the atherogenic indices (Castelli’s Risk Index I, Castelli’s Risk Index II, Atherogenic Index of Plasma, Atherogenic Coefficient) were statistically significantly higher in animals on a high-fructose corn syrup diet compared to both the control group and those on a sucrose diet. The effect of the 55% high-fructose corn syrup on the tested parameters of lipid metabolism was not equivalent to that of sucrose. Using HFCS-55 instead of sucrose has an adverse effect on blood lipid parameters, while weight gains and peri-organ fat deposits are comparable. Moreover, the obtained results confirm that tested animals were susceptible to the adverse effects of sugars added to their diet, even in small amounts. This emphasises the need to precisely control the amount of added sugars in the diet.

Effects of Castration on Expression of Lipid Metabolism Genes in the Liver of Korean Cattle

PubMed Central

Baik, Myunggi; Nguyen, Trang Hoa; Jeong, Jin Young; Piao, Min Yu; Kang, Hyeok Joong

2015-01-01

Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001) hepatic lipids contents and higher (p<0.01) mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration. PMID:25557684

Silk protein hydrolysate increases glucose uptake through up-regulation of GLUT 4 and reduces the expression of leptin in 3T3-L1 fibroblast.

PubMed

Lee, Hyun-Sun; Lee, Hyun Jung; Suh, Hyung Joo

2011-12-01

The purpose of our research was to test the hypothesis that silk protein hydrolysate increases glucose uptake in cultured murine embryonic fibroblasts. Insulin sensitizing activity was observed in a cell-based glucose uptake assay using 3T3-L1 embryonic fibroblasts. The treatment of 1 mg/mL of silk peptide E5K6 plus 0.2 nM insulin was associated with a significant increase in glucose uptake (124.0% ± 2.5%) compared to treatment with 0.2 nM insulin alone. When the 3T3-L1 cells were induced to differentiate into fibroblasts, fat droplets formed inside the cells. Silk peptide E5K6 reduced the formation of fat droplets at the 1-mg/mL dosage (86.1% ± 2.5%) when compared to the control (100.0% ± 5.8%). A 1 mg/mL dose of silk peptide E5K6 significantly increased GLUT 4 expression (131.5% ± 4.0%). The treatment of 1 mg/mL of silk peptide E5K6 did not present any changes for adipogenic expressed genes, but leptin expression was significantly increased by silk peptide E5K6 supplementation (175.9% ± 11.1%). From these results, silk peptide E5K6 increased glucose uptake via up-regulation of GLUT 4 and decreased fat accumulation via the up-regulation of leptin. Copyright © 2011 Elsevier Inc. All rights reserved.

High hydrostatic pressure extract of garlic increases the HDL cholesterol level via up-regulation of apolipoprotein A-I gene expression in rats fed a high-fat diet

PubMed Central

2012-01-01

Background Cardiovascular disease (CVD) is the number one cause of mortality worldwide and a low high-density lipoprotein cholesterol (HDL-C) level is an important marker of CVD risk. Garlic (Allium sativum) has been widely used in the clinic for treatment of CVD and regulation of lipid metabolism. This study investigated the effects of a high hydrostatic pressure extract of garlic (HEG) on HDL-C level and regulation of hepatic apolipoprotein A-I (apoA-I) gene expression. Methods Male Sprague–Dawley rats were divided into two groups and maintained on a high-fat control diet (CON) or high-fat control diet supplemented with high hydrostatic pressure extract of garlic (HEG) for 5 weeks. Changes in the expression of genes related to HDL-C metabolism were analyzed in liver, together with biometric and blood parameters. Results In the HEG group, the plasma triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased in comparison with the CON group (P < 0.05). Dietary HEG also lowered the hepatic TG and total cholesterol (TC) levels compared to the CON group. While the plasma HDL-C level and mRNA level of hepatic apoA-I, which is one of primarily proteins of HDL-C particle, were significantly increased in the HEG group compared to the CON group (P < 0.05). The gene expression of ATP-binding cassette transporter A1 (ABCA1) and lecithin:cholesterol acyltransferase (LCAT), importantly involved in the biogenesis in HDL, were also up-regulated by dietary HEG. Conclusions These results suggest that HEG ameliorates plasma lipid profiles and attenuates hepatic lipid accumulation in the high-fat fed rats. Our findings provides that the effects of HEG on the increase of the plasma HDL-C level was at least partially mediated by up-regulation of hepatic genes expression such as apoA-I, ABCA1, and LCAT in rats fed a high-fat diet. PMID:22713542

Protective effects of various ratios of DHA/EPA supplementation on high-fat diet-induced liver damage in mice.

PubMed

Shang, Tingting; Liu, Liang; Zhou, Jia; Zhang, Mingzhen; Hu, Qinling; Fang, Min; Wu, Yongning; Yao, Ping; Gong, Zhiyong

2017-03-29

A sedentary lifestyle and poor diet are risk factors for the progression of non-alcoholic fatty liver disease. However, the pathogenesis of hepatic lipid accumulation is not completely understood. Therefore, the present study explored the effects of dietary supplementation of various ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on a high-fat diet-induced lipid metabolism disorder and the concurrent liver damage. Using high-fat diet-fed C57BL/6 J mice as the animal model, diets of various ratios of DHA/EPA (2:1, 1:1, and 1:2) with an n-6/n-3 ratio of 4:1 were prepared using fish and algae oils enriched in DHA and/or EPA and sunflower seed oils to a small extent instead of the high-fat diet. Significantly decreased hepatic lipid deposition, body weight, serum lipid profile, inflammatory reactions, lipid peroxidation, and expression of adipogenesis-related proteins and inflammatory factors were observed for mice that were on a diet supplemented with DHA/EPA compared to those in the high-fat control group. The DHA/EPA 1:2 group showed lower serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein-cholesterol levels, lower SREBP-1C, FAS, and ACC-1 relative mRNA expression, and higher Fra1 mRNA expression, with higher relative mRNA expression of enzymes such as AMPK, PPARα, and HSL observed in the DHA/EPA 1:1 group. Lower liver TC and TG levels and higher superoxide dismutase levels were found in the DHA/EPA 2:1 group. Nonetheless, no other notable effects were observed on the biomarkers mentioned above in the groups treated with DHA/EPA compared with the DHA group. The results showed that supplementation with a lower DHA/EPA ratio seems to be more effective at alleviating high-fat diet-induced liver damage in mice, and a DHA/EPA ratio of 1:2 mitigated inflammatory risk factors. These effects of n-3 polyunsaturated fatty acids (PUFA) on lipid metabolism may be linked to the upregulation of Fra1 and attenuated activity of c-Jun and c-Fos, thus ultimately reducing the severity of the lipid metabolism disorder and liver damage to some extent.

4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV. San Diego, California, USA 22-25 September 2002.

PubMed

Nolan, David; Christiansen, Frank

2003-01-01

Highlights are presented from this annual workshop, which was devoted to the investigation of adverse effects associated with antiretroviral therapy for HIV infection. Topics covered included the lipodystrophy syndrome, which encompasses body composition changes (subcutaneous fat wasting, visceral fat accumulation) and metabolic abnormalities (insulin resistance and dyslipidaemia). The relevance of HIV protease inhibitor-induced metabolic abnormalities to cardiovascular disease is discussed. Research in the areas of hyperlactataemia, abacavir hypersensitivity, and bone mineral density in the context of HIV infection is also briefly reviewed.

Accumulation of Oxidized LDL in the Tendon Tissues of C57BL/6 or Apolipoprotein E Knock-Out Mice That Consume a High Fat Diet: Potential Impact on Tendon Health

PubMed Central

Grewal, Navdeep; Thornton, Gail M.; Behzad, Hayedeh; Sharma, Aishwariya; Lu, Alex; Zhang, Peng; Reid, W. Darlene; Granville, David J.; Scott, Alex

2014-01-01

Objective Clinical studies have suggested an association between dyslipidemia and tendon injuries or chronic tendon pain; the mechanisms underlying this association are not yet known. The objectives of this study were (1) to evaluate the impact of a high fat diet on the function of load-bearing tendons and on the distribution in tendons of oxidized low density lipoprotein (oxLDL), and (2) to examine the effect of oxLDL on tendon fibroblast proliferation and gene expression. Methods Gene expression (Mmp2, Tgfb1, Col1a1, Col3a1), fat content (Oil Red O staining), oxLDL levels (immunohistochemistry) and tendon biomechanical properties were examined in mice (C57Bl/6 or ApoE -/-) receiving a standard or a high fat diet. Human tendon fibroblast proliferation and gene expression (COL1A1, COL3A1, MMP2) were examined following oxLDL exposure. Results In both types of mice (C57Bl/6 or ApoE -/-), consumption of a high fat diet led to a marked increase in oxLDL deposition in the load-bearing extracellular matrix of the tendon. The consumption of a high fat diet also reduced the failure stress and load of the patellar tendon in both mouse types, and increased Mmp2 expression. ApoE -/- mice exhibited more pronounced reductions in tendon function than wild-type mice, and decreased expression of Col1a1 compared to wild type mice. Human tendon fibroblasts responded to oxLDL by increasing their proliferation and their mRNA levels of MMP2, while decreasing their mRNA levels for COL1A1 and COL3A1. Conclusion The consumption of a high fat diet resulted in deleterious changes in tendon function, and these changes may be explained in part by the effects of oxLDL, which induced a proliferative, matrix-degrading phenotype in human tenocytes. PMID:25502628

High-salt in addition to high-fat diet may enhance inflammation and fibrosis in liver steatosis induced by oxidative stress and dyslipidemia in mice.

PubMed

Uetake, Yuzaburo; Ikeda, Hitoshi; Irie, Rie; Tejima, Kazuaki; Matsui, Hiromitsu; Ogura, Sayoko; Wang, Hong; Mu, ShengYu; Hirohama, Daigoro; Ando, Katsuyuki; Sawamura, Tatsuya; Yatomi, Yutaka; Fujita, Toshiro; Shimosawa, Tatsuo

2015-02-13

It is widely known that salt is an accelerating factor for the progression of metabolic syndrome and causes cardiovascular diseases, most likely due to its pro-oxidant properties. We hypothesized that excessive salt intake also facilitates the development of nonalcoholic steatohepatitis (NASH), which is frequently associated with metabolic syndrome. We examined the exacerbating effect of high-salt diet on high-fat diet-induced liver injury in a susceptible model to oxidative stress, apoE knockout and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transgenic mice. High-salt diet led to NASH in high-fat diet-fed LOX-1 transgenic/apoE knockout mice without affecting high-fat diet-induced dyslipidemia or hepatic triglyceride accumulation. Additionally, a high-salt and high-fat diet stimulated oxidative stress production and inflammatory reaction to a greater extent than did a high-fat diet in the liver of LOX-1 transgenic/apoE knockout mice. We demonstrated that high-salt diet exacerbated NASH in high-fat diet-fed LOX-1 transgenic /apoE knockout mice and that this effect was associated with the stimulation of oxidative and inflammatory processes; this is the first study to suggest the important role of excessive salt intake in the development of NASH.