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Sample records for diet-induced weight reduction

  1. Voluntary exercise contributed to an amelioration of abnormal feeding behavior, locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats.

    PubMed

    Mifune, Hiroharu; Tajiri, Yuji; Nishi, Yoshihiro; Hara, Kento; Iwata, Shimpei; Tokubuchi, Ichiro; Mitsuzono, Ryouichi; Yamada, Kentaro; Kojima, Masayasu

    2015-09-01

    In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague-Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.

  2. Corn gluten hydrolysate and capsaicin have complimentary actions on body weight reduction and lipid-related genes in diet-induced obese rats.

    PubMed

    Mun, Joo-Mi; Ok, Hyang Mok; Kwon, Oran

    2014-05-01

    The aim of this study was to test the hypothesis that a combination of corn gluten hydrolysate (CGH) and capsaicin may have an additive or synergistic effect on body weight reduction. For 13 weeks, male Sprague-Dawley rats were provided a diet to induce obesity. Afterward, the rats were randomly divided into 5 dietary groups: the normal control (n = 5), the high-fat control (n = 8), the high-fat diet (HFD) containing 35% CGH (n = 7), the HFD containing 0.02% capsaicin (HF-P) (n = 8), and the HFD containing both CGH and capsaicin (HF-CP) (n = 7) for an additional 4 weeks. Administration of CGH plus capsaicin, along with a HFD, led to significant decreases in body weight, fat mass, lipids in the liver, and plasma leptin as well as increases in plasma adiponectin. The pattern of gene expression was different in each target organ. In the liver, up-regulation of peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1α, and acyl-coenzyme A oxidase was found in the HF-CP group. In contrast, down-regulation of peroxisome proliferator-activated receptor γ was found in both the HFD containing 35% CGH and HF-CP groups. In skeletal muscle, up-regulation of insulin receptor and uncoupling protein 3 was found in the HF-P group only, whereas up-regulation of the glucose transporter 4 gene was observed in both the HF-CP and HF-P groups. In adipose tissue, up-regulation of peroxisome proliferator-activated receptor γ and hormone-sensitive lipase was only found in the HF-CP group. In summary, this study suggests that CGH and capsaicin perform complementary actions on food intake, lipid metabolism, and insulin sensitivity by a coordinated control of energy metabolism in the liver, adipose tissue, and skeletal muscle, thus exerting an additive effect on body weight reduction.

  3. Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss

    PubMed Central

    Nedeltcheva, A. V.; Imperial, J. G.; Penev, P. D.

    2012-01-01

    Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-hour blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean [SD] age 41 [5] y; BMI 27.4 [2.0] kg/m2) completed two 14-day treatments with hypocaloric diet and 8.5 or 5.5-h nighttime sleep opportunity in random order 7 [3] months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free-fatty acids (FFA), and 24-hour blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 [0.3] BMI units) during each treatment. Bedtime restriction reduced sleep by 131 [30] min/day. Recurrent sleep curtailment decreased 24-hour serum insulin concentrations (i.e. enhanced 24-hour insulin economy) without changes in oral glucose tolerance and 24-hour glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA which suppressed normally following glucose ingestion, and lower total and LDL cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-hour insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability. PMID:22513492

  4. Ginseng panaxoside Rb1 reduces body weight in diet-induced obese mice.

    PubMed

    Lin, Ning; Cai, Dong-Lian; Jin, Di; Chen, Yi; Shi, Jiao-Jiao

    2014-01-01

    Crude extracts from ginseng demonstrated anti-obesity properties. Ginsenoside Rb1 is the main component of ginseng, however, there are only few studies examining its effects in obesity. In the present study, we evaluated its potential anti-obesity effects in the murine model of diet-induced obesity. Seventy male C57BL/6 mice were randomly divided to consume for 12 weeks either chow diet (N = 8) or high-fat (HF) diet (N = 62). The latter mice were then divided into four groups: diet-induced obesity group (DIO; N = 10), obesity-resistant group (OR; N = 10), HF group (N = 5), and the group whose diet was changed from HF to normal diet (DC; N = 5). Intraperitoneal injections of Rb-1 were administered daily to mice in the DIO and OR groups for 3 weeks. Body weight and energy intake were monitored, and fasting blood glucose, lipids, neuropeptide Y, Y2 receptor, and peptide YY were quantified. Compared with HF group, weight gain and food intake of DIO mice with Rb-1 injection was significantly decreased (p < 0.05). Further, levels of blood glucose and some lipids were also decreased in DIO-Rb1 group compared with HF group. Furthermore, Rb1 was also found to modulate serum levels of PYY and NPY, and mRNA expression of NPY, Y2 receptor and PYY in tissue samples of DIO mice. Taken together, ginsenoside Rb1 may be useful in the treatment of obesity via modifying the serum content and mRNA expression of NPY, Y2 receptor and PYY.

  5. Predictors of Diet-Induced Weight Loss in Overweight Adults with Type 2 Diabetes

    PubMed Central

    Mulder, Monique T.; Verhoeven, Adrie J. M.; van Wietmarschen, Herman; Boessen, Ruud; Pellis, Linette P.; van t Spijker, Adriaan; Timman, Reinier; Ozcan, Behiye; Sijbrands, Eric J. G.

    2016-01-01

    Aims A very low calorie diet improves the metabolic regulation of obesity related type 2 diabetes, but not for all patients, which leads to frustration in patients and professionals alike. The aim of this study was to develop a prediction model of diet-induced weight loss in type 2 diabetes. Methods 192 patients with type 2 diabetes and BMI>27 kg/m2 from the outpatient diabetes clinic of the Erasmus Medical Center underwent an 8-week very low calorie diet. Baseline demographic, psychological and physiological parameters were measured and the C-index was calculated of the model with the largest explained variance of relative weight loss using backward linear regression analysis. The model was internally validated using bootstrapping techniques. Results Weight loss after the diet was 7.8±4.6 kg (95%CI 7.2–8.5; p<0.001) and was independently associated with the baseline variables fasting glucose (B = -0.33 (95%CI -0.49, -0.18), p = 0.001), anxiety (HADS; B = -0.22 (95%CI -0.34, -0.11), p = 0.001), numb feeling in extremities (B = 1.86 (95%CI 0.85, 2.87), p = 0.002), insulin dose (B = 0.01 (95%CI 0.00, 0.02), p = 0.014) and waist-to-hip ratio (B = 6.79 (95%CI 2.10, 11.78), p = 0.003). This model explained 25% of the variance in weight loss. The C-index of this model to predict successful (≥5%) weight loss was 0.74 (95%CI 0.67–0.82), with a sensitivity of 0.93 (95% CI 0.89–0.97) and specificity of 0.29 (95% CI 0.16–0.42). When only the obese T2D patients (BMI≥30 kg/m2; n = 181) were considered, age also contributed to the model (B = 0.06 (95%CI 0.02, 0.11), p = 0.008), whereas waist-to-hip ratio did not. Conclusions Diet-induced weight loss in overweight adults with T2D was predicted by five baseline parameters, which were predominantly diabetes related. However, failure seems difficult to predict. We propose to test this prediction model in future prospective diet intervention studies in patients with type 2 diabetes. PMID:27494531

  6. Defining a longitudinal survival model to examine forced treadmill running as a countermeasure for diet-induced weight gain.

    PubMed

    Esposito, Lisa M; Simpson, Richard J; Strohacker, Kelley; Carpenter, Katie C; McFarlin, Brian K

    2010-10-01

    Diet-induced weight gain increases disease risk via disruption of the innate immune system. Flow cytometry is commonly used to assess the immune system; however, in mice such measurements traditionally require terminal procedures and tissue collection to generate sufficient sample. The present study refined an existing flow cytometry method to reduce the number of mice needed to longitudinally measure monocytes. CD-1 male mice were randomly assigned to one of the three groups: DS (diet-induced weight gain + sedentary), DE (diet-induced weight gain + forced treadmill running [total distance 35,755 ± 1832 m]) or NS (normal weight gain + sedentary). DS and DE consumed a 60% fat diet and NS consumed a 10% fat diet ad libitum. Saphenous vein blood samples were collected weekly for a period of six weeks and three-colour flow cytometry was used to measure changes in monocyte (CD11b(+)/14(+)) concentration and cell-surface toll-like receptor 4 (TLR4) expression. DS (18%) and DE (17%) gained more weight than NS (P < 0.001). On a group basis, DS expressed 17% more TLR4 than DE and NS (P = 0.005). The present study demonstrates that a longitudinal survival model can be used to reduce the number of animals needed to complete flow cytometry experiments. Exercise during diet-induced weight prevented some (decreased monocyte TLR4 expression) but not all aspects of innate immune system function.

  7. Prior exercise training blunts short-term high-fat diet-induced weight gain.

    PubMed

    Snook, Laelie A; MacPherson, Rebecca E K; Monaco, Cynthia M F; Frendo-Cumbo, Scott; Castellani, Laura; Peppler, Willem T; Anderson, Zachary G; Buzelle, Samyra L; LeBlanc, Paul J; Holloway, Graham P; Wright, David C

    2016-08-01

    High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (-30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet.

  8. Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats.

    PubMed

    Devenny, James J; Godonis, Helen E; Harvey, Susan J; Rooney, Suzanne; Cullen, Mary J; Pelleymounter, Mary Ann

    2012-08-01

    Dapagliflozin is a potent and selective sodium glucose cotransporter-2 (SGLT2) inhibitor which promotes urinary glucose excretion and induces weight loss. Since metabolic compensation can offset a negative energy balance, we explored the potential for a compensatory physiological response to the weight loss induced by dapagliflozin. Dapagliflozin was administered (0.5-5 mpk; p.o.) to diet-induced obese (DIO) rats with or without ad libitum access to food for 38 days. Along with inducing urinary glucose excretion, chronic administration of dapagliflozin dose-dependently increased food and water intake relative to vehicle-treated controls. Despite this, it reduced body weight by 4% (relative to controls) at the highest dose. The degree of weight loss was increased by an additional 9% if hyperphagia was prevented by restricting food intake to that of vehicle controls. Neither oxygen consumption (vO2) or the respiratory exchange ratio (RER) were altered by dapagliflozin treatment alone. Animals treated with dapagliflozin and pair-fed to vehicle controls (5 mpk PF-V) showed a reduction in RER and an elevation in nonfasting β-hydroxybutyrate (BHBA) relative to ad libitum-fed 5 mpk counterparts. Fasting BHBA was elevated in the 1 mpk, 5 mpk, and 5 mpk PF-V groups. Serum glucose was reduced in the fasted, but not the unfasted state. Insulin was reduced in the non-fasted state. These data suggest that in rodents, the persistent urinary glucose excretion induced by dapagliflozin was accompanied by compensatory hyperphagia, which attenuated the weight loss induced by SGLT2 inhibition. Therefore, it is possible that dapagliflozin-induced weight loss could be enhanced with dietary intervention.

  9. Caffeine treatment prevented from weight regain after calorie shifting diet induced weight loss.

    PubMed

    Davoodi, Sayed Hossein; Hajimiresmaiel, Seyed Javad; Ajami, Marjan; Mohseni-Bandpei, Anoushiravan; Ayatollahi, Seyyed Abdulmajid; Dowlatshahi, Kamran; Javedan, Gholamali; Pazoki-Toroudi, Hamidreza

    2014-01-01

    Low calorie diets are always difficult for obese subjects to follow and lead to metabolic and behavioral adaptation. Therefore, we evaluated the effect of caffeine treatment with calorie shifting diet (CSD) on weight loss. Female subjects (n=60; BMI≥25) completed 4-weeks control diet, 6-weeks CSD (3 repeated phases; each 2-weeks) and 4-weeks follow-up diet, with or without caffeine treatment (5 mg/Kg/day). The first 11 days of each phase included calorie restriction with four meals every day and 4 hours intervals. Significant weight and fat loss were observed after 4-weeks of CSD (5.7 ± 1.24 Kg and 4.84 ± 1.53 Kg) or CSD+Caffeine (7.57 ± 2.33 Kg and 5.24 ± 2.07 Kg) which was consistent for one month of the follow-up (CSD: 5.24 ± 1.83 Kg and 4.3 ± 1.62 Kg, CSD+Caffeine: 12.11 ± 2.31 Kg and 9.85 ± 1.6 Kg, p < 0.05 vs CSD group) and correlated to the restricted energy intake (p < 0.05). During three CSD phases, RMR tended to remain unchanged in both groups.While, CSD or CSD + Caffeine treatments, significantly decreased plasma glucose, total-cholesterol, and triacylglycerol (p < 0.05), even during follow-up period (p < 0.05). HDL-cholesterol was not changed by CSD. Feeling of hunger decreased and subject's satisfaction increased after 4-weeks of CSD (p < 0.05) and remained low to the end of study, while satiety was not affected. Coffeine increased the effect of CSD on feeling of hunger and subject's satisfaction after week 7 (p < 0.05 vs. CSD). These findings indicated that combination of caffeine treatment with CSD could be an effective alternative approach to weight and fat loss with small changes in RMR and improved tolerance of subjects to the new diet.

  10. Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice.

    PubMed

    Al-Barazanji, Kamal; McNulty, Judi; Binz, Jane; Generaux, Claudia; Benson, William; Young, Andrew; Chen, Lihong

    2015-06-01

    G protein-coupled receptor 119 (GPR119) is a G protein-coupled receptor expressed predominantly in pancreatic β-cells and gastrointestinal enteroendocrine cells. Metformin is a first-line treatment of type 2 diabetes, with minimal weight loss in humans. In this study, we investigated the effects of GSK2041706 [2-([(1S)-1-(1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl)ethyl]oxy)-5-[4-(methylsulfonyl)phenyl]pyrazine], a GPR119 agonist, and metformin as monotherapy or in combination on body weight in a diet-induced obese (DIO) mouse model. Relative to vehicle controls, 14-day treatment with GSK2041706 (30 mg/kg b.i.d.) or metformin at 30 and 100 mg/kg b.i.d. alone caused a 7.4%, 3.5%, and 4.4% (all P < 0.05) weight loss, respectively. The combination of GSK2041706 with metformin at 30 or 100 mg/kg resulted in a 9.5% and 16.7% weight loss, respectively. The combination of GSK2041706 and metformin at 100 mg/kg caused a significantly greater weight loss than the projected additive weight loss of 11.8%. This body weight effect was predominantly due to a loss of fat. Cumulative food intake was reduced by 17.1% with GSK2041706 alone and 6.6% and 8.7% with metformin at 30 and 100 mg/kg, respectively. The combination of GSK2041706 with metformin caused greater reductions in cumulative food intake (22.2% at 30 mg/kg and 37.5% at 100 mg/kg) and higher fed plasma glucagon-like peptide 1 and peptide tyrosine tyrosine levels and decreased plasma insulin and glucose-dependent insulinotropic polypeptide levels compared with their monotherapy groups. In addition, we characterized the effect of GSK2041706 and metformin as monotherapy or in combination on neuronal activation in the appetite regulating centers in fasted DIO mice. In conclusion, our data demonstrate the beneficial effects of combining a GPR119 agonist with metformin in the regulation of body weight in DIO mice.

  11. Peripheral reduction of FGFR4 with antisense oligonucleotides increases metabolic rate and lowers adiposity in diet-induced obese mice.

    PubMed

    Yu, Xing Xian; Watts, Lynnetta M; Manchem, Vara Prasad; Chakravarty, Kaushik; Monia, Brett P; McCaleb, Michael L; Bhanot, Sanjay

    2013-01-01

    Obesity is a primary risk factor for multiple metabolic disorders. Many drugs for the treatment of obesity, which mainly act through CNS as appetite suppressants, have failed during development or been removed from the market due to unacceptable adverse effects. Thus, there are very few efficacious drugs available and remains a great unmet medical need for anti-obesity drugs that increase energy expenditure by acting on peripheral tissues without severe side effects. Here, we report a novel approach involving antisense inhibition of fibroblast growth factor receptor 4 (FGFR4) in peripheral tissues. Treatment of diet-induce obese (DIO) mice with FGFR4 antisense oligonucleotides (ASO) specifically reduced liver FGFR4 expression that not only resulted in decrease in body weight (BW) and adiposity in free-feeding conditions, but also lowered BW and adiposity under caloric restriction. In addition, combination treatment with FGFR4 ASO and rimonabant showed additive reduction in BW and adiposity. FGFR4 ASO treatment increased basal metabolic rate during free-feeding conditions and, more importantly, prevented adaptive decreases of metabolic rate induced by caloric restriction. The treatment increased fatty acid oxidation while decreased lipogenesis in both liver and fat. Mechanistic studies indicated that anti-obesity effect of FGFR4 ASO was mediated at least in part through an induction of plasma FGF15 level resulted from reduction of hepatic FGFR4 expression. The anti-obesity effect was accompanied by improvement in plasma glycemia, whole body insulin sensitivity, plasma lipid levels and liver steatosis. Therefore, FGFR4 could be a potential novel target and antisense reduction of hepatic FGFR4 expression could be an efficacious therapy as an adjunct to diet restriction or to an appetite suppressant for the treatment of obesity and related metabolic disorders.

  12. Calorie-restricted weight loss reverses high-fat diet-induced ghrelin resistance, which contributes to rebound weight gain in a ghrelin-dependent manner.

    PubMed

    Briggs, Dana I; Lockie, Sarah H; Wu, Qunli; Lemus, Moyra B; Stark, Romana; Andrews, Zane B

    2013-02-01

    Twelve weeks of high-fat diet feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/agouti-related protein (AgRP) neurons. In the current study, we investigated whether diet-induced weight loss could restore NPY/AgRP neuronal responsiveness to ghrelin and whether ghrelin mediates rebound weight gain after calorie-restricted (CR) weight loss. Diet-induced obese (DIO) mice were allocated to one of two dietary interventions until they reached the weight of age-matched lean controls. DIO mice received chow diet ad libitum or chow diet with 40% CR. Chow-fed and high-fat-fed mice served as controls. Both dietary interventions normalized body weight, glucose tolerance, and plasma insulin. We show that diet-induced weight loss with CR increases total plasma ghrelin, restores ghrelin sensitivity, and increases hypothalamic NPY and AgRP mRNA expression. We propose that long-term DIO creates a higher body weight set-point and that weight loss induced by CR, as seen in the high-fat CR group, provokes the brain to protect the new higher set-point. This adaptation to weight loss likely contributes to rebound weight gain by increasing peripheral ghrelin concentrations and restoring the function of ghrelin-responsive neuronal populations in the hypothalamic arcuate nucleus. Indeed, we also show that DIO ghrelin-knockout mice exhibit reduced body weight regain after CR weight loss compared with ghrelin wild-type mice, suggesting ghrelin mediates rebound weight gain after CR weight loss.

  13. Quercetin decreases high-fat diet induced body weight gain and accumulation of hepatic and circulating lipids in mice.

    PubMed

    Hoek-van den Hil, E F; van Schothorst, E M; van der Stelt, I; Swarts, H J M; Venema, D; Sailer, M; Vervoort, J J M; Hollman, P C H; Rietjens, I M C M; Keijer, J

    2014-09-01

    Dietary flavonoids may protect against cardiovascular diseases (CVD). Increased circulating lipid levels and hepatic lipid accumulation are known risk factors for CVD. The aim of this study was to investigate the effects and underlying molecular mechanisms of the flavonoid quercetin on hepatic lipid metabolism in mice with high-fat diet induced body weight gain and hepatic lipid accumulation. Adult male mice received a 40 energy% high-fat diet without or with supplementation of 0.33 % (w/w) quercetin for 12 weeks. Body weight gain was 29 % lower in quercetin fed mice (p < 0.01), while the energy intake was not significantly different. Quercetin supplementation lowered hepatic lipid accumulation to 29 % of the amount present in the control mice (p < 0.01). (1)H nuclear magnetic resonance serum lipid profiling revealed that the supplementation significantly lowered serum lipid levels. Global gene expression profiling of liver showed that cytochrome P450 2b (Cyp2b) genes, key target genes of the transcription factor constitutive androstane receptor (Car; official symbol Nr1i3), were downregulated. Quercetin decreased high-fat diet induced body weight gain, hepatic lipid accumulation and serum lipid levels. This was accompanied by regulation of cytochrome P450 2b genes in liver, which are possibly under transcriptional control of CAR. The quercetin effects are likely dependent on the fat content of the diet.

  14. Deoxynivalenol-induced weight loss in the diet-induced obese mouse is reversible and PKR-independent.

    PubMed

    Flannery, Brenna M; He, Kaiyu; Pestka, James J

    2013-07-31

    The trichothecene deoxynivalenol (DON), a potent ribotoxic mycotoxin produced by the cereal blight fungus Fusarium graminearum, commonly contaminates grain-based foods. Oral exposure to DON causes decreased food intake, reduced weight gain and body weight loss in experimental animals - effects that have been linked to dysregulation of hormones responsible for mediating satiety at the central nervous system level. When diet-induced obese (DIO) mice are fed DON, they consume less food, eventually achieving body weights of control diet-fed mice. Here, we extended these findings by characterizing: (1) reversibility of DON-induced body weight loss and anorexia in DIO mice and (2) the role of double-stranded RNA-activated protein kinase (PKR) which has been previously linked to initiation of the ribotoxic stress response. The results demonstrated that DON-induced weight loss was reversible in DIO mice and this effect corresponded to initiation of a robust hyperphagic response. When DIO mice deficient in PKR were exposed to DON, they exhibited weight suppression similar to DIO wild-type fed the toxin, suggesting the toxin's weight effects were not dependent on PKR. Taken together, DON's effects on food consumption and body weight are not permanent and, furthermore, PKR is not an essential signaling molecule for DON's anorectic and weight effects.

  15. Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice.

    PubMed

    Chikamoto, Keita; Misu, Hirofumi; Takayama, Hiroaki; Kikuchi, Akihiro; Ishii, Kiyo-Aki; Lan, Fei; Takata, Noboru; Tajima-Shirasaki, Natsumi; Takeshita, Yumie; Tsugane, Hirohiko; Kaneko, Shuichi; Matsugo, Seiichi; Takamura, Toshinari

    2016-09-23

    Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days. In contrast, a switch from a RD to a HFD rapidly elevated serum LECT2 levels. Serum LECT2 levels showed a positive correlation with liver triglyceride contents but not with adipose tissue weight. This study demonstrates the rapid response of LECT2 preceding body weight alterations during weight cycling in mice and suggests that measurement of serum LECT2 may be clinically useful in the management of obesity. PMID:27562717

  16. Effects of exendin-4 alone and with peptide YY(3-36) on food intake and body weight in diet-induced obese rats.

    PubMed

    Reidelberger, Roger D; Haver, Alvin C; Apenteng, Bettye A; Anders, Krista L; Steenson, Sharalyn M

    2011-01-01

    Significant weight loss following Roux-en-Y gastric bypass surgery (RYGB) in obese humans correlates with enhanced secretion of anorexigenic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) (PYY(3-36)). Our aim here was to identify a dosing strategy for intraperitoneal (IP) infusion of GLP-1 homologue exendin-4 alone and with PYY(3-36) that produces a sustained reduction in daily food intake and body weight in diet-induced obese (DIO) rats. We tested 12 exendin-4 strategies over 10 weeks. Exendin-4 infused during the first and last 3 h of the dark period at 15-20 pmol/h (0.15 nmol/kg/day) produced a sustained 24 ± 1% reduction in daily food intake for 17 days, and decreased body weight by 7%. In a separate group of DIO rats, none of seven dosing strategies combining exendin-4 and PYY(3-36) produced a similar reduction in daily food intake for >10 days. The subsequent decline in efficacies of exendin-4 alone and with PYY(3-36) on food intake and body weight in each experiment suggested possible receptor downregulation and tolerance to treatments. However, when treatments were discontinued for 1 day following losses in efficacies, daily food intake significantly increased. Together, these results demonstrate that (i) intermittent IP infusion of a low dose of exendin-4 can produce a relatively prolonged reduction in daily food intake and body weight in DIO rats, (ii) co-infusion of exendin-4 and PYY(3-36) does not further prolong this response, and (iii) activation of an orexigenic mechanism gradually occurs to counteract the inhibitory effects of exendin-4 alone and with PYY(3-36) on food intake and body weight.

  17. The Effect of PPARα, PPARδ, PPARγ, and PPARpan Agonists on Body Weight, Body Mass, and Serum Lipid Profiles in Diet-Induced Obese AKR/J Mice

    PubMed Central

    Harrington, W. Wallace; S. Britt, Christy; G. Wilson, Joan; O. Milliken, Naphtali; G. Binz, Jane; C. Lobe, David; R. Oliver, William; C. Lewis, Michael; M. Ignar, Diane

    2007-01-01

    Activation of peroxisome proliferator-activated receptor (PPAR) α, δ, and γ subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. PPARpan agonists which activate all three receptor subtypes have antidiabetic activity in animal models without the weight gain associated with selective PPARγ agonists. Herein we report the effects of selective PPAR agonists (GW9578, a PPARα agonist, GW0742, a PPARδ agonist, GW7845, a PPARγ agonist), combination of PPARα and δ agonists, and PPARpan (PPARα/γ/δ) activators (GW4148 or GW9135) on body weight (BW), body composition, food consumption, fatty acid oxidation, and serum chemistry of diet-induced obese AKR/J mice. PPARα or PPARδ agonist treatment induced a slight decrease in fat mass (FM) while a PPARγ agonist increased BW and FM commensurate with increased food consumption. The reduction in BW and food intake after cotreatment with PPARα and δ agonists appeared to be synergistic. GW4148, a PPARpan agonist, induced a significant and sustained reduction in BW and FM similar to an efficacious dose of rimonabant, an antiobesity compound. GW9135, a PPARpan agonist with weak activity at PPARδ, induced weight loss initially followed by rebound weight gain reaching vehicle control levels by the end of the experiment. We conclude that PPARα and PPARδ activations are critical to effective weight loss induction. These results suggest that the PPARpan compounds may be expected to maintain the beneficial insulin sensitization effects of a PPARγ agonist while either maintaining weight or producing weight loss. PMID:17710237

  18. The Effect of PPARalpha, PPARdelta, PPARgamma, and PPARpan Agonists on Body Weight, Body Mass, and Serum Lipid Profiles in Diet-Induced Obese AKR/J Mice.

    PubMed

    Harrington, W Wallace; S Britt, Christy; G Wilson, Joan; O Milliken, Naphtali; G Binz, Jane; C Lobe, David; R Oliver, William; C Lewis, Michael; M Ignar, Diane

    2007-01-01

    Activation of peroxisome proliferator-activated receptor (PPAR) alpha, delta, and gamma subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. PPARpan agonists which activate all three receptor subtypes have antidiabetic activity in animal models without the weight gain associated with selective PPARgamma agonists. Herein we report the effects of selective PPAR agonists (GW9578, a PPARalpha agonist, GW0742, a PPARdelta agonist, GW7845, a PPARgamma agonist), combination of PPARalpha and delta agonists, and PPARpan (PPARalpha/gamma/delta) activators (GW4148 or GW9135) on body weight (BW), body composition, food consumption, fatty acid oxidation, and serum chemistry of diet-induced obese AKR/J mice. PPARalpha or PPARdelta agonist treatment induced a slight decrease in fat mass (FM) while a PPARgamma agonist increased BW and FM commensurate with increased food consumption. The reduction in BW and food intake after cotreatment with PPARalpha and delta agonists appeared to be synergistic. GW4148, a PPARpan agonist, induced a significant and sustained reduction in BW and FM similar to an efficacious dose of rimonabant, an antiobesity compound. GW9135, a PPARpan agonist with weak activity at PPARdelta, induced weight loss initially followed by rebound weight gain reaching vehicle control levels by the end of the experiment. We conclude that PPARalpha and PPARdelta activations are critical to effective weight loss induction. These results suggest that the PPARpan compounds may be expected to maintain the beneficial insulin sensitization effects of a PPARgamma agonist while either maintaining weight or producing weight loss.

  19. Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats

    PubMed Central

    Fisas, Angels; Codony, Xavier; Romero, Gonzalo; Dordal, Alberto; Giraldo, Jesus; Mercé, Ramon; Holenz, Jörg; Heal, David; Buschmann, Helmut; Pauwels, Petrus Johan

    2006-01-01

    E-6837 is a novel, selective and high-affinity 5-HT6 receptor ligand (pKi: 9.13) which in vitro demonstrates partial agonism at a presumably silent rat 5-HT6 receptor and full agonism at a constitutively active human 5-HT6 receptor by monitoring the cAMP signaling pathway. The effects of chronic treatment with E-6837 were determined in diet-induced obese (DIO)-rats on changes in body weight, food and water intake, plasma indices of comorbid risk factors, and weight regain on compound withdrawal. The centrally acting antiobesity drug, sibutramine, was used as the reference comparator. Sustained body weight loss and decreased cumulative food intake of DIO-rats was observed with E-6837 (30 mg kg−1, p.o., twice a day) during the 4-week treatment period. The onset of the E-6837 effect on body weight was slower than that of sibutramine (5 mg kg−1, p.o.), while its maximal effect was greater, that is −15.7 versus −11.0%. E-6837-induced weight loss was exclusively mediated by a decrease (31.7%) in fat mass, with a concomitant reduction (49.6%) in plasma leptin. Reduced obesity was also reflected in improved glycemic control. Although weight regain occurred after withdrawal from either compound, the body weights after E-6837 (−6.6%) remained lower than after sibutramine (−3.8%) indicating that the greater efficacy of the former did not result in profound rebound hyperphagia/weight gain. These results show that the 5-HT6 receptor partial agonist, E-6837, is a promising new approach to the management of obesity with the potential to produce greater sustained weight loss than sibutramine. PMID:16783408

  20. Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats.

    PubMed

    Fisas, Angels; Codony, Xavier; Romero, Gonzalo; Dordal, Alberto; Giraldo, Jesus; Mercé, Ramon; Holenz, Jörg; Vrang, N; Sørensen, R V; Heal, David; Buschmann, Helmut; Pauwels, Petrus Johan

    2006-08-01

    E-6837 is a novel, selective and high-affinity 5-HT(6) receptor ligand (pK(i): 9.13) which in vitro demonstrates partial agonism at a presumably silent rat 5-HT(6) receptor and full agonism at a constitutively active human 5-HT(6) receptor by monitoring the cAMP signaling pathway.The effects of chronic treatment with E-6837 were determined in diet-induced obese (DIO)-rats on changes in body weight, food and water intake, plasma indices of comorbid risk factors, and weight regain on compound withdrawal. The centrally acting antiobesity drug, sibutramine, was used as the reference comparator. Sustained body weight loss and decreased cumulative food intake of DIO-rats was observed with E-6837 (30 mg kg(-1), p.o., twice a day) during the 4-week treatment period. The onset of the E-6837 effect on body weight was slower than that of sibutramine (5 mg kg(-1), p.o.), while its maximal effect was greater, that is -15.7 versus -11.0%.E-6837-induced weight loss was exclusively mediated by a decrease (31.7%) in fat mass, with a concomitant reduction (49.6%) in plasma leptin. Reduced obesity was also reflected in improved glycemic control. Although weight regain occurred after withdrawal from either compound, the body weights after E-6837 (-6.6%) remained lower than after sibutramine (-3.8%) indicating that the greater efficacy of the former did not result in profound rebound hyperphagia/weight gain. These results show that the 5-HT(6) receptor partial agonist, E-6837, is a promising new approach to the management of obesity with the potential to produce greater sustained weight loss than sibutramine.

  1. Consumption of Clarified Grapefruit Juice Ameliorates High-Fat Diet Induced Insulin Resistance and Weight Gain in Mice

    PubMed Central

    Chudnovskiy, Rostislav; Thompson, Airlia; Tharp, Kevin; Hellerstein, Marc; Napoli, Joseph L.; Stahl, Andreas

    2014-01-01

    To determine the metabolic effects of grapefruit juice consumption we established a model in which C57Bl/6 mice drank 25–50% sweetened GFJ, clarified of larger insoluble particles by centrifugation (cGFJ), ad libitum as their sole source of liquid or isocaloric and sweetened water. cGFJ and control groups consumed similar amounts of liquids and calories. Mice fed a high-fat diet and cGFJ experienced a 18.4% decrease in weight, a 13–17% decrease in fasting blood glucose, a three-fold decrease in fasting serum insulin, and a 38% decrease in liver triacylglycerol values, compared to controls. Mice fed a low-fat diet that drank cGFJ experienced a two-fold decrease in fasting insulin, but not the other outcomes observed with the high-fat diet. cGFJ consumption decreased blood glucose to a similar extent as the commonly used anti-diabetic drug metformin. Introduction of cGFJ after onset of diet-induced obesity also reduced weight and blood glucose. A bioactive compound in cGFJ, naringin, reduced blood glucose and improved insulin tolerance, but did not ameliorate weight gain. These data from a well-controlled animal study indicate that GFJ contains more than one health-promoting neutraceutical, and warrant further studies of GFJ effects in the context of obesity and/or the western diet. PMID:25296035

  2. Diets containing Sophora japonica L. prevent weight gain in high-fat diet-induced obese mice.

    PubMed

    Park, Kye Won; Lee, Ji-Eun; Park, Ki-Moon

    2009-11-01

    Obesity, a worldwide epidemic, is associated with metabolic diseases such as insulin resistance, dyslipidemia, hypertension, and heart disease. Many strategies, including natural alternative antiobesity agents, have been widely used to prevent obesity. Polyphenolic compounds and flavonoids from natural products are shown to inhibit adipogenesis. Because mature fruits of Sophora japonica L. were previously shown to contain antiadipogenic compounds, we hypothesized that diets with mature fruits of S japonica L. would prevent body weight gain in high-fat diet-induced obesity. Four-week-old mice were fed either a control high-fat diet, or high-fat diet containing 1% or 5% of S japonica L. for 4 weeks. The administration of S japonica L. fed in combination with a 30% high-fat diet significantly decreased body weight gain. S japonica L. also reduced serum and hepatic triglyceride, serum total, and high-density lipoprotein cholesterol. Consistent with the effects of lowering glucose level and fat mass, S japonica L. caused a decrease in the number of large adipocytes and a concomitant increase in the number of small adipocytes, which may explain at least in part the antiobesity effects of S japonica L. Together, these data provide evidence for roles of S japonica L. in the control of body weight and obesity-related metabolic diseases. PMID:19932871

  3. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

    PubMed Central

    Seimon, Radhika V.; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A.; Nguyen, Amy D.; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F.; Lau, Jackie

    2016-01-01

    Background Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. Methods Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5–6 consecutive days, and ad libitum intake for 1–3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)–(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. Results Mice on the ID showed transient hyperphagia relative to controls during each 1–3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01). Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC) relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups. Conclusion Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces

  4. Diet induced weight loss accelerates onset of negative alliesthesia in obese women

    PubMed Central

    Frankham, Patrick; Gosselin, Caroline; Cabanac, Michel

    2005-01-01

    Background The physiological and behavioral responses to hypocaloric diet are to increase energy intake to defend a steady body weight. We utilized the method of "negative alliesthesia" for measuring the hedonic reponse to sweet stimulus before (Initial session) and 3 months after entering a weight loss program. The negative alliesthesia test is known by physiologists but few clinical data exist. It is based on the observation that repeated pleasant gustatory stimuli turn into unpleasantness in the process of alliesthesia. At first visit participants repeatedly ingested sweet stimuli until they found them unpleasant and rated quantitatively on a linear analogue scale their hedonic experience. This procedure was repeated every 3 min until participants felt displeasure to end the session. The same protocol was followed after three months of following a weight loss diet. Dieting energy intake was from 1400 – 2000 kcal/d for 8 wk. Energy composition was 50% carb:25% prot: 25% lipid. After 8 wk caloric intake increased by 50 kcal/wk, to reach daily intake of 1800 – 2400 kcal/d. Energy composition was 50% carb:22% prot: 27% lipid. We report results on the effect of slow weight loss on negative alliesthesia in ten obese female participants enrolled in a commercial diet program based on Canada's Food Guide (Mincavi®). Results Results showed that diet lowered the mean BMI (Initial session 36.8 +/- 1.8 vs. 3 mo 34.9 +/- 1.8 kg/m2). At 3 mo the onset of negative alliesthesia, time to abandon experimental session, was shortened (Initial session 33 vs. 3 mo 24 min). The same trend was observed in the time to reach indifference (Initial session 21.9 +/- 3.8 vs. 3 mo 16.2 +/-2.4 min). There was no observed difference in maximum (Initial session +79.5 +/- 11.7; 3 mo +94.5 +/- 9.9 mm) and minimum (Initial session -90.0 +/- 14.4; 3 mo -106 +/- 11.1 mm) hedonic rating. Conclusion Earlier onset of negative alliesthesia, as seen in our participants, is not consistent with previous

  5. Zingiber mioga reduces weight gain, insulin resistance and hepatic gluconeogenesis in diet-induced obese mice

    PubMed Central

    LEE, DA-HYE; AHN, JIYUN; JANG, YOUNG JIN; HA, TAE-YOUL; JUNG, CHANG HWA

    2016-01-01

    Zingiber mioga is a perennial herb belonging to the ginger family (Zingiberaceae) that is used medicinally to treat cough and rheumatism in China and consumed throughout Japan. The aim of the present study was to investigate the anti-obesity effects of Z. mioga following extraction with distilled water or 70% ethanol. In 3T3-L1 preadipocyte cells, Z. mioga water extract (ZMW) markedly inhibited adipogenesis, whereas the ethanol extract had no effect. In addition, we conducted ZMW feeding experiments (0.25 or 0.5% ZMW) in high-fat diet (HFD)-fed mice to examine the anti-obesity effects of Z. mioga in vivo. Body weight and serum triglyceride and cholesterol levels significantly decreased in the HFD + ZMW 0.5% group. Notably, ZMW decreased liver weight but not adipose tissue weight. Furthermore, insulin resistance and hepatic mRNA expression of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase and G6Pase, were improved in the HFD + ZMW 0.5% group. Furthermore, ZMW treatment decreased hepatic lipogenic gene expression; however, it did not alter adipogenesis in fat tissue, suggesting that ZMW inhibits hepatosteatosis through the suppression of lipogenesis. ZMW improved HFD-induced hepatic inflammation. Collectively, the present findings suggest that ZMW may serve as a new and promising strategy for the treatment of hepatosteatosis. PMID:27347064

  6. High-Density Lipoprotein-Associated miR-223 Is Altered after Diet-Induced Weight Loss in Overweight and Obese Males

    PubMed Central

    Tabet, Fatiha; Cuesta Torres, Luisa F.; Ong, Kwok Leung; Shrestha, Sudichhya; Choteau, Sébastien A.; Barter, Philip J.; Clifton, Peter; Rye, Kerry-Anne

    2016-01-01

    Background and Aims microRNAs (miRNAs) are small, endogenous non-coding RNAs that regulate metabolic processes, including obesity. The levels of circulating miRNAs are affected by metabolic changes in obesity, as well as in diet-induced weight loss. Circulating miRNAs are transported by high-density lipoproteins (HDL) but the regulation of HDL-associated miRNAs after diet-induced weight loss has not been studied. We aim to determine if HDL-associated miR-16, miR-17, miR-126, miR-222 and miR-223 levels are altered by diet-induced weight loss in overweight and obese males. Methods HDL were isolated from 47 subjects following 12 weeks weight loss comparing a high protein diet (HP, 30% of energy) with a normal protein diet (NP, 20% of energy). HDL-associated miRNAs (miR-16, miR-17, miR-126, miR-222 and miR-223) at baseline and after 12 weeks of weight loss were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. Serum concentrations of human HDL constituents were measured immunoturbidometrically or enzymatically. Results miR-16, miR-17, miR-126, miR-222 and miR-223 were present on HDL from overweight and obese subjects at baseline and after 12 weeks of the HP and NP weight loss diets. The HP diet induced a significant decrease in HDL-associated miR-223 levels (p = 0.015), which positively correlated with changes in body weight (r = 0.488, p = 0.032). Changes in miR-223 levels were not associated to changes in HDL composition or size. Conclusion HDL-associated miR-223 levels are significantly decreased after HP diet-induced weight loss in overweight and obese males. This is the first study reporting changes in HDL-associated miRNA levels with diet-induced weight loss. PMID:26962854

  7. Diet-induced changes in n-3 and n-6 derived endocannabinoids and reductions in headache pain and psychological distress

    PubMed Central

    Ramsden, Christopher E.; Zamora, Daisy; Makriyannis, Alexandros; Wood, JodiAnne T.; Mann, J. Douglas; Faurot, Keturah R.; MacIntosh, Beth A.; Majchrzak-Hong, Sharon F.; Gross, Jacklyn R.; Courville, Amber B.; Davis, John M.; Hibbeln, Joseph R.

    2015-01-01

    Omega-3 and omega-6 fatty acids are biosynthetic precursors to endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation—increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)—reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (n=55) to investigate (1) whether the H3-L6 intervention altered omega-3 and omega-6 derived endocannabinoids in plasma, and (2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, p<0.001) and docosahexaenoylethanolamine (+99%, p<0.001), and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, p=0.001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans, and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties. Trial Registration: ClinicalTrials.gov (NCT01157208) Perspective This article demonstrates that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids, and that these changes are related to reductions in headache pain and psychological distress. These findings suggest that dietary interventions could provide an effective, complementary approach for managing chronic pain and related

  8. Ostα-/- mice are not protected from western diet-induced weight gain.

    PubMed

    Hammond, Christine L; Wheeler, Sadie G; Ballatori, Nazzareno; Hinkle, Patricia M

    2015-01-01

    Organic solute transporterα-OSTβ is a bile acid transporter important for bile acid recycling in the enterohepatic circulation. In comparison to wild-type mice, Ostα(-/-) mice have a lower bile acid pool and increased fecal lipids and they are relatively resistant to age-related weight gain and insulin resistance. These studies tested whether Ostα(-/-) mice are also protected from weight gain, lipid changes, and insulin resistance which are normally observed with a western-style diet high in both fat and cholesterol (WD). Wild-type and Ostα(-/-) mice were fed a WD, a control defined low-fat diet (LF) or standard laboratory chow (CH). Surprisingly, although the Ostα(-/-) mice remained lighter on LF and CH diets, they weighed the same as wild-type mice after 12 weeks on the WD even though bile acid pool levels remained low and fecal lipid excretion remained elevated. Mice of both genotypes excreted relatively less lipid when switched from CH to LF or WD. WD caused slightly greater changes in expression of genes involved in lipid transport in the small intestines of Ostα(-/-) mice than wild-type, but the largest differences were between CH and defined diets. After WD feeding, Ostα(-/-) mice had lower serum cholesterol and hepatic lipids, but Ostα(-/-) and wild-type mice had equivalent levels of muscle lipids and similar responses in glucose and insulin tolerance tests. Taken together, the results show that Ostα(-/-) mice are able to adapt to a western-style diet despite low bile acid levels.

  9. Does Diet-Induced Weight Loss Lead to Bone Loss in Overweight or Obese Adults? A Systematic Review and Meta-Analysis of Clinical Trials.

    PubMed

    Zibellini, Jessica; Seimon, Radhika V; Lee, Crystal M Y; Gibson, Alice A; Hsu, Michelle S H; Shapses, Sue A; Nguyen, Tuan V; Sainsbury, Amanda

    2015-12-01

    Diet-induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta-analysis (using a random-effects model) to quantify the effect of diet-induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight-loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual-energy X-ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet-induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm(2) in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], -0.014 to -0.005, -0.021 to -0.008, and -0.024 to -0.000 g/cm(2), at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet-induced weight loss on lumbar spine or whole-body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (-0.011 g/cm(2); 95% CI, -0.018 to -0.003 g/cm(2)) after 6 months. Although no statistically significant changes occurred in serum concentrations of N-terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L; 95% CI, 0.13 to 0.39 nmol/L), C-terminal telopeptide of type I collagen (CTX) (4.72 nmol/L; 95% CI, 2.12 to 7.30 nmol/L) or N-terminal telopeptide of type I collagen (NTX) (3.70 nmol/L; 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet-induced weight loss to promote bone breakdown. These data show that in overweight and obese individuals, a single diet-induced weight-loss intervention induces a small decrease in total hip BMD, but not lumbar spine

  10. Improved nutritional status and bone health after diet-induced weight loss in sedentary osteoarthritis patients: a prospective cohort study

    PubMed Central

    Christensen, P; Bartels, E M; Riecke, B F; Bliddal, H; Leeds, A R; Astrup, A; Winther, K; Christensen, R

    2012-01-01

    BACKGROUND/OBJECTIVES: Obese subjects are commonly deficient in several micronutrients. Weight loss, although beneficial, may also lead to adverse changes in micronutrient status and body composition. The objective of the study is to assess changes in micronutrient status and body composition in obese individuals after a dietary weight loss program. SUBJECTS/METHODS: As part of a dietary weight loss trial, enrolling 192 obese patients (body mass index >30 kg/m2) with knee osteoarthritis (>50 years of age), vitamin D, ferritin, vitamin B12 and body composition were measured at baseline and after 16 weeks. All followed an 8-week formula weight-loss diet 415–810 kcal per day, followed by 8 weeks on a hypo-energetic 1200 kcal per day diet with a combination of normal food and formula products. Statistical analyses were based on paired samples in the completer population. RESULTS: A total of 175 patients (142 women), 91%, completed the 16-week program and had a body weight loss of 14.0 kg (95% confidence interval: 13.3–14.7; P<0.0001), consisting of 1.8 kg (1.3–2.3; P<0.0001) lean body mass (LBM) and 11.0 kg (10.4–11.6; P<0.0001) fat mass. Bone mineral content (BMC) did not change (-13.5 g; P=0.18), whereas bone mineral density (BMD) increased by 0.004 g/cm2 (0.001–0.008 g/cm2; P=0.025). Plasma vitamin D and B12 increased by 15.3 nmol/l (13.2–17.3; P<0.0001) and 43.7 pmol/l (32.1–55.4; P<0.0001), respectively. There was no change in plasma ferritin. CONCLUSIONS: This intensive program with formula diet resulted in increased BMD and improved vitamin D and B12 levels. Ferritin and BMC were unchanged and loss of LBM was only 13% of the total weight loss. This observational evidence supports use of formula diet-induced weight loss therapy in obese osteoarthritis patients. PMID:22190136

  11. Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men.

    PubMed

    Williams, P T; Krauss, R M; Vranizan, K M; Wood, P D

    1990-04-01

    We studied separately the effects of weight loss by calorie restriction (dieting) and by calorie expenditure (primarily, running) on lipoprotein subfraction concentrations in sedentary, moderately overweight men assigned at random into three groups as follows: exercise without calorie restriction (n = 46), calorie restriction without exercise (n = 42), and control (n = 42). Plasma lipoprotein mass concentrations were measured by analytic ultracentrifugation for flotation rates (F0(1.20), S0f) within high density lipoprotein (HDL) (F0(1.20) 0-9), low density lipoprotein (LDL) (S0f 0-12), intermediate density lipoprotein (IDL) (S0f 12-20), and very low density lipoprotein (VLDL) (S0f 20-400) particle distributions. Particle diameter and flotation rate of the most abundant LDL species were determined by nondenaturing polyacrylamide gradient gel electrophoresis and analytic ultracentrifugation, respectively. During the 1-year trial, the exercisers ran (mean +/- SD) 15.6 +/- 9.1 km/wk, and the dieters ate 340 +/- 71 fewer kilocalories per day than at baseline. Total body weight was reduced significantly more in dieters (-7.2 +/- 4.1 kg) and exercisers (-4.0 +/- 3.9 kg) than controls (0.6 +/- 3.7 kg). As compared with mean changes in controls, the exercisers and dieters significantly increased HDL2 mass (48.6% and 47.1%, respectively), decreased VLDL mass (-23.9% and -25.5%), and increased LDL peak particle diameter (2.4 and 3.2 A). When adjusted to an equivalent change in body mass index by analysis of covariance, 1) exercise-induced and diet-induced weight loss produced comparable mean changes in the mass of small LDL and VLDL, and in LDL peak particle diameter; 2) the exercisers versus control group difference in HDL2 was attributed to the exercisers' reduced body mass index; and 3) HDL2 increased significantly less in dieters than in exercisers. In dieters, low calorie intake might mitigate the effects of weight loss on HDL2.

  12. Effect of physical activity on weight loss, energy expenditure and energy intake during diet induced weight loss

    PubMed Central

    DeLany, James P.; Kelley, David E.; Hames, Kazanna C.; Jakicic, John M.; Goodpaster, Bret H.

    2016-01-01

    Objective Objective measurements of physical activity (PA), energy expenditure (EE) and energy intake can provide valuable information regarding appropriate strategies for successful sustained weight loss. Design and methods We examined total EE by doubly labeled water, resting metabolic rate, PA with activity monitors, and energy intake by the Intake/Balance technique in 116 severely obese undergoing intervention with diet alone (DO) or diet plus PA (D-PA). Results Weight loss of 9.6±6.8 kg resulted in decreased EE which was not minimized in the D-PA group. Comparing the highest and lowest quartiles of increase in PA revealed a lower decrease in TDEE (−122±319 vs. −376±305 kcal/d), elimination of the drop in AEE (83±279 vs. −211±284 kcal/d) and greater weight loss (13.0±7.0 vs. 8.1±6.3 kg). Increased PA was associated with greater adherence to energy restriction and maintenance of greater weight loss during months 7–12. Conclusion Noncompliance to prescribed PA in the DO and D-PA groups partially masked the effects of PA to increase weight loss and to minimize the reduced EE. Increased PA was also associated with improved adherence to prescribed caloric restriction. A strong recommendation needs to be made to improve interventions that promote PA within the context of behavioral weight loss interventions. PMID:23804562

  13. Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol

    PubMed Central

    Cluny, Nina L.; Keenan, Catherine M.; Reimer, Raylene A.; Le Foll, Bernard; Sharkey, Keith A.

    2015-01-01

    Objective Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice. Methods Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally. Results THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. Conclusions Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity. PMID:26633823

  14. Rhein Reduces Fat Weight in db/db Mouse and Prevents Diet-Induced Obesity in C57Bl/6 Mouse through the Inhibition of PPARγ Signaling

    PubMed Central

    Zhang, Yu; Fan, Shengjie; Hu, Na; Gu, Ming; Chu, Chunxiao; Li, Yiming; Lu, Xiong; Huang, Cheng

    2012-01-01

    Rheum palmatum has been used most frequently in the weight-reducing formulae in traditional Chinese medicine. However, the components of Rheum palmatum that play the antiobesity role are still uncertain. Here, we tested the weight-reducing effect of two major Rheum palmatum compounds on db/db mouse. We found that rhein (100 mg kg−1 day−1), but not emodin, reduced the fat weight in db/db mouse. Using diet-induced obese (DIO) C57BL/6 mice, we identified that rhein blocked high-fat diet-induced obesity, decreased fat mass and the size of white and brown adipocytes, and lowered serum cholesterol, LDL cholesterol, and fasting blood glucose levels in the mice. To elucidate the underlying mechanisms, we used reporter assay and gene expression analysis and found that rhein inhibited peroxisome proliferator-activated receptor γ (PPARγ) transactivity and the expression of its target genes, suggesting that rhein may act as a PPARγ antagonist. Our data indicate that rhein may be a promising choice for antiobesity therapy. PMID:23049539

  15. Chrysobalanus icaco L. Leaves Normalizes Insulin Sensitivity and Blood Glucose and Inhibits Weight Gain in High-Fat Diet-Induced Obese Mice.

    PubMed

    White, Pollyanna A S; Araújo, Jessica M D; Cercato, Luana M; Souza, Lucas A; Barbosa, Ana Paula Oliveira; Quintans-Junior, Lucindo José; Machado, Ubiratan F; Camargo, Enilton A; Brito, Luciana C; Santos, Marcio Roberto V

    2016-02-01

    Chrysobalanus icaco L. is a medicinal plant present in the Brazilian coastline and known for its hypoglicemic and antioxidant properties. Here, we assessed the beneficial metabolic effects of the aqueous extract of C. icaco (AECI) leaves in diet-induced obese mice. Swiss mice were fed standard chow (SC used as controls) or high-fat diet (HFD) to induce obesity. After 10 weeks, mice on each diet were divided into two groups with one group used as control while the other group treated with AECI for 4 weeks resulting in four groups of mice: SC; SC treated with AECI (SC + AECI); HFD; and HFD treated with AECI (HFD + AECI). AECI was administered drinking water at about 200 mg/kg. AECI was able to normalize insulin (13,682 ± 1090 vs. 9828 ± 485 AU, P < .05) and fasting blood glucose (192.8 ± 14.2 vs. 132.3 ± 6.4 mg/dL, P < .05) and inhibit weight gain (39 ± 5.7%) and fat storage in liver (72.60 ± 3.83%, P < .0001), despite the high-fat intake. These findings reinforce the use of AECI in hyperglycemia and highlight the potential extract's effect in preventing weight gain and fat accumulation in liver of diet-induced obese mice. PMID:26854845

  16. Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways.

    PubMed

    Kim, Jongwan; Yun, Eun-Young; Park, Seong-Won; Goo, Tae-Won; Seo, Minchul

    2016-02-18

    Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress.

  17. The DPP-IV inhibitor linagliptin and GLP-1 induce synergistic effects on body weight loss and appetite suppression in the diet-induced obese rat.

    PubMed

    Hansen, Henrik H; Hansen, Gitte; Paulsen, Sarah; Vrang, Niels; Mark, Michael; Jelsing, Jacob; Klein, Thomas

    2014-10-15

    Linagliptin is a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes. DPP-IV inhibitors are considered weight neutral, suggesting that elevation of endogenous incretin levels is not sufficient to promote weight loss per se. Here we evaluated the effect of linagliptin in combination with subcutaneous treatment of GLP-1(7-36) on body weight regulation in diet-induced obese (DIO) rats. Linagliptin administered perorally (1.5mg/kg, b.i.d.), but not subcutaneously (0.5mg/kg, b.i.d.), evoked a very modest body weight loss (2.2%) after 28 days of treatment. GLP-1 (0.5mg/kg, s.c.) treatment alone induced a body weight loss of 4.1%. In contrast, combined linagliptin (1.5mg/kg, p.o., or 0.5mg/kg, s.c.) and GLP-1 (0.5mg/kg) treatment evoked a marked anorectic response with both routes of linagliptin administration being equally effective on final body weight loss (7.5-8.0%). In comparison, liraglutide monotherapy (0.2mg/kg, s.c., b.i.d.) reduced body weight by 10.1%. Interestingly, the weight lowering effect of combined linagliptin and GLP-1 treatment was associated with a marked increase in chow preference, being more pronounced as compared to liraglutide treatment. In addition, linagliptin and GLP-1 co-treatment, but not liraglutide, specifically increased prepro-dynorphin mRNA levels in the caudate-putamen, an effect not obtained with administration of the compounds individually. In conclusion, co-treatment with linagliptin and GLP-1 synergistically reduces body weight in obese rats. The anti-obesity effect was caused by appetite suppression with a concomitant change in diet preference, which may potentially be associated with increased dynorphin activity in forebrain regions involved in reward anticipation and habit learning.

  18. Lack of weight gain after angiotensin AT1 receptor blockade in diet-induced obesity is partly mediated by an angiotensin-(1–7)/ Mas-dependent pathway

    PubMed Central

    Schuchard, Johanna; Winkler, Martina; Stölting, Ines; Schuster, Franziska; Vogt, Florian M; Barkhausen, Jörg; Thorns, Christoph; Santos, Robson A; Bader, Michael; Raasch, Walter

    2015-01-01

    Background and Purpose Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II. As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascular and metabolic effects. Experimental Approach We investigated the anti-obesity effects of transgenically overexpressed angiotensin-(1-7) in rats. We secondly examined whether weight loss due to telmisartan (8 mg·kg−1·d−1) in diet-induced obese Sprague Dawley (SD) rats can be blocked when the animals were co-treated with the Mas receptor antagonist A779 (24 or 72 μg·kg−1·d−1). Key Results In contrast to wild-type controls, transgenic rats overexpressing angiotensin-(1-7) had 1.) diminished body weight when they were regularly fed with chow; 2.) were protected from developing obesity although they were fed with cafeteria diet (CD); 3.) showed a reduced energy intake that was mainly related to a lower CD intake; 5.) remained responsive to leptin despite chronic CD feeding; 6.) had a higher, strain-dependent energy expenditure, and 7.) were protected from developing insulin resistance despite CD feeding. Telmisartan-induced weight loss in SD rats was partially antagonized after a high, but not a low dose of A779. Conclusions and Implications Angiotensin-(1-7) regulated food intake and body weight and contributed to the weight loss after AT1 receptor blockade. Angiotensin-(1-7)-like agonists may be drug candidates for treating obesity. PMID:25906670

  19. Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats.

    PubMed

    van de Giessen, Elsmarieke; de Bruin, Kora; la Fleur, Susanne E; van den Brink, Wim; Booij, Jan

    2012-04-01

    The novel triple monoamine inhibitor tesofensine blocks dopamine, serotonin and norepinephrine re-uptake and is a promising candidate for the treatment of obesity. Obesity is associated with lower striatal dopamine D2 receptor availability, which may be related to disturbed regulation of food intake. This study assesses the effects of chronic tesofensine treatment on food intake and body weight in association with changes in striatal dopamine D2/D3 receptor (D2/3R) availability of diet-induced obese (DIO) rats. Four groups of 15 DIO rats were randomized to one of the following treatments for 28 days: 1. tesofensine (2.0 mg/kg), 2. vehicle, 3. vehicle+restricted diet isocaloric to caloric intake of group 1, and 4. tesofensine (2.0 mg/kg)+ a treatment-free period of 28 days. Caloric intake and weight gain decreased significantly more in the tesofensine-treated rats compared to vehicle-treated rats, which confirms previous findings. After treatment discontinuation, caloric intake and body weight gain gradually increased again. Tesofensine-treated rats showed significantly lower D2/3R availability in nucleus accumbens and dorsal striatum than both vehicle-treated rats and vehicle-treated rats on restricted isocaloric diet. No correlations were observed between food intake or body weight and D2/3R availability. Thus, chronic tesofensine treatment leads to decreased food intake and weight gain. However, this appears not to be directly related to the decreased striatal D2/3R availability, which is mainly a pharmacological effect.

  20. Cheonggukjang, a soybean paste fermented with B. licheniformis-67 prevents weight gain and improves glycemic control in high fat diet induced obese mice

    PubMed Central

    Choi, Joo-Hee; Pichiah, P.B.Tirupathi; Kim, Min-Jung; Cha, Youn-Soo

    2016-01-01

    In this study, we investigated the anti-obesity effects of soybean paste—Cheonggukjang, fermented with poly gamma glutamic acid producing Bacillus licheniformis-67 in diet induced obese C57BL/6J mice. Forty male C57BL/6J mice aged 4 weeks were divided into four dietary groups; normal diet control, high fat diet control, high fat diet containing 30% of unfermented soybean and high fat diet containing 30% Cheonggukjang fermented with Bacillus licheniformis-67. After 13 weeks of dietary intervention the mice were sacrificed; serum and tissue samples were examined. Serum and hepatic lipid profile, blood glucose, insulin, leptin level were lower (<0.05) along with the body weight and epididymal fat pad weight in the 30% Cheonggukjang supplemented group compared with the high fat diet control group. The expression level of lipid anabolic gene was significantly decreased; whereas the expression level of lipid catabolic genes were significantly increased in the 30% Cheonggukjang supplemented group compared to the high fat diet control group. Collectively, these results suggested that intake of Cheonggukjang fermented with Bacillus licheniformis-67 significantly prevents obesity related parameters. PMID:27499576

  1. Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

    PubMed

    Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

    2016-09-01

    Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc.

  2. Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

    PubMed

    Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

    2016-09-01

    Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc. PMID:26852013

  3. Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss12

    PubMed Central

    Josse, Andrea R; Gburcik, Valentina; Raymond, Frederic; Good, Liam; Atherton, Philip J

    2016-01-01

    Background: A hypothesis exists whereby an exercise- or dietary-induced negative energy balance reduces human subcutaneous white adipose tissue (scWAT) mass through the formation of brown-like adipocyte (brite) cells. However, the validity of biomarkers of brite formation has not been robustly evaluated in humans, and clinical data that link brite formation and weight loss are sparse. Objectives: We used rosiglitazone and primary adipocytes to stringently evaluate a set of biomarkers for brite formation and determined whether the expression of biomarker genes in scWAT could explain the change in body composition in response to exercise training combined with calorie restriction in obese and overweight women (n = 79). Design: Gene expression was derived from exon DNA microarrays and preadipocytes from obesity-resistant and -sensitive mice treated with rosiglitazone to generate candidate brite biomarkers from a microarray. These biomarkers were evaluated against data derived from scWAT RNA from obese and overweight women before and after supervised exercise 5 d/wk for 16 wk combined with modest calorie restriction (∼0.84 MJ/d). Results: Forty percent of commonly used brite gene biomarkers exhibited an exon or strain-specific regulation. No biomarkers were positively related to weight loss in human scWAT. Greater weight loss was significantly associated with less uncoupling protein 1 expression (P = 0.006, R2 = 0.09). In a follow-up global analysis, there were 161 genes that covaried with weight loss that were linked to greater CCAAT/enhancer binding protein α activity (z = 2.0, P = 6.6 × 10−7), liver X receptor α/β agonism (z = 2.1, P = 2.8 × 10−7), and inhibition of leptin-like signaling (z = −2.6, P = 3.9 × 10−5). Conclusion: We identify a subset of robust RNA biomarkers for brite formation and show that calorie-restriction–mediated weight loss in women dynamically remodels scWAT to take on a more-white rather than a more-brown adipocyte phenotype

  4. Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular Hypothalamic Nucleus.

    PubMed

    Luchtman, Dirk W; Chee, Melissa J S; Doslikova, Barbora; Marks, Daniel L; Baracos, Vickie E; Colmers, William F

    2015-01-01

    Some animals and humans fed a high-energy diet (HED) are diet-resistant (DR), remaining as lean as individuals who were naïve to HED. Other individuals become obese during HED exposure and subsequently defend the obese weight (Diet-Induced Obesity- Defenders, DIO-D) even when subsequently maintained on a low-energy diet. We hypothesized that the body weight setpoint of the DIO-D phenotype resides in the hypothalamic paraventricular nucleus (PVN), where anorexigenic melanocortins, including melanotan II (MTII), increase presynaptic GABA release, and the orexigenic neuropeptide Y (NPY) inhibits it. After prolonged return to low-energy diet, GABA inputs to PVN neurons from DIO-D rats exhibited highly attenuated responses to MTII compared with those from DR and HED-naïve rats. In DIO-D rats, melanocortin-4 receptor expression was significantly reduced in dorsomedial hypothalamus, a major source of GABA input to PVN. Unlike melanocortin responses, NPY actions in PVN of DIO-D rats were unchanged, but were reduced in neurons of the ventromedial hypothalamic nucleus; in PVN of DR rats, NPY responses were paradoxically increased. MTII-sensitivity was restored in DIO-D rats by several weeks' refeeding with HED. The loss of melanocortin sensitivity restricted to PVN of DIO-D animals, and its restoration upon prolonged refeeding with HED suggest that their melanocortin systems retain the ability to up- and downregulate around their elevated body weight setpoint in response to longer-term changes in dietary energy density. These properties are consistent with a mechanism of body weight setpoint.

  5. Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular Hypothalamic Nucleus

    PubMed Central

    Luchtman, Dirk W.; Chee, Melissa J. S.; Doslikova, Barbora; Marks, Daniel L.; Baracos, Vickie E.; Colmers, William F.

    2015-01-01

    Some animals and humans fed a high-energy diet (HED) are diet-resistant (DR), remaining as lean as individuals who were naïve to HED. Other individuals become obese during HED exposure and subsequently defend the obese weight (Diet-Induced Obesity- Defenders, DIO-D) even when subsequently maintained on a low-energy diet. We hypothesized that the body weight setpoint of the DIO-D phenotype resides in the hypothalamic paraventricular nucleus (PVN), where anorexigenic melanocortins, including melanotan II (MTII), increase presynaptic GABA release, and the orexigenic neuropeptide Y (NPY) inhibits it. After prolonged return to low-energy diet, GABA inputs to PVN neurons from DIO-D rats exhibited highly attenuated responses to MTII compared with those from DR and HED-naïve rats. In DIO-D rats, melanocortin-4 receptor expression was significantly reduced in dorsomedial hypothalamus, a major source of GABA input to PVN. Unlike melanocortin responses, NPY actions in PVN of DIO-D rats were unchanged, but were reduced in neurons of the ventromedial hypothalamic nucleus; in PVN of DR rats, NPY responses were paradoxically increased. MTII-sensitivity was restored in DIO-D rats by several weeks’ refeeding with HED. The loss of melanocortin sensitivity restricted to PVN of DIO-D animals, and its restoration upon prolonged refeeding with HED suggest that their melanocortin systems retain the ability to up- and downregulate around their elevated body weight setpoint in response to longer-term changes in dietary energy density. These properties are consistent with a mechanism of body weight setpoint. PMID:26444289

  6. Black Currant Anthocyanins Attenuate Weight Gain and Improve Glucose Metabolism in Diet-Induced Obese Mice with Intact, but Not Disrupted, Gut Microbiome.

    PubMed

    Esposito, Debora; Damsud, Thanakorn; Wilson, Mickey; Grace, Mary H; Strauch, Renee; Li, Xu; Lila, Mary Ann; Komarnytsky, Slavko

    2015-07-15

    Black currant (Ribes nigrum L.) is a rich source of anthocyanins; however, the relationship between their apparently limited bioavailability and significant protection against metabolic pathologies is poorly understood. This study examined the gastrointestinal distribution of black currant anthocyanins and their phenolic acid metabolites in lean and diet-induced obese mice with healthy and antibiotic-disrupted microbiomes. Daily consumption of low- or high-fat diet supplemented with 1% black currant powdered extract (32% anthocyanins) for 8 weeks reduced body weight gain and improved glucose metabolism only in mice with the intact gut microbiome. Administration of antibiotic cocktail resulted in a 16-25-fold increase (P < 0.001) in anthocyanin content of feces, and cyanidin-based anthocyanins showed the largest increase in fecal content upon disruption of gut microbiome (92.3 ± 16.3 vs 4719 ± 158 μg/g feces), indicating their high susceptibility to microbial degradation in the gut. A 3-fold enrichment (P < 0.05) in gallic over protocatechuic acid was observed in the jejunum of both intact and antibiotic-treated animals, suggesting that this effect was likely independent of their gut microbiome status. Taken together, the data clearly demonstrate that gut microbiome and the type of the anthocyanin aglycone moiety can alter the protective effect of anthocyanins against obesity and associated insulin resistance.

  7. Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways

    PubMed Central

    Kim, Jongwan; Yun, Eun-Young; Park, Seong-Won; Goo, Tae-Won; Seo, Minchul

    2016-01-01

    Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress. PMID:26901224

  8. Weight loss induced by rimonabant is associated with an altered leptin expression and hypothalamic leptin signaling in diet-induced obese mice.

    PubMed

    Lazzari, Paolo; Sanna, Angela; Mastinu, Andrea; Cabasino, Simona; Manca, Ilaria; Pani, Luca

    2011-03-01

    This study investigates the molecular mechanisms and the center-periphery cross talk underlying the anti-obesity effect of the cannabinoid receptor 1 (CB(1)) antagonist/inverse agonist rimonabant in diet-induced obese (DIO) mice exposed to a 31 days chronic treatment with the drug. Present data showed a significant and stable weight loss both in animals treated with rimonabant 10mg/kg by oral gavage exposed to a high fat diet (SRFD) and in vehicle treated mice switched to a regular chow (VEND) with respect to vehicle fat diet fed mice (VEFD). Caloric intake was significantly lowered in SRFD and VEND during the first two and four days, respectively, then reaching the VEFD consume throughout the treatment. The drop of body weight was accompanied by leptin mRNA decrease in visceral fat tissue both in VEND and SRFD, as revealed by Real time PCR analysis. No difference in CB(1) mRNA receptor expression in hypothalamus and in visceral fat tissue among groups was observed. Leptin receptors were decreased in the hypothalamus of SRFD but not of VEND mice. Moreover, in SRFD and VEND mice the expression of orexigenic genes Neuropeptide Y and Agouti Related Protein (AGRP) was increased, while anorexigenic ones, Pro-OpioMelanoCortin (POMC) and Cocaine-and-Amphetamine-Regulated Transcript (CART) displayed no alteration in any group. This data contribute to clarify the molecular basis of the anti-obesity properties of rimonabant, underlying the role of the peripheral modulators which affect central circuits involved in the regulation of food intake and energy homeostasis.

  9. Performance on the Iowa gambling task is related to magnitude of weight loss and salivary cortisol in a diet-induced weight loss intervention in overweight women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The overall objective of this study was to examine the relationship between executive function, specifically decision making, and weight loss. We used the Iowa Gambling Task (IGT) to characterize decision making and compared performance on this task to weight loss in obese women (n=29) participatin...

  10. Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.

    PubMed Central

    Mizuno, T M; Bergen, H; Funabashi, T; Kleopoulos, S P; Zhong, Y G; Bauman, W A; Mobbs, C V

    1996-01-01

    Mutations in the obese (ob) gene lead to obesity. This gene has been recently cloned, but the factors regulating its expression have not been elucidated. To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used to assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional conditions. ob mRNA was elevated in both forms of obesity, compared to lean controls, correlated with elevations in plasma insulin and body weight, but not plasma glucose. In lean C57BL/6J mice, but not in mice with diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similarly, in lean C57BL/6J controls, but not in obese yellow mice, i.p. glucose injection significantly increased ob mRNA. For up to 30 min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin. In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated approximately 2-fold 30 min after i.p. injection of either glucose or insulin. These results suggest that in lean animals glucose and insulin enhance ob gene expression. In contrast to our results in lean mice, in obese animals ob mRNA is elevated and relatively insensitive to nutritional state, possibly due to chronic exposure to elevated plasma insulin and/or glucose. Images Fig. 1 Fig. 4 PMID:8622953

  11. Mice that are resistant to diet-induced weight loss have greater food anticipatory activity and altered melanocortin-3 receptor (MC3R) and dopamine receptor 2 (D2) gene expression.

    PubMed

    Vaanholt, Lobke M; Mitchell, Sharon E; Sinclair, Rachel E; Speakman, John R

    2015-07-01

    Diet-induced weight loss varies considerably between individuals, but the mechanisms driving these individual differences remain largely unknown. Here we investigated whether key neuropeptides involved in the regulation of energy balance or reward systems were differentially expressed in mice that were prone or resistant to caloric restriction (CR) induced weight loss. Mice (n=30 males and n=34 females) were fed 70% of their own baseline ad libitum intake for 25days, after which their brains were collected and expression of various neuropeptides were investigated and compared between the 10 male and 10 female mice that showed the greatest (high weight loss, HWL) or lowest weight loss (LWL) (n=40 in total). HWL mice showed a differential neuropeptide profile to LWL in both sexes, characterised by increased expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), leptin receptor (ObRb), and melanocortin 3 receptor (MC3R) in the arcuate nucleus. No changes in the expression of fat mass and obesity related gene (FTO) or suppressor of cytokine signalling 3 (Socs3) were observed. Levels of dopamine D2 receptor were decreased in the nucleus accumbens in HWL compared to LWL mice. HWL mice showed a stronger increase in food anticipatory activity (FAA) in response to CR than LWL mice. These results indicate that the mice prone to diet-induced weight loss experienced greater hunger, potentially driving their elevated FAA.

  12. SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity

    PubMed Central

    Ramadori, Giorgio; Fujikawa, Teppei; Fukuda, Makoto; Anderson, Jason; Morgan, Donald A.; Mostoslavsky, Raul; Stuart, Ronald C.; Perello, Mario; Vianna, Claudia R.; Nillni, Eduardo A.; Rahmouni, Kamal; Coppari, Roberto

    2010-01-01

    Summary Feeding on high-calorie (HC) diets induces serious metabolic imbalances, including obesity. Understanding the mechanisms against excessive body weight gain is critical for developing effective anti-obesity strategies. Here, we show that lack of nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase SIRT1 in pro-opiomelanocortin (POMC) neurons causes hypersensitivity to diet-induced obesity due to reduced energy expenditure. The ability of leptin to properly engage the phosphoinositide 3-kinase (PI3K) signaling in POMC neurons and elicit remodeling of perigonadal white adipose tissue (WAT) is severely compromised in mutant mice. Also, electrophysiological and histomorphomolecular analyses indicate a selective reduction in sympathetic nerve activity and brown-fat-like characteristics in perigonadal WAT of mutant mice; suggesting a physiologically important role for POMC neurons in controlling this visceral fat depot. In summary, our results provide direct genetic evidence that SIRT1 in POMC neurons is required for normal autonomic adaptations against diet-induced obesity. PMID:20620997

  13. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    PubMed

    Litwak, Sara A; Loh, Kim; Stanley, William J; Pappas, Evan G; Wali, Jibran A; Selck, Claudia; Strasser, Andreas; Thomas, Helen E; Gurzov, Esteban N

    2016-04-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14-17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity.

  14. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    PubMed Central

    Litwak, Sara A.; Loh, Kim; Stanley, William J.; Pappas, Evan G.; Wali, Jibran A.; Selck, Claudia; Strasser, Andreas; Thomas, Helen E.; Gurzov, Esteban N.

    2016-01-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14–17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity. PMID:27033313

  15. Impact of Korean pine nut oil on weight gain and immune responses in high-fat diet-induced obese mice

    PubMed Central

    Park, Soyoung; Lim, Yeseo; Shin, Sunhye

    2013-01-01

    Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative responses of splenocytes upon stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and interferon (IFN)-γ, and LPS-stimulated production of IL-6, IL-1β, and prostaglandin E2 (PGE2) by splenocytes were determined. Consumption of HFDs containing PNO resulted in significantly less weight gain (17% less, P < 0.001), and lower weight gain was mainly due to less white adipose tissue (18% less, P = 0.001). The reduction in weight gain did not result in the overall enhancement in splenocyte proliferation. Overall, PNO consumption resulted in a higher production of IL-1β (P = 0.04). Replacement of SBO with PNO had no effect on the production of IL-2, IFN-γ, IL-6, or PGE2 in mice fed with either the control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in mice fed with HFD, but this effect did not result in the overall improvement in immune responses. PMID:24133613

  16. Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats

    PubMed Central

    Adam, Clare L.; Gratz, Silvia W.; Peinado, Diana I.; Thomson, Lynn M.; Garden, Karen E.; Williams, Patricia A.; Richardson, Anthony J.; Ross, Alexander W.

    2016-01-01

    Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity. PMID:27224646

  17. Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats.

    PubMed

    Adam, Clare L; Gratz, Silvia W; Peinado, Diana I; Thomson, Lynn M; Garden, Karen E; Williams, Patricia A; Richardson, Anthony J; Ross, Alexander W

    2016-01-01

    Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity.

  18. Theaflavin Synthesized in a Selective, Domino-Type, One-Pot Enzymatic Biotransformation Method with Camellia sinensis Cell Culture Inhibits Weight Gain and Fat Accumulation to High-Fat Diet-Induced Obese Mice.

    PubMed

    Takemoto, Masumi; Takemoto, Hiroaki; Saijo, Ryoyasu

    2016-08-01

    The polyphenolic compound theaflavin, which is the main red pigment present in black tea, is reported to elicit various physiological effects. Because of the extremely low concentration of theaflavin present in black tea, its extraction from black tea leaves in quantities sufficient for use in medical studies has been difficult. We have developed a simple, inexpensive, selective, domino-type, one-pot enzymatic biotransformation method for the synthesis of theaflavin that is suitable for use in medical studies. Subsequent administration of this synthetic theaflavin to high-fat diet-induced obese mice inhibited both body weight gain and visceral fat accumulation, with no significant difference in the amount of faeces between the experimental and control mice.

  19. Maternal low protein diet-induced low birth weight in male, neonate Sprague-Dawley rats is mediated by altered brown adipose tissue thermogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT...

  20. Bone, body weight, and weight reduction: what are the concerns?

    PubMed

    Shapses, Sue A; Riedt, Claudia S

    2006-06-01

    Of the U.S. population, 65% is either overweight or obese, and weight loss is recommended to reduce co-morbid conditions. However, bone mobilization and loss may also occur with weight loss. The risk for bone loss depends on initial body weight, age, gender, physical activity, and conditions of dieting such as the extent of energy restriction and specific levels of nutrient intake. Older populations are more prone to bone loss with weight loss; in women, this is due at least in part to a reduced dietary Ca intake and/or efficiency of absorption. Potential hormonal mechanisms regulating bone loss during weight loss are discussed, including decreases in estrogen, leptin, glucagon-like peptide-2, growth hormone, and insulin-like growth factor-1, or an increase in cortisol. In contrast, the rise in adiponectin and ghrelin with weight reduction should not be detrimental to bone. Combining energy restriction with exercise does not necessarily prevent bone loss, but may attenuate loss as was shown with additional Ca intake or osteoporosis medications. Future controlled weight loss trials should be designed to further address mechanisms influencing the density and quality of bone sites vulnerable to fracture, in the prevention of osteoporosis. PMID:16702302

  1. Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

    PubMed

    Cyr, Nicole E; Steger, Jennifer S; Toorie, Anika M; Yang, Jonathan Z; Stuart, Ronald; Nillni, Eduardo A

    2015-03-01

    In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of hypothalamic Sirt1 in body weight and energy balance regulation is debated. The first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague-Dawley rats. Central inhibition of Sirt1 decreased body weight and food intake as a result of a forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which in turn increased phosphorylated FoxO1 via improved insulin/phosphorylated AKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-melanocyte-stimulating hormone (α-MSH) maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (triiodothyronine, thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

  2. Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

    PubMed

    Cyr, Nicole E; Steger, Jennifer S; Toorie, Anika M; Yang, Jonathan Z; Stuart, Ronald; Nillni, Eduardo A

    2014-07-01

    In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of Sirt1 in the brain, particularly the hypothalamus, in body weight and energy balance regulation is debated. Among the first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague Dawley rats. In that study, central inhibition of Sirt1 decreased body weight and food intake as a result of a Forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which, in turn, increased phosphorylated FoxO1 via improved insulin/pAKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-MSH maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

  3. Spexin is a Novel Human Peptide that Reduces Adipocyte Uptake of Long Chain Fatty Acids and Causes Weight Loss in Rodents with Diet-induced Obesity*

    PubMed Central

    Walewski, José L.; Ge, Fengxia; Lobdell, Harrison; Levin, Nancy; Schwartz, Gary J.; Vasselli, Joseph; Pomp, Afons; Dakin, Gregory; Berk, Paul D.

    2014-01-01

    Objective Microarray studies identified Ch12:orf39 (Spexin) as the most dysregulated gene in obese human fat. Therefore we examined its role in obesity pathogenesis. Design and Methods Spexin effects on food intake, meal patterns, body weight, Respiratory Exchange Ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with dietary-induced obesity (DIO). Its effects on adipocyte [3H]-oleate uptake were determined. Results In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = −0.797) with Leptin. In rats, Spexin (35 μg/kg/day s.c) reduced caloric intake ~32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 μg/kg/day i.p.) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70μg/kg/day i.p.) demonstrated no aversive Spexin effects. Conclusions Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy. PMID:24550067

  4. Weight Stigma Reduction and Genetic Determinism

    PubMed Central

    Hilbert, Anja

    2016-01-01

    One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of—and responsibility for—obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention’s gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity. PMID:27631384

  5. Weight Stigma Reduction and Genetic Determinism.

    PubMed

    Hilbert, Anja

    2016-01-01

    One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of-and responsibility for-obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention's gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity. PMID:27631384

  6. Circadian variation of diet-induced thermogenesis.

    PubMed

    Romon, M; Edme, J L; Boulenguez, C; Lescroart, J L; Frimat, P

    1993-04-01

    The objective of this study was to assess a circadian variation of diet-induced thermogenesis (DIT) that could favor weight gain among night workers used to eating a night time snack. Nine young men were given the same mean at 0900, 1700, or 0100. Energy expenditure was measured by indirect calorimetry 1 h before and during the 6 h after the snack. DIT was calculated as the 3 h of energy expenditure above basal metabolic rate. Morning DIT was significantly higher than afternoon DIT (P = 0.04) and night DIT (P = 0.002). Afternoon DIT was higher than night DIT (P = 0.06). We conclude that the time when a meal is consumed affects the thermogenic response and must be considered in the energy balance.

  7. Simple noise reduction for diffusion weighted images.

    PubMed

    Konishi, Yuto; Kanazawa, Yuki; Usuda, Takatoshi; Matsumoto, Yuki; Hayashi, Hiroaki; Matsuda, Tsuyoshi; Ueno, Junji; Harada, Masafumi

    2016-07-01

    Our purpose in this study was to reduce the noise in order to improve the SNR of Dw images with high b-value by using two correction schemes. This study was performed with use of phantoms made from water and sucrose at different concentrations, which were 10, 30, and 50 weight percent (wt%). In noise reduction for Dw imaging of the phantoms, we compared two correction schemes that are based on the Rician distribution and the Gaussian distribution. The highest error values for each concentration with use of the Rician distribution scheme were 7.3 % for 10 wt%, 2.4 % for 30 wt%, and 0.1 % for 50 wt%. The highest error values for each concentration with use of the Gaussian distribution scheme were 20.3 % for 10 wt%, 11.6 % for 30 wt%, and 3.4 % for 50 wt%. In Dw imaging, the noise reduction makes it possible to apply the correction scheme of Rician distribution. PMID:26984734

  8. Lymphotoxin regulates commensal responses to enable diet-induced obesity.

    PubMed

    Upadhyay, Vaibhav; Poroyko, Valeriy; Kim, Tae-jin; Devkota, Suzanne; Fu, Sherry; Liu, Donald; Tumanov, Alexei V; Koroleva, Ekaterina P; Deng, Liufu; Nagler, Cathryn; Chang, Eugene B; Tang, Hong; Fu, Yang-Xin

    2012-10-01

    Microbiota are essential for weight gain in mouse models of diet-induced obesity (DIO), but the pathways that cause the microbiota to induce weight gain are unknown. We report that mice deficient in lymphotoxin, a key molecule in gut immunity, were resistant to DIO. Ltbr(-/-) mice had different microbial community composition compared to their heterozygous littermates, including an overgrowth of segmented filamentous bacteria (SFB). Furthermore, cecal transplantation conferred leanness to germ-free recipients. Housing Ltbr(-/-) mice with their obese siblings rescued weight gain in Ltbr(-/-) mice, demonstrating the communicability of the obese phenotype. Ltbr(-/-) mice lacked interleukin 23 (IL-23) and IL-22, which can regulate SFB. Mice deficient in these pathways also resisted DIO, demonstrating that intact mucosal immunity guides diet-induced changes to the microbiota to enable obesity.

  9. Empagliflozin Protects against Diet-Induced NLRP-3 Inflammasome Activation and Lipid Accumulation.

    PubMed

    Benetti, Elisa; Mastrocola, Raffaella; Vitarelli, Giovanna; Cutrin, Juan Carlos; Nigro, Debora; Chiazza, Fausto; Mayoux, Eric; Collino, Massimo; Fantozzi, Roberto

    2016-10-01

    The aim of this study was to evaluate the effects of chronic treatment with empagliflozin, a potent and selective sodium glucose cotransporter-2 inhibitor, in a murine model of diet-induced obesity and insulin resistance, focusing on drug effects on body weight reduction and nucleotide-binding domain, leucine-rich repeat containing protein (NLRP)-3 inflammasome activation, which have never been investigated to date. Male C57BL/6 mice were fed control or a high fat-high sugar (HFHS) diet for 4 months. Over the last 2 months, subsets of animals were treated with empagliflozin (1-10 mg/kg) added to the diet. Empagliflozin evoked body weight reduction (P < 0.001 for the highest dose) and positive effects on fasting glycemia and homeostasis model assessment of insulin resistance. In addition, the drug was able to reduce renal tubular damage and liver triglycerides level in a dose-dependent manner. Interestingly, empagliflozin also decreased cardiac lipid accumulation. Moreover, diet-induced activation of NLRP-3 in kidney and liver (not observed in the heart) was dose-dependently attenuated by empagliflozin. Our results clearly demonstrate the ability of empagliflozin to counteract the deleterious effects evoked by chronic exposure to HFHS diet. Most notably, empagliflozin treatment was associated with NLRP-3 inflammasome signaling modulation, suggesting that this inhibition may contribute to the drug therapeutic effects. PMID:27440421

  10. Predictors of weight reduction in obese children.

    PubMed

    Nuutinen, O; Knip, M

    1992-11-01

    The characteristics of successful and unsuccessful weight losers were studied in 48 obese children (relative weight > 120%) aged 6-15 years who were treated for 1 year and observed for another. Successful weight loss was defined as a decrease in relative weight of > or = 0.8 in the standard deviation score (SDS) at the end of the study. Thirty-two children were treated intensively, 16 with individual counselling and 16 in group therapy, while the remaining 16 children were treated conventionally in a school health care setting. Three children dropped out of the study. In 2 years, the relative body weight decreased by 1.7 SDS in those who were successful weight losers (n = 21, 47%), but remained unchanged in those who had been unsuccessful (n = 24). At baseline there were no differences between the two groups. At 1 year, the successful weight losers had lower body weight (P < 0.05), less lean body mass (0.05) and lower fasting concentrations of circulating insulin (P < 0.01) than the unsuccessful children did. A decrease in mothers' body mass index (BMI) and in documented energy intake over the first year as well as energy intake at 1 year were significant predictors of success at 2 years. The combination of these three predictors resulted in correct classification of about 3/4 of the cases as successful or unsuccessful weight losers. It appears, however, difficult to develop a clinically useful model for predicting the treatment outcome in obese children.

  11. Further weight reduction of applications in long glass reinforced polymers

    NASA Astrophysics Data System (ADS)

    Yanev, A.; Schijve, W.; Martin, C.; Brands, D.

    2014-05-01

    Long glass reinforced materials are broadly used in the automotive industry due to their good mechanical performance, competitive price and options for functional integration in order to reduce weight. With rapidly changing environmental requirements, a demand for further weight reduction is growing constantly. Designs in LGF-PP can bring light weight solutions in combination with system cost improvement. There are quite some possibilities for applying weight reduction technologies nowadays. These technologies have to be evaluated based on weight reduction potential, but also on mechanical performance of the end application, where the latter is often the key to success. Different weight reduction technologies are applied to SABIC®STAMAX{trade mark, serif} material, a long glass fiber reinforced polypropylene (LGF-PP), in order to investigate and define best application performance. These techniques include: chemical foaming, physical foaming and thin wall applications. Results from this research will be presented, giving a guideline for your development.

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

    PubMed Central

    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. PMID:26977813

  13. 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.

  14. 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. PMID:26977813

  15. Cannabis exposure associated with weight reduction and β-cell protection in an obese rat model.

    PubMed

    Levendal, R-A; Schumann, D; Donath, M; Frost, C L

    2012-05-15

    The aim of this study was to investigate the effect of an organic cannabis extract on β-cell secretory function in an in vivo diet-induced obese rat model and determine the associated molecular changes within pancreatic tissue. Diet-induced obese Wistar rats and rats fed on standard pellets were subcutaneously injected with an organic cannabis extract or the vehicle over a 28-day period. The effect of diet and treatment was evaluated using the intraperitoneal glucose tolerance tests (IPGTTs) and qPCR analysis on rat pancreata harvested upon termination of the experiment. The cafeteria diet induced an average weight difference of 32g and an overall increase in body weight in the experimental groups occurred at a significantly slower rate than the control groups, irrespective of diet. Area under the curve for glucose (AUC(g)) in the obese group was significantly lower compared to the lean group (p<0.001), with cannabis treatment significantly reducing the AUC(g) in the lean group (p<0.05), and remained unchanged in the obese group, relative to the obese control group. qPCR analysis showed that the cafeteria diet induced down-regulation of the following genes in the obese control group, relative to lean controls: UCP2, c-MYC and FLIP. Cannabis treatment in the obese group resulted in up-regulation of CB1, GLUT2, UCP2 and PKB, relative to the obese control group, while c-MYC levels were down-regulated, relative to the lean control group. Treatment did not significantly change gene expression in the lean group. These results suggest that the cannabis extract protects pancreatic islets against the negative effects of obesity. PMID:22421529

  16. Method of glitch reduction in DAC with weight redundancy

    NASA Astrophysics Data System (ADS)

    Azarov, Olexiy D.; Murashchenko, Olexander G.; Chernyak, Olexander I.; Smolarz, Andrzej; Kashaganova, Gulzhan

    2015-12-01

    The appearance of glitches in digital-to-analog converters leads to significant limitations of conversion accuracy and speed, which is critical for DAC and limits their usage. This paper researches the possibility of using the redundant positional number system in order to reduce glitches in DAC. There had been described the usage pattern of number systems with fractional digit weights of bits as well as with the whole number weights of bits. Hereafter there had been suggested the algorithm for glitches reduction in the DAC generation mode of incessant analogue signal. There had also been estimated the efficiency of weight redundancy application with further presentation of the most efficient parameters of number systems. The paper describes a block diagram of a low-glitch DAC based on Fibonacci codes. The simulation results prove the feasibility of weight redundancy application and show a significant reduction of glitches in DAC in comparison with the classical binary system.

  17. Effects of aspartame in young persons during weight reduction.

    PubMed

    Knopp, R H; Brandt, K; Arky, R A

    1976-11-01

    Given the potential use of a low-calorie sweetener during weight reduction, a toxicity study of chronic aspartame ingestion was conducted. Particular attention was given to possible long-term effects of aspartame on the fuel hormonal alterations characteristically caused by weight reduction. As a group mean age was 19.3 yr, body weight was 164.6 lb, and mean height was 65.4 in. Subjects were an average of 33% in excess of ideal body weight. The aspartame dose was 2.7 g/day and was compared on a double-blind randomized basis with a lactose placebo. Both materials were given in gelatin capsules. An average of 6.9 +/- 1.5 lb was lost by the aspartame group during the 13-wk study on a calculated 1,000-calorie diet. The placebo group lost 4.5 +/- 1.2 lb (no significant difference between the two groups). After an overnight fast, reductions in glucose and immunoreactive insulin were seen in both groups, while rising trends in immunoreactive glucagon were observed. These changes are all characteristic of calorie restriction. In no instance was there a detectable effect of the ingested aspartame. No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol, nor on any other parameter of hematologic, hepatic, or renal function that was measured. Similarly, side effects were equally distributed between asparatame and placebo.

  18. Charting of daily weight pattern reinforces maintenance of weight reduction in moderately obese patients.

    PubMed

    Fujimoto, K; Sakata, T; Etou, H; Fukagawa, K; Ookuma, K; Terada, K; Kurata, K

    1992-03-01

    To maintain reduced body weight by behavioral therapy in moderately obese patients, body weight was measured four times daily and charted in a weekly graph. Seventy-two female patients with simple obesity were divided into two groups: 55 patients with appliance of charting of weight pattern (group-I), and 17 patients without the charting (group-II). The percentage of patients followed for 2 years was different between group-I (87%) and group-II (65%) during 2 years after completion of weight reduction therapy interviews (p less than 0.05). Forty-eight of group-I patients succeeded in decreasing their weight by 15.2 +/- 1.5 (mean +/- SEM) kg during the 6.5 +/- 0.8 months of the therapy interviews. They were followed up for 3.8 years with no rebound weight gain. Eleven patients in group-II also succeeded in decreasing their weight by 16.8 +/- 1.9 kg during 7.8 +/- 1.3 months but their body weight rebounded by 9.0 kg during the 2-year followup period. Twelve of 15 male patients with weight charting maintained reduced weight during 4.3 years. It was easier and more effective for obese patients to maintain weight graphs for the longer period than to record no weight graphs. Obese patients could themselves monitor irregular weight patterns produced by overeating and correct the irregularities in food intake and daily lifestyles. This seems to explain why the illustration of daily fluctuations of weight measurements was useful for long-term maintenance of weight reduction.

  19. Wispy Prosthesis: A Novel Method in Denture Weight Reduction

    PubMed Central

    Anne, Gopinadh; Budeti, Sreedevi; Anche, Sampath Kumar; Zakkula, Srujana; Atla, Jyothi; Jyothula, Ravi Rakesh Dev; Peddinti, Vijaya Kumar

    2016-01-01

    Introduction Stability and retention of the denture becomes at stake with the increase in weight of the denture prosthesis. As a consequence, different materials and methods have been introduced to overcome these issues but denture weight reduction still remains to be a cumbersome and strenuous procedure. Aim To introduce a novel technique for the fabrication of denture prosthesis where in the weight of the denture will not affect the retention and stability of the denture. Materials and Methods Four groups with a sample size of 10 each, were included where in one group was control and other three were study groups. The control group samples were made completely solid and the study group samples were packed with materials like bean balls, cellulose balls and polyacrylic fibers. The weight of all the samples of each study group was measured and compared with the control group. The observations were analyzed statistically by paired t-test. Results It was observed that the bean balls group produced a weight reduction of 31.3%, cellulose balls group 27.4% and polyacrylic fibers group 24.5% when compared to that of the control group. Conclusion This novel technique will eliminate the problems that were associated in creating hollowness and at the same time will reduce the weight of the prosthesis and among all the study groups, bean balls group were found to reduce maximum weight of the prosthesis. PMID:27190947

  20. Arterial stiffening precedes systolic hypertension in diet-induced obesity.

    PubMed

    Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

    2013-12-01

    Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

  1. Diet-induced hypercholesterolaemia in the rabbit.

    PubMed

    Ivanov, A S; Torkhovskaya, T I; Khalilov, E M; Archakov, A I

    1991-01-01

    Intraspecies variation in diet-induced hypercholesterolaemia in rabbits, simulating atherosclerosis, was studied. The chinchilla rabbit population examined contained several subpopulations, as indicated by polymodal forms of histograms of plasma cholesterol levels. This finding indicates that the inclusion of subpopulations in an investigation can lead to erroneous conclusions, and that subpopulations should be identified before such work is undertaken. The relationship between the molar cholesterol/phospholipid ratio in rabbit erythrocyte membranes and the plasma cholesterol level in experimental atherosclerosis was also studied. A correlation was evident only over the range of 1-5 g cholesterol per litre of plasma. PMID:1751762

  2. A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice

    PubMed Central

    Rössger, Katrin; Charpin-El-Hamri, Ghislaine; Fussenegger, Martin

    2013-01-01

    Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly monitors blood fatty acid levels in the setting of diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of the peroxisome proliferator-activated receptor-α onto the phloretin-responsive repressor TtgR produces a synthetic intracellular lipid-sensing receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a fatty acid-adjustable manner. Mice with diet-induced obesity in which microencapsulated cells engineered for LSR-driven expression of pramlintide are implanted show significant reduction in food consumption, blood lipid levels and body weight when put on a high-fat diet. Therapeutic designer circuits that monitor levels of pathologic metabolites and link these with the tailored expression of protein pharmaceuticals may provide new opportunities for the treatment of metabolic disorders. PMID:24281397

  3. Diet-induced obese mice retain endogenous leptin action.

    PubMed

    Ottaway, Nickki; Mahbod, Parinaz; Rivero, Belen; Norman, Lee Ann; Gertler, Arieh; D'Alessio, David A; Perez-Tilve, Diego

    2015-06-01

    Obesity is characterized by hyperleptinemia and decreased response to exogenous leptin. This has been widely attributed to the development of leptin resistance, a state of impaired leptin signaling proposed to contribute to the development and persistence of obesity. To directly determine endogenous leptin activity in obesity, we treated lean and obese mice with a leptin receptor antagonist. The antagonist increased feeding and body weight (BW) in lean mice, but not in obese models of leptin, leptin receptor, or melanocortin-4 receptor deficiency. In contrast, the antagonist increased feeding and BW comparably in lean and diet-induced obese (DIO) mice, an increase associated with decreased hypothalamic expression of Socs3, a primary target of leptin. These findings demonstrate that hyperleptinemic DIO mice retain leptin suppression of feeding comparable to lean mice and counter the view that resistance to endogenous leptin contributes to the persistence of DIO in mice.

  4. Constraint optimized weight adaptation for Gaussian mixture reduction

    NASA Astrophysics Data System (ADS)

    Chen, H. D.; Chang, K. C.; Smith, Chris

    2010-04-01

    Gaussian mixture model (GMM) has been used in many applications for dynamic state estimation such as target tracking or distributed fusion. However, the number of components in the mixture distribution tends to grow rapidly when multiple GMMs are combined. In order to keep the computational complexity bounded, it is necessary to approximate a Gaussian mixture by one with reduced number of components. Gaussian mixture reduction is traditionally conducted by recursively selecting two components that appear to be most similar to each other and merging them. Different definitions on similarity measure have been used in literature. For the case of one-dimensional Gaussian mixtures, Kmeans algorithms and some variations are recently proposed to cluster Gaussian mixture components in groups, use a center component to represent all in each group, readjust parameters in the center components, and finally perform weight optimization. In this paper, we focus on multi-dimensional Gaussian mixture models. With a variety of reduction algorithms and possible combinations, we developed a hybrid algorithm with constraint optimized weight adaptation to minimize the integrated squared error (ISE). In additions, with extensive simulations, we showed that the proposed algorithm provides an efficient and effective Gaussian mixture reduction performance in various random scenarios.

  5. Metabolic effects of very low calorie weight reduction diets.

    PubMed Central

    Hoffer, L J; Bistrian, B R; Young, V R; Blackburn, G L; Matthews, D E

    1984-01-01

    A randomized comparison trial of two very low calorie weight reduction diets was carried out for 5 or 8 wk in 17 healthy obese women. One diet provided 1.5 g protein/kg ideal body weight; the other provided 0.8 g protein/kg ideal body weight plus 0.7 g carbohydrate/kg ideal body weight. The diets were isocaloric (500 kcal). Amino acid metabolism was studied by means of tracer infusions of L-[1-13C]leucine and L-[15N]alanine. After 3 wk of adaptation to the diets, nitrogen balance was zero for the 1.5 g protein diet but -2 g N/d for the 0.8 g protein diet. Postabsorptive plasma leucine and alanine flux decreased from base line by an equal extent with both diets by approximately 20 and 40%, respectively. It was concluded that protein intakes at the level of the recommended dietary allowance (0.8 g/kg) are not compatible with nitrogen equilibrium when the energy intake is severely restricted, and that nitrogen balance is improved by increasing the protein intake above that level. Basal rates of whole body nitrogen turnover are relatively well maintained, compared with total fasting, at both protein intakes. However, turnover in the peripheral compartment, as evidenced by alanine flux, may be markedly diminished with either diet. PMID:6707202

  6. Appetite suppression and weight reduction by a centrally active aminosterol.

    PubMed

    Ahima, Rexford S; Patel, Hiralben R; Takahashi, Nobuhiko; Qi, Yong; Hileman, Stanley M; Zasloff, Michael A

    2002-07-01

    The rise in obesity and its complications has generated enormous interest in the regulation of feeding and body weight. We show that a spermine metabolite of cholesterol (MSI-1436) decreases body weight, specifically fat, by suppressing feeding and preventing the reduction in energy expenditure, hormonal changes, and patterns of neuropeptide expression normally associated with weight loss. MSI-1436 enters the brain after peripheral injection and is more potent when injected into the cerebral ventricle (intracerebroventricular [ICV]). Systemic or ICV MSI-1436 administration induced similar patterns of Fos immunoreactivity in the brain, especially the paraventricular hypothalamic nucleus (PVN). This brain region integrates neural signals from hypothalamic and brain stem nuclei and regulates feeding behavior, autonomic function, and neuroendocrine function. Microinjection of MSI-1436 into the PVN potently suppressed feeding and reduced body weight for several days. Unlike caloric restriction, MSI-1436 decreased mRNA levels of agouti-related peptide and neuropeptide Y in the hypothalamus. These findings indicate that MSI-1436 acts in the brain to regulate food intake and energy expenditure, likely through suppression of orexigenic hypothalamic pathways. PMID:12086938

  7. Combinatorial gene construct and non-viral delivery for anti-obesity in diet-induced obese mice.

    PubMed

    Park, Hongsuk; Cho, Sungpil; Han, Yong Hwan; Janat-Amsbury, Margit M; Boudina, Sihem; Bae, You Han

    2015-06-10

    The combinatorial peptidergic therapy of islet amyloid polypeptide (IAPP) and leptin (LEP) analogues was once an optimistic option in treating obese animals and patients. However, the need for frequent administrations and its negative side effects prevent it from being a viable choice. Here, we developed a combinatorial gene therapy of IAPP and LEP, where two genes are inserted into a single plasmid with self-cleaving furin and 2A sites to treat diet-induced obese (DIO) mice. The developed plasmid DNA (pDNA) individually produced both IAPP and LEP peptides in vitro and in vivo. The pDNA was delivered with a non-viral polymeric carrier, and its once-a-week administrations demonstrated a synergistic loss of body weight and significant reductions of fat mass, blood glucose, and lipid levels in DIO mice. The results suggest that the combinatorial gene therapy would have higher potential than the peptidergic approach for future translation due to its improved practicability.

  8. Tocotrienols and Whey Protein Isolates Substantially Increase Exercise Endurance Capacity in Diet -Induced Obese Male Sprague-Dawley Rats

    PubMed Central

    Aguila, Jay; McConell, Glenn K.; McAinch, Andrew J.; Mathai, Michael L.

    2016-01-01

    Background and Aims Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. Methods Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9), TCT (n = 9), WPI (n = 8) or TCT + WPI (n = 9) and placed on a high-fat diet (40% of energy from fat) for 10 weeks. Animals received 50mg/kg body weight and 8% of total energy intake per day of TCTs and/or WPIs respectively. Food intake, body composition, glucose tolerance, insulin sensitivity, exercise capacity, skeletal muscle glycogen content and oxidative enzyme activity were determined. Results Both TCT and WPI groups ran >50% longer (2271 ± 185m and 2195 ± 265m respectively) than the Control group (1428 ± 139m) during the run to exhaustion test (P<0.05), TCT + WPI did not further improve exercise endurance (2068 ± 104m). WPIs increased the maximum in vitro activity of beta-hydroxyacyl-CoA in the soleus muscle (P<0.05 vs. Control) but not in the plantaris. Citrate synthase activity was not different between groups. Neither supplement had any effect on weight gain, adiposity, glucose tolerance or insulin sensitivity. Conclusion Ten weeks of both TCTs and WPIs increased exercise endurance by 50% in sedentary, diet-induced obese rats. These positive effects of TCTs and WPIs were independent of body weight, adiposity or glucose tolerance. PMID:27058737

  9. Utilizing the Health Belief Model to predicting female middle school students' behavioral intention of weight reduction by weight status

    PubMed Central

    2011-01-01

    Weight reduction behavior is common among adolescent girls. The present study examined the status of weight reduction behavior and factors affecting the behavioral intention of weight reduction using the Health Belief Model (HBM) for female middle school students by weight category. Survey data was collected from three girl's middle schools in Gyeongju, Korea. A total of 299 female middle school students participated in this study. The questionnaire had questions about general characteristics, weight reduction behavior, and variables of HBM (perceived threat, perceived benefits, perceived barriers, cues to action, self-efficacy in dietary life and exercise, and behavioral intention of weight reduction). Descriptive statistics, Chi-square tests, ANOVA, and multiple regression analysis were applied to analyze the variables. A higher percentage of students in the overweight group attempted weight reduction than those in the underweight and the normal weight groups (P < 0.001). Among students who had attempted weight reduction, 73% tried diet therapy, while 78% tried exercise. Students in the normal and overweight groups showed significantly higher threat (P < 0.01) and cues to action (P < 0.001) than those in the underweight group. As for perceived benefits, barriers, and self-efficacy in dietary life and exercise, there were no significant differences among weight groups. Students in the overweight group showed the strongest intention of weight reduction and there were significant differences among the three weight groups (P < 0.001). Perceive threat (P < 0.01), cues to action (P < 0.001), and perceived self-efficacy (P < 0.01) were significantly associated to behavioral intention of weight reduction for all respondents. For the underweight group, perceived threat (P < 0.05) and perceived self-efficacy (P < 0.01) were the significant variables. For the overweight group, cue to action was the significant variable (P < 0.05). PMID:21994529

  10. Biodrying for municipal solid waste: volume and weight reduction.

    PubMed

    Bilgin, Melayib; Tulun, Şevket

    2015-01-01

    Biodrying is a variation of aerobic decomposition used for the mechanical-biological treatment organic substances to dry and partially stabilize residual municipal waste. This study focuses on the volume and weight reduction biodegradation of the biodrying process using municipal solid waste and the appearance of a stable, final product. The materials were placed in a reactor with invariant airflow rates of 50 L/h and initial moisture contents of 48.49-50.00%. The laboratory-scale experiments were implemented using a 36-L biodrying reactor equipped with an air supply system, a biomass temperature sensor and air sensors. To determine the effect of temperature on biodrying, the process was repeated at various temperatures between 30 °C and 50 °C. The results obtained indicated that after 13 days, biodrying reduced the volume content of waste by 32% and the final product had a high calorific value (4680 kcal/kg).

  11. Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model

    PubMed Central

    Baek, Hye Kyung; Shim, Hyeji; Lim, Hyunmook; Shim, Minju; Kim, Chul-Kyu; Park, Sang-Kyu; Lee, Yong Seok; Song, Ki-Duk; Kim, Sung-Jo

    2015-01-01

    Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipogenic effects of AA in animal models have not yet been investigated. Therefore, we conducted daily oral administration with AA water extract in a diet-induced obesity animal model and treated 3T3-L1 cells with AA to confirm the anti-adipogenic effects in the related protein expressions. We then evaluated the physiology, adipose tissue histology and mRNA expressions of many related genes. Inhibition of adipogenesis by the AA water extract was observed in vitro. In the animal model, weight gain was significantly lower in the AA treated group, but there were no changes in food intake volume or calories. Reductions in lipid droplet size and mRNA expression associated with adipogenesis were also observed in animal epididymal fat. This study is the first to report that AA has an anti-obese effects in vivo. PMID:26243598

  12. AHNAK KO mice are protected from diet-induced obesity but are glucose intolerant.

    PubMed

    Ramdas, M; Harel, C; Armoni, M; Karnieli, E

    2015-04-01

    AHNAK is a 700 KD phosphoprotein primarily involved in calcium signaling in various cell types and regulating cytoskeletal organization and cell membrane architecture. AHNAK expression has also been associated with obesity. To investigate the role of AHNAK in regulating metabolic homeostasis, we studied whole body AHNAK knockout mice (KO) on either regular chow or high-fat diet (HFD). KO mice had a leaner phenotype and were resistant to high-fat diet-induced obesity (DIO), as reflected by a reduction in adipose tissue mass in conjunction with higher lean mass compared to wild-type controls (WT). However, KO mice exhibited higher fasting glucose levels, impaired glucose tolerance, and diminished serum insulin levels on either diet. Concomitantly, KO mice on HFD displayed defects in insulin signaling, as evident from reduced Akt phosphorylation and decreased cellular glucose transporter (Glut4) levels. Glucose intolerance and insulin resistance were also associated with changes in expression of genes regulating fat, glucose, and energy metabolism in adipose tissue and liver. Taken together, these data demonstrate that (a) AHNAK is involved in glucose homeostasis and weight balance (b) under normal feeding KO mice are insulin sensitive yet insulin deficient; and (c) AHNAK deletion protects against HFD-induced obesity, but not against HFD-induced insulin resistance and glucose intolerance in vivo.

  13. Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model.

    PubMed

    Baek, Hye Kyung; Shim, Hyeji; Lim, Hyunmook; Shim, Minju; Kim, Chul-Kyu; Park, Sang-Kyu; Lee, Yong Seok; Song, Ki-Duk; Kim, Sung-Jo; Yi, Sun Shin

    2015-01-01

    Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipogenic effects of AA in animal models have not yet been investigated. Therefore, we conducted daily oral administration with AA water extract in a diet-induced obesity animal model and treated 3T3-L1 cells with AA to confirm the anti-adipogenic effects in the related protein expressions. We then evaluated the physiology, adipose tissue histology and mRNA expressions of many related genes. Inhibition of adipogenesis by the AA water extract was observed in vitro. In the animal model, weight gain was significantly lower in the AA treated group, but there were no changes in food intake volume or calories. Reductions in lipid droplet size and mRNA expression associated with adipogenesis were also observed in animal epididymal fat. This study is the first to report that AA has an anti-obese effects in vivo. PMID:26243598

  14. Vitis thunbergii var. taiwaniana Extracts and Purified Compounds Ameliorate Obesity in High-Fat Diet-Induced Obese Mice.

    PubMed

    Lin, Shyr-Yi; Huang, Guan-Cheng; Hsieh, Ying-Ying; Lin, Yin-Shiou; Han, Chuan-Hsiao; Wen, Chi-Luan; Chang, Chi-I; Hou, Wen-Chi

    2015-10-28

    The increasing prevalence of obesity continues to gain more attention worldwide. In this study, diet-induced obese mice were used to evaluate the antiobesity effects of extracts, fractions, and purified compounds from Vitis thunbergii var. taiwaniana (VTT). The C57BL/6J mice were fed a 5-week high-fat diet (HF) concurrently with ethanol extracts (Et-ext, 80 mg/kg) from roots (R), stems (S), and leaves (L) by oral gavage daily. Only R-Et-ext interventions showed significant weight reduction in mice compared with those in the HF group; however, mouse plasma contents of total cholesterols (TC), total triglycerides (TG) and low-density lipoproteins (LDL) of all three Et-ext intervened groups showed significant reductions compared with those in the HF group. Furthermore, intervention with the ethyl acetate-partitioned fraction (EA-fra, 60 mg/kg) from R-Et-ext but not the n-butanol-partitioned fraction or water fraction from R-Et-ext showed significant weight reduction in mice compared with those in the HF group. The same molecular weights of three resveratrol tetramers, (+)-hopeaphenol, (+)-vitisin A, and (-)-vitisin B, were isolated from the EA-fra of VTT-R. The (+)-vitisin A and fenofibrate (25 mg/kg) but not the (+)-hopeaphenol and (-)-vitisin B interventions showed significant weight reduction in mice compared with those in the HF group. The total feed intake among the HF groups with or without interventions showed no significant differences. The mouse plasma contents of TC, TG, LDL, free fatty acid, and plasma lipase activity of the three resveratrol tetramer-intervened groups showed reductions in the mice compared with those in the HF group. It was proposed that the lipase inhibitory activities of VTT extracts and purified resveratrol tetramers might contribute in part to the antiobesity effect, and these results suggested that VTT may be developed as functional food for achieving antiobesity objectives and requires further investigation.

  15. Reductions with lithium in low molecular weight amines and ethylenediamine

    PubMed

    Garst; Dolby; Esfandiari; Fedoruk; Chamberlain; Avey

    2000-10-20

    Reductions of several types of compounds with lithium and ethylenediamine using low molecular weight amines as solvent are described. In all cases 1 mol of ethylenediamine or N, N'-dimethylethylenediamine per gram-atom of lithium was used. In some cases it was beneficial to add an alcohol as a proton donor. These reaction conditions were applied to the debenzylation of N-benzylamide and lactams which are refractory to hydrogenolysis with hydrogen and a catalyst. N-Benzylpilolactam 2, synthesized from pilocarpine hydrochloride in refluxing benzylamine, was debenzylated in good yield using 10 gram-atoms of lithium per mole (10 Li/mol) of 2 in n-propylamine. The debenzylation of N-benzyl-N-methyldecanoic acid amide, 4 (6 Li/mol), in t-butylamine/N, N'-dimethylethylenediamine gave N-methyldecanoic acid amide 6 in 70% yield. Alternatively, reduction of 4 (7 Li/mol) in t-butanol/n-propylamine/ethylenediamine gave n-decanal 12 in 36% yield. Using the same conditions, thioanisole, 1-adamantane-p-toluenesulfonamide, and 1-adamantane methyl p-toluenesulfonate were reduced with 3, 7, and 7.2 Li/mol of compound to give thiophenol (74%), adamantamine (91%), and 1-adamantane methanol (75%), respectively. In this solvent system naphthalene and 3-methyl-2-cyclohexene-1-one were reduced to isotetralin (74%) and 3-methyl cyclohexanone (quantitative) with 5 and 2.2 Li/mol of starting compound, respectively. Oximes and O-methyloximes were reduced to their corresponding amines using 5 and 8 Li/mol of compound, respectively. Anisole was also reduced to 1-methoxy-1,4-cyclohexadiene with 2.5 Li/mol of anisole. Undecanenitrile was reduced to undecylamine with 8.6 Li/mol. Additionally, a base-catalyzed formation of imidazolines from a nitrile and ethylenediamine was also explored.

  16. Transgenerational changes of metabolic phenotypes in two selectively bred mouse colonies for different susceptibilities to diet-induced glucose intolerance.

    PubMed

    Nagao, Mototsugu; Asai, Akira; Sugihara, Hitoshi; Oikawa, Shinichi

    2015-01-01

    We recently established 2 mouse lines with different susceptibilities (prone and resistant) to high-fat diet (HFD)-induced glucose intolerance by selective breeding (designated selectively bred diet-induced glucose intolerance-prone [SDG-P] and -resistant [SDG-R], respectively). In the present study, we analyzed transgenerational changes in metabolic phenotypes in these 2 mouse colonies to explore how the distinct phenotypes have emerged through the repetitive selection. Using C57BL/6, C3H, and AKR as background strains, mice showing inferior and superior glucose tolerance after HFD feeding were selected and bred repetitively over 20 generations to produce SDG-P and SDG-R, respectively. In addition to the blood glucose levels, HFD intake and body weight were also measured over the selective breeding period. As the generations proceeded, SDG-P mice became more susceptible to HFD-induced glucose intolerance and body weight gain, whereas SDG-R mice had gradually reduced HFD intake. The differences in fasting and post-glucose challenge blood glucose levels, body weight, and HFD intake became more evident between the 2 colonies through the selective breeding, mainly due to the HFD-induced glucose metabolism impairment and body weight gain in SDG-P mice and the reduction of HFD intake in SDG-R mice. These transgenerational changes in the metabolic phenotypes suggest that the genetic loci associated with the quantitative traits have been selectively enriched in SDG-P and SDG-R.

  17. High-fat diet-induced reduction of peroxisome proliferator-activated receptor-γ coactivator-1α messenger RNA levels and oxidative capacity in the soleus muscle of rats with metabolic syndrome.

    PubMed

    Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

    2012-02-01

    Animal models of type 2 diabetes exhibit reduced peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) messenger RNA (mRNA) levels, which are associated with decreased oxidative capacity, in skeletal muscles. In contrast, animal models with metabolic syndrome show normal PGC-1α mRNA levels. We hypothesized that a high-fat diet decreases PGC-1α mRNA levels in skeletal muscles of rats with metabolic syndrome, reducing muscle oxidative capacity and accelerating metabolic syndrome or inducing type 2 diabetes. We examined mRNA levels and fiber profiles in the soleus muscles of rats with metabolic syndrome (SHR/NDmcr-cp [cp/cp]; CP) fed a high-fat diet. Five-week-old CP rats were assigned to a sedentary group (CP-N) that was fed a standard diet (15.1 kJ/g, 23.6% protein, 5.3% fat, and 54.4% carbohydrates) or a sedentary group (CP-H) that was fed a high-fat diet (21.6 kJ/g, 23.6% protein, 34.9% fat, and 25.9% carbohydrates) and were housed for 10 weeks. Body weight, energy intake, and systolic blood pressure were higher in the CP-H group than in the CP-N group. Nonfasting glucose, triglyceride, total cholesterol, and leptin levels were higher in the CP-H group than in the CP-N group. There was no difference in insulin levels between the CP-N and CP-H groups. Muscle PGC-1α mRNA levels and succinate dehydrogenase activity were lower in the CP-H group than in the CP-N group. We concluded that a high-fat diet reduces PGC-1α mRNA levels and oxidative capacity in skeletal muscles and accelerates metabolic syndrome.

  18. Central Administration of Resveratrol Improves Diet-Induced Diabetes

    PubMed Central

    Ramadori, Giorgio; Gautron, Laurent; Fujikawa, Teppei; Vianna, Claudia R.; Elmquist, Joel K.; Coppari, Roberto

    2009-01-01

    Resveratrol is a natural polyphenolic compound that activates nicotinamide adenosine dinucleotide-dependent deacetylase SIRT1. Resveratrol has recently been shown to exert potent antidiabetic actions when orally delivered to animal models of type 2 diabetes. However, the tissue(s) mediating these beneficial effects is unknown. Because SIRT1 is expressed in central nervous system (CNS) neurons known to control glucose and insulin homeostasis, we hypothesized that resveratrol antidiabetic effects are mediated by the brain. Here, we report that long-term intracerebroventricular infusion of resveratrol normalizes hyperglycemia and greatly improves hyperinsulinemia in diet-induced obese and diabetic mice. It is noteworthy that these effects are independent of changes in body weight, food intake, and circulating leptin levels. In addition, CNS resveratrol delivery improves hypothalamic nuclear factor-κB inflammatory signaling by reducing acetylated-RelA/p65 and total RelA/p65 protein contents, and inhibitor of nuclear factor-κB α and IκB kinase β mRNA levels. Furthermore, this treatment leads to reduced hepatic phosphoenolpyruvate carboxykinase 1 mRNA and protein levels and ameliorates pyruvate-induced hyperglycemia in this mouse model of type 2 diabetes. Collectively, our results unveiled a previously unrecognized key role for the CNS in mediating the antidiabetic actions of resveratrol. PMID:19819963

  19. Effects of 5-aminolevulinic acid on a murine model of diet-induced obesity

    PubMed Central

    Koganei, Megumi; Saitou, Yuri; Tsuchiya, Kyoko; Abe, Fuminori; Tanaka, Toru; Horinouchi, Izumi; Izumi, Yoshiya; Yamaji, Taketo; Takahashi, Takeshi

    2015-01-01

    The effects of 5-aminolevulinic acid (5-ALA) on obesity were investigated using a murine model (diet-induced obese mice). Diet-induced obese mice were divided into 4 groups: a control group (C group), which was fed a high-fat diet; a low-5-ALA dose (10 mg/kg/day) group (10A group); a moderate-5-ALA dose (30 mg/kg/day) group (30A group); and a high-5-ALA dose (100 mg/kg/day) group (100A group). 5-ALA was administered by mixing the high fat diet for 8 weeks. Body weight increases in the 30A and 100A groups were significantly smaller compared with those of the C group. Body fat measurements by X-ray computed tomography indicated that the 100A group showed a tendency toward low visceral fat quantities during the final week of the study. Visceral fat weights in the 30A and 100A groups were slightly low. The levels of serum alanine aminotransferase (ALT) and total cholesterol (TC) in the 10A group was slightly low, whereas the 30A and 100A groups showed significantly lower ALT and TC values. Liver lipid concentration showed a dose-dependent decrease with ALA. Thus, in this diet-induced obese murine model, administration of 5-ALA had a significantly beneficial impact on the visceral fat, serum ALT and TC, and liver lipid concentration. PMID:26388673

  20. Onion peel tea ameliorates obesity and affects blood parameters in a mouse model of high-fat-diet-induced obesity.

    PubMed

    Matsunaga, Shogo; Azuma, Kazuo; Watanabe, Mayumi; Tsuka, Takeshi; Imagawa, Tomohiro; Osaki, Tomohiro; Okamoto, Yoshiharu

    2014-02-01

    The present study examined the effects of onion peel tea (OPT) in a mouse model of high-fat-diet-induced obesity. BALB/c mice were fed a high-fat diet for three weeks, followed by a normal diet with or without OPT for 28 days. OPT suppressed the increases in body weight and level of epididymal fat tissue; it also significantly reduced the serum concentrations of total cholesterol on day 14 and those of glucose and leptin on day 28. The results indicate that OPT has anti-obesity effects in an experimental mouse model of high-fat-diet-induced obesity. PMID:24396409

  1. The Effect of Weight Reduction on the Blood and Urine Measurements of College Wrestlers.

    ERIC Educational Resources Information Center

    Segurson, Jack

    It has been suggested that the weight reduction practices of wrestlers results in kidney and liver problems. To observe the effect of wrestlers' weight reduction, diagnostic tests for kidney and liver problems were done on the blood and urine samples of 22 college wrestlers over the course of a wrestling season. Results obtained after reduction to…

  2. Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats.

    PubMed

    Kumar, V; Bhandari, Uma; Tripathi, C D; Khanna, Geetika

    2014-07-01

    Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na(+)/K(+) ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na(+)/K(+) ATPase activity and DNA laddering, visceral fat pad and organ's weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus.

  3. Rapid Rather than Gradual Weight Reduction Impairs Hemorheological Parameters of Taekwondo Athletes through Reduction in RBC-NOS Activation

    PubMed Central

    Yang, Woo Hwi; Heine, Oliver; Pauly, Sebastian; Kim, Pilsang; Bloch, Wilhelm; Mester, Joachim; Grau, Marijke

    2015-01-01

    Purpose Rapid weight reduction is part of the pre-competition routine and has been shown to negatively affect psychological and physiological performance of Taekwondo (TKD) athletes. This is caused by a reduction of the body water and an electrolyte imbalance. So far, it is unknown whether weight reduction also affects hemorheological properties and hemorheology-influencing nitric oxide (NO) signaling, important for oxygen supply to the muscles and organs. Methods For this purpose, ten male TKD athletes reduced their body weight by 5% within four days (rapid weight reduction, RWR). After a recovery phase, athletes reduced body weight by 5% within four weeks (gradual weight reduction, GWR). Each intervention was preceded by two baseline measurements and followed by a simulated competition. Basal blood parameters (red blood cell (RBC) count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean cellular hemoglobin and mean cellular hemoglobin concentration), RBC-NO synthase activation, RBC nitrite as marker for NO synthesis, RBC deformability and aggregation parameters were determined on a total of eight investigation days. Results Basal blood parameters were not affected by the two interventions. In contrast to GWR, RWR decreased activation of RBC-NO synthase, RBC nitrite, respective NO concentration and RBC deformability. Additionally, RWR increased RBC aggregation and disaggregation threshold. Conclusion The results point out that a rapid weight reduction negatively affects hemorheological parameters and NO signaling in RBC which might limit performance capacity. Thus, GWR should be preferred to achieve the desired weight prior to a competition to avoid these negative effects. PMID:25875585

  4. Validation of a Weight Reduction Treatment Package for the Retarded.

    ERIC Educational Resources Information Center

    Rotatori, Anthony F.; And Others

    Five studies are reviewed which indicated the effectiveness on weight loss by mentally retarded persons of a treatment program stressing self control. The intervention included procedures which increased the dieter's self awareness of overeating behavior patterns and body weight, reduced food cues, reduced eating rates, increased activity level…

  5. Interventions for Weight Reduction: Facing the Maintenance Problem

    ERIC Educational Resources Information Center

    Anderson, Drew A.; Simmons, Angela M.; Milnes, Suzanne M.

    2005-01-01

    Behavioral treatments are perhaps the cornerstone of modern obesity treatment. Maintenance of weight lost via behavioral treatments has been less than hoped for, however. Weight regain is the result of complex interactions between physiological, behavioral, cognitive, and environmental factors; in this paper we review some of these factors and…

  6. Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions

    PubMed Central

    Beilharz, Jessica E.; Maniam, Jayanthi; Morris, Margaret J.

    2015-01-01

    It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments. PMID:26274972

  7. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

    PubMed Central

    Ram, Heera; Jatwa, Rameshwar; Purohit, Ashok

    2014-01-01

    Acacia senegal L. (Fabaceae) seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides, and VLDL-cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34 ± 0.72) and increased lumen volume (51.65 ± 3.66), administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics. PMID:25544897

  8. Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions.

    PubMed

    Beilharz, Jessica E; Maniam, Jayanthi; Morris, Margaret J

    2015-08-12

    It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.

  9. Divergent effects of weight reduction and oral anticonception treatment on adrenergic lipolysis regulation in obese women with the polycystic ovary syndrome.

    PubMed

    Wahrenberg, H; Ek, I; Reynisdottir, S; Carlström, K; Bergqvist, A; Arner, P

    1999-06-01

    The influence of weight reduction and female sex hormones on the regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 20 obese hyperandrogenic women with polycystic ovary syndrome (PCOS). Nine PCOS women were reinvestigated after 8-12 weeks of weight reduction therapy (WR) with a very low calorie diet, inducing a mean loss of 8 +/- 3 kg, and 8 PCOS women were reinvestigated after 12 weeks of treatment with combined oral contraceptives (OC), containing ethinyl estradiol and norethisterone; the remaining 3 subjects were drop-outs. Both WR and OC normalized hyperandrogenicity. WR caused a 50% reduction of basal lipolysis rate and a 5- to 7-fold increased noradrenaline and terbutaline sensitivity (P < 0.02); the latter could be ascribed to a 2-fold increased beta2-adrenoceptor density (P < 0.02) as determined with radioligand binding. There was no change with regard to dobutamine (beta1-adrenoceptor sensitivity) or clonidine, (alpha2-adrenoceptor sensitivity) or to beta1-adrenoceptor density. OC treatment did not influence the basal lipolysis rate or beta2- or alpha2-adrenoceptor sensitivity, but lowered the beta1-adrenoceptor sensitivity 7-fold (P < 0.03) without a reduction in beta1-adrenoceptor density. The OC treatment effect was not observed when forskolin and dibutyryl cAMP, acting on adenylate cyclase or protein kinase A, respectively, were used, suggesting a partial uncoupling of beta1-adrenoceptors. WR therapy, but not OC therapy, caused, in addition to changes in lipolysis function, improved in vivo insulin sensitivity and lower plasma noradrenaline levels. These findings suggest that factors other than hyperandrogenicity modulate lipolysis regulation in obese subjects with PCOS. Disturbances in sympathetic pathways could be of pathogenic importance. PMID:10372729

  10. Genetic resistance to diet-induced obesity in chromosome substitution strains of mice

    PubMed Central

    Burrage, Lindsay C.; Baskin-Hill, Annie E.; Sinasac, David S.; Singer, Jonathan B.; Croniger, Colleen M.; Kirby, Andrew; Kulbokas, E. J.; Daly, Mark J.; Lander, Eric S.; Broman, Karl W.

    2013-01-01

    Discovery of genes that confer resistance to diseases such as diet-induced obesity could have tremendous therapeutic impact. We previously demonstrated that the C57BL/6J-ChrA/J/NaJ panel of chromosome substitution strains (CSSs) is a unique model for studying resistance to diet-induced obesity. In the present study, three replicate CSS surveys showed remarkable consistency, with 13 A/J-derived chromosomes reproducibly conferring resistance to high-fat-diet-induced obesity. Twenty CSS intercrosses, one derived from each of the 19 autosomes and chromosome X, were used to determine the number and location of quantitative trait loci (QTLs) on individual chromosomes and localized six QTLs. However, analyses of mean body weight in intercross progeny versus C57BL/6J provided strong evidence that many QTLs discovered in the CSS surveys eluded detection in these CSS intercrosses. Studies of the temporal effects of these QTLs suggest that obesity resistance was dynamic, with QTLs acting at different ages or after different durations of diet exposure. Thus, these studies provide insight into the genetic architecture of complex traits such as resistance to diet-induced obesity in the C57BL/6J-ChrA/J/NaJ CSSs. Because some of the QTLs detected in the CSS intercrosses were not detected using a traditional C57BL/6J × A/J intercross, our results demonstrate that surveys of CSSs and congenic strains derived from them are useful complementary tools for analyzing complex traits. PMID:20127486

  11. Characteristics influencing weight reduction among veterans in the MOVE!® Program.

    PubMed

    Garvin, Jane T; Marion, Lucy N; Narsavage, Georgia L; Finnegan, Lorna

    2015-01-01

    Obesity is a common health problem for veterans. This study explored background and program characteristics associated with a 5% weight reduction for veterans enrolled in MOVE!(®), a weight management program. For data analysis, 404 veteran records were examined using logistic regression. Background characteristics included socio-demographic variables, comorbidity, body mass index, rurality, and Veterans Administration (VA) priority group. Program characteristics included the program type (group attendee or self-managed) as well as the number and type of provider contacts. Thirteen percent of participants achieved a 5% weight reduction. Age in years (odds ratio [OR] = 1.04) and the number of group visits (OR = 1.05) were significant predictors for achieving a 5% weight reduction. Given the importance of weight reduction, health professionals should consider these significant predictors when planning weight-reduction programs for veterans.

  12. Hypoglycemic effects of brassinosteroid in diet-induced obese mice.

    PubMed

    Esposito, Debora; Kizelsztein, Pablo; Komarnytsky, Slavko; Raskin, Ilya

    2012-09-01

    The prevalence of obesity is increasing globally, and obesity is a major risk factor for metabolic diseases such as type 2 diabetes. Previously, we reported that oral administration of homobrassinolide (HB) to healthy rats triggered a selective anabolic response that was associated with lower blood glucose. Therefore, the aim of this study was to evaluate the effects of HB administration on glucose metabolism, insulin sensitivity, body composition, and gluconeogenic gene expression profiles in liver of C57BL/6J high-fat diet-induced obese mice. Acute oral administration of 50-300 mg/kg HB to obese mice resulted in a dose-dependent decrease in fasting blood glucose within 3 h of treatment. Daily chronic administration of HB (50 mg/kg for 8 wk) ameliorated hyperglycemia and improved oral glucose tolerance associated with obesity without significantly affecting body weight or body composition. These changes were accompanied by lower expression of two key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase), and increased phosphorylation of AMP-activated protein kinase in the liver and muscle tissue. In vitro, HB treatment (1-15 μM) inhibited cyclic AMP-stimulated but not dexamethasone-stimulated upregulation of PEPCK and G-6-Pase mRNA levels in H4IIE rat hepatoma cells. Among a series of brassinosteroid analogs related to HB, only homocastasterone decreased glucose production in cell culture significantly. These results indicate the antidiabetic effects of brassinosteroids and begin to elucidate their putative cellular targets both in vitro and in vivo. PMID:22785239

  13. LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity.

    PubMed

    Tajan, Mylène; Batut, Aurélie; Cadoudal, Thomas; Deleruyelle, Simon; Le Gonidec, Sophie; Saint Laurent, Céline; Vomscheid, Maëlle; Wanecq, Estelle; Tréguer, Karine; De Rocca Serra-Nédélec, Audrey; Vinel, Claire; Marques, Marie-Adeline; Pozzo, Joffrey; Kunduzova, Oksana; Salles, Jean-Pierre; Tauber, Maithé; Raynal, Patrick; Cavé, Hélène; Edouard, Thomas; Valet, Philippe; Yart, Armelle

    2014-10-21

    LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, sensorineural Deafness; LS), also called Noonan syndrome with multiple lentigines (NSML), is a rare autosomal dominant disorder associating various developmental defects, notably cardiopathies, dysmorphism, and short stature. It is mainly caused by mutations of the PTPN11 gene that catalytically inactivate the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). Besides its pleiotropic roles during development, SHP2 plays key functions in energetic metabolism regulation. However, the metabolic outcomes of LS mutations have never been examined. Therefore, we performed an extensive metabolic exploration of an original LS mouse model, expressing the T468M mutation of SHP2, frequently borne by LS patients. Our results reveal that, besides expected symptoms, LS animals display a strong reduction of adiposity and resistance to diet-induced obesity, associated with overall better metabolic profile. We provide evidence that LS mutant expression impairs adipogenesis, triggers energy expenditure, and enhances insulin signaling, three features that can contribute to the lean phenotype of LS mice. Interestingly, chronic treatment of LS mice with low doses of MEK inhibitor, but not rapamycin, resulted in weight and adiposity gains. Importantly, preliminary data in a French cohort of LS patients suggests that most of them have lower-than-average body mass index, associated, for tested patients, with reduced adiposity. Altogether, these findings unravel previously unidentified characteristics for LS, which could represent a metabolic benefit for patients, but may also participate to the development or worsening of some traits of the disease. Beyond LS, they also highlight a protective role of SHP2 global LS-mimicking modulation toward the development of obesity and associated disorders

  14. LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity.

    PubMed

    Tajan, Mylène; Batut, Aurélie; Cadoudal, Thomas; Deleruyelle, Simon; Le Gonidec, Sophie; Saint Laurent, Céline; Vomscheid, Maëlle; Wanecq, Estelle; Tréguer, Karine; De Rocca Serra-Nédélec, Audrey; Vinel, Claire; Marques, Marie-Adeline; Pozzo, Joffrey; Kunduzova, Oksana; Salles, Jean-Pierre; Tauber, Maithé; Raynal, Patrick; Cavé, Hélène; Edouard, Thomas; Valet, Philippe; Yart, Armelle

    2014-10-21

    LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, sensorineural Deafness; LS), also called Noonan syndrome with multiple lentigines (NSML), is a rare autosomal dominant disorder associating various developmental defects, notably cardiopathies, dysmorphism, and short stature. It is mainly caused by mutations of the PTPN11 gene that catalytically inactivate the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). Besides its pleiotropic roles during development, SHP2 plays key functions in energetic metabolism regulation. However, the metabolic outcomes of LS mutations have never been examined. Therefore, we performed an extensive metabolic exploration of an original LS mouse model, expressing the T468M mutation of SHP2, frequently borne by LS patients. Our results reveal that, besides expected symptoms, LS animals display a strong reduction of adiposity and resistance to diet-induced obesity, associated with overall better metabolic profile. We provide evidence that LS mutant expression impairs adipogenesis, triggers energy expenditure, and enhances insulin signaling, three features that can contribute to the lean phenotype of LS mice. Interestingly, chronic treatment of LS mice with low doses of MEK inhibitor, but not rapamycin, resulted in weight and adiposity gains. Importantly, preliminary data in a French cohort of LS patients suggests that most of them have lower-than-average body mass index, associated, for tested patients, with reduced adiposity. Altogether, these findings unravel previously unidentified characteristics for LS, which could represent a metabolic benefit for patients, but may also participate to the development or worsening of some traits of the disease. Beyond LS, they also highlight a protective role of SHP2 global LS-mimicking modulation toward the development of obesity and associated disorders.

  15. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice.

    PubMed

    Tomimoto, Daisuke; Okuma, Chihiro; Ishii, Yukihito; Kobayashi, Akio; Ohta, Takeshi; Kakutani, Makoto; Imanaka, Tsuneo; Ogawa, Nobuya

    2015-09-01

    Type 2 diabetes mellitus (T2DM) arises primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important in the development of T2DM, including obesity. JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase 1 inhibitor, reduced body weight depending on dietary fat in diet-induced obesity (DIO) rats in our previous study. Here, the effect of JTT-553 on glucose metabolism was evaluated using body weight reduction in T2DM mice. JTT-553 was repeatedly administered to DIO and KK-A(y) mice. JTT-553 reduced body weight gain and fat weight in both mouse models. In DIO mice, JTT-553 decreased insulin, non-esterified fatty acid (NEFA), total cholesterol (TC), and liver triglyceride (TG) plasma concentrations in non-fasting conditions. JTT-553 also improved insulin-dependent glucose uptake in adipose tissues and glucose intolerance in DIO mice. In KK-A(y) mice, JTT-553 decreased glucose, NEFA, TC and liver TG plasma concentrations in non-fasting conditions. JTT-553 also decreased glucose, insulin, and TC plasma concentrations in fasting conditions. In addition, JTT-553 decreased TNF-α mRNA levels and increased GLUT4 mRNA levels in adipose tissues in KK-A(y) mice. These results suggest that JTT-553 improves insulin resistance in adipose tissues and systemic glucose metabolism through reductions in body weight.

  16. Comparison of established and innovative weight-reduction treatment procedures.

    PubMed

    Loro, A D; Fisher, E B; Levenkron, J C

    1979-01-01

    A central component of a commonly used weight-loss procedure developed by Stuart (1967), which emphasizes situational engineering (SE), was compared to eating behavior control (EBC), a treatment employing reinforcement of changes in eating habits. A third treatment encouraged development of individuals' own applications of a model of self-control and attempted to provide effective feedback regarding progress toward weight-loss goals. This self-initiated treatment (SI) was designed to be less directive than many behavioral treatment packages and to be more realistic about the expectations of subjects and the actual eating habits of overweight and normalweight people. Following baseline, treatment lasted six weeks and followup lasted 16 weeks. While all treatments produced weight losses, EBC surpassed SE during treatment. SI losses during treatment did not differ from SE or EBC, but SI was the only group that lost weight throughout followup, indicating the possible utility of more subtle, less directive interventions than those that have often been associated with behavioral approaches. The results of SE question the applicability to clinical procedures of the external cue hypersensitivity theory of obesity (Schachter and Rodin, 1974), to which SE is closely related.

  17. Anti-obesity and anti-diabetic effects of flavonoid derivative (Fla-CN) via microRNA in high fat diet induced obesity mice.

    PubMed

    Qin, Nan; Chen, Ying; Jin, Mei-Na; Zhang, Chang; Qiao, Wei; Yue, Xiao-Long; Duan, Hong-Quan; Niu, Wen-Yan

    2016-01-20

    3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl]kaempferol (Fla-CN), a semi-synthesized flavonoid derivative of tiliroside, reduces whole-body adiposity, ameliorates metabolic lipid disorder, improves insulin sensitivity and benefits other disorders characterized by insulin resistance in high fat diet induced obesity mice. The improvement of insulin sensitivity and the reduction of weight gain are correlated with the changes of leptin and adiponectin levels. As a result, Fla-CN treatment could increase the expressions of pAMPK and miR-27 in the liver and adipose tissues. Meanwhile, we discovered that the expressions of various adipogenesis genes were downregulated, which were target genes of miR-27. This is the first report for the action of miR-27 by flavonoid derivative in rodents. The action of Fla-CN might be through multiple approaches including AMPK activation and enhancement in miR-27 expression.

  18. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870) on Mechanical Sensitivity in Diet-Induced Obesity Model.

    PubMed

    Dardmeh, Fereshteh; Nielsen, Hans Ingolf; Alipour, Hiva; Kjærgaard, Benedict; Brandsborg, Erik; Gazerani, Parisa

    2016-01-01

    Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 10(9) CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) supplement on mechanical pain thresholds in behaving diet-induced obese (DIO) mice and their normal weight (NW) controls. The mice (N = 24, 6-week-old male) were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P < 0.05). Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P < 0.05) lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation. PMID:27647980

  19. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870) on Mechanical Sensitivity in Diet-Induced Obesity Model

    PubMed Central

    Brandsborg, Erik

    2016-01-01

    Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 109 CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) supplement on mechanical pain thresholds in behaving diet-induced obese (DIO) mice and their normal weight (NW) controls. The mice (N = 24, 6-week-old male) were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P < 0.05). Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P < 0.05) lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation. PMID:27647980

  20. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870) on Mechanical Sensitivity in Diet-Induced Obesity Model

    PubMed Central

    Brandsborg, Erik

    2016-01-01

    Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 109 CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) supplement on mechanical pain thresholds in behaving diet-induced obese (DIO) mice and their normal weight (NW) controls. The mice (N = 24, 6-week-old male) were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P < 0.05). Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P < 0.05) lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation.

  1. Brown fat and the myth of diet-induced thermogenesis.

    PubMed

    Kozak, Leslie P

    2010-04-01

    The notion that brown adipose tissue (BAT) in mice or humans maintains energy balance by burning off excess calories seems incompatible with evolutionary biology. Studies in obese rats and mice lacking UCP1 indicate that diet-induced thermogenesis by BAT is unlikely. PMID:20374958

  2. Multifoil insulation study for weight reduction. Technical information report

    SciTech Connect

    Glazer, S.D.

    1984-01-01

    The purpose of the present task is to develop high temperature multi-foil insulation suitable for use in the SP-100 thermoelectric converter project. Part of this task involves careful examination of alternative foil and foil spacing materials with the goal of effecting significant weight savings over current state-of-the-art foil insulation. This task involved the determination of the state-of-the-art foils, ascertaining what data is available, what additional data is required, preliminary assessment of the suitability of alternate foil and spacer materials, and specific recommendations for additional tests required to qualify new and existing insulation designs for use in the SP-100.

  3. Hypolipidemic activity of haritaki (terminalia chebula) in atherogenic diet induced hyperlipidemic rats.

    PubMed

    Maruthappan, V; Shree, K Sakthi

    2010-04-01

    Haritaki (Terminalia chebula) family Combretaceae is an important plant used traditionally for medicinal purposes. It is component of the classic Ayurvedic combination called "Triphala". Hyperlipidemia was induced by treated orally with atherogemc diet. In atherogenic diet induced hyperlipidemic model, the rats receiving treatment with Haritaki showed significant reduction in total cholesterol, triglycerides, total protein and elevation of high density lipoprotein cholesterol. Haritaki was found to possess significant hypolipidemic activity. The results also suggest that Haritaki at 1.05 and 2.10 mg/kg b.wt. concentrations are an excellent lipid-lowering agent. PMID:22247850

  4. Cafeteria diet-induced obesity causes oxidative damage in white adipose.

    PubMed

    Johnson, Amy R; Wilkerson, Matthew D; Sampey, Brante P; Troester, Melissa A; Hayes, D Neil; Makowski, Liza

    2016-04-29

    Obesity continues to be one of the most prominent public health dilemmas in the world. The complex interaction among the varied causes of obesity makes it a particularly challenging problem to address. While typical high-fat purified diets successfully induce weight gain in rodents, we have described a more robust model of diet-induced obesity based on feeding rats a diet consisting of highly palatable, energy-dense human junk foods - the "cafeteria" diet (CAF, 45-53% kcal from fat). We previously reported that CAF-fed rats became hyperphagic, gained more weight, and developed more severe hyperinsulinemia, hyperglycemia, and glucose intolerance compared to the lard-based 45% kcal from fat high fat diet-fed group. In addition, the CAF diet-fed group displayed a higher degree of inflammation in adipose and liver, mitochondrial dysfunction, and an increased concentration of lipid-derived, pro-inflammatory mediators. Building upon our previous findings, we aimed to determine mechanisms that underlie physiologic findings in the CAF diet. We investigated the effect of CAF diet-induced obesity on adipose tissue specifically using expression arrays and immunohistochemistry. Genomic evidence indicated the CAF diet induced alterations in the white adipose gene transcriptome, with notable suppression of glutathione-related genes and pathways involved in mitigating oxidative stress. Immunohistochemical analysis indicated a doubling in adipose lipid peroxidation marker 4-HNE levels compared to rats that remained lean on control standard chow diet. Our data indicates that the CAF diet drives an increase in oxidative damage in white adipose tissue that may affect tissue homeostasis. Oxidative stress drives activation of inflammatory kinases that can perturb insulin signaling leading to glucose intolerance and diabetes. PMID:27033600

  5. Cafeteria diet-induced obesity causes oxidative damage in white adipose.

    PubMed

    Johnson, Amy R; Wilkerson, Matthew D; Sampey, Brante P; Troester, Melissa A; Hayes, D Neil; Makowski, Liza

    2016-04-29

    Obesity continues to be one of the most prominent public health dilemmas in the world. The complex interaction among the varied causes of obesity makes it a particularly challenging problem to address. While typical high-fat purified diets successfully induce weight gain in rodents, we have described a more robust model of diet-induced obesity based on feeding rats a diet consisting of highly palatable, energy-dense human junk foods - the "cafeteria" diet (CAF, 45-53% kcal from fat). We previously reported that CAF-fed rats became hyperphagic, gained more weight, and developed more severe hyperinsulinemia, hyperglycemia, and glucose intolerance compared to the lard-based 45% kcal from fat high fat diet-fed group. In addition, the CAF diet-fed group displayed a higher degree of inflammation in adipose and liver, mitochondrial dysfunction, and an increased concentration of lipid-derived, pro-inflammatory mediators. Building upon our previous findings, we aimed to determine mechanisms that underlie physiologic findings in the CAF diet. We investigated the effect of CAF diet-induced obesity on adipose tissue specifically using expression arrays and immunohistochemistry. Genomic evidence indicated the CAF diet induced alterations in the white adipose gene transcriptome, with notable suppression of glutathione-related genes and pathways involved in mitigating oxidative stress. Immunohistochemical analysis indicated a doubling in adipose lipid peroxidation marker 4-HNE levels compared to rats that remained lean on control standard chow diet. Our data indicates that the CAF diet drives an increase in oxidative damage in white adipose tissue that may affect tissue homeostasis. Oxidative stress drives activation of inflammatory kinases that can perturb insulin signaling leading to glucose intolerance and diabetes.

  6. Anti-obesity Effect of Fermented Whey Beverage using Lactic Acid Bacteria in Diet-induced Obese Rats.

    PubMed

    Hong, Sung-Moon; Chung, Eui-Chun; Kim, Cheol-Hyun

    2015-01-01

    High-protein fermented whey beverage (FWB) was manufactured using whey protein concentrate (WPC) and Lactobacillus plantarum DK211 isolated from kimchi. This study was designed to evaluate the anti-obesity activity of FWB in male rats fed a high-fat diet. Male Sprague-Dawley rats were randomly assigned to three groups (n=8 per group). The three groups differed in their diet; one group received a normal diet (ND), another, a high-fat diet (HD), and the third, a HD plus fermented whey beverage (HDFWB), for 4 wk. Supplementation with FWB (the HDFWB group) prevented weight gain and body fat accumulation. The food intake in the HDWFB group was significantly lower (p<0.05) than that of the HD group. The HDWFB group also showed a significant decrease in organ weights (p<0.05), except for the weight of the testis. There was a significant decrease in total cholesterol, LDL-cholesterol, and triglycerides in the HDFWB group compared with the HD group (p<0.05), but there was no significant difference in serum HDL-cholesterol levels among the experimental groups. Rats ingesting FWB (the HDFWB group) also showed a significant decrease in blood glucose levels, and plasma levels of insulin, leptin, and ghrelin compared to HD group (p<0.05). These results indicate that FWB has beneficial effects on dietary control, weight control, and reduction in fat composition and serum lipid level; consequently, it may provide antiobesity and hypolipidemic activity against high fat diet-induced obesity in rats. PMID:26761894

  7. Anti-obesity Effect of Fermented Whey Beverage using Lactic Acid Bacteria in Diet-induced Obese Rats

    PubMed Central

    2015-01-01

    High-protein fermented whey beverage (FWB) was manufactured using whey protein concentrate (WPC) and Lactobacillus plantarum DK211 isolated from kimchi. This study was designed to evaluate the anti-obesity activity of FWB in male rats fed a high-fat diet. Male Sprague-Dawley rats were randomly assigned to three groups (n=8 per group). The three groups differed in their diet; one group received a normal diet (ND), another, a high-fat diet (HD), and the third, a HD plus fermented whey beverage (HDFWB), for 4 wk. Supplementation with FWB (the HDFWB group) prevented weight gain and body fat accumulation. The food intake in the HDWFB group was significantly lower (p<0.05) than that of the HD group. The HDWFB group also showed a significant decrease in organ weights (p<0.05), except for the weight of the testis. There was a significant decrease in total cholesterol, LDL-cholesterol, and triglycerides in the HDFWB group compared with the HD group (p<0.05), but there was no significant difference in serum HDL-cholesterol levels among the experimental groups. Rats ingesting FWB (the HDFWB group) also showed a significant decrease in blood glucose levels, and plasma levels of insulin, leptin, and ghrelin compared to HD group (p<0.05). These results indicate that FWB has beneficial effects on dietary control, weight control, and reduction in fat composition and serum lipid level; consequently, it may provide antiobesity and hypolipidemic activity against high fat diet-induced obesity in rats. PMID:26761894

  8. [Effects of rapid weight reduction diet on protein metabolism and physical performance].

    PubMed

    Morita, Y; Igawa, S; Takahashi, H; Tomida, K; Hirota, K

    1991-01-01

    The purpose of this study was to provide information on the requirement of nutrition, especially of the protein during rapid weight reduction immediately before a competition of a weight-classification system sport, boxing. Weight reduction period was 9 days. Subjects were divided into three groups of free diet group (group A: n = 5), high protein diet group (group B: n = 5) and ordinary protein diet group (group C: n = 4). Group A had taken food ad libitum. Group B had taken 2.0 g/kg/day of protein in the first half and 1.5 g/kg/day of protein in the second half of weight reduction period, and Group C had taken 1.0 g/kg/day of protein throughout weight reduction period. Groups B and C had taken 2,000 kcal/day in the first half and 1,200 kcal/day in the second half of weight reduction period. Anthropometry and nutritional investigation were performed, and urine components were analyzed. The main results obtained were as follows: 1) Calorie and protein intake in Group A averaged 883 kcal/day and 0.9 g/kg/day in the second half of weight reduction period. 2) 3-methylhistidine and urea nitrogen in urine and 3-Me/Cr increased significantly at the end of weight reduction period in Group A, but decreased significantly in groups B and C. Nitrogen balance changed to a negative value only in group A. Differences in each of urine components were statistically significant between group A and the other two groups at the end of period. 3) Heart rate and oxygen intake at the same submaximal work load increased significantly in group A at the end of weight reduction period, but in groups B and C no noticeable changes were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Diet-induced obesity: dopamine transporter function, impulsivity and motivation

    PubMed Central

    Narayanaswami, V; Thompson, AC; Cassis, LA; Bardo, MT; Dwoskin, LP

    2013-01-01

    OBJECTIVE A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. DESIGN To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure. METHODS Striatal D2-receptor density was determined by in vitro kinetic analysis of [3H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [3H]dopamine uptake, methamphetamine-evoked [3H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively. RESULTS Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [3H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO. CONCLUSION Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The

  10. Ubc13 haploinsufficiency protects against age-related insulin resistance and high-fat diet-induced obesity

    PubMed Central

    Joo, Erina; Fukushima, Toru; Harada, Norio; Reed, John C.; Matsuzawa, Shu-ichi; Inagaki, Nobuya

    2016-01-01

    Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity. We compared wild-type (WT) and Ubc13 haploinsufficient (ubc13+/−) mice under normal diet (ND) and HFD, since homozygous knockout mice (ubc13−/−) are embryonic lethal. Male and female ubc13+/− mice were protected against age-related insulin resistance under ND and HFD compared to WT mice. Interestingly, only female ubc13+/− mice were protected against HFD-induced obesity and hepatic steatosis. Moreover, only female HFD-fed ubc13+/− mice showed lower expression of inflammatory cytokines that was secondary to reduction in weight gain not present in the other groups. In summary, our results indicate that suppression of Ubc13 activity may play a metabolic role independent of its inflammatory function. Thus, Ubc13 could represent a therapeutic target for insulin resistance, diet-induced obesity, and associated metabolic dysfunctions. PMID:27796312

  11. Hypolipidemic effect of aqueous extract of Carum carvi (black Zeera) seeds in diet induced hyperlipidemic rats.

    PubMed

    Saghir, Muhammad Rashad; Sadiq, Soban; Nayak, Salma; Tahir, Muhammad Usman

    2012-04-01

    Medicinal plants play a key role in preventing various diseases. Hyperlipidemia is a major contributor to the pathogenesis of cardiovascular diseases. The purpose of the present study was to assess the effect of aqueous extract of Carum carvi seeds in diet induced hyperlipidemia in rats. 2% cholesterol diet were given to rats for six weeks and rats showed high lipid levels were included in the study. Then all rats were divided into, normal control group (A), hyperlipidemia positive control group (B), and the remaining two groups (C and D) served as experimental groups. Group C hyperlipidemic experimental rats received aqueous dried extract of Carum carvi seeds at 60 mg/kg of body weight for eight weeks on daily basis. On the other hand group D rats received simvastatin at 1.0 mg/kg body weight for eight weeks. Blood samples were collected after eight weeks. The hyperlipidemic positive control group rats showed variable increase in serum triglycerides, LDL and total cholesterol levels. Serum HDL levels decreased in hyperlipidemic positive control groups. Carum carvi and simvastatin significantly decreased the levels of these parameters in rats. On comparison Carum carvi reduced lipid levels more, effectively than the simvastatin. Carum carvi constituents, especially flavonoids and carvone have strong anti-oxidant activity which might be involved in hypolipidemia. In conclusion, Carum carvi aqueous seeds extract decrease lipid levels in diet induced hyperlipidemic rats.

  12. JTP-103237, a novel monoacylglycerol acyltransferase inhibitor, modulates fat absorption and prevents diet-induced obesity.

    PubMed

    Okuma, Chihiro; Ohta, Takeshi; Tadaki, Hironobu; Hamada, Hiromi; Oda, Tomohiro; Taniuchi, Hideyuki; Yamanaka, Kenji; Ishii, Yukihito; Ohe, Yasuhiro; Yata, Shinji; Nishiu, Jun; Aratsu, Yusuke; Oshida, Shinichi; Kume, Shinichi; Kakutani, Makoto

    2015-07-01

    Monoacylglycerol acyltransferase 2 (MGAT2) plays an important role in intestinal fat absorption. We discovered the novel MGAT2 inhibitor, JTP-103237, and evaluated its pharmacological profile. JTP-103237 selectively inhibited MGAT2 without remarkable species differences and reduced absorbed lipids in circulation. After lipid administration, JTP-103237 slightly but significantly decreased triglyceride content in proximal small intestine and significantly increased the lipids content in the distal small intestine. In addition, JTP-103237 significantly increased MGAT substrate (monoacylglycerol and fatty acid) content in the small intestine. JTP-103237 increased plasma peptide YY levels after lipid loading and reduced food intake in a dietary fat-dependent manner. After chronic treatment, JTP-103237 significantly decreased body weight and increased O2 consumption in the early dark phase in high fat diet induced obese (DIO) mice. Moreover, JTP-103237 improved glucose tolerance and decreased fat weight and hepatic triglyceride content in DIO mice. Our findings indicate that JTP-103237 prevents diet-induced obesity by inhibiting intestinal MGAT2 and has unique properties as a drug for the treatment of obesity.

  13. Dmbt1 does not affect a Western style diet-induced liver damage in mice.

    PubMed

    Reichold, Astrid; Brenner, Sibylle A; Förster-Fromme, Karin; Bergheim, Ina; Mollenhauer, Jan; Bischoff, Stephan C

    2013-11-01

    In the last three decades the prevalence of non-alcoholic fatty liver disease has markedly increased. Results from epidemiologic studies indicate that not only a general overnutrition but rather a diet rich in sugar, fat and cholesterol (= Western style diet) maybe a risk factor for the development of non-alcoholic fatty liver disease. Concerning liver diseases, it is known that Deleted in malignant brain tumors 1 is amongst others related to liver injury and repair. In addition Deleted in malignant brain tumors 1 seems to play a role in regard to the maintenance of the intestinal homeostasis and the regulation of food intake. Starting from this background the aim of the present study was to investigate if Dmbt1 plays a role in Western style diet-induced non-alcoholic steatohepatitis in mice. Dmbt1 (+/+) and Dmbt1 (-/-) mice were fed a Western style diet or control diet ad libitum for 12 weeks. Both Western style diet fed groups gained significant more weight than the controls and developed a mild non-alcoholic steatohepatitis. The presence/absence of functional Deleted in malignant brain tumors 1 had no effect on parameters like food intake, weight gain, fasting glucose, and liver damage. These results suggest that Deleted in malignant brain tumors 1 plays a minor part on the development of a diet-induced liver damage in mice.

  14. Diet-induced obese mice develop peripheral, but not central, resistance to leptin.

    PubMed Central

    Van Heek, M; Compton, D S; France, C F; Tedesco, R P; Fawzi, A B; Graziano, M P; Sybertz, E J; Strader, C D; Davis, H R

    1997-01-01

    Leptin administration reduces obesity in leptin-deficient ob/ob mice; its effects in obese humans, who have high circulating leptin levels, remain to be determined. This longitudinal study was designed to determine whether diet-induced obesity in mice produces resistance to peripheral and/or central leptin treatment. Obesity was induced in two strains of mice by exposure to a 45% fat diet. Serum leptin increased in proportion to body weight (P < 0.00001). Whereas C57BL/6 mice initially responded to peripherally administered leptin with a marked decrease in food intake, leptin resistance developed after 16 d on high fat diet; mice on 10% fat diet retained leptin sensitivity. In AKR mice, peripheral leptin significantly decreased food intake in both 10 and 45% fat-fed mice after 16 d of dietary treatment. However, after 56 d, both groups became resistant to peripherally administered leptin. Central administration of leptin to peripherally leptin-resistant AKR mice on 45% fat diet resulted in a robust response to leptin, with a dose-dependent decrease in food intake (P < 0.00001) and body weight (P < 0.0001) after a single intracerebroventricular infusion. These data demonstrate that, in a diet-induced obesity model, mice exhibit resistance to peripherally administered leptin, while retaining sensitivity to centrally administered leptin. PMID:9022070

  15. Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice

    PubMed Central

    Koza, Robert A; Nikonova, Larissa; Hogan, Jessica; Rim, Jong-Seop; Mendoza, Tamra; Faulk, Christopher; Skaf, Jihad; Kozak, Leslie P

    2006-01-01

    High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4-fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansion, since differences in gene expression observed in biopsies of epididymal fat at 7 wk of age (before the high-fat diet) correlated with adiposity after 8 wk on a high-fat diet. We propose that C57BL/6J mice have the phenotypic characteristics suitable for a model to investigate epigenetic mechanisms within adipose tissue that underlie diet-induced obesity. PMID:16733553

  16. Antiobesity effect of Tamarindus indica L. pulp aqueous extract in high-fat diet-induced obese rats.

    PubMed

    Azman, Khairunnuur Fairuz; Amom, Zulkhairi; Azlan, Azrina; Esa, Norhaizan Mohd; Ali, Rasadah Mat; Shah, Zamree Md; Kadir, Khairul Kamilah Abdul

    2012-04-01

    Obesity and overweight are associated with atherosclerosis, fatty liver, hyperlipemia, diabetes mellitus, and various types of cancer. The global prevalence of overweight and obesity has reached epidemic proportions. Here, we investigated the effect of Tamarindus indica pulp aqueous extract (TIE) in diet-induced obese Sprague-Dawley rats. The animals were divided into five groups and labeled as follows: the normal control (NC) group received normal diet; the positive control (PC) group received high-fat diet; and the TIE 5, 25, and 50 groups, after the induction of obesity via a high-fat diet, received TIE at 5, 25, or 50 mg/kg orally for 10 weeks. It was observed that TIE decreased the levels of plasma total cholesterol, low-density lipoprotein (LDL), and triglyceride, and increased high-density lipoprotein (HDL), with the concomitant reduction of body weight. Moreover, TIE decreased plasma leptin and reduced fatty acid synthase (FAS) activity and enhanced the efficiency of the antioxidant defense system. TIE exhibits antiobesity effects, as indicated by a significant reduction in adipose tissue weights, as well as lowering the degree of hepatic steatosis in the obesity-induced rats. The extract possesses hepatoprotective activity, as it reversed the plasma liver enzymes level elevation prior to the high-fat diet. In conclusion, TIE improved obesity-related parameters in blood, liver, and adipose tissue in a rat model and suppressed obesity induced by a high-fat diet, possibly by regulating lipid metabolism and lowering plasma leptin and FAS levels. A dose-dependant effect of TIE is detected, where TIE at 50 mg/kg showed the most prominent effect, followed by TIE at 25 mg/kg and, subsequently, 5 mg/kg.

  17. Antiobesity effect of Tamarindus indica L. pulp aqueous extract in high-fat diet-induced obese rats.

    PubMed

    Azman, Khairunnuur Fairuz; Amom, Zulkhairi; Azlan, Azrina; Esa, Norhaizan Mohd; Ali, Rasadah Mat; Shah, Zamree Md; Kadir, Khairul Kamilah Abdul

    2012-04-01

    Obesity and overweight are associated with atherosclerosis, fatty liver, hyperlipemia, diabetes mellitus, and various types of cancer. The global prevalence of overweight and obesity has reached epidemic proportions. Here, we investigated the effect of Tamarindus indica pulp aqueous extract (TIE) in diet-induced obese Sprague-Dawley rats. The animals were divided into five groups and labeled as follows: the normal control (NC) group received normal diet; the positive control (PC) group received high-fat diet; and the TIE 5, 25, and 50 groups, after the induction of obesity via a high-fat diet, received TIE at 5, 25, or 50 mg/kg orally for 10 weeks. It was observed that TIE decreased the levels of plasma total cholesterol, low-density lipoprotein (LDL), and triglyceride, and increased high-density lipoprotein (HDL), with the concomitant reduction of body weight. Moreover, TIE decreased plasma leptin and reduced fatty acid synthase (FAS) activity and enhanced the efficiency of the antioxidant defense system. TIE exhibits antiobesity effects, as indicated by a significant reduction in adipose tissue weights, as well as lowering the degree of hepatic steatosis in the obesity-induced rats. The extract possesses hepatoprotective activity, as it reversed the plasma liver enzymes level elevation prior to the high-fat diet. In conclusion, TIE improved obesity-related parameters in blood, liver, and adipose tissue in a rat model and suppressed obesity induced by a high-fat diet, possibly by regulating lipid metabolism and lowering plasma leptin and FAS levels. A dose-dependant effect of TIE is detected, where TIE at 50 mg/kg showed the most prominent effect, followed by TIE at 25 mg/kg and, subsequently, 5 mg/kg. PMID:21989999

  18. Short-Chain Fructo-Oligosaccharides Modulate Intestinal Microbiota and Metabolic Parameters of Humanized Gnotobiotic Diet Induced Obesity Mice

    PubMed Central

    Respondek, Frederique; Gerard, Philippe; Bossis, Mathilde; Boschat, Laura; Bruneau, Aurélia; Rabot, Sylvie; Wagner, Anne; Martin, Jean-Charles

    2013-01-01

    Prebiotic fibres like short-chain fructo-oligosaccharides (scFOS) are known to selectively modulate the composition of the intestinal microbiota and especially to stimulate Bifidobacteria. In parallel, the involvement of intestinal microbiota in host metabolic regulation has been recently highlighted. The objective of the study was to evaluate the effect of scFOS on the composition of the faecal microbiota and on metabolic parameters in an animal model of diet-induced obesity harbouring a human-type microbiota. Forty eight axenic C57BL/6J mice were inoculated with a sample of faecal human microbiota and randomly assigned to one of 3 diets for 7 weeks: a control diet, a high fat diet (HF, 60% of energy derived from fat)) or an isocaloric HF diet containing 10% of scFOS (HF-scFOS). Mice fed with the two HF gained at least 21% more weight than mice from the control group. Addition of scFOS partially abolished the deposition of fat mass but significantly increased the weight of the caecum. The analysis of the taxonomic composition of the faecal microbiota by FISH technique revealed that the addition of scFOS induced a significant increase of faecal Bifidobacteria and the Clostridium coccoides group whereas it decreased the Clostridium leptum group. In addition to modifying the composition of the faecal microbiota, scFOS most prominently affected the faecal metabolome (e.g. bile acids derivatives, hydroxyl monoenoic fatty acids) as well as urine, plasma hydrophilic and plasma lipid metabolomes. The increase in C. coccoides and the decrease in C. leptum, were highly correlated to these metabolic changes, including insulinaemia, as well as to the weight of the caecum (empty and full) but not the increase in Bifidobacteria. In conclusion scFOS induce profound metabolic changes by modulating the composition and the activity of the intestinal microbiota, that may partly explain their effect on the reduction of insulinaemia. PMID:23951074

  19. Examining the relationship between diet-induced acidosis and cancer

    PubMed Central

    2012-01-01

    Increased cancer risk is associated with select dietary factors. Dietary lifestyles can alter systemic acid-base balance over time. Acidogenic diets, which are typically high in animal protein and salt and low in fruits and vegetables, can lead to a sub-clinical or low-grade state of metabolic acidosis. The relationship between diet and cancer risk prompts questions about the role of acidosis in the initiation and progression of cancer. Cancer is triggered by genetic and epigenetic perturbations in the normal cell, but it has become clear that microenvironmental and systemic factors exert modifying effects on cancer cell development. While there are no studies showing a direct link between diet-induced acidosis and cancer, acid-base disequilibrium has been shown to modulate molecular activity including adrenal glucocorticoid, insulin growth factor (IGF-1), and adipocyte cytokine signaling, dysregulated cellular metabolism, and osteoclast activation, which may serve as intermediary or downstream effectors of carcinogenesis or tumor promotion. In short, diet-induced acidosis may influence molecular activities at the cellular level that promote carcinogenesis or tumor progression. This review defines the relationship between dietary lifestyle and acid-base balance and discusses the potential consequences of diet-induced acidosis and cancer occurrence or progression. PMID:22853725

  20. Weight stigmatization and bias reduction: perspectives of overweight and obese adults.

    PubMed

    Puhl, Rebecca M; Moss-Racusin, Corinne A; Schwartz, Marlene B; Brownell, Kelly D

    2008-04-01

    This study employed qualitative methods with a sample of overweight and obese adults to identify and describe their subjective experiences of weight bias. Participants (274 females and 44 males) completed an online battery of self-report questionnaires, including several open-ended questions about weight stigmatization. These questions asked them to describe their worst experiences of weight stigmatization, their perceptions of common weight-based stereotypes, their feelings about being overweight and their suggestions for strategies to reduce weight stigma in our culture. Participants reported experiencing weight stigma across a range of contexts and involving a variety of interpersonal sources. Close relationship partners (such as friends, parents and spouses) were the most common source of their worst stigmatizing encounters. Participants challenged common weight-based stereotypes (notably, that obese individuals are 'lazy') and reported that they would like the public to gain a better understanding of the difficulties of weight loss, the causes of obesity and the emotional consequences of being stigmatized. Education was reported as the most promising avenue for future stigma-reduction efforts. The experiences and opinions expressed were not significantly different for men versus women or overweight versus obese individuals. A minority of participants expressed beliefs suggestive of self-blame and internalization of weight-based stereotypes. These results indicate that while obese individuals experience weight bias across many domains, more stigma-reduction efforts should target stigmatizing encounters in close relationships, including parents, spouses and friends of obese persons. PMID:17884836

  1. Increasing dietary leucine intake reduces diet-induced obesity and improves glucose and cholesterol metabolism in mice via multimechanisms.

    PubMed

    Zhang, Yiying; Guo, Kaiying; LeBlanc, Robert E; Loh, Daniella; Schwartz, Gary J; Yu, Yi-Hao

    2007-06-01

    Leucine, as an essential amino acid and activator of mTOR (mammalian target of rapamycin), promotes protein synthesis and suppresses protein catabolism. However, the effect of leucine on overall glucose and energy metabolism remains unclear, and whether leucine has beneficial effects as a long-term dietary supplement has not been examined. In the present study, we doubled dietary leucine intake via leucine-containing drinking water in mice with free excess to either a rodent chow or a high-fat diet (HFD). While it produced no major metabolic effects in chow-fed mice, increasing leucine intake resulted in up to 32% reduction of weight gain (P < 0.05) and a 25% decrease in adiposity (P < 0.01) in HFD-fed mice. The reduction of adiposity resulted from increased resting energy expenditure associated with increased expression of uncoupling protein 3 in brown and white adipose tissues and in skeletal muscle, while food intake was not decreased. Increasing leucine intake also prevented HFD-induced hyperglycemia, which was associated with improved insulin sensitivity, decreased plasma concentrations of glucagon and glucogenic amino acids, and downregulation of hepatic glucose-6-phosphatase. Additionally, plasma levels of total and LDL cholesterol were decreased by 27% (P < 0.001) and 53% (P < 0.001), respectively, in leucine supplemented HFD-fed mice compared with the control mice fed the same diet. The reduction in cholesterol levels was largely independent of leucine-induced changes in adiposity. In conclusion, increases in dietary leucine intake substantially decrease diet-induced obesity, hyperglycemia, and hypercholesterolemia in mice with ad libitum consumption of HFD likely via multiple mechanisms.

  2. Shortened blood coagulation times in genetically obese rats and diet-induced obese mice.

    PubMed

    Kaji, Noriyuki; Nagakubo, Dai; Hashida, Shin-Ichi; Takahashi, Saya; Kuratani, Motoi; Hirai, Norihiko; Shirai, Mitsuyuki; Asai, Fumitoshi

    2013-01-01

    The aim of this study was to investigate blood coagulation times in genetically obese rats and diet-induced obese (DIO) mice in order to clarify the relationship between visceral obesity and blood coagulation. WBN/Kob-Lepr(fa) (fa/fa) rats, a genetically obese model, exhibited a significantly shorter activated partial thromboplastin time (aPTT) and prothrombin time (PT) than age-matched Wistar rats. C57BL/6J mice fed a high-fat diet (60%), a DIO model, exhibited significantly shorter aPTT, PT and thrombin time than lean mice fed a standard diet. Higher body weight, visceral fat weight and insulin resistance were also shared by fa/fa rats and DIO mice. These results suggest that visceral obesity is related to accelerated blood coagulation in addition to disrupted metabolism of glucose and lipids.

  3. Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats.

    PubMed

    Iyer, Abishek; Kauter, Kathleen; Alam, Md Ashraful; Hwang, Sung Hee; Morisseau, Christophe; Hammock, Bruce D; Brown, Lindsay

    2012-01-01

    The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.

  4. Antihyperlipidemic and antiatherogenic activities of Terminalia pallida Linn. fruits in high fat diet-induced hyperlipidemic rats

    PubMed Central

    Sampathkumar, M. T.; Kasetti, R. B.; Nabi, S. A.; Sudarshan, P. Renuka; Swapna, S.; Apparao, C.

    2011-01-01

    Hyperlipidemia contributes significantly in the manifestation and development of atherosclerosis and coronary heart disease (CHD). Although synthetic lipid-lowering drugs are useful in treating hyperlipidemia, there are number of adverse effects. So the current interest has stimulated the search for new lipid-lowering agents with minimal side effects from natural sources. The present study was designed to investigate the antihyperlipidemic and antiatherogenic potentiality of ethanolic extract of Terminalia pallida fruits in high fat diet-induced hyperlipidemic rats. T. pallida fruits ethanolic extract (TPEt) was prepared using Soxhlet apparatus. Sprague-Dawley male rats were made hyperlipidemic by giving high fat diet, supplied by NIN (National Institute of Nutrition), Hyderabad, India. TPEt was administered in a dose of 100 mg/kg.b.w./day for 30 days in high fat diet-induced hyperlipidemic rats. The body weights, plasma lipid, and lipoprotein levels were measured before and after the treatment. TPEt showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels coupled together with elevation of high-density lipoprotein cholesterol levels and diminution of atherogenic index in high fat diet-induced hyperlipidemic rats. There was a significantly reduced body weight gain in TPEt-treated hyperlipidemic rats than in the control group. The present study demonstrates that TPEt possesses significant antihyperlipidemic and antiatherogenic properties, thus suggesting its beneficial effect in the treatment of cardiovascular diseases. PMID:21966168

  5. Antihyperlipidemic and antiatherogenic activities of Terminalia pallida Linn. fruits in high fat diet-induced hyperlipidemic rats.

    PubMed

    Sampathkumar, M T; Kasetti, R B; Nabi, S A; Sudarshan, P Renuka; Swapna, S; Apparao, C

    2011-07-01

    Hyperlipidemia contributes significantly in the manifestation and development of atherosclerosis and coronary heart disease (CHD). Although synthetic lipid-lowering drugs are useful in treating hyperlipidemia, there are number of adverse effects. So the current interest has stimulated the search for new lipid-lowering agents with minimal side effects from natural sources. The present study was designed to investigate the antihyperlipidemic and antiatherogenic potentiality of ethanolic extract of Terminalia pallida fruits in high fat diet-induced hyperlipidemic rats. T. pallida fruits ethanolic extract (TPEt) was prepared using Soxhlet apparatus. Sprague-Dawley male rats were made hyperlipidemic by giving high fat diet, supplied by NIN (National Institute of Nutrition), Hyderabad, India. TPEt was administered in a dose of 100 mg/kg.b.w./day for 30 days in high fat diet-induced hyperlipidemic rats. The body weights, plasma lipid, and lipoprotein levels were measured before and after the treatment. TPEt showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels coupled together with elevation of high-density lipoprotein cholesterol levels and diminution of atherogenic index in high fat diet-induced hyperlipidemic rats. There was a significantly reduced body weight gain in TPEt-treated hyperlipidemic rats than in the control group. The present study demonstrates that TPEt possesses significant antihyperlipidemic and antiatherogenic properties, thus suggesting its beneficial effect in the treatment of cardiovascular diseases.

  6. Antihyperlipidemic and antiatherogenic activities of Terminalia pallida Linn. fruits in high fat diet-induced hyperlipidemic rats.

    PubMed

    Sampathkumar, M T; Kasetti, R B; Nabi, S A; Sudarshan, P Renuka; Swapna, S; Apparao, C

    2011-07-01

    Hyperlipidemia contributes significantly in the manifestation and development of atherosclerosis and coronary heart disease (CHD). Although synthetic lipid-lowering drugs are useful in treating hyperlipidemia, there are number of adverse effects. So the current interest has stimulated the search for new lipid-lowering agents with minimal side effects from natural sources. The present study was designed to investigate the antihyperlipidemic and antiatherogenic potentiality of ethanolic extract of Terminalia pallida fruits in high fat diet-induced hyperlipidemic rats. T. pallida fruits ethanolic extract (TPEt) was prepared using Soxhlet apparatus. Sprague-Dawley male rats were made hyperlipidemic by giving high fat diet, supplied by NIN (National Institute of Nutrition), Hyderabad, India. TPEt was administered in a dose of 100 mg/kg.b.w./day for 30 days in high fat diet-induced hyperlipidemic rats. The body weights, plasma lipid, and lipoprotein levels were measured before and after the treatment. TPEt showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels coupled together with elevation of high-density lipoprotein cholesterol levels and diminution of atherogenic index in high fat diet-induced hyperlipidemic rats. There was a significantly reduced body weight gain in TPEt-treated hyperlipidemic rats than in the control group. The present study demonstrates that TPEt possesses significant antihyperlipidemic and antiatherogenic properties, thus suggesting its beneficial effect in the treatment of cardiovascular diseases. PMID:21966168

  7. Loss of SFRP4 Alters Body Size, Food Intake, and Energy Expenditure in Diet-Induced Obese Male Mice.

    PubMed

    Mastaitis, Jason; Eckersdorff, Mark; Min, Soo; Xin, Yurong; Cavino, Katie; Aglione, Johnpaul; Okamoto, Haruka; Na, Erqian; Stitt, Trevor; Dominguez, Melissa G; Schmahl, Jennifer P; Lin, Calvin; Gale, Nicholas W; Valenzuela, David M; Murphy, Andrew J; Yancopoulos, George D; Gromada, Jesper

    2015-12-01

    Secreted frizzled-related protein 4 (SFRP4) is an extracellular regulator of the wingless-type mouse mammary tumor virus integration site family (WNT) pathway. SFRP4 has been implicated in adipocyte dysfunction, obesity, insulin resistance, and impaired insulin secretion in patients with type 2 diabetes. However, the exact role of SFRP4 in regulating whole-body metabolism and glucose homeostasis is unknown. We show here that male Sfrp4(-/-) mice have increased spine length and gain more weight when fed a high-fat diet. The body composition and body mass per spine length of diet-induced obese Sfrp4(-/-) mice is similar to wild-type littermates, suggesting that the increase in body weight can be accounted for by their longer body size. The diet-induced obese Sfrp4(-/-) mice have reduced energy expenditure, food intake, and bone mineral density. Sfrp4(-/-) mice have normal glucose and insulin tolerance and β-cell mass. Diet-induced obese Sfrp4(-/-) and control mice show similar impairments of glucose tolerance and a 5-fold compensatory expansion of their β-cell mass. In summary, our data suggest that loss of SFRP4 alters body length and bone mineral density as well as energy expenditure and food intake. However, SFRP4 does not control glucose homeostasis and β-cell mass in mice.

  8. Diet-induced obesity and mammary tumor development in MMTV-neu female mice.

    PubMed

    Cleary, Margot P; Grande, Joseph P; Juneja, Subhash C; Maihle, Nita J

    2004-01-01

    Obesity is a risk factor for postmenopausal breast cancer and is associated with shortened latency and/or increased mammary tumor (MT) incidence in animals. Elevated body weight is usually associated with hormone-responsive tumors. In agreement with these data we previously showed that latency of hormone-responsive MTs in MMTV-TGF-alpha mice with diet-induced obesity was significantly shortened. Here, we used the same protocol to determine the impact of diet-induced obesity on estrogen receptor-negative MT development in MMTV-neu (strain 202) mice. Mice were fed a low-fat diet (n=20) or a high-fat diet (n=54) from 10 wk of age. Body weight at 19 wk of age was used to assign high-fat mice to obesity-prone, overweight, and obesity-resistant groups. Mice were euthanized due to MT size or at 85 wk of age. Final body weights of obesity-prone mice were heaviest, and those of obesity-resistant and low-fat groups were similar. Fat pad weights were heaviest in obesity-prone mice followed by overweight and obesity-resistant groups, and lightest in low-fat mice. Serum IGF-I levels were similar for low-fat and high-fat mice, whereas leptin was higher in high-fat mice (P <0.0001). MT latency, incidence, metastasis, and burden were similar for all groups. These findings support that obesity is not a risk factor for development of estrogen-negative breast cancer.

  9. Cannabinoid receptor 1 antagonist treatment induces glucagon release and shows an additive therapeutic effect with GLP-1 agonist in diet-induced obese mice.

    PubMed

    Patel, Kartikkumar Navinchandra; Joharapurkar, Amit Arvind; Patel, Vishal; Kshirsagar, Samadhan Govind; Bahekar, Rajesh; Srivastava, Brijesh Kumar; Jain, Mukul R

    2014-12-01

    Cannabinoid 1 (CB1) receptor antagonists reduce body weight and improve insulin sensitivity. Preclinical data indicates that an acute dose of CB1 antagonist rimonabant causes an increase in blood glucose. A stable analog of glucagon-like peptide 1 (GLP-1), exendin-4 improves glucose-stimulated insulin secretion in pancreas, and reduces appetite through activation of GLP-1 receptors in the central nervous system and liver. We hypothesized that the insulin secretagogue effect of GLP-1 agonist exendin-4 may synergize with the insulin-sensitizing action of rimonabant. Intraperitoneal as well as intracerebroventricular administration of rimonabant increased serum glucose upon glucose challenge in overnight fasted, diet-induced obese C57 mice, with concomitant rise in serum glucagon levels. Exendin-4 reversed the acute hyperglycemia induced by rimonabant. The combination of exendin-4 and rimonabant showed an additive effect in the food intake, and sustained body weight reduction upon repeated dosing. The acute efficacy of both the compounds was additive for inducing nausea-like symptoms in conditioned aversion test in mice, whereas exendin-4 treatment antagonized the effect of rimonabant on forced swim test upon chronic dosing. Thus, the addition of exendin-4 to rimonabant produces greater reduction in food intake owing to increased aversion, but reduces the other central nervous system side effects of rimonabant. The hyperglucagonemia induced by rimonabant is partially responsible for enhancing the antiobesity effect of exendin-4. PMID:25361428

  10. αB-crystallin and HspB2 deficiency is protective from diet-induced glucose intolerance.

    PubMed

    Toft, Daniel J; Fuller, Miles; Schipma, Matthew; Chen, Feng; Cryns, Vincent L; Layden, Brian T

    2016-09-01

    Emerging evidence suggests molecular chaperones have a role in the pathogenesis of obesity and diabetes. As αB-crystallin and HspB2 are molecular chaperones and data suggests their expression is elevated in the skeletal muscle of diabetic and obese animals, we sought to determine if αB-crystallin and HspB2 collectively play a functional role in the metabolic phenotype of diet-induced obesity. Using αB-crystallin/HspB2 knockout and littermate wild-type controls, it was observed that mice on the high fat diet gained more weight as compared to the normal chow group and genotype did not impact this weight gain. To test if the genotype and/or diet influenced glucose homeostasis, intraperitoneal glucose challenge was performed. While similar on normal chow diet, wild-type mice on the high fat diet exhibited higher glucose levels during the glucose challenge compared to the αB-crystallin/HspB2 knockout mice. Although wild-type mice had higher glucose levels, insulin levels were similar for both genotypes. Insulin tolerance testing revealed that αB-crystallin/HspB2 knockout mice were more sensitive to insulin, leading to lower glucose levels over time, which is indicative of a difference in insulin sensitivity between the genotypes on a high fat diet. Transcriptome analyses of skeletal muscle in αB-crystallin/HspB2 knockout and wild-type mice on a normal or high fat diet revealed reductions in cytokine pathway genes in αB-crystallin/HspB2 knockout mice, which may contribute to their improved insulin sensitivity. Collectively, these data reveal that αB-crystallin/HspB2 plays a role in development of insulin resistance during a high fat diet challenge. PMID:27330996

  11. When Should Open Reduction and Internal Fixation Ankle Fractures Begin Weight Bearing? A Systematic Review.

    PubMed

    Smith, Toby O; Davies, Leigh

    2008-02-01

    The objective of this paper was to review the literature to assess when open reduction and internal fixation ankle fractures should commence weight bearing for the best outcome. An electronic search was undertaken of the databases AMED, Cinahl, Embase, Medline (via Ovid), Pedro and Pubmed, from their inception to November 2005. References lists were scrutinised and a hand search was also performed. We included all English language, human subject, controlled clinical trials, comparing the effects of early against later weight bearing following open reduction and internal fixation of ankle fractures. Two reviewers independently assessed the methodological quality of the literature using the PEDro (Physiotherapy Evidence Database) scoring system. Five papers comprising of 366 ankle fractures were reviewed. Overall, there was no significant difference between commencing early, compared to later weight bearing in subjects following open reduction and internal fixation, when evaluated against function, pain, range of movement, radiological assessment, complications, and return to work. The evidence reviewed was generally poor, with numerous methodological design limitations. The literature suggested that were was little difference between encouraging early or delayed weight bearing after open reduction and internal fixation of ankle fractures. Neither early nor later weight bearing significantly improves or jeopardises outcomes. However, due to the plethora of methodological limitations and limited evidence, it is not possible to reference this conclusion with conviction. Further large, well-designed randomized controlled trials are required to evaluate this area. PMID:26815494

  12. A study of electrical conductance of meridian in the obese during weight reduction.

    PubMed

    Weng, Ching-Sung; Hung, Yu-Li; Shyu, Liang-Yu; Chang, Yung-Hsien

    2004-01-01

    This study was designed to investigate the electrical conductance of meridian in the obese during weight reduction. Ten obese including overweight (Body Mass Index, BMI > 26) and 30 healthy (non-overweight) people were recruited from Chung Yuan Christian University. The obese subjects were instructed to follow a weight reduction program that included diet control, exercise and oral intake of Prozac. A device, the design of which is based on the Ryodoraku theorem, was used to measure the electrical conductance of 12 meridians on both sides of the subjects. The results showed that: (1) the average coefficient of variation of the electrical conductances in 24 meridians of the obese group was statistically different from that of the healthy group (p < 0.05); (2) the average coefficient of variation of electrical conductance in the obese after weight reduction was significantly decreased than before the weight reduction program (p < 0.05); (3) the BMI and the electrical conductance of meridian was correlated in the obese (r = -0.77, p < 0.001) as well as in the healthy group (r = -0.92, p < 0.001). These findings suggest that electrical conductance of meridians can be a parameter to monitor weight, especially for obese people. PMID:15344425

  13. Metabolic Effects of Sleeve Gastrectomy in a Female Rat Model of Diet-Induced Obesity

    PubMed Central

    Brinckerhoff, Tatiana Z.; Bondada, Sandhya; Lewis, Catherine E.; French, Sam; DeUgarte, Daniel A.

    2011-01-01

    Background While females disproportionately undergo bariatric surgery, rodent models investigating mechanisms of bariatric surgery have been limited to males. Female rodent models can also potentially allow us to understand the effects of surgical intervention on future generations of offspring. Sleeve gastrectomy is an attractive weight loss procedure for reproductive-age female patients as it avoids the malabsorption associated with intestinal bypass. Objectives We sought to evaluate the impact of sleeve gastrectomy on young female rats with diet-induced obesity. Settings David Geffen School of Medicine at UCLA Methods Sprague Dawley female rats were fed a 60% high-fat diet. At 12 weeks of age, animals underwent either sleeve gastrectomy or sham surgery. Animals were sacrificed four weeks after surgery. A chemistry panel was performed, and serum adipokines and gut hormones were assayed. Homeostasis model assessment score (HOMA) was calculated. Liver histology was graded for steatosis. Two-sample t-test was used to compare groups. Results Sleeve gastrectomy was associated with significant weight loss (5±6% vs. −4±6%; p<0.001), lower leptin levels (1.3±1.2 vs. 3.5±2.3 ng/ml; p<0.01), and higher adiponectin levels (0.43 ± 0.19 vs. 0.17 ± 0.14 ng/ml; p<0.004) when compared to sham animals. There were no significant differences in fasting ghrelin. Furthermore, we did not observe evidence of insulin resistance or steatohepatitis after 11 weeks of high-fat diet. Despite these limitations, further gender-specific studies are warranted given that the majority of bariatric surgeries are performed in females. Conclusion Sleeve gastrectomy appears to result in weight loss and improvements in adiponectin and leptin via mechanisms independent of ghrelin in a female model of diet-induced obesity. PMID:22093377

  14. Prevention of diet-induced hepatic steatosis and hepatic insulin resistance by second generation antisense oligonucleotides targeted to the longevity gene mIndy (Slc13a5).

    PubMed

    Pesta, Dominik H; Perry, Rachel J; Guebre-Egziabher, Fitsum; Zhang, Dongyan; Jurczak, Michael; Fischer-Rosinsky, Antje; Daniels, Martin A; Willmes, Diana M; Bhanot, Sanjay; Bornstein, Stefan R; Knauf, Felix; Samuel, Varman T; Shulman, Gerald I; Birkenfeld, Andreas L

    2015-12-01

    Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life span by mechanisms resembling caloric restriction. Similarly, deletion of the mammalian homolog, mIndy (Slc13a5), encoding for a plasma membrane tricarboxylate transporter, protects from aging- and diet-induced adiposity and insulin resistance in mice. The organ specific contribution to this phenotype is unknown. We examined the impact of selective inducible hepatic knockdown of mIndy on whole body lipid and glucose metabolism using 2'-O-methoxyethyl chimeric anti-sense oligonucleotides (ASOs) in high-fat fed rats. 4-week treatment with 2'-O-methoxyethyl chimeric ASO reduced mIndy mRNA expression by 91% (P=0.001) compared to control ASO. Besides similar body weights between both groups, mIndy-ASO treatment lead to a 74% reduction in fasting plasma insulin concentrations as well as a 35% reduction in plasma triglycerides. Moreover, hepatic triglyceride content was significantly reduced by the knockdown of mIndy, likely mediating a trend to decreased basal rates of endogenous glucose production as well as an increased suppression of hepatic glucose production by 25% during a hyperinsulinemic-euglycemic clamp. Together, these data suggest that inducible liver-selective reduction of mIndy in rats is able to ameliorate hepatic steatosis and insulin resistance, conditions occurring with high calorie diets and during aging. PMID:26647160

  15. The effects of prior weight reduction on the running wheel-induced feeding suppression in rats.

    PubMed

    Hertel, Amanda; Botzang, Laura; Parfeniuk, Graham G; Eikelboom, Roelof

    2009-09-01

    Adult male rats given ad lib access to food and a running wheel show an initial feeding and weight suppression. Over 6-10 days feeding recovers, but body weight remains low. It is not clear which effect is primary, the wheel-induced feeding or weight change. To test this, rats were first restricted to 15g of food a day for 8 or 16 days to reduce their weight relative to control non-restricted rats. They were then returned to ad lib feeding and half the restricted and non-restricted control rats were introduced to the wheel either immediately (Experiment 1) or 4 days later (Experiment 2). Food intake, body weight, and wheel running were monitored throughout the experiments. At the return to ad lib feeding, prior food restriction elevated feeding. Both immediate and delayed wheel access suppressed feeding in both groups of wheel access rats compared to the appropriate control rats. Feeding history did not have a significant effect on wheel running. The wheel-induced reductions in feeding from baseline were similar in the weight reduced and normal weight animals suggesting that prior weight restriction did not prevent the onset of the wheel-induced feeding suppression. It is therefore suggested that the feeding suppression is not driven by a reduced weight set point.

  16. Alliance for a Healthy Border: factors related to weight reduction and glycemic success.

    PubMed

    Wang, Xiaohui; Ghaddar, Suad; Brown, Cynthia; Pagán, José A; Balboa, Marvelia

    2012-04-01

    We examined the factors related to success in achieving weight reduction and glycemic control in Alliance for a Healthy Border (AHB), a chronic disease prevention program implemented from 2006 to 2009 through 12 federally qualified community health centers serving primarily Hispanics in communities located along the US-Mexico border region. We analyzed data from Phase I of AHB using logistic regression to examine the determinants of success in achieving weight reduction and glycemic control among the participants in AHB programs. Factors affecting weight reduction success were sex, age, employment status, income, insurance, diabetes, baseline body mass index (BMI), smoking status, family history of diabetes, session type, program duration, and physical activity changes. Factors affecting achievement of glycemic success included sex, age, employment status, diabetes, baseline BMI, family history of diabetes, program duration, and physical activity changes. We found that the AHB interventions were more successful in reducing participants' HbA1c level than BMI. In addition to sociodemographic factors, participants with better baseline health conditions (ie, participants without diabetes or family history of diabetes, normal BMI, former smokers) were more likely to achieve success after the interventions. Of the 4 key features defining each of the 12 interventions, session type and program duration were associated with success. Within a relatively short time period, physical activity improvements had a stronger effect on weight reduction and glycemic success than improvements in dietary habits. The effectiveness of diabetes and cardiovascular disease prevention programs can be improved substantially by considering these factors during program design and structure.

  17. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  18. A Comparison of Two Weight Reduction Programs for Moderately Retarded Adolescents.

    ERIC Educational Resources Information Center

    Rotatori, Anthony T.; Fox, Robert

    A study of obesity management contrasted the effectiveness for 30 moderately mentally retarded adolescents of a multicomponent behavioral weight reduction program with a more traditional, nutrition based approach. Twelve Ss each were assigned to a behavior therapy (BT) and a social nutrition (SN) group, with the remaining six Ss in a wait-list…

  19. An Original Behavior Modification Program for Weight Reduction: Minimal Intervention and Permanent Habit Change.

    ERIC Educational Resources Information Center

    Lublin, Irwin; Kirkish, Patricia

    This description of a weight reduction program, based on generalizations derived from eight years of work with overweight persons, discusses the clients' rationalization of overeating behaviors. In this behavior modification program, the client is required to permanently give up one high calorie food and to write down all foods eaten before actual…

  20. The development of a rating scale for the prediction of success in weight reduction.

    PubMed

    Dash, J D; Brown, R A

    1977-07-01

    A valid and reliable rating instrument was developed that has predictive value with regard to the ability to lose weight. The major constructs that the test was intended to measure were knowledge of the pragmatics of weight reduction and obesity and the role of fantasy in weight loss. Test items were drawn from research findings in the obesity literature and from subject matter experts in the fields of nutrition, internal medicine and clinical psychology. Test-retest reliability coefficients for the new instrument range from .64 to .95. Construct validity was ascertained through administration of the scale to groups of high school students (N=20), college nutrition students (N=30) and successful and unsuccessful dieters (Ns=28 and 20, respectively). It appears that the scale, The Dash-Brown Survey of Fact and Fiction in Weight Reduction (DBS), may be employed usefully to assess the remediability of obesity for potential dieters. The data further suggest that cognitive awareness of diet-related issues is significant in weight reduction.

  1. Successful maintenance of body weight reduction after individualized dietary counseling in obese subjects

    PubMed Central

    Stelmach-Mardas, Marta; Mardas, Marcin; Warchoł, Wojciech; Jamka, Małgorzata; Walkowiak, Jarosław

    2014-01-01

    The aim of this study was to describe the effectiveness of individualized dietary counseling in obese subjects based on narrative interview technique on the maintenance of body weight reduction, changes in dietary behaviors, including type of cooking and physical activity. One-hundred subjects out of four-hundred patients met the inclusion criteria. Individually, 45-minute educational program with motivation counseling was performed in 0, 6 and 12 weeks of the study. Patients were advised to follow individually well-balanced diet for 12 weeks. The individuals were asked about the changes in their dietary habits (Food Frequency Questionnaire). The mean percentage of body weight changes from the baseline were as follows: in 6th week- 5.9%, in 12th week - 10.9% and in 52th week - 9.7% (P < 0.0001), however there were no statistically significant changes while comparing body weight in 12th and 52th week. The maintenance of body weight reduction was connected with the dietary habits changes, mainly the type of cooking and increased consumption of vegetable oils. In conclusion, individualized dietary counseling, based on narrative interview technique is an effective intervention for obesity treatment that may help maintain body weight reduction and adapt the pro-healthy changes in type of cooking and sources of dietary fat. PMID:25311271

  2. Successful maintenance of body weight reduction after individualized dietary counseling in obese subjects.

    PubMed

    Stelmach-Mardas, Marta; Mardas, Marcin; Warchoł, Wojciech; Jamka, Małgorzata; Walkowiak, Jarosław

    2014-10-14

    The aim of this study was to describe the effectiveness of individualized dietary counseling in obese subjects based on narrative interview technique on the maintenance of body weight reduction, changes in dietary behaviors, including type of cooking and physical activity. One-hundred subjects out of four-hundred patients met the inclusion criteria. Individually, 45-minute educational program with motivation counseling was performed in 0, 6 and 12 weeks of the study. Patients were advised to follow individually well-balanced diet for 12 weeks. The individuals were asked about the changes in their dietary habits (Food Frequency Questionnaire). The mean percentage of body weight changes from the baseline were as follows: in 6th week- 5.9%, in 12th week - 10.9% and in 52th week - 9.7% (P < 0.0001), however there were no statistically significant changes while comparing body weight in 12th and 52th week. The maintenance of body weight reduction was connected with the dietary habits changes, mainly the type of cooking and increased consumption of vegetable oils. In conclusion, individualized dietary counseling, based on narrative interview technique is an effective intervention for obesity treatment that may help maintain body weight reduction and adapt the pro-healthy changes in type of cooking and sources of dietary fat.

  3. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice

    PubMed Central

    Fagman, Johan B.; Wilhelmson, Anna S.; Motta, Benedetta M.; Pirazzi, Carlo; Alexanderson, Camilla; De Gendt, Karel; Verhoeven, Guido; Holmäng, Agneta; Anesten, Fredrik; Jansson, John-Olov; Levin, Malin; Borén, Jan; Ohlsson, Claes; Krettek, Alexandra; Romeo, Stefano; Tivesten, Åsa

    2015-01-01

    Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)–dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)–deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (−41%; thoracic aorta), subcutaneous fat mass (−44%), and cholesterol levels (−35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism.—Fagman, J. B., Wilhelmson, A. S., Motta, B. M., Pirazzi, C., Alexanderson, C., De Gendt, K., Verhoeven, G., Holmäng, A., Anesten, F., Jansson, J.-O., Levin, M., Borén, J., Ohlsson, C., Krettek, A., Romeo, S., Tivesten, A. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice. PMID:25550469

  4. Chlorogenic Acid Improves High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice

    PubMed Central

    Ma, Yongjie; Gao, Mingming

    2015-01-01

    Purpose Chlorogenic acid (CGA), the most abundant component in coffee, has exhibited many biological activities. The objective of this study is to assess preventive and therapeutic effects of CGA on obesity and obesity-related liver steatosis and insulin resistance. Methods Two sets of experiments were conducted. In set 1, 6-week old C57BL/6 mice were fed a regular chow or high-fat diet (HFD) for 15 weeks with twice intra-peritoneal (IP) injection of CGA (100 mg/kg) or DMSO (carrier solution) per week. In set 2, obese mice (average 50 g) were treated by CGA (100 mg/kg, IP, twice weekly) or DMSO for 6 weeks. Body weight, body composition and food intake were monitored. Blood glucose, insulin and lipid levels were measured at end of the study. Hepatic lipid accumulation and glucose homeostasis were evaluated. Additionally, genes involved in lipid metabolism and inflammation were analyzed by real time PCR. Results CGA significantly blocked the development of diet-induced obesity but did not affect body weight in obese mice. CGA treatment curbed HFD-induced hepatic steatosis and insulin resistance. Quantitative PCR analysis shows that CGA treatment suppressed hepatic expression Pparγ, Cd36, Fabp4, and Mgat1 gene. CGA treatment also attenuated inflammation in the liver and white adipose tissue accompanied by a decrease in mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and Tnfa, Mcp-1 and Ccr2 encoding inflammatory proteins. Conclusion Our study provides direct evidence in support of CGA as a potent compound in preventing diet-induced obesity and obesity-related metabolic syndrome. Our results suggest that drinking coffee is beneficial in maintaining metabolic homeostasis when on a high fat diet. PMID:25248334

  5. Genetic Dissection of Tissue-Specific Apolipoprotein E Function for Hypercholesterolemia and Diet-Induced Obesity

    PubMed Central

    Schlein, Christian; Heeren, Joerg

    2015-01-01

    ApoE deficiency in mice (Apoe−/−) results in severe hypercholesterolemia and atherosclerosis. In diet-induced obesity, Apoe−/− display steatohepatitis but reduced accumulation of triacylglycerides and enhanced insulin sensitivity in white adipose tissue (WAT). Although the vast majority of apoE is expressed by hepatocytes apoE is also abundantly expressed in WAT. As liver and adipose tissue play important roles for metabolism, this study aims to outline functions of both hepatocyte- and adipocyte-derived apoE separately by investigating a novel mouse model of tissue-specific apoE deficiency. Therefore we generated transgenic mice carrying homozygous floxed Apoe alleles. Mice lacking apoE either in hepatocytes (ApoeΔHep) or in adipose tissue (ApoeΔAT) were fed experimental diets. ApoeΔHep exhibited slightly higher body weights, adiposity and liver weights on diabetogenic high fat diet (HFD). Accordingly, hepatic steatosis and markers of inflammation were more pronounced compared to controls. Hypercholesterolemia evoked by lipoprotein remnant accumulation was present in ApoeΔHep mice fed a Western type diet (WTD). Lipidation of VLDL particles and tissue uptake of VLDL were disturbed in ApoeΔHep while the plasma clearance rate remained unaltered. ApoeΔAT did not display any detectable phenotype, neither on HFD nor on WTD. In conclusion, our novel conditional apoE deletion model has proven here the role of hepatocyte apoE for VLDL production and diet-induced dyslipidemia. Specific deletion of apoE in adipocytes cannot reproduce the adipose phenotype of global Apoe−/− mice, suggesting that apoE produced in other cell types than hepatocytes or adipocytes explains the lean and insulin-sensitive phenotype described for Apoe−/− mice. PMID:26695075

  6. Ineffectiveness of human chorionic gonadotropin in weight reduction: a double-blind study.

    PubMed

    Stein, M R; Julis, R E; Peck, C C; Hinshaw, W; Sawicki, J E; Deller, J J

    1976-09-01

    Our investigation was designed to retest the hypothesis of the efficacy of human chorionic gonadotropin (HCG) on weight reduction in obese women in a clinic setting. We sought to duplicate the Asher-Harper study (1973) which had found that the combination of 500 cal diet and HCG had a statistically significant benefit over the diet and placebo combination as evidenced by greater weight loss and decrease in hunger. Fifty-one women between the ages of 18 and 60 participated in our 32-day prospective, randomized, double-blind comparison of HCG versus placebo. Each patient was given the same diet (the one prescribed in the Asher-Harper study), was weighed daily Monday through Saturday and was counselled by one of the investigators who administered the injections. Laboratory studies were performed at the time of initial physical examinations and at the end of the study. Twenty of 25 in the HCG and 21 of 26 patients in the placebo groups completed 28 injections. There was no statistically significant difference in the means of the two groups in number of injections received, weight loss, percent of weight loss, hip and waist circumference, weight loss per injections, or in hunger ratings. HCG does not appear to enhance the effectiveness of a rigidly imposed regimen for weight reduction. PMID:786001

  7. The phospholipase A2 inhibitor methyl indoxam suppresses diet-induced obesity and glucose intolerance in mice

    PubMed Central

    Hui, DY; Cope, MJ; Labonté, ED; Chang, H-T; Shao, J; Goka, E; Abousalham, A; Charmot, D; Buysse, J

    2009-01-01

    Background and purpose: Previous results have shown that mice lacking in the group 1B phospholipase A2 (Pla2g1b) are resistant to obesity and diabetes induced by feeding a diabetogenic high-fat/high-carbohydrate diet. This study examined the potential of using the Pla2g1b inhibitor methyl indoxam as therapy to suppress diet-induced obesity and diabetes. Experimental approach: Male C57BL/6 mice were fed the diabetogenic diet with or without methyl indoxam supplementation. Body weight gain, fasting plasma glucose levels, glucose tolerance and postprandial lysophospholipid absorption were compared. Key results: Wild-type C57BL/6 mice fed the diabetogenic diet without Pla2g1b inhibitor showed 31 and 69% body weight gain after 4 and 10 weeks respectively. These animals also showed elevated plasma glucose levels and were glucose intolerant. In contrast, C57BL/6 mice fed the diabetogenic diet with 90 mg·kg−1 of methyl indoxam gained only 5% body weight after 10 weeks. These animals were also euglycaemic and displayed normal glucose excursion rates in glucose tolerance test. Methyl indoxam suppression of diet-induced body weight gain and glucose intolerance was correlated with the inhibition of Pla2g1b-mediated postprandial lysophospholipid absorption. Conclusions and implications: These results show that oral supplementation of a diabetogenic diet with the Pla2g1b inhibitor methyl indoxam effectively suppresses diet-induced obesity and diabetes in mice. This suggests that Pla2g1b inhibition may be a potentially effective oral therapeutic option for treatment of obesity and diabetes. PMID:19563529

  8. Cuidando El Corazon--a weight-reduction intervention for Mexican Americans.

    PubMed

    Foreyt, J P; Ramirez, A G; Cousins, J H

    1991-06-01

    Cuidando El Corazon (CEC; Taking Care of Your Heart) was designed to assess the effectiveness of a culturally adapted weight-reduction and exercise program for achieving long-term weight loss in Mexican Americans. CEC used a family-oriented approach to achieve lifestyle change in behavior. Participants were assigned to 1) a booklet-only comparison group that received a manual including behavior change, nutrition, and exercise information and traditional recipes modified in fat content; 2) an individual group that received the same manual and attended year-long classes; or 3) a family group that received a manual and attended classes that emphasized techniques for making changes in the family's eating and exercising habits. The family and individual groups had significantly greater weight losses than the information-only group. Weight loss was greatest in the family-involvement group and least in the information-only comparison group.

  9. Weight reduction effect of Puerh tea in male patients with metabolic syndrome.

    PubMed

    Yang, Tsung-Yuan; Chou, Janet I; Ueng, Kwo-Chang; Chou, Ming-Yung; Yang, Jaw-Ji; Lin-Shiau, Shoei-Yn; Hu, Ming-E; Lin, Jen-Kun

    2014-07-01

    Puerh tea has been proposed to promote weight loss and favorably modify glucose, insulin and blood lipids. This study tested the effect of daily Puerh tea consumption for 3 months on weight and body mass index (BMI), and select metabolic parameters. The effect of daily Puerh tea intake on weight, BMI and changes in glucose, HbA1c and lipids was evaluated in patients with metabolic syndrome. The patients (N = 70) were randomized into two groups: those taking Puerh tea extract capsule (333 mg Puerh tea extract) three times a day and those taking a placebo tea for 3 months. There was a decrease in body weight of 1.3 kg in the Puerh tea group (p = 0.077) versus 0.23 kg in the placebo arm (p = 0.186). There was also a slight decrease in BMI 0.47 kg/m(2) in the Puerh tea group (p = 0.076) versus 0.09 kg/m(2) in the placebo arm (p = 0.185), suggesting a trend of weight change, but without statistical significance. Subgroup analysis of the male patients demonstrated statistically significant improvements in body weight reduction (p = 0.004) and BMI (p = 0.004). However, the change in other metabolic parameters (cholesterol or triglyceride) or HbA1c was not statistically significant. Intake of Puerh tea for 3 months was associated with a slight reduction in body weight and BMI, especially in the male patients. Therefore, daily Puerh tea consumption may be an alternative choice to modify body weight.

  10. Anti-obesity Effect of Yogurt Fermented by Lactobacillus plantarum Q180 in Diet-induced Obese Rats.

    PubMed

    Park, Sun-Young; Seong, Ki-Seung; Lim, Sang-Dong

    2016-01-01

    This study aimed to investigate the anti-obesity effects of yogurt fermented by Lactobacillus plantarum Q180 in diet-induced obese rats. To examine the effects, male Sprague-Dawley rats were fed on six different diets, as follows: Group A was fed an ND and orally administrated saline solution; Group B, an HFD and orally administrated saline solution; Group C, an HFD and orally administrated yogurt fermented by ABT-3 and L. plantarum Q180; Group D, an HFD and orally administrated yogurt with added Garcinia cambogia extract, fermented by ABT-3 and L. plantarum Q180; Group E, an HFD and orally administrated yogurt fermented by L. plantarum Q180; and Group F, an HFD and orally administrated yogurt with added Garcinia cambogia extract, fermented by L. plantarum Q180 for eight weeks. After eight weeks, the rate of increase in bodyweight was 5.14%, 6.5%, 3.35% and 10.81% lower in groups C, D, E and F, respectively, compared with group B; the epididymal fat weight of groups E and F was significantly lower than that of group B; and the level of triglyceride and leptin was significantly reduced in groups C, D, E and F compared to group B. In addition, the level of AST was reduced in group C compared to the other groups. To examine the effects of yogurt on the reduction of adipocyte size, the adipocyte sizes were measured. The number of large-size adipose tissue was less distributed in groups A, C, D, E and F than in group B. PMID:27499667

  11. Anti-obesity Effect of Yogurt Fermented by Lactobacillus plantarum Q180 in Diet-induced Obese Rats

    PubMed Central

    2016-01-01

    This study aimed to investigate the anti-obesity effects of yogurt fermented by Lactobacillus plantarum Q180 in diet-induced obese rats. To examine the effects, male Sprague-Dawley rats were fed on six different diets, as follows: Group A was fed an ND and orally administrated saline solution; Group B, an HFD and orally administrated saline solution; Group C, an HFD and orally administrated yogurt fermented by ABT-3 and L. plantarum Q180; Group D, an HFD and orally administrated yogurt with added Garcinia cambogia extract, fermented by ABT-3 and L. plantarum Q180; Group E, an HFD and orally administrated yogurt fermented by L. plantarum Q180; and Group F, an HFD and orally administrated yogurt with added Garcinia cambogia extract, fermented by L. plantarum Q180 for eight weeks. After eight weeks, the rate of increase in bodyweight was 5.14%, 6.5%, 3.35% and 10.81% lower in groups C, D, E and F, respectively, compared with group B; the epididymal fat weight of groups E and F was significantly lower than that of group B; and the level of triglyceride and leptin was significantly reduced in groups C, D, E and F compared to group B. In addition, the level of AST was reduced in group C compared to the other groups. To examine the effects of yogurt on the reduction of adipocyte size, the adipocyte sizes were measured. The number of large-size adipose tissue was less distributed in groups A, C, D, E and F than in group B. PMID:27499667

  12. Korean red ginseng (Panax ginseng) prevents obesity by inhibiting angiogenesis in high fat diet-induced obese C57BL/6J mice.

    PubMed

    Lee, Hyunghee; Park, Dongmin; Yoon, Michung

    2013-03-01

    Adipose tissue growth and development are thought to be associated with angiogenesis and extracellular matrix remodeling. Because ginseng has been shown to inhibit angiogenesis and matrix metalloproteinase (MMP) activity, we hypothesized that adipose tissue growth and obesity can be regulated by Korean ginseng (Panax ginseng C.A. Meyer). Wild-type C57BL/6J mice were fed for 8 weeks with a low fat diet, a high fat diet (HFD), or HFD supplemented with 0.5% or 5% Korean red ginseng extract. We measured body weight, adipose tissue mass, food intake, MMP activity, and the expression of genes involved in angiogenesis and MMPs. Administering ginseng to HFD-induced obese mice produced reductions in body weight and adipose tissue mass compared with untreated counterparts. Ginseng treatment decreased blood vessel density and MMP activity in adipose tissues. Ginseng also reduced mRNA levels of angiogenic factors (e.g., VEGF-A and FGF-2) and MMPs (e.g., MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (e.g., TSP-1, TIMP-1, and TIMP-2) in adipose tissues. These results demonstrate that ginseng effectively reduces adipose tissue mass and prevents obesity in diet-induced obese mice and that this process may be mediated in part through the anti-angiogenic actions of ginseng.

  13. Effects of Body Weight Reduction on Serum Irisin and Metabolic Parameters in Obese Subjects

    PubMed Central

    Kurose, Satoshi; Shinno, Hiromi; Thi Thu, Ha Cao; Takao, Nana; Tsutsumi, Hiromi; Hasegawa, Takaaki; Nakajima, Toshiaki; Kimura, Yutaka

    2016-01-01

    Background Irisin is a myokine implicated in lipid and glucose metabolism. The objective of this study is to examine the effect of a body weight reduction on the serum irisin level and physical indicators in obese Japanese patients without diabetes. Methods The subjects were 22 patients (male/female, 5/17; age, 46.1±16.0 years; body mass index [BMI], 36.9±5.0 kg/m2) who completed a 6-month body weight reduction program at our clinic. The program included diet, exercise therapy and cognitive behavioral therapy. Blood parameters, body composition, exercise tolerance, homeostasis model assessment of insulin resistance (HOMA-IR), and serum irisin were determined before and after intervention, and relationships among changes in these data were examined. Results There were significant decreases in body weight and BMI after the intervention. Irisin before the intervention was significantly positively correlated with HOMA-IR (r=0.434, P<0.05). The mean irisin level showed no significant change after the intervention in all participants. However, improvements in % body fat, subcutaneous fat area, triglycerides, and fasting glucose were significantly greater in patients with an increase in irisin compared to those with a decrease in irisin after the intervention. Patients with an increase in irisin also had significantly lower fasting insulin (9.7±4.8 vs. 16.4±8.2, P<0.05) and HOMA-IR (2.2±1.1 vs. 3.7±1.6, P<0.05) after the intervention, compared to patients with a decrease in irisin. Conclusion Body weight reduction did not alter irisin levels. However, irisin may play important roles in fat and glucose metabolism and insulin resistance, and the effects of body weight reduction on irisin kinetics may be a key for obesity treatment. PMID:27766246

  14. A Multifactorial Weight Reduction Programme for Children with Overweight and Asthma: A Randomized Controlled Trial

    PubMed Central

    Willeboordse, Maartje; van de Kant, Kim D. G.; Tan, Frans E. S.; Mulkens, Sandra; Schellings, Julia; Crijns, Yvonne; van der Ploeg, Liesbeth; van Schayck, Constant P.; Dompeling, Edward

    2016-01-01

    Background There is increasing evidence that obesity is related to asthma development and severity. However, it is largely unknown whether weight reduction can influence asthma management, especially in children. Objective To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with (a high risk of developing) asthma. Methods An 18-month weight-reduction randomized controlled trial was conducted in 87 children with overweight/obesity and asthma. Every six months, measurements of anthropometry, lung function, lifestyle parameters and inflammatory markers were assessed. Analyses were performed with linear mixed models for longitudinal analyses. Results After 18 months, the body mass index-standard deviation score decreased by -0.14±0.29 points (p<0.01) in the intervention group and -0.12±0.34 points (p<0.01) in the control group. This change over time did not differ between groups (p>0.05). Asthma features (including asthma control and asthma-related quality of life) and lung function indices (static and dynamic) improved significantly over time in both groups. The FVC% predicted improved over time by 10.1 ± 8.7% in the intervention group (p<0.001), which was significantly greater than the 6.1 ± 8.4% in the control group (p<0.05). Conclusions & clinical relevance Clinically relevant improvements in body weight, lung function and asthma features were found in both the intervention and control group, although some effects were more pronounced in the intervention group (FVC, asthma control, and quality of life). This implies that a weight reduction intervention could be clinically beneficial for children with asthma. Trial Registration ClinicalTrials.gov NCT00998413 PMID:27294869

  15. Prediction of Resection Weight in Reduction Mammaplasty Based on Anthropometric Measurements

    PubMed Central

    Kececi, Yavuz; Sir, Emin

    2014-01-01

    Summary Background The aim of this study was to develop a simple, clinically useful method to accurately predict resection weight in women undergoing reduction mammaplasty. Patients and Methods 39 women undergoing breast reduction participated in the study. Sternal notch to nipple distance, nipple to inframammary fold distance (NIMF), medial end point to nipple distance (MN), lateral endpoint to nipple distance (LN), superior border of the breast to nipple distance (SN), breast circumference (BC), and chest circumference (CC) were measured. 5 other predicting variables were also derived; horizontal breast measurement (H) by adding MN to LN, vertical breast measurement (V) by adding NIMF to SN, the product of H and V (H*V), the product of H and NIMF (H*NIMF), and the difference between BC and CC (D). Regression analysis was used to compose a formula for predicting resection weight. Results Among the predicting variables, H*NIMF measurements had the highest correlation coefficient value (Pearson correlation = 0.809) with the resection weight. The following formula was obtained with regression analysis: Predicted resection weight = (1.45 × H*NIMF) + (31.5 × D) – 576. Conclusion Breast resection weights can be accurately predicted by the presented method based on anthropomorphic measurements. PMID:24803886

  16. Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPARγ-Dependent Switch From Lipogenesis to Fat Oxidation.

    PubMed

    den Besten, Gijs; Bleeker, Aycha; Gerding, Albert; van Eunen, Karen; Havinga, Rick; van Dijk, Theo H; Oosterveer, Maaike H; Jonker, Johan W; Groen, Albert K; Reijngoud, Dirk-Jan; Bakker, Barbara M

    2015-07-01

    Short-chain fatty acids (SCFAs) are the main products of dietary fiber fermentation and are believed to drive the fiber-related prevention of the metabolic syndrome. Here we show that dietary SCFAs induce a peroxisome proliferator-activated receptor-γ (PPARγ)-dependent switch from lipid synthesis to utilization. Dietary SCFA supplementation prevented and reversed high-fat diet-induced metabolic abnormalities in mice by decreasing PPARγ expression and activity. This increased the expression of mitochondrial uncoupling protein 2 and raised the AMP-to-ATP ratio, thereby stimulating oxidative metabolism in liver and adipose tissue via AMPK. The SCFA-induced reduction in body weight and stimulation of insulin sensitivity were absent in mice with adipose-specific disruption of PPARγ. Similarly, SCFA-induced reduction of hepatic steatosis was absent in mice lacking hepatic PPARγ. These results demonstrate that adipose and hepatic PPARγ are critical mediators of the beneficial effects of SCFAs on the metabolic syndrome, with clearly distinct and complementary roles. Our findings indicate that SCFAs may be used therapeutically as cheap and selective PPARγ modulators.

  17. Modulatory effect of green tea extract on hepatic key enzymes of glucose metabolism in streptozotocin and high fat diet induced diabetic rats.

    PubMed

    Sundaram, Ramalingam; Naresh, Rajendran; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2013-05-15

    The study was undertaken to evaluate the antidiabetic effect of green tea extract on carbohydrate metabolic key enzymes in control and streptozotocin high fat diet -induced diabetic rats. The daily oral treatment of green tea extract (300 mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of green tea extract. Further, green tea extract administration to diabetic rats improved muscle and hepatic glycogen content suggesting the antihyperglycemic potential of green tea extract in diabetic rats. The obtained results were compared with metformin, a standard oral hypoglycemic drug. Thus, this study indicates that the administration of green tea extract to diabetic rats resulted in alterations in the metabolism of glucose with subsequent reduction in plasma glucose levels.

  18. Chitooligosaccharide ameliorates diet-induced obesity in mice and affects adipose gene expression involved in adipogenesis and inflammation.

    PubMed

    Choi, Eun Hye; Yang, Hyun Pil; Chun, Hyang Sook

    2012-03-01

    Chitooligosaccharide (CO) has been reported to have potential antiobestic effects in a few studies, but the antiobesity properties of CO and its related mechanisms in models of dietary obesity remain unclear. We investigated the effect of CO on body weight gain, size of adipocytes, adipokines, and lipid profiles in high-fat (HF) diet-induced obese mice and on the gene expression in adipose tissue using a complementary DNA microarray approach to test the hypothesis that CO supplementation would alleviate HF diet-induced obesity by the alteration of adipose tissue-specific gene expression. Male C57BL/6N mice were fed a normal diet (control), HF diet, or CO-supplemented HF diet (1% or 3%) for 5 months. Compared with the HF diet mice, mice fed the 3% CO-supplemented diet gained 15% less weight but did not display any change in food and energy intake. Chitooligosaccharide supplementation markedly improved serum and hepatic lipid profiles. Histologic examination showed that epididymal adipocyte size was smaller in mice fed the HF + 3% CO. Microarray analysis showed that dietary CO supplementation modulated adipogenesis-related genes such as matrix metallopeptidases 3, 12, 13, and 14; tissue inhibitor of metalloproteinase 1; and cathepsin k in the adipose tissues. Twenty-five percent of the CO-responsive genes identified are involved in immune responses including the inflammatory response and cytokine production. These results suggest that CO supplementation may help ameliorate HF diet-induced weight gain and improve serum and liver lipid profile abnormalities, which are associated, at least in part, with altered adipose tissue gene expression involved in adipogenesis and inflammation.

  19. [Health risks and economic costs associated with obesity requiring a comprehensive weight reduction program].

    PubMed

    Hainer, V; Kunesová, M; Parízková, J; Stunkard, A

    1997-06-12

    defined a comprehensive weight reduction program carried out in weight reduction clubs, out-patient obesity clinics and in specialized departments attached to the university hospitals. In order to provide an integrated knowledge from many different disciplines connected with obesity three week postgraduate course has been organized for physicians involved in obesity management. Even the most spread weight reduction clubs in our country (STOB) are supervised by the trained counselors. The main goal of different weight management programs is to find out optimal approaches leading to long-term beneficial outcome and ameliorating the variety of disorders associated with obesity. PMID:9333508

  20. Fuel Consumption Reduction and Weight Estimate of an Intercooled-Recuperated Turboprop Engine

    NASA Astrophysics Data System (ADS)

    Andriani, Roberto; Ghezzi, Umberto; Ingenito, Antonella; Gamma, Fausto

    2012-09-01

    The introduction of intercooling and regeneration in a gas turbine engine can lead to performance improvement and fuel consumption reduction. Moreover, as first consequence of the saved fuel, also the pollutant emission can be greatly reduced. Turboprop seems to be the most suitable gas turbine engine to be equipped with intercooler and heat recuperator thanks to the relatively small mass flow rate and the small propulsion power fraction due to the exhaust nozzle. However, the extra weight and drag due to the heat exchangers must be carefully considered. An intercooled-recuperated turboprop engine is studied by means of a thermodynamic numeric code that, computing the thermal cycle, simulates the engine behavior at different operating conditions. The main aero engine performances, as specific power and specific fuel consumption, are then evaluated from the cycle analysis. The saved fuel, the pollution reduction, and the engine weight are then estimated for an example case.

  1. Reduction of food intake and body weight by chronic intraventricular insulin infusion.

    PubMed

    Brief, D J; Davis, J D

    1984-05-01

    This study examined the effect of chronic infusions of insulin in one of three doses (5, 7.5 or 10 mU/day) into the third ventricle, on food and water intake and body weight in the rat. Solutions were infused via osmotic minipumps at a rate of 1 microliter/hour for seven days. The two highest doses of insulin produced a dose-related suppression of food intake and weight loss, which was greater than the effect produced by 5 mU/day or a control infusion of Ringers solution. The effect of 5 mU/day on food and water intake and body weight was similar to the effect of the control infusion. All groups treated with insulin decreased food intake during the day and night, although only differences in nighttime food intake were statistically significant. Ten mU/day also produced a significantly greater reduction in water intake than each of the other solutions. Weight loss in the animals infused with insulin could not be explained by a decrease in caloric intake alone. Food intake returned to normal in all groups by the end of a seven day post-infusion period, with recovery being slowest among the animals receiving the highest doses of insulin. All animals recovered body weight at approximately the same rate. These results provide further evidence for the view that brain insulin plays a role in the regulation of food intake and body weight.

  2. Alliance for a Healthy Border: factors related to weight reduction and glycemic success.

    PubMed

    Wang, Xiaohui; Ghaddar, Suad; Brown, Cynthia; Pagán, José A; Balboa, Marvelia

    2012-04-01

    We examined the factors related to success in achieving weight reduction and glycemic control in Alliance for a Healthy Border (AHB), a chronic disease prevention program implemented from 2006 to 2009 through 12 federally qualified community health centers serving primarily Hispanics in communities located along the US-Mexico border region. We analyzed data from Phase I of AHB using logistic regression to examine the determinants of success in achieving weight reduction and glycemic control among the participants in AHB programs. Factors affecting weight reduction success were sex, age, employment status, income, insurance, diabetes, baseline body mass index (BMI), smoking status, family history of diabetes, session type, program duration, and physical activity changes. Factors affecting achievement of glycemic success included sex, age, employment status, diabetes, baseline BMI, family history of diabetes, program duration, and physical activity changes. We found that the AHB interventions were more successful in reducing participants' HbA1c level than BMI. In addition to sociodemographic factors, participants with better baseline health conditions (ie, participants without diabetes or family history of diabetes, normal BMI, former smokers) were more likely to achieve success after the interventions. Of the 4 key features defining each of the 12 interventions, session type and program duration were associated with success. Within a relatively short time period, physical activity improvements had a stronger effect on weight reduction and glycemic success than improvements in dietary habits. The effectiveness of diabetes and cardiovascular disease prevention programs can be improved substantially by considering these factors during program design and structure. PMID:22506803

  3. Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis.

    PubMed Central

    Hoeg, J M; Santamarina-Fojo, S; Bérard, A M; Cornhill, J F; Herderick, E E; Feldman, S H; Haudenschild, C C; Vaisman, B L; Hoyt, R F; Demosky, S J; Kauffman, R D; Hazel, C M; Marcovina, S M; Brewer, H B

    1996-01-01

    Lecithin:cholesterol acyltransferase (LCAT) is a key plasma enzyme in cholesterol and high density lipoprotein (HDL) metabolism. Transgenic rabbits overexpressing human LCAT had 15-fold greater plasma LCAT activity that nontransgenic control rabbits. This degree of overexpression was associated with a 6.7-fold increase in the plasma HDL cholesterol concentration in LCAT transgenic rabbits. On a 0.3% cholesterol diet, the HDL cholesterol concentrations increased from 24 +/- 1 to 39 +/- 3 mg/dl in nontransgenic control rabbits (n = 10; P < 0.05) and increased from 161 +/- 5 to 200 +/- 21 mg/dl (P < 0.001) in the LCAT transgenic rabbits (n = 9). Although the baseline non-HDL concentrations of control (4 +/- 3 mg/dl) and transgenic rabbits (18 +/- 4 mg/dl) were similar, the cholesterol-rich diet raised the non-HDL cholesterol concentrations, reflecting the atherogenic very low density, intermediate density, and low density lipoprotein particles observed by gel filtration chromatography. The non-HDL cholesterol rose to 509 +/- 57 mg/dl in controls compared with only 196 +/- 14 mg/dl in the LCAT transgenic rabbits (P < 0.005). The differences in the plasma lipoprotein response to a cholesterol-rich diet observed in the transgenic rabbits paralleled the susceptibility to developing aortic atherosclerosis. Compared with nontransgenic controls, LCAT transgenic rabbits were protected from diet-induced atherosclerosis with significant reductions determined by both quantitative planimetry (-86%; P < 0.003) and quantitative immunohistochemistry (-93%; P < 0.009). Our results establish the importance of LCAT in the metabolism of both HDL and apolipoprotein B-containing lipoprotein particles with cholesterol feeding and the response to diet-induced atherosclerosis. In addition, these findings identify LCAT as a new target for therapy to prevent atherosclerosis. Images Fig. 2 Fig. 3 Fig. 4 PMID:8876155

  4. Targeting the NLRP3 Inflammasome to Reduce Diet-Induced Metabolic Abnormalities in Mice

    PubMed Central

    Chiazza, Fausto; Couturier-Maillard, Aurélie; Benetti, Elisa; Mastrocola, Raffaella; Nigro, Debora; Cutrin, Juan C; Serpe, Loredana; Aragno, Manuela; Fantozzi, Roberto; Ryffel, Bernard; Collino, Massimo

    2015-01-01

    Although the molecular links underlying the causative relationship between chronic low-grade inflammation and insulin resistance are not completely understood, compelling evidence suggests a pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Here we tested the hypothesis that either a selective pharmacological inhibition or a genetic downregulation of the NLRP3 inflammasome results in reduction of the diet-induced metabolic alterations. Male C57/BL6 wild-type mice and NLRP3−/− littermates were fed control diet or high-fat, high-fructose diet (HD). A subgroup of HD-fed wild-type mice was treated with the NLRP3 inflammasome inhibitor BAY 11-7082 (3 mg/kg intraperitoneally [IP]). HD feeding increased plasma and hepatic lipids and impaired glucose homeostasis and renal function. Renal and hepatic injury was associated with robust increases in profibrogenic markers, while only minimal fibrosis was recorded. None of these metabolic abnormalities were detected in HD-fed NLRP3−/− mice, and they were dramatically reduced in HD-mice treated with the NLRP3 inflammasome inhibitor. BAY 11-7082 also attenuated the diet-induced increase in NLRP3 inflammasome expression, resulting in inhibition of caspase-1 activation and interleukin (IL)-1β and IL-18 production (in liver and kidney). Interestingly, BAY 11-7082, but not gene silencing, inhibited nuclear factor (NF)-κB nuclear translocation. Overall, these results demonstrate that the selective pharmacological modulation of the NLRP3 inflammasome attenuates the metabolic abnormalities and the related organ injury/dysfunction caused by chronic exposure to HD, with effects similar to those obtained by NLRP3 gene silencing. PMID:26623925

  5. [Dietary supplements and functional food for weight reduction -- expectations and reality].

    PubMed

    Hahn, A; Ströhle, A; Wolters, M

    2003-10-16

    Looked at with scientific dispassion, much of the frequently aggressive advertising for slimming products must be considered to be dishonest and misleading. This applies, for example, to the "fat burner" carnitine or for chromium-containing preparations such as chromium picolinate, which in large doses have been shown to have detrimental effects on health. Products for which there actually is a scientific rationale all have minor weight-reducing effects, so that they must be considered to have at most an adjuvant role within the framework of evidence-based concepts for losing weight. Examples of alleged slimming substances that in reality can do no more than support weight reduction are the so-called medium-chain triglycerides (MCT) or caffeine, with the latter showing an effect vis-à-vis placebo only in combination studies with ephedrine.

  6. Recombinant human tumor necrosis factor induces acute reductions in food intake and body weight in mice

    PubMed Central

    1988-01-01

    We examined the effects of treatment with rHuTNF on food consumption and body weight in C3H/HeJ mice. rHuTNF was administered intraperitoneally either by injections of 3, 12, or 24 micrograms twice a day or by implantation of osmotic pumps that released 0.75, 3, or 12 micrograms per day. Dose-dependent reductions in both food intake and weight were induced by rHuTNF. However, in spite of continued exposure to rHuTNF, the mice developed a resistance to rHuTNF and resumed their pretreatment food intake and weight. Non-immunological factors may play a role in the development of this tolerance, since it developed rapidly and faded within 2 wk of cessation of exposure to rHuTNF. PMID:3385359

  7. Hybrid Wing-Body (HWB) Pressurized Fuselage Modeling, Analysis, and Design for Weight Reduction

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, Vivek

    2012-01-01

    This paper describes the interim progress for an in-house study that is directed toward innovative structural analysis and design of next-generation advanced aircraft concepts, such as the Hybrid Wing-Body (HWB) and the Advanced Mobility Concept-X flight vehicles, for structural weight reduction and associated performance enhancement. Unlike the conventional, skin-stringer-frame construction for a cylindrical fuselage, the box-type pressurized fuselage panels in the HWB undergo significant deformation of the outer aerodynamic surfaces, which must be minimized without significant structural weight penalty. Simple beam and orthotropic plate theory is first considered for sizing, analytical verification, and possible equivalent-plate analysis with appropriate simplification. By designing advanced composite stiffened-shell configurations, significant weight reduction may be possible compared with the sandwich and ribbed-shell structural concepts that have been studied previously. The study involves independent analysis of the advanced composite structural concepts that are presently being developed by The Boeing Company for pressurized HWB flight vehicles. High-fidelity parametric finite-element models of test coupons, panels, and multibay fuselage sections, were developed for conducting design studies and identifying critical areas of potential failure. Interim results are discussed to assess the overall weight/strength advantages.

  8. Efficacy of two different materials used in auricular acupressure on weight reduction and abdominal obesity.

    PubMed

    Hsieh, Ching Hsiu; Su, Tsann-Juu; Fang, Yu-Wen; Chou, Pei-Hsuan

    2012-01-01

    The current study was designed to test the efficacy of different materials used in an auricular acupressure program on weight reduction, changes to waist circumference and waist-to-hip ratio. This study used a randomized design with two groups who were treated with auricular acupressure using Semen Vaccariae or the Japanese Magnetic Pearl. Both groups consisted of Asian young adults with a waist circumference ≥ 80 cm in the females and ≥ 90 cm in the males. At completion of the eight-week treatment period, the total sample size was 56 young adults who ranged in age from 18 to 20 years old. Each participant was met with weekly for ten-minute sessions during which ear acupressure treatment was performed. Sessions continued for eight weeks wherein both groups received acupressure with the Japanese Magnetic Pearl or Semen Vaccariae on the ear acupoints. While both groups showed significant reductions (p ≤ 0.05) to body weight and waist circumference after eight weeks of treatments, the group treated with Semen Vaccariae group showed a more effective weight loss over the short term. Given that auricular acupressure is a safe and cost-effective treatment for weight loss, our results suggest that auricular acupressure is a reasonable option for the treatment of overweight and obesity in young adults. PMID:22809026

  9. Design for size and weight reduction of lap-winding type three-phase variable inductor

    NASA Astrophysics Data System (ADS)

    Nakamura, Kenji; Honma, Koya; Ohinata, Takashi; Arimatsu, Kenji; Ichinokura, Osamu

    2015-05-01

    Variable inductors have a simple structure that consists of only magnetic core and primary dc and secondary ac windings, but can control effective inductance of the secondary ac winding by the primary dc current due to magnetic saturation effect. Hence, the variable inductors can be applied as a var compensator in electric power systems. In a previous paper, a lap-winding type three-phase variable inductor, which has the primary dc and secondary ac windings concentrically arranged on the same leg, was presented. It has a good controllability and low distortion current. This paper describes size and weight reduction of the lap-winding type three-phase variable inductor by focusing on the leg width. First, an initial design method of the leg width considering the influence of the dc-biased magnetization is presented. Next, a detailed design of the leg width for the size and weight reduction of the proposed variable inductor is described. Finally, characteristics of the size- and weight-reduced variable inductor were compared to those of the previous variable inductor. It is demonstrated that the core diameter is reduced by about 6% and the weight is decreased by about 50% in comparison with the previous variable inductor.

  10. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice

    PubMed Central

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-01-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice. After obesity was induced by a 20-week high-fat (60%) diet, treadmill exercise was performed for 12 weeks. In the present results, cognitive function was impaired in the high-fat diet-induced obese mice. Brain-derived neurotrophic factor (BDNF) and tyrosin kinase B (TrkB) expression and cell proliferation were decreased in the high-fat diet-induced obese mice. Treadmill exercise improved cognitive function through enhancing neuroplasticity, including increased expression of BDNF and TrkB and enhanced cell proliferation. The present results suggest that treadmill exercise enhances hippocampal neuroplasticity, and then potentially plays a protective role against obesity-induced cognitive impairment. PMID:27419109

  11. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice.

    PubMed

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-06-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice. After obesity was induced by a 20-week high-fat (60%) diet, treadmill exercise was performed for 12 weeks. In the present results, cognitive function was impaired in the high-fat diet-induced obese mice. Brain-derived neurotrophic factor (BDNF) and tyrosin kinase B (TrkB) expression and cell proliferation were decreased in the high-fat diet-induced obese mice. Treadmill exercise improved cognitive function through enhancing neuroplasticity, including increased expression of BDNF and TrkB and enhanced cell proliferation. The present results suggest that treadmill exercise enhances hippocampal neuroplasticity, and then potentially plays a protective role against obesity-induced cognitive impairment. PMID:27419109

  12. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice.

    PubMed

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-06-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice. After obesity was induced by a 20-week high-fat (60%) diet, treadmill exercise was performed for 12 weeks. In the present results, cognitive function was impaired in the high-fat diet-induced obese mice. Brain-derived neurotrophic factor (BDNF) and tyrosin kinase B (TrkB) expression and cell proliferation were decreased in the high-fat diet-induced obese mice. Treadmill exercise improved cognitive function through enhancing neuroplasticity, including increased expression of BDNF and TrkB and enhanced cell proliferation. The present results suggest that treadmill exercise enhances hippocampal neuroplasticity, and then potentially plays a protective role against obesity-induced cognitive impairment.

  13. Codonopsis lanceolata Extract Prevents Diet-Induced Obesity in C57BL/6 Mice

    PubMed Central

    Lee, Jong Seok; Kim, Kui-Jin; Kim, Young-Hyun; Kim, Dan-Bi; Shin, Gi-Hae; Cho, Ju-Hyun; Kim, Bong Kyun; Lee, Boo-Yong; Lee, Ok-Hwan

    2014-01-01

    Codonopsis lanceolata extract (CLE) has been used in traditional medicine in the Asian-Pacific region for the treatment of bronchitis, cough, and inflammation. However, it is still unclear whether obesity in mice can be altered by diet supplementation with CLE. To investigate whether CLE could have preventative effects on high fat diet (HFD)-induced obesity, male C57BL/6 mice were placed on either a normal chow diet, 60% HFD, or a HFD supplemented with CLE (60, 180, and 360 mg/kg/day) for 12 weeks. CLE decreased body weight and subcutaneous and visceral fat weights in HFD-induced obese mice. CLE group mice showed lower fat accumulation and a smaller adipocyte area in the adipose tissue compared with the HFD group mice. CLE group mice exhibited lower serum levels of triglycerides, total cholesterol, low density lipoprotein (LDL), glucose, and insulin compared with the HFD group mice. In addition, CLE decreased liver weight and lowered the increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in HFD-induced obese mice. These results indicate that CLE can inhibit the development of diet-induced obesity and hyperlipidemia in C57BL/6 mice. PMID:25353662

  14. 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.

  15. Noise reduction of a tilt-rotor aircraft including effects on weight and performance

    NASA Technical Reports Server (NTRS)

    Gibs, J.; Stepniewski, W. Z.; Spencer, R.; Kohler, G.

    1973-01-01

    Various methods for far-field noise reduction of a tilt-rotor acoustic signature and the performance and weight tradeoffs which result from modification of the noise sources are considered in this report. In order to provide a realistic approach for the investigation, the Boeing tilt-rotor flight research aircraft (Model 222), was selected as the baseline. This aircraft has undergone considerable engineering development. Its rotor has been manufactured and tested in the Ames full-scale wind tunnel. The study reflects the current state-of-the-art of aircraft design for far-field acoustic signature reduction and is not based solely on an engineering feasibility aircraft. This report supplements a previous study investigating reduction of noise signature through the management of the terminal flight trajectory.

  16. Diet-Induced Obesity Exacerbates Auditory Degeneration via Hypoxia, Inflammation, and Apoptosis Signaling Pathways in CD/1 Mice

    PubMed Central

    Hwang, Juen-Haur; Hsu, Chuan-Jen; Yu, Wei-Hsuan; Liu, Tien-Chen; Yang, Wei-Shiung

    2013-01-01

    The aim of this study was to investigate the mechanisms of diet-induced obesity on hearing degeneration in CD/1 mice. Sixty 4-week-old male CD/1 mice were randomly and equally divided into 2 groups. For 16 weeks, the diet-induced obesity (DIO) group was fed a high fat diet and the control group was fed a standard diet of 13.43 % kcal fat. The morphometry, biochemistry, auditory brainstem response thresholds, omental fat, and histopathology of the cochlea were compared between the beginning and end of the study (4 vs. 20 weeks old). The results show that the body weight, fasting plasma triglyceride concentrations, and omental fat weight were higher in the DIO group than in the control group at the end of experiment. The auditory brainstem response thresholds at high frequencies were significantly elevated in the DIO group compared to those of the control group. Histology studies showed that, compared to the control group, the DIO group had blood vessels with smaller diameters and thicker walls in the stria vascularis at the middle and basal turns of the cochlea. The cell densities in the spiral ganglion and spiral ligament at the basal turn of the cochlea were significantly lower in the DIO group. Immunohistochemical staining showed that hypoxia-induced factor 1 (HIF-1), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB), caspase 3, poly(ADP-ribose) polymerase-1, and apoptosis inducing factor were all significantly more dense in the spiral ganglion and spiral ligament at the basal turn of cochlea in the DIO group. Our results suggest that diet-induced obesity exacerbates hearing degeneration via increased hypoxia, inflammatory responses, and cell loss in the spiral ganglion and spiral ligament and is associated with the activation of both caspase-dependent and -independent apoptosis signaling pathways in CD/1 mice. PMID:23637762

  17. A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents

    PubMed Central

    Hansen, Gitte; Fabricius, Katrine; Hansen, Henrik B.; Jelsing, Jacob; Vrang, Niels

    2015-01-01

    Aim Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO) and hypercholesterolemia Golden Syrian hamster model. Methods and Results Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS) for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days), normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin (3.0 mg/kg, PO, QD) also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day) or neuromedin U (NMU, 1.5 mg/kg/day), continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD) for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents. PMID:26266945

  18. Body composition and power performance improved after weight reduction in male athletes without hampering hormonal balance.

    PubMed

    Huovinen, Heikki T; Hulmi, Juha J; Isolehto, Juha; Kyröläinen, Heikki; Puurtinen, Risto; Karila, Tuomo; Mackala, Krzysztof; Mero, Antti A

    2015-01-01

    The aim of this study was to investigate the effects of a 4-week weight reduction period with high protein and reduced carbohydrate intake on body composition, explosive power, speed, serum hormones, and acid-base balance in male track and field jumpers and sprinters. Eight participants were assigned to a high weight reduction group (HWR; energy restriction 750 kcal·d) and 7 to a low weight reduction group (LWR; energy restriction 300 kcal·d). Energy and carbohydrate intake decreased significantly (p ≤ 0.05) only in HWR by 740 ± 330 kcal·d and 130 ± 29 g·d, respectively. Furthermore, total body mass and fat mass decreased (p ≤ 0.05) only in HWR by 2.2 ± 1.0 kg and 1.7 ± 1.6 kg, respectively. Fat-free mass (FFM), serum testosterone, cortisol, and sex hormone-binding globulin did not change significantly. Ca ion and pH decreased (p ≤ 0.05) only in HWR (3.1 ± 2.8% and 0.8 ± 0.8%, respectively), whereas (Equation is included in full-text article.)declined (p ≤ 0.05) in both groups by 19.3 ± 6.2% in HWR and by 13.1 ± 8.5% in LWR. The countermovement jump and 20-m sprint time improved consistently (p ≤ 0.05) only in HWR, by 2.6 ± 2.5 cm and 0.04 ± 0.04 seconds, respectively. Finally, athletes with a fat percentage of 10% or more at the baseline were able to preserve FFM. In conclusion, altered acid-base balance but improved weight-bearing power performance was observed without negative consequences on serum hormones and FFM after a 4-week weight reduction of 0.5 kg·wk achieved by reduced carbohydrate but maintained high protein intake.

  19. Populus balsamifera Extract and Its Active Component Salicortin Reduce Obesity and Attenuate Insulin Resistance in a Diet-Induced Obese Mouse Model.

    PubMed

    Harbilas, Despina; Vallerand, Diane; Brault, Antoine; Saleem, Ammar; Arnason, John T; Musallam, Lina; Haddad, Pierre S

    2013-01-01

    Populus balsamifera L. (BP) is a medicinal plant stemming from the traditional pharmacopoeia of the Cree of Eeyou Istchee (CEI-Northern Quebec). In vitro screening studies revealed that it strongly inhibited adipogenesis in 3T3-L1 adipocytes, suggesting potential antiobesity activity. Salicortin was identified, through bioassay-guided fractionation, as the active component responsible for BP's activity. The present study aimed to assess the potential of BP and salicortin at reducing obesity and features of the metabolic syndrome, in diet-induced obese C57Bl/6 mice. Mice were subjected to high fat diet (HFD) for sixteen weeks, with BP (125 or 250 mg/kg) or salicortin (12.5 mg/kg) introduced in the HFD for the last eight of the sixteen weeks. BP and salicortin effectively reduced whole body and retroperitoneal fat pad weights, as well as hepatic triglyceride accumulation. Glycemia, insulinemia, leptin, and adiponectin levels were also improved. This was accompanied by a small yet significant reduction in food intake in animals treated with BP. BP and salicortin (slightly) also modulated key components in signaling pathways involved with glucose regulation and lipid oxidation in the liver, muscle, and adipose tissue. These results confirm the validity of the CEI pharmacopoeia as alternative and complementary antiobesity and antidiabetic therapies.

  20. Effect of Green Tea Extract on Systemic Metabolic Homeostasis in Diet-Induced Obese Mice Determined via RNA-Seq Transcriptome Profiles

    PubMed Central

    Choi, Ji-Young; Kim, Ye Jin; Ryu, Ri; Cho, Su-Jung; Kwon, Eun-Young; Choi, Myung-Sook

    2016-01-01

    Green tea (GT) has various health effects, including anti-obesity properties. However, the multiple molecular mechanisms of the effects have not been fully determined. The aim of this study was to elucidate the anti-obesity effects of GT via the analysis of its metabolic and transcriptional responses based on RNA-seq profiles. C57BL/6J mice were fed a normal, high-fat (60% energy as fat), or high-fat + 0.25% (w/w) GT diet for 12 weeks. The GT extract ameliorated obesity, hepatic steatosis, dyslipidemia, and insulin resistance in diet-induced obesity (DIO) mice. GT supplementation resulted in body weight gain reduction than mice fed high-fat through enhanced energy expenditure, and reduced adiposity. The transcriptome profiles of epididymal white adipose tissue (eWAT) suggested that GT augments transcriptional responses to the degradation of branched chain amino acids (BCAAs), as well as AMP-activated protein kinase (AMPK) signaling, which suggests enhanced energy homeostasis. Our findings provide some significant insights into the effects of GT for the prevention of obesity and its comorbidities. We demonstrated that the GT extract contributed to the regulation of systemic metabolic homeostasis via transcriptional responses to not only lipid and glucose metabolism, but also amino acid metabolism via BCAA degradation in the adipose tissue of DIO mice. PMID:27754422

  1. Optimization of brain penetrant 11β-hydroxysteroid dehydrogenase type I inhibitors and in vivo testing in diet-induced obese mice.

    PubMed

    Goldberg, Frederick W; Dossetter, Alexander G; Scott, James S; Robb, Graeme R; Boyd, Scott; Groombridge, Sam D; Kemmitt, Paul D; Sjögren, Tove; Gutierrez, Pablo Morentin; deSchoolmeester, Joanne; Swales, John G; Turnbull, Andrew V; Wild, Martin J

    2014-02-13

    11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine compound, we removed hydrogen-bond donors to yield 3, which had modest CNS penetration. More significant progress was achieved by changing the core to give 40, which combines good potency and CNS penetration. Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS. However, no body weight reduction or effects on glucose or insulin were observed in this model. Similar data were obtained with a structurally diverse thiazole compound 51. This work casts doubt on the hypothesis that localized tissue modulation of 11β-HSD1 activity alleviates metabolic syndrome.

  2. Populus balsamifera Extract and Its Active Component Salicortin Reduce Obesity and Attenuate Insulin Resistance in a Diet-Induced Obese Mouse Model

    PubMed Central

    Harbilas, Despina; Vallerand, Diane; Brault, Antoine; Saleem, Ammar; Arnason, John T.; Musallam, Lina; Haddad, Pierre S.

    2013-01-01

    Populus balsamifera L. (BP) is a medicinal plant stemming from the traditional pharmacopoeia of the Cree of Eeyou Istchee (CEI—Northern Quebec). In vitro screening studies revealed that it strongly inhibited adipogenesis in 3T3-L1 adipocytes, suggesting potential antiobesity activity. Salicortin was identified, through bioassay-guided fractionation, as the active component responsible for BP's activity. The present study aimed to assess the potential of BP and salicortin at reducing obesity and features of the metabolic syndrome, in diet-induced obese C57Bl/6 mice. Mice were subjected to high fat diet (HFD) for sixteen weeks, with BP (125 or 250 mg/kg) or salicortin (12.5 mg/kg) introduced in the HFD for the last eight of the sixteen weeks. BP and salicortin effectively reduced whole body and retroperitoneal fat pad weights, as well as hepatic triglyceride accumulation. Glycemia, insulinemia, leptin, and adiponectin levels were also improved. This was accompanied by a small yet significant reduction in food intake in animals treated with BP. BP and salicortin (slightly) also modulated key components in signaling pathways involved with glucose regulation and lipid oxidation in the liver, muscle, and adipose tissue. These results confirm the validity of the CEI pharmacopoeia as alternative and complementary antiobesity and antidiabetic therapies. PMID:23781256

  3. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice.

    PubMed

    Lee, Hui-Young; Park, Jong-Hwan; Seok, Seung-Hyeok; Baek, Min-Won; Kim, Dong-Jae; Lee, Ki-Eun; Paek, Kyung-Soo; Lee, Yeonhee; Park, Jae-Hak

    2006-07-01

    Many previous studies have reported that conjugated linoleic acid could be produced by starter culture bacteria, but the effects of the bacteria were not investigated. Moreover, there was no evidence of the conjugated linoleic acid-producing bacteria having potential health or nutritional effects related to conjugated linoleic acid, including reducing body fat. Here, we investigated the anti-obesity effect of Lactobacillus rhamnosus PL60, a human originated bacterium that produces t10, c12-conjugated linoleic acid, on diet-induced obese mice. After 8 weeks of feeding, L. rhamnosus PL60 reduced body weight without reducing energy intake, and caused a significant, specific reduction of white adipose tissue (epididymal and perirenal). Although the size of epididymal adipocytes was not reduced by L. rhamnosus PL60, apoptotic signals and UCP-2 mRNA levels increased in adipose tissue. Liver steatosis, a well known side effect of CLA, was not observed by L. rhamnosus PL60 treatment; on the contrary it seemed to be normalized. Results showed that the amount of conjugated linoleic acid produced by Lactobacillus rhamnosus PL60 was enough to produce an anti-obesity effect.

  4. Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia

    PubMed Central

    Cotter, David G.; Ercal, Baris; Huang, Xiaojing; Leid, Jamison M.; d’Avignon, D. André; Graham, Mark J.; Dietzen, Dennis J.; Brunt, Elizabeth M.; Patti, Gary J.; Crawford, Peter A.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide–induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease. PMID:25347470

  5. Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia.

    PubMed

    Cotter, David G; Ercal, Baris; Huang, Xiaojing; Leid, Jamison M; d'Avignon, D André; Graham, Mark J; Dietzen, Dennis J; Brunt, Elizabeth M; Patti, Gary J; Crawford, Peter A

    2014-12-01

    Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide-induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease.

  6. Threonine-deficient diets induced changes in hepatic bioenergetics

    PubMed Central

    Ross-Inta, Catherine M.; Zhang, Yi-Fan; Almendares, Andrew; Giulivi, Cecilia

    2009-01-01

    Diets deficient in an indispensable amino acid are known to suppress food intake in rats. Few studies were focused at understanding how amino acid-deficient diets may elicit biochemical changes at the mitochondrial level. The goal of this study was to evaluate mitochondrial function in rats fed diets with 0.00, 0.18, 0.36, and 0.88% threonine (Thr) (set at 0, 30, 60, and 140% of Thr requirement for growth). Here, it is described for the first time that Thr-deficient diets induce a specific uncoupling of mitochondria in liver, especially with NADH-linked substrates, not observed in heart (except for Thr-devoid diet). The advantage of this situation would be to provide ATP to support growth and maintenance when high-quality protein food (or wealth of high-quality food in general) is available, whereas Thr-deficient diets (or deficient-quality protein food) promote the opposite, increasing mitochondrial uncoupling in liver. The uncoupling with NADH substrates would favor the use of nutrients as energy sources with higher FADH-to-NADH ratios, such as fat, minimizing the first irreversible NADH-dependent catabolism of many amino acids, including Thr, thus enhancing the use of the limiting amino acid for protein synthesis when a low quality protein source is available. PMID:19228885

  7. Effects of Astrocaryum aculeatum Meyer (Tucumã) on Diet-Induced Dyslipidemic Rats

    PubMed Central

    Craveiro Holanda Malveira Maia, Geórgia; da Silva Campos, Mozer; Barros-Monteiro, Janice; Eduardo Lucas Castillo, Juan; Soares Faleiros, Murilo; Souza de Aquino Sales, Rejane; Moraes Lopes Galeno, Denise; Lira, Edson; das Chagas do Amaral Souza, Francisca; Ortiz, Carmen

    2014-01-01

    An in vivo study was conducted to assess the effects of the consumption of Astrocaryum aculeatum Amazon Meyer (tucumã) in the treatment of diet-induced dyslipidemia in sedentary and exercised Wistar rats. With an average weight of 350 grams, 40 male rats were divided into 4 subgroups of 10. The sedentary control group (SCG) was fed with commercial feed, while the sedentary treatment group (STG) was fed with a ration of tucumã. In addition to the sedentary groups, two exercise groups were formed. The Exercised control group (ECG) was fed with commercial food and the exercised treatment group (ETG) was fed with a ration of tucumã. Body weight gain and food intake were monitored during the experiment. Plasma was analyzed for cholesterol, triglycerides, HDL-C, LDL-C, VLDL, total protein, glucose, insulin, and leptin concentrations. Our results show that the ECG group tended to consume more food, while the groups that were fed with tucumã pulp (STG and ETG) presented a greater tendency to gain body mass. ECG group showed a tendency towards a higher concentration of cholesterol in plasma, while STG and ETG presented higher absolute values for triglycerides and VLDL. No hypolipiemic effect was observed related to tucuma ingestion. PMID:25165578

  8. Alternating Diet as a Preventive and Therapeutic Intervention for High Fat Diet-induced Metabolic Disorder

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    This study presents the alternating diet as a new strategy in combating obesity and metabolic diseases. Lean or obese mice were fed a high-fat diet (HFD) for five days and switched to a regular diet for one (5 + 1), two (5 + 2), or five (5 + 5) days before switching back to HFD to start the second cycle, for a total of eight weeks (for prevention) or five weeks (for treatment) without limiting animals’ access to food. Our results showed that animals with 5 + 2 and 5 + 5 diet alternations significantly inhibited body weight and fat mass gain compared to animals fed an HFD continuously. The dietary switch changed the pattern of daily caloric intake and suppressed HFD-induced adipose macrophage infiltration and chronic inflammation, resulting in improved insulin sensitivity and alleviated fatty liver. Alternating diet inhibited HFD-induced hepatic Pparγ-mediated lipid accumulation and activated the expression of Pparα and its target genes. Alternating diet in the 5 + 5 schedule induced weight loss in obese mice and reversed the progression of metabolic disorders, including hepatic steatosis, glucose intolerance, and inflammation. The results provide direct evidence to support that alternating diet represents a new intervention in dealing with the prevalence of diet-induced obesity. PMID:27189661

  9. miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity

    PubMed Central

    Gaudet, Andrew D.; Fonken, Laura K.; Gushchina, Liubov V.; Aubrecht, Taryn G.; Maurya, Santosh K.; Periasamy, Muthu; Nelson, Randy J.; Popovich, Phillip G.

    2016-01-01

    Obesity is a growing epidemic in developed countries. Obese individuals are susceptible to comorbidities, including cardiovascular disease and metabolic disorder. Increasing the ability of adipose tissue to expend excess energy could improve protection from obesity. One promising target is microRNA (miR)-155-5p. We demonstrate that deletion of miR-155 (-5p and -3p) in female mice prevents diet-induced obesity. Body weight gain did not differ between wild-type (WT) and miR-155 knockout (KO) mice fed control diet (CD); however, miR-155 KO mice fed high-fat diet (HFD) gained 56% less body weight and 74% less gonadal white adipose tissue (WAT) than WT mice. Enhanced WAT thermogenic potential, brown adipose tissue differentiation, and/or insulin sensitivity might underlie this obesity resistance. Indeed, miR-155 KO mice on HFD had 21% higher heat release than WT HFD mice. Compared to WT adipocytes, miR-155 KO adipocytes upregulated brown (Ucp1, Cidea, Pparg) and white (Fabp4, Pnpla2, AdipoQ, Fasn) adipogenic genes, and glucose metabolism genes (Glut4, Irs1). miR-155 deletion abrogated HFD-induced adipocyte hypertrophy and WAT inflammation. Therefore, miR-155 deletion increases adipogenic, insulin sensitivity, and energy uncoupling machinery, while limiting inflammation in WAT, which together could restrict HFD-induced fat accumulation. Our results identify miR-155 as a novel candidate target for improving obesity resistance. PMID:26953132

  10. Meta-chlorophenylpiperazine enhances leptin sensitivity in diet-induced obese mice

    PubMed Central

    Yan, Chunling; Yang, Yongjie; Saito, Kenji; Xu, Pingwen; Wang, Chunmei; Hinton Jr, Antentor Othrell; Yan, Xiaofeng; Wu, Qi; Tong, Qingchun; Elmquist, Joel K; Fukuda, Makoto; Xu, Yong

    2015-01-01

    Background and Purpose Most forms of human obesity are characterized by impaired leptin sensitivity and, therefore, the effectiveness of anti-obesity leptin therapy in these leptin-resistant obese patients is marginal. Hence, the development of strategies to increase leptin sensitivity is of high priority in the field of obesity research. Experimental Approach We first examined the effects of co-administration of leptin and meta-chlorophenylpiperazine (mCPP), an agonist of 5-HT2C and 5-HT1B receptors, on energy balance in leptin-resistant diet-induced obese (DIO) mice. We further assessed leptin-induced phosphorylation of the STAT-3 (pSTAT3) in various brain regions of DIO mice pretreated with mCPP or in mice genetically lacking 5-HT2C receptors. Results Co-administration of mCPP with leptin had an additive effect on reducing body weight in DIO mice. Furthermore, mCPP pretreatment in DIO mice enhanced leptin-induced pSTAT3 in the arcuate nucleus, the ventromedial hypothalamic nucleus, and the ventral premammillary nucleus. Finally, deletion of 5-HT2C receptors significantly blunted leptin-induced pSTAT3 in these same hypothalamic regions. Conclusions and Implications Our study provides evidence that drugs, which activate 5-HT2C receptors, could function as leptin sensitizers and be used in combination with leptin to provide additional weight loss in DIO. PMID:25817043

  11. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer.

    PubMed

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARγ-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID:27184920

  12. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARγ-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID:27184920

  13. Adverse events of herbal food supplements for body weight reduction: systematic review.

    PubMed

    Pittler, M H; Schmidt, K; Ernst, E

    2005-05-01

    Herbal weight-loss supplements are marketed with claims of effectiveness. Our earlier systematic review identified data from double-blind, randomized controlled trials for a number of herbal supplements. The aim of this systematic review was to assess all clinical evidence of adverse events of herbal food supplements for body weight reduction for which effectiveness data from rigorous clinical trials exist. We assessed Ephedra sinica, Garcinia cambogia, Paullinia cupana, guar gum, Plantago psyllium, Ilex paraguariensis and Pausinystalia yohimbe. Literature searches were conducted on Medline, Embase, Amed and The Cochrane Library. Data were also requested from the spontaneous reporting scheme of the World Health Organization. We hand-searched relevant medical journals and our own files. There were no restrictions regarding the language of publication. The results show that adverse events including hepatic injury and death have been reported with the use of some herbal food supplements. For herbal ephedra and ephedrine-containing food supplements an increased risk of psychiatric, autonomic or gastrointestinal adverse events and heart palpitations has been reported. In conclusion, adverse events are reported for a number of herbal food supplements, which are used for reducing body weight. Although the quality of the data does not justify definitive attribution of causality in most cases, the reported risks are sufficient to shift the risk-benefit balance against the use of most of the reviewed herbal weight-loss supplements. Exceptions are Garcinia cambogia and yerba mate, which merit further investigation.

  14. Size, weight, and power reduction regimes in achromatic gradient-index singlets.

    PubMed

    Campbell, Sawyer D; Brocker, Donovan E; Nagar, Jogender; Werner, Douglas H

    2016-05-01

    By analyzing the limitations that achromatic gradient-index (GRIN) lens solutions in the radial and axial extremes place on lens thickness and surface curvature, a radial-axial hybrid GRIN theory is developed in order to overcome these restrictions and expose a larger solution space. With the achromatic hybrid GRIN theory, the trade-offs between thickness, curvature, and GRIN type can be directly studied in the context of size, weight, and power (SWaP) reduction. Finally, the achromatic solution space of a silicon-germanium-based material system is explored, and several designs are verified with ray tracing. PMID:27140376

  15. Numerical solution for weight reduction model due to health campaigns in Spain

    NASA Astrophysics Data System (ADS)

    Mohammed, Maha A.; Noor, Noor Fadiya Mohd; Siri, Zailan; Ibrahim, Adriana Irawati Nur

    2015-10-01

    Transition model between three subpopulations based on Body Mass Index of Valencia community in Spain is considered. No changes in population nutritional habits and public health strategies on weight reduction until 2030 are assumed. The system of ordinary differential equations is solved using Runge-Kutta method of higher order. The numerical results obtained are compared with the predicted values of subpopulation proportion based on statistical estimation in 2013, 2015 and 2030. Relative approximate error is calculated. The consistency of the Runge-Kutta method in solving the model is discussed.

  16. Verification of the history-score moment equations for weight-window variance reduction

    SciTech Connect

    Solomon, Clell J; Sood, Avneet; Booth, Thomas E; Shultis, J. Kenneth

    2010-12-06

    The history-score moment equations that describe the moments of a Monte Carlo score distribution have been extended to weight-window variance reduction, The resulting equations have been solved deterministically to calculate the population variance of the Monte Carlo score distribution for a single tally, Results for one- and two-dimensional one-group problems are presented that predict the population variances to less than 1% deviation from the Monte Carlo for one-dimensional problems and between 1- 2% for two-dimensional problems,

  17. Thermal Earth Resource Monitoring Instrument (THERMI) size, weight and power reduction

    NASA Astrophysics Data System (ADS)

    Newswander, T.; Bergen, Z.; Hancock, J.; Hansen, S.; Shumway, A.; Stauder, J.; Williams, D.

    2015-09-01

    The Thermal Earth Resource Monitoring Instrument (THERMI) has been designed to meet stringent Landsat heritage requirements with reduced size, weight and power (SWaP). The instrument design provides Earth resource monitoring through the use of two long-wave infrared bands that measure the land surface temperatures. These bands are especially valuable for monitoring water resources and water use. Instrument subsystems, including electronics, cryocooler, thermal management, optical telescope assembly, focal plane module, in-flight calibrator, and scene select mirror were studied and conceptually designed to reduce overall THERMI SWaP. Reductions in SWaP make it possible for THERMI to fit on a small satellite bus with room available for an additional optical instrument. Since mission cost historically correlates well with mass and power on-orbit, it is expected that significant cost savings will result from the predicted SWaP reductions.

  18. ARYL HYDROCARBON RECEPTOR DEFICIENCY PROTECTS MICE FROM DIET-INDUCED ADIPOSITY AND METABOLIC DISORDERS THROUGH INCREASED ENERGY EXPENDITURE

    PubMed Central

    Zhang, Zhi-Ming; Jaeger, Cassie D.; Krager, Stacey L.; Bottum, Kathleen M.; Liu, Jianghua; Liao, Duan-Fang; Tischkau, Shelley A.

    2015-01-01

    BACKGROUND/OBJECTIVES Epidemics of obesity and diabetes are escalating. High-calorie/high-fat food is a major cause for these global health issues, but molecular mechanisms underlying high-fat, diet-induced obesity are still not well understood. The aryl hydrocarbon receptor (AhR), a transcription factor that acts as a xenobiotic sensor, mediates environmental toxicant-induced obesity, insulin resistance and development of diabetes. AhR also influences lipid metabolism and diet-induced obesity. The effects of AhR deficiency on diet-induced obesity, hepatic steatosis and insulin resistance were examined. METHODS : Male wild type (WT), AhR null (AhR−/−) and AhR heterozygote (AhR+/−) mice were fed a normal chow diet (NCD, 10% kcal from fat) or a high-fat diet (HFD, 60% kcal from fat) for up to 14 weeks. Adiposity, adipose and liver morphology, insulin signaling, metabolic parameters and gene profiles were assessed. RESULTS AhR deficiency protected against HFD-induced obesity, hepatic steatosis, insulin resistance and inflammation. Moreover, AhR deficiency preserved insulin signaling in major metabolic tissues. These protective effects result from a higher energy expenditure in AhR-deficient mice compared to WT. Levels of transcript for both the thermogenic gene, uncoupling protein 1 (Ucp1), in brown adipose tissue and mitochondrial β-oxidation genes in muscle were significantly higher in AhR−/− and AhR+/− mice compared to WT. CONCLUSIONS This work documents a physiologically relevant function for AhR in regulation of body weight, hepatic fat deposition, insulin sensitivity and energy expenditure under HFD exposure, suggesting that AhR signaling may be developed as a potential therapeutic target for treatment of obesity and metabolic disorders. PMID:25907315

  19. Inhibiting myostatin signaling prevents femoral trabecular bone loss and microarchitecture deterioration in diet-induced obese rats

    PubMed Central

    Tang, Liang; Yang, Xiaoying; Gao, Xiaohang; Du, Haiping; Han, Yanqi; Zhang, Didi; Wang, Zhiyuan

    2015-01-01

    Besides resulting in a dramatic increase in skeletal muscle mass, myostatin (MSTN) deficiency has a positive effect on bone formation. However, the issue about whether blocking MSTN can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of MSTN blocking on bone quality in high-fat (HF), diet-induced obese rats using a prepared polyclonal antibody for MSTN (MsAb). Twenty-four rats were randomly assigned to the Control, HF and HF + MsAb groups. Rats in the HF + MsAb group were injected once a week with purified MsAb for eight weeks. The results showed that MsAb significantly reduced body and fat weight, and increased muscle mass and strength in the HF group. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by MsAb treatment, as evidenced by increased bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor MsAb treatment had an impact on femoral biomechanical properties including maximum load, stiffness, energy absorption and elastic modulus. Moreover, MsAb significantly increased adiponectin concentrations, and decreased TNF-α and IL-6 levels in diet-induced obese rats. Taken together, blocking MSTN by MsAb improves bone quality in diet-induced obese rats through a mechanotransduction pathway from skeletal muscle, and the accompanying changes occurring in the levels of circulating adipokines and pro-inflammatory cytokines may also be involved in this process. It indicates that the administration of MSTN antagonists may be a promising therapy for treating obesity and obesity-induced bone loss. PMID:26438721

  20. Susceptibility of Different Mouse Wild Type Strains to Develop Diet-Induced NAFLD/AFLD-Associated Liver Disease

    PubMed Central

    Fengler, Vera H. I.; Macheiner, Tanja; Kessler, Sonja M.; Czepukojc, Beate; Gemperlein, Katja; Müller, Rolf; Kiemer, Alexandra K.; Magnes, Christoph; Haybaeck, Johannes; Lackner, Carolin; Sargsyan, Karine

    2016-01-01

    Although non-alcoholic and alcoholic fatty liver disease have been intensively studied, concerning pathophysiological mechanisms are still incompletely understood. This may be due to the use of different animal models and resulting model-associated variation. Therefore, this study aimed to compare three frequently used wild type mouse strains in their susceptibility to develop diet-induced features of non-alcoholic/alcoholic fatty liver disease. Fatty liver disease associated clinical, biochemical, and histological features in C57BL/6, CD-1, and 129Sv WT mice were induced by (i) high-fat diet feeding, (ii) ethanol feeding only, and (iii) the combination of high-fat diet and ethanol feeding. Hepatic and subcutaneous adipose lipid profiles were compared in CD-1 and 129Sv mice. Additionally hepatic fatty acid composition was determined in 129Sv mice. In C57BL/6 mice dietary regimens resulted in heterogeneous hepatic responses, ranging from pronounced steatosis and inflammation to a lack of any features of fatty liver disease. Liver-related serum biochemistry showed high deviations within the regimen groups. CD-1 mice did not exhibit significant changes in metabolic and liver markers and developed no significant steatosis or inflammation as a response to dietary regimens. Although 129Sv mice showed no weight gain, this strain achieved most consistent features of fatty liver disease, apparent from concentration alterations of liver-related serum biochemistry as well as moderate steatosis and inflammation as a result of all dietary regimens. Furthermore, the hepatic lipid profile as well as the fatty acid composition of 129Sv mice were considerably altered, upon feeding the different dietary regimens. Accordingly, diet-induced non-alcoholic/alcoholic fatty liver disease is most consistently promoted in 129Sv mice compared to C57BL/6 and CD-1 mice. As a conclusion, this study demonstrates the importance of genetic background of used mouse strains for modeling diet-induced

  1. Weight and blood pressure reduction among participants engaged in a cancer awareness and prevention program

    PubMed Central

    Carter, Vivian L.; Dawkins, Norma L.; Howard, Barbara

    2015-01-01

    Objectives African–Americans consume a diet high in fat, salt and sugar; such dietary habits increase the risks of cancer and other chronic diseases. The objective of this study was to engage rural communities in a nutrition and physical activity behavior modification program to promote cancer awareness and risk reduction. Methods Focus group discussions were conducted to generate information for the development of a nutrition and physical activity program. African Americans (N = 62) from two rural counties (Bullock and Macon) in Alabama participated in a year-long intervention program in 2012 and 2013. Weight loss and blood pressure were evaluated to measure the impact of the intervention. Results Themes emerged for the focus group discussions were: nutrition, health, family, environment, and resource access. In Macon County participants lost weight irrespective of the exercise regimen, with those involved in floor exercise losing the most weight (− 22.4 lbs, or − 11.18% change), while in Bullock county walking was most effective in weight loss (6.1 lbs or − 3.40% change) p < 0.05. Systolic and diastolic pressure decreased from 5.3 to 10.5 mm Hg; − 2.0 to − 6.4 mm Hg, respectively, for Bullock county, except for the walking group. In Macon County, both systolic and diastolic pressure % change ranged from − 8.94 to 12.66 and − 5.34 to 12.66 mm Hg respectively, irrespective of physical activity respectively. Conclusion In this study, changes in weight lost and blood pressure were observed among individuals engaged in a nutrition education and physical activity program. PMID:26601053

  2. γδ T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice.

    PubMed

    Mehta, Pooja; Nuotio-Antar, Alli Martina; Smith, C Wayne

    2015-01-01

    γδ T cells are resident in AT and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5 to 10 week milk HFD. The HFD resulted in significant increases in CD44(hi), CD62L(lo), and TNF-α(+) γδ T cells in eAT of WT mice. Mice deficient in all γδ T cells (TCRδ(-/-)) or only Vγ4 and Vγ6 subsets (Vγ4/6(-/-)) were compared with WT mice with regard to proinflammatory cytokine production and macrophage accumulation in eAT. Obesity among these mouse strains did not differ, but obese TCRδ(-/-) and Vγ4/6(-/-) mice had significantly reduced eAT expression of F4/80, a macrophage marker, and inflammatory mediators CCL2 and IL-6 compared with WT mice. Obese TCRδ(-/-) mice had significantly reduced CD11c(+) and TNF-α(+) macrophage accumulation in eAT after 5 and 10 weeks on the HFD, and obese Vγ4/6(-/-) mice had significantly increased CD206(+) macrophages in eAT after 5 weeks on the diet and significantly reduced macrophages after 10 weeks. Obese TCRδ(-/-) mice had significant reductions in systemic insulin resistance and inflammation in liver and skeletal muscle after longer-term HFD feeding (10 and 24 weeks). In vitro studies revealed that isolated γδ T cells directly stimulated RAW264.7 macrophage TNF-α expression but did not stimulate inflammatory mediator expression in 3T3-L1 adipocytes. These findings are consistent with a role for γδ T cells in the proinflammatory response that accompanies diet-induced obesity.

  3. Alcohol-free fermented blueberry-blackberry beverage phenolic extract attenuates diet-induced obesity and blood glucose in C57BL/6J mice.

    PubMed

    Johnson, Michelle H; Wallig, Matthew; Luna Vital, Diego A; de Mejia, Elvira G

    2016-05-01

    The aim of this study was to determine the potential of phenolic compounds from a fermented blackberry-blueberry beverage to reduce diet-induced obesity and hyperglycemia in mice fed a 60% high-fat diet (HFD) for 10weeks after 1week of pretreatment. C57BL/6J mice were randomized into six groups and allowed to drink (ad libitum) an alcohol-free blackberry-blueberry beverage [alcohol-free fermented beverage (AFFB), 8.4mg anthocyanin (ANC)/kg body weight (BW)/day]; three doses of a phenolic extract [postamberlite extract (PAE)] from AFFB at 0.1×, 1× and 2× ANC concentrations; sitagliptin (hypoglycemic positive control); or water (negative control). Weight and fat mass gain were attenuated in mice receiving the highest doses of PAE (18.9mg ANC/kg BW/day, P<.05). There were also reductions (P<.05) in percent fat mass, epididymal fat pad weights, mean adipocyte diameters and plasma triglycerides and cholesterol associated with PAE treatments. By the end of the study, fasting blood glucose for mice receiving 9mg (1×) or 18.9mg (2×) ANC/kg BW/day was significantly lower than in the water and the sitagliptin groups (P<.05). Histological and histochemical analyses revealed an unexpected change in liver of mice fed ANC at 1× or 2× doses consisting of liver enlargement and increased lipid deposition. PAE also induced the most differential gene expression changes, including highly significant downstream effects at all doses to reduce d-glucose concentrations. Overall, phenolic compounds from the fermented blueberry-blackberry beverage had an impact to attenuate the development of obesity and fasting blood glucose in C57BL/6J mice. PMID:27133423

  4. Diet-induced obesity in zebrafish shares common pathophysiological pathways with mammalian obesity

    PubMed Central

    2010-01-01

    Background Obesity is a multifactorial disorder influenced by genetic and environmental factors. Animal models of obesity are required to help us understand the signaling pathways underlying this condition. Zebrafish possess many structural and functional similarities with humans and have been used to model various human diseases, including a genetic model of obesity. The purpose of this study was to establish a zebrafish model of diet-induced obesity (DIO). Results Zebrafish were assigned into two dietary groups. One group of zebrafish was overfed with Artemia (60 mg dry weight/day/fish), a living prey consisting of a relatively high amount of fat. The other group of zebrafish was fed with Artemia sufficient to meet their energy requirements (5 mg dry weight/day/fish). Zebrafish were fed under these dietary protocols for 8 weeks. The zebrafish overfed with Artemia exhibited increased body mass index, which was calculated by dividing the body weight by the square of the body length, hypertriglyceridemia and hepatosteatosis, unlike the control zebrafish. Calorie restriction for 2 weeks was applied to zebrafish after the 8-week overfeeding period. The increased body weight and plasma triglyceride level were improved by calorie restriction. We also performed comparative transcriptome analysis of visceral adipose tissue from DIO zebrafish, DIO rats, DIO mice and obese humans. This analysis revealed that obese zebrafish and mammals share common pathophysiological pathways related to the coagulation cascade and lipid metabolism. Furthermore, several regulators were identified in zebrafish and mammals, including APOH, IL-6 and IL-1β in the coagulation cascade, and SREBF1, PPARα/γ, NR1H3 and LEP in lipid metabolism. Conclusion We established a zebrafish model of DIO that shared common pathophysiological pathways with mammalian obesity. The DIO zebrafish can be used to identify putative pharmacological targets and to test novel drugs for the treatment of human obesity

  5. Preventing leptin resistance by blocking angiotensin II AT1 receptors in diet-induced obese rats

    PubMed Central

    Müller-Fielitz, Helge; Lau, Margot; Geißler, Cathleen; Werner, Lars; Winkler, Martina; Raasch, Walter

    2015-01-01

    Background and Purpose AT1 receptor blockers (ARBs) represent an approach for treating metabolic syndrome due to their potency in reducing hypertension, body weight and onset of type 2 diabetes. The mechanism underlying ARB-induced weight loss is still unclear. Experimental Approach Leptin resistance tests (LRTs) in diet-induced obese or lean rats were conducted to determine whether telmisartan (8 mg·kg−1·day−1, 14 days) enhances leptin sensitivity. Phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) staining was performed in hypothalami to determine leptin transport across the blood–brain barrier. Key Results Telmisartin reduced weight gain, food intake and plasma leptin but blood pressure remained unchanged. The 24 h profiles of plasma leptin after saline injections were similar in controls and telmisartan-treated rats, but after leptin injections were higher in controls and slightly lower in telmisartan-treated animals. After telmisartan, energy intake during LRT was lower in leptin-than in saline-pretreated rats, but remained unchanged in controls, irrespectively of whether rats received saline or leptin. Leptin minimized the gain in body weight during LRT in telmisartan-treated rats as compared with saline-treated animals. pSTAT3 staining was reduced in cafeteria diet-fed rats as compared with chow-fed rats but this was normalized by telmisartan. Telmisartin reduced hypothalamic mRNA levels of the orexigenic peptides melanin-concentrating hormone and prepro-orexin. Conclusions and Implications Rats fed a cafeteria diet develop leptin resistance after 2 weeks. Leptin sensitivity was preserved by telmisartan treatment even in rats fed a cafeteria diet. This pleiotropic effect is not related to the hypotensive action of telmisartan. PMID:25258168

  6. Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment.

    PubMed

    Slocum, Nikki; Durrant, Jessica R; Bailey, David; Yoon, Lawrence; Jordan, Holly; Barton, Joanna; Brown, Roger H; Clifton, Lisa; Milliken, Tula; Harrington, Wallace; Kimbrough, Carie; Faber, Catherine A; Cariello, Neal; Elangbam, Chandikumar S

    2013-07-01

    Drug-induced weight loss in humans has been associated with undesirable side effects not present in weight loss from lifestyle interventions (caloric restriction or exercise). To investigate the mechanistic differences of weight loss by drug-induced and lifestyle interventions, we examined the gene expression (mRNA) in brown adipose tissue (BAT) and conducted histopathologic assessments in diet-induced obese (DIO) mice given ephedrine (18 mg/kg/day orally), treadmill exercise (10 m/min, 1-h/day), and dietary restriction (DR: 26% dietary restriction) for 7 days. Exercise and DR mice lost more body weight than controls and both ephedrine and exercise reduced percent body fat. All treatments reduced BAT and liver lipid accumulation (i.e., cytoplasmic lipids in brown adipocytes and hepatocytes) and increased oxygen consumption (VO2 ml/kg/h) compared with controls. Mitochondrial biogenesis/function-related genes (TFAM, NRF1 and GABPA) were up-regulated in the BAT of all groups. UCP-1 was up-regulated in exercise and ephedrine groups, whereas MFSD2A was up-regulated in ephedrine and DR groups. PGC-1α up-regulation was observed in exercise and DR groups but not in ephedrine group. In all experimental groups, except for ephedrine, fatty acid transport and metabolism genes were up-regulated, but the magnitude of change was higher in the DR group. PRKAA1 was up-regulated in all groups but not significantly in the ephedrine group. ADRß3 was slightly up-regulated in the DR group only, whereas ESRRA remained unchanged in all groups. Although our data suggest a common pathway of BAT activation elicited by ephedrine treatment, exercise or DR, mRNA changes were indicative of additional nutrient-sensing pathways in exercise and DR.

  7. Very low calorie ketogenic weight reduction diet in patients with cirrhosis: a case series

    PubMed Central

    Temmerman, J C; Friedman, A N

    2013-01-01

    Weight reduction may be necessary in patients with end-stage liver disease (ESLD) before liver transplantation. Although very low calorie diets (VLCDs) are a highly effective weight loss strategy, they risk inducing protein-calorie malnutrition, sarcopenia and hepatic encephalopathy in ESLD patients. We report for the first time on the use of VCLDs in ESLD. Two severely obese individuals with ESLD underwent a modified VLCD to become eligible for liver transplantation. Patients consumed four protein supplements and one lean meal daily, equivalent to 800 kilocalories (kcal) and were closely monitored during the diet period. Subject 1, a 46-year-old male with alcoholic cirrhosis, lost 44.1 kg after 28 weeks on a modified VLCD. Liver function and MELD (model for end-stage liver disease) scores improved and he currently does not require listing for transplantation. Subject 2, a 64-year-old female with non-alcoholic steatohepatitis, lost 39.7 kg after a 30-week modified VLCD. She is awaiting liver transplantation listing with a stable MELD score. VLCDs were well tolerated by both patients without adverse effects. In conclusion, under close medical supervision VLCDs in patients with ESLD can be safe and effective in reducing weight, facilitating liver transplantation listing, and possibly improving liver damage. PMID:24247485

  8. Burst noise reduction of image by decimation and adaptive weighted median filter

    NASA Astrophysics Data System (ADS)

    Nakayama, Fumitaka; Meguro, Mitsuhiko; Hamada, Nozomu

    2000-12-01

    The removal of noise in image is one of the important issues, and useful as a preprocessing for edge detection, motion estimation and so on. Recently, many studies on the nonlinear digital filter for impulsive noise reduction have been reported. The median filter, the representative of the nonlinear filters, is very effective for removing impulsive noise and preserving sharp edge. In some cases, burst (i.e., successive) impulsive noise is added to image, and this type of noise is difficult to remove by using the median filter. In this paper, we propose an Adaptive Weighted Median (AWM) filter with Decimation (AWM-D filter) for burst noise reduction. This method can also be applied to recover large destructive regions, such as blotch and scratch. The proposed filter is an extension of the Decimated Median (DM) filter, which is useful for reducing successive impulsive noise. The DM filter can split long impulsive noise sequences into short ones, and remove burst noise in spite of the short filter window. Nevertheless, the DM filter also has two disadvantages. One is that the signals without added noise is unnecessary filtered. The other is that the position information in the window is not considered in the weight determinative process, as common in the median type filter. To improve detail-preserving property of the DM filter, we use the noise detection procedure and the AWM-D filter, which can be tuned by Least Mean Absolute (LMA) algorithm. The AWM-D filter preserves details more precisely than the median-type filter, because the AWM-D filter has the weights that can control the filter output. Through some simulations, the higher performance of the proposed filter is shown compared with the simple median, the WM filter, and the DM filter.

  9. The effect of psychological stress on diet-induced thermogenesis and resting metabolic rate.

    PubMed

    Weststrate, J A; Van der Kooy, K; Deurenberg, P; Hautvast, J G

    1990-04-01

    The effect of psychological stress on resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) was assessed in 12 healthy young non-obese men of body weight 70.2 +/- 1.2 kg (mean +/- s.e.m.) and age 25 +/- 0.6 years. Two types of commercially available motion pictures (video films) were shown to the subjects during the measurements, ie stress-inducing horror films and as a control, romantic family films. The study was conducted according to a cross-over design. RMR and respiratory quotients were not significantly influenced by the type of film shown to the subjects. DIT, assessed over 4 h, was significantly increased by the stress-inducing treatment, 0.95 +/- 0.05 kJ/min (mean +/- s.e.m.) versus 0.76 +/- 0.06 kJ/min (control). No significant effect was observed of psychological stress on postprandial substrate oxidation rates, nutrient balances, and urinary catecholamine excretion.

  10. Antiatherogenic Potential of Nigella sativa Seeds and Oil in Diet-Induced Hypercholesterolemia in Rabbits.

    PubMed

    Al-Naqeep, Ghanya; Al-Zubairi, Adel S; Ismail, Maznah; Amom, Zulkhairi Hj; Esa, Norhaizan Mohd

    2011-01-01

    Nigella sativa or Black seed (N. sativa L.) is traditionally used for several ailments in many Middle Eastern countries. It is an annual herbaceous plant that belongs to the Ranuculacea family with many beneficial properties as antitumor, antidiabetic, antihypertensive, antioxidative and antibacterial. This work attempted to study the effect of N. sativa seeds powder and oil on atherosclerosis in diet-induced hypercholesterolemic (HC) rabbits in comparison with simvastatin (ST). Twenty-five adult New Zealand male white rabbits, weighing 1.5-2.5 kg, were divided into five groups; normal group (NC, n = 5) and four hypercholesterolemic groups (n = 20): a positive control (PC) and three HC groups force fed diet supplemented with 1000 mg Kg(-1) body weight of N. sativa powder (NSP), 500 mg Kg(-1) body N. sativa oil (NSO) and 10 mg Kg(-1) ST for 8 weeks. Feeding HC rabbits with N. sativa either in powder or oil forms was shown to significantly reduce (P < .05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels and enhance high-density lipoprotein cholesterol (HDL) levels after treatment for 2, 4, 6 and 8 weeks compared to the PC group. Plaque formation was significantly inhibited while the intima: media ratio was significantly reduced in the NSP and NSO supplemented groups compared to the PC group. In conclusion, treatment of HC rabbits with N. sativa seeds powder or oil showed hypocholesterolemic and antiatherogenic cardioprotective properties. PMID:21792359

  11. Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance.

    PubMed

    Amine, Hamza; Benomar, Yacir; Haimeur, Adil; Messaouri, Hafida; Meskini, Nadia; Taouis, Mohammed

    2016-01-01

    The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways.

  12. Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance.

    PubMed

    Amine, Hamza; Benomar, Yacir; Haimeur, Adil; Messaouri, Hafida; Meskini, Nadia; Taouis, Mohammed

    2016-01-01

    The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways. PMID:26459640

  13. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice

    PubMed Central

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism. PMID:26914024

  14. Enhanced thermogenic program by non-viral delivery of combinatory browning genes to treat diet-induced obesity in mice.

    PubMed

    Park, Hongsuk; Cho, Sungpil; Janat-Amsbury, Margit M; Bae, You Han

    2015-12-01

    Thermogenic program (also known as browning) is a promising and attractive anti-obesity approach. Islet amyloid polypeptide (IAPP) and irisin have emerged as potential browning hormones that hold high potential to treat obesity. Here, we have constructed a dual browning gene system containing both IAPP and irisin (derived from fibronectin type III domain containing 5; FNDC5) combined with 2A and furin self-cleavage sites. Intraperitoneal administration of the construct complexed with a linear polyethylenimine into diet-induced obese mice demonstrated the elevation of anti-obesogenic effects characterized as the decreased body weight, adiposity, and levels of glucose and insulin. In addition, the construct delivery increased energy expenditure and the expression of core molecular determinants associated with browning. The additional advantages of the dual browning gene construct delivery compared to both single gene construct delivery and dual peptide delivery can be emphasized on efficacy and practicability. Hence, we have concluded that dual browning gene delivery makes it therapeutically attractive for diet-induced obesity treatment.

  15. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    PubMed

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism. PMID:26914024

  16. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    PubMed

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism.

  17. Anti-obesity activity of Allium fistulosum L. extract by down-regulation of the expression of lipogenic genes in high-fat diet-induced obese mice.

    PubMed

    Sung, Yoon-Young; Yoon, Taesook; Kim, Seung Ju; Yang, Won-Kyung; Kim, Ho Kyoung

    2011-01-01

    This study investigated the anti-obesity activity and underlying mechanism of a 70% ethanol extract from Allium fistulosum L. (AFE) in high-fat diet-induced obese mice. AFE was orally administered to mice with the high-fat diet at a dose of 400 mg/kg/day for 6.5 weeks. AFE treatment significantly reduced body weight and white adipose tissue (subcutaneous, epididymal and retroperitoneal) weight as well as adipocyte size compared to high-fat diet-induced control mice. AFE also significantly decreased triglyceride, total cholesterol, low density lipoprotein-cholesterol and leptin concentrations in the serum of the mice, whereas it increased adiponectin levels. Furthermore, AFE suppressed the mRNA expression of transcription factors, such as sterol regulatory element binding protein-1c and peroxisome proliferator activated receptor γ, as well as fatty acid synthase in the subcutaneous adipose tissue. These results suggest that AFE inhibited the adipose size, fat accumulation and serum lipid concentrations by down-regulation of the expression of genes involved in lipogenesis in the adipose tissue of high-fat diet-induced obese mice. PMID:21468588

  18. Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

    PubMed Central

    Lee, Young-Seob; Han, Sin-Hee; Ahn, Young-Sup; Cha, Seon-Woo; Seo, Yun-Soo; Kong, Ryong; Kwon, Dong-Yeul

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD

  19. Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

    PubMed

    Kim, Sung-Bae; Kang, Ok-Hwa; Lee, Young-Seob; Han, Sin-Hee; Ahn, Young-Sup; Cha, Seon-Woo; Seo, Yun-Soo; Kong, Ryong; Kwon, Dong-Yeul

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD

  20. Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility.

    PubMed

    Chiang, Shian-Huey; Harrington, W Wallace; Luo, Guizhen; Milliken, Naphtali O; Ulrich, John C; Chen, Jing; Rajpal, Deepak K; Qian, Ying; Carpenter, Tiffany; Murray, Rusty; Geske, Robert S; Stimpson, Stephen A; Kramer, Henning F; Haffner, Curt D; Becherer, J David; Preugschat, Frank; Billin, Andrew N

    2015-01-01

    Nicotinamide adenine dinucleotide (NAD+) is a key cofactor required for essential metabolic oxidation-reduction reactions. It also regulates various cellular activities, including gene expression, signaling, DNA repair and calcium homeostasis. Intracellular NAD+ levels are tightly regulated and often respond rapidly to nutritional and environmental changes. Numerous studies indicate that elevating NAD+ may be therapeutically beneficial in the context of numerous diseases. However, the role of NAD+ on skeletal muscle exercise performance is poorly understood. CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet. PMID:26287487

  1. Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility

    PubMed Central

    Chiang, Shian-Huey; Harrington, W. Wallace; Luo, Guizhen; Milliken, Naphtali O.; Ulrich, John C.; Chen, Jing; Rajpal, Deepak K.; Qian, Ying; Carpenter, Tiffany; Murray, Rusty; Geske, Robert S.; Stimpson, Stephen A.; Kramer, Henning F.; Haffner, Curt D.; Becherer, J. David; Preugschat, Frank; Billin, Andrew N.

    2015-01-01

    Nicotinamide adenine dinucleotide (NAD+) is a key cofactor required for essential metabolic oxidation-reduction reactions. It also regulates various cellular activities, including gene expression, signaling, DNA repair and calcium homeostasis. Intracellular NAD+ levels are tightly regulated and often respond rapidly to nutritional and environmental changes. Numerous studies indicate that elevating NAD+ may be therapeutically beneficial in the context of numerous diseases. However, the role of NAD+ on skeletal muscle exercise performance is poorly understood. CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet. PMID:26287487

  2. Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE(-/-) mice.

    PubMed

    Kumar, Saran; Chen, Mo; Li, Yan; Wong, Fiona H S; Thiam, Chung Wee; Hossain, Md Zakir; Poh, Kian Keong; Hirohata, Satoshi; Ogawa, Hiroko; Angeli, Véronique; Ge, Ruowen

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease characterized by formation of lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that regulates versican turnover in the arterial wall and atherosclerotic plaques. Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques and in the plasma of acute coronary syndrome patients. Nevertheless, whether increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal role in atherogenesis remains unknown. In this work, we investigated the role of ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE(-/-)) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in plaques as atherosclerosis progresses in ApoE(-/-) mice. ApoE(-/-)Adamts4(-/-) double knockout mice presented a significant reduction in plaque burden at 18 weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a significantly reduced plaque vulnerability index characterized by reduced lipid content and macrophages accompanied with a significant increase in smooth muscle cells, collagen deposition and fibrotic cap thickness. The reduced atherosclerosis is accompanied by an altered plasma inflammatory cytokine profile. These results demonstrate for the first time that ADAMTS4 contributes to diet induced atherosclerosis in ApoE(-/-) mice. PMID:27491335

  3. Acute exercise modulates the Foxo1/PGC-1α pathway in the liver of diet-induced obesity rats

    PubMed Central

    Ropelle, Eduardo R; Pauli, José R; Cintra, Dennys E; Frederico, Marisa J S; de Pinho, Ricardo A; Velloso, Lício A; De Souza, Cláudio T

    2009-01-01

    PGC-1α expression is a tissue-specific regulatory feature that is extremely relevant to diabetes. Several studies have shown that PGC-1α activity is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. PGC-1α and Foxo1 can physically interact with one another and represent an important signal transduction pathway that governs the synthesis of glucose in the liver. However, the effect of physical activity on PGC-1α/Foxo1 association is unknown. Here we investigate the expression of PGC-1α and the association of PGC-1α/Foxo1 in the liver of diet-induced obese rats after acute exercise. Wistar rats swam for two 3 h-long bouts, separated by a 45 min rest period. Eight hours after the acute exercise protocol, the rats were submitted to an insulin tolerance test (ITT) and biochemical and molecular analysis. Results demonstrate that acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing PGC-1α expression and PGC-1α/Foxo1 interaction in the liver of diet-induced obesity rats under fasting conditions. These phenomena are accompanied by a reduction in the expression of gluconeogenesis genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate (G6Pase). Thus, these results provide new insights into the mechanism by which exercise could improve fasting hyperglycaemia. PMID:19273580

  4. Effect of Dietary Cocoa Tea (Camellia ptilophylla) Supplementation on High-Fat Diet-Induced Obesity, Hepatic Steatosis, and Hyperlipidemia in Mice

    PubMed Central

    Yang, Xiao Rong; Wat, Elaine; Wang, Yan Ping; Ko, Chun Hay; Koon, Chi Man; Siu, Wing Sum; Gao, Si; Cheung, David Wing Shing; Lau, Clara Bik San; Ye, Chuang Xing; Leung, Ping Chung

    2013-01-01

    Recent studies suggested that green tea has the potential to protect against diet-induced obesity. The presence of caffeine within green tea has caused limitations. Cocoa tea (Camellia ptilophylla) is a naturally decaffeinated tea plant. To determine whether cocoa tea supplementation results in an improvement in high-fat diet-induced obesity, hyperlipidemia and hepatic steatosis, and whether such effects would be comparable to those of green tea extract, we studied six groups (n = 10) of C57BL/6 mice that were fed with (1) normal chow (N); (2) high-fat diet (21% butterfat + 0.15% cholesterol, wt/wt) (HF); (3) a high-fat diet supplemented with 2% green tea extract (HFLG); (4) a high-fat diet supplemented with 4% green tea extract (HFHG); (5) a high-fat diet supplemented with 2% cocoa tea extract (HFLC); and (6) a high-fat diet supplemented with 4% cocoa tea extract (HFHC). From the results, 2% and 4% dietary cocoa tea supplementation caused a dose-dependent decrease in (a) body weight, (b) fat pad mass, (c) liver weight, (d) total liver lipid, (e) liver triglyceride and cholesterol, and (f) plasma lipids (triglyceride and cholesterol). These data indicate that dietary cocoa tea, being naturally decaffeinated, has a beneficial effect on high-fat diet-induced obesity, hepatomegaly, hepatic steatosis, and elevated plasma lipid levels in mice, which are comparable to green tea. The present findings have provided the proof of concept that dietary cocoa tea might be of therapeutic value and could therefore provide a safer and cost effective option for patients with diet-induced metabolic syndrome. PMID:23935682

  5. Discovery of 1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-4-((pyrrolidine-1-sulfonamido)methyl)-5-(5-((4-(trifluoromethyl)phenyl)ethynyl)thiophene-2-yl)-1H-pyrazole-3-carboxamide as a novel peripherally restricted cannabinoid-1 receptor antagonist with significant weight-loss efficacy in diet-induced obese mice.

    PubMed

    Chang, Chun-Ping; Wu, Chien-Huang; Song, Jen-Shin; Chou, Ming-Chen; Wong, Ying-Chieh; Lin, Yinchiu; Yeh, Teng-Kuang; Sadani, Amit A; Ou, Ming-Hung; Chen, Kun-Hung; Chen, Pei-Hsuan; Kuo, Po-Chu; Tseng, Chen-Tso; Chang, Kuei-Hua; Tseng, Shi-Liang; Chao, Yu-Sheng; Hung, Ming-Shiu; Shia, Kak-Shan

    2013-12-27

    After extensive synthetic efforts, we found that many structurally diverse bioisosteres could be generated via derivatizing the C-4 alkyl chain on the pyrazole ring of compound 3 (B/P = 1/33) with different electronegative groups. Especially when a sulfonamide or sulfamide moiety was added, resulting compounds exhibited not only potent CB1R activity but also a desired tPSA value over 90 Å(2), a threshold considered to possess a low probability to cross BBB, leading to the identification of compound 4 (B/P = 1/64) as a peripherally restricted CB1R antagonist. Apart from its significant weight-loss efficacy in DIO mice, compound 4 also displays 163 clean off-target profiles and is currently under development for treating obesity and the related metabolic syndrome. PMID:24224693

  6. Psychodynamic mechanism and weight reduction in obesity group therapy – first observations with different attachment styles

    PubMed Central

    Kiesewetter, Sybille; Köpsel, Andrea; Köpp, Werner; Kallenbach-Dermutz, Bettina; Pfeiffer, Andreas F.H.; Spranger, Joachim; Deter, Hans-Christian

    2010-01-01

    Objectives: Successful long-term results are extremely rare in non-surgical obesity treatment. Interactional difficulties with the attending physicians and the limited compliance of obese patients are a frequently described dilemma in repeated psychotherapeutic group treatment attempts. The type of relationship initiation and the attachment behavior probably play a central role in this connection but have not yet been systematically investigated. Methods: This paper focuses on the attachment styles of obese subjects and their effects on psychodynamic group therapy within the context of a weight-reduction program. Results: The attachment styles are characterized in 107 pre-obese and obese patients, and their effects on patients and therapists in group therapy are described. Conclusion: The paper surveys the motivational situation, clinical pictures, and repeated group topics. PMID:20930928

  7. Obesity and headache/migraine: the importance of weight reduction through lifestyle modifications.

    PubMed

    Verrotti, Alberto; Di Fonzo, Alessia; Penta, Laura; Agostinelli, Sergio; Parisi, Pasquale

    2014-01-01

    The aim of this study is to determine a possible relationship between prevalence, frequency, and severity of migraine and obesity. All pertinent data from the literature have been critically examined and reviewed in order to assess the possible relationship between obesity and migraine, in particular migraine frequency and disability in children, as well as in adult population studies. Prevalence, frequency, and severity of migraine appear to increase in relation to the body mass index, although this evidence is not supported by all the studies examined. Data from literature suggest that obesity can be linked with migraine prevalence, frequency, and disability both in pediatric and adult subjects. These data have important clinical implications and suggest that clinicians should have a special interest for weight reduction of obese children suffering from migraine, prescribing and supporting intensive lifestyle modifications (dietary, physical activities, and behavioral) for the patient and the entire family.

  8. Mechanisms of body weight reduction and metabolic syndrome alleviation by tea.

    PubMed

    Yang, Chung S; Zhang, Jinsong; Zhang, Le; Huang, Jinbao; Wang, Yijun

    2016-01-01

    Tea, a popular beverage made from leaves of the plant Camellia sinensis, has been shown to reduce body weight, alleviate metabolic syndrome, and prevent diabetes and cardiovascular diseases in animal models and humans. Such beneficial effects have generally been observed in most human studies when the level of tea consumption was three to four cups (600-900 mg tea catechins) or more per day. Green tea is more effective than black tea. In spite of numerous studies, the fundamental mechanisms for these actions still remain unclear. From a review of the literature, we propose that the two major mechanisms are: (i) decreasing absorption of lipids and proteins by tea constituents in the intestine, thus reducing calorie intake; and (ii) activating AMP-activated protein kinase by tea polyphenols that are bioavailable in the liver, skeletal muscle, and adipose tissues. The relative importance of these two mechanisms depends on the types of tea and diet consumed by individuals. The activated AMP-activated protein kinase would decrease gluconeogenesis and fatty acid synthesis and increase catabolism, leading to body weight reduction and metabolic syndrome alleviation. Other mechanisms and the health relevance of these beneficial effects of tea consumption remain to be further investigated.

  9. Effect of molecular weight reduction by gamma irradiation on chitosan film properties.

    PubMed

    García, Mario A; Pérez, Liliam; de la Paz, Nilia; González, Juan; Rapado, Manuel; Casariego, Alicia

    2015-10-01

    The present work aimed the influence of molecular weight (MW) reduction by irradiation with (60)Co and polymer concentration on some physical properties of chitosan films. Irradiation of chitosan with a MW of 275.221 kDa and 74.74% of deacetylation degree was performed using a (60)Co source to provide doses of 5, 10, 20 and 50 kGy to obtain chitosans with molecular weights of 247.847, 221.563, 126.469 and 77.063 kDa, respectively. Films were prepared via the solution casting method. Film-forming solutions (FFS) of chitosan irradiated or not, were prepared at 1.5 and 2% (w/v) in a solution of lactic acid at 1% (v/v) and 0.1% (v/v) of Tween 80. The FFS were poured into glass plates of 400 cm(2) and dried at 60 °C during 10h without airflow. The decrease of MW and increase of chitosan concentration increased the tensil strength and water vapor permeability while decreased the elongation at break of the films. The chitosan MW did not significantly influence (p>0.05) the water solubility of films within a same polymer concentration. There was a decrease in the films' brightness with the increase of concentration and a decrease of the MW of irradiated chitosan, while the b* values of films increased and there was an increasing tendency of their apparent opacity.

  10. Impacts of Vehicle Weight Reduction via Material Substitution on Life-Cycle Greenhouse Gas Emissions.

    PubMed

    Kelly, Jarod C; Sullivan, John L; Burnham, Andrew; Elgowainy, Amgad

    2015-10-20

    This study examines the vehicle-cycle and vehicle total life-cycle impacts of substituting lightweight materials into vehicles. We determine part-based greenhouse gas (GHG) emission ratios by collecting material substitution data and evaluating that alongside known mass-based GHG ratios (using and updating Argonne National Laboratory's GREET model) associated with material pair substitutions. Several vehicle parts are lightweighted via material substitution, using substitution ratios from a U.S. Department of Energy report, to determine GHG emissions. We then examine fuel-cycle GHG reductions from lightweighting. The fuel reduction value methodology is applied using FRV estimates of 0.15-0.25, and 0.25-0.5 L/(100km·100 kg), with and without powertrain adjustments, respectively. GHG breakeven values are derived for both driving distance and material substitution ratio. While material substitution can reduce vehicle weight, it often increases vehicle-cycle GHGs. It is likely that replacing steel (the dominant vehicle material) with wrought aluminum, carbon fiber reinforced plastic (CRFP), or magnesium will increase vehicle-cycle GHGs. However, lifetime fuel economy benefits often outweigh the vehicle-cycle, resulting in a net total life-cycle GHG benefit. This is the case for steel replaced by wrought aluminum in all assumed cases, and for CFRP and magnesium except for high substitution ratio and low FRV. PMID:26393414

  11. Impacts of Vehicle Weight Reduction via Material Substitution on Life-Cycle Greenhouse Gas Emissions.

    PubMed

    Kelly, Jarod C; Sullivan, John L; Burnham, Andrew; Elgowainy, Amgad

    2015-10-20

    This study examines the vehicle-cycle and vehicle total life-cycle impacts of substituting lightweight materials into vehicles. We determine part-based greenhouse gas (GHG) emission ratios by collecting material substitution data and evaluating that alongside known mass-based GHG ratios (using and updating Argonne National Laboratory's GREET model) associated with material pair substitutions. Several vehicle parts are lightweighted via material substitution, using substitution ratios from a U.S. Department of Energy report, to determine GHG emissions. We then examine fuel-cycle GHG reductions from lightweighting. The fuel reduction value methodology is applied using FRV estimates of 0.15-0.25, and 0.25-0.5 L/(100km·100 kg), with and without powertrain adjustments, respectively. GHG breakeven values are derived for both driving distance and material substitution ratio. While material substitution can reduce vehicle weight, it often increases vehicle-cycle GHGs. It is likely that replacing steel (the dominant vehicle material) with wrought aluminum, carbon fiber reinforced plastic (CRFP), or magnesium will increase vehicle-cycle GHGs. However, lifetime fuel economy benefits often outweigh the vehicle-cycle, resulting in a net total life-cycle GHG benefit. This is the case for steel replaced by wrought aluminum in all assumed cases, and for CFRP and magnesium except for high substitution ratio and low FRV.

  12. Impacts of Vehicle Weight Reduction via Material Substitution on Life-Cycle Greenhouse Gas Emissions

    SciTech Connect

    Kelly, Jarod C.; Sullivan, John L.; Burnham, Andrew; Elgowainy, Amgad

    2015-10-20

    This study examines the vehicle-cycle impacts associated with substituting lightweight materials for those currently found in light-duty passenger vehicles. We determine part-based energy use and greenhouse gas (GHG) emission ratios by collecting material substitution data from both the literature and automotive experts and evaluating that alongside known mass-based energy use and GHG emission ratios associated with material pair substitutions. Several vehicle parts, along with full vehicle systems, are examined for lightweighting via material substitution to observe the associated impact on GHG emissions. Results are contextualized by additionally examining fuel-cycle GHG reductions associated with mass reductions relative to the baseline vehicle during the use phase and also determining material pair breakeven driving distances for GHG emissions. The findings show that, while material substitution is useful in reducing vehicle weight, it often increases vehicle-cycle GHGs depending upon the material substitution pair. However, for a vehicle’s total life cycle, fuel economy benefits are greater than the increased burdens associated with the vehicle manufacturing cycle, resulting in a net total life-cycle GHG benefit. The vehicle cycle will become increasingly important in total vehicle life-cycle GHGs, since fuel-cycle GHGs will be gradually reduced as automakers ramp up vehicle efficiency to meet fuel economy standards.

  13. Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion.

    PubMed

    Shibue, Kimitaka; Yamane, Shunsuke; Harada, Norio; Hamasaki, Akihiro; Suzuki, Kazuyo; Joo, Erina; Iwasaki, Kanako; Nasteska, Daniela; Harada, Takanari; Hayashi, Yoshitaka; Adachi, Yasuhiro; Owada, Yuji; Takayanagi, Ryoichi; Inagaki, Nobuya

    2015-04-01

    Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K cells in response to nutrient intake, especially fat. GIP is one of the contributing factors inducing fat accumulation that results in obesity. A recent study shows that fatty acid-binding protein 5 (FABP5) is expressed in murine K cells and is involved in fat-induced GIP secretion. We investigated the mechanism of fat-induced GIP secretion and the impact of FABP5-related GIP response on diet-induced obesity (DIO). Single oral administration of glucose and fat resulted in a 40% reduction of GIP response to fat but not to glucose in whole body FABP5-knockout (FABP5(-/-)) mice, with no change in K cell count or GIP content in K cells. In an ex vivo experiment using isolated upper small intestine, oleic acid induced only a slight increase in GIP release, which was markedly enhanced by coadministration of bile and oleic acid together with attenuated GIP response in the FABP5(-/-) sample. FABP5(-/-) mice exhibited a 24% reduction in body weight gain and body fat mass under a high-fat diet compared with wild-type (FABP5(+/+)) mice; the difference was not observed between GIP-GFP homozygous knock-in (GIP(gfp/gfp))-FABP5(+/+) mice and GIP(gfp/gfp)-FABP5(-/-) mice, in which GIP is genetically deleted. These results demonstrate that bile efficiently amplifies fat-induced GIP secretion and that FABP5 contributes to the development of DIO in a GIP-dependent manner.

  14. Statistical CT noise reduction with multiscale decomposition and penalized weighted least squares in the projection domain

    SciTech Connect

    Tang Shaojie; Tang Xiangyang

    2012-09-15

    Purposes: The suppression of noise in x-ray computed tomography (CT) imaging is of clinical relevance for diagnostic image quality and the potential for radiation dose saving. Toward this purpose, statistical noise reduction methods in either the image or projection domain have been proposed, which employ a multiscale decomposition to enhance the performance of noise suppression while maintaining image sharpness. Recognizing the advantages of noise suppression in the projection domain, the authors propose a projection domain multiscale penalized weighted least squares (PWLS) method, in which the angular sampling rate is explicitly taken into consideration to account for the possible variation of interview sampling rate in advanced clinical or preclinical applications. Methods: The projection domain multiscale PWLS method is derived by converting an isotropic diffusion partial differential equation in the image domain into the projection domain, wherein a multiscale decomposition is carried out. With adoption of the Markov random field or soft thresholding objective function, the projection domain multiscale PWLS method deals with noise at each scale. To compensate for the degradation in image sharpness caused by the projection domain multiscale PWLS method, an edge enhancement is carried out following the noise reduction. The performance of the proposed method is experimentally evaluated and verified using the projection data simulated by computer and acquired by a CT scanner. Results: The preliminary results show that the proposed projection domain multiscale PWLS method outperforms the projection domain single-scale PWLS method and the image domain multiscale anisotropic diffusion method in noise reduction. In addition, the proposed method can preserve image sharpness very well while the occurrence of 'salt-and-pepper' noise and mosaic artifacts can be avoided. Conclusions: Since the interview sampling rate is taken into account in the projection domain

  15. Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice

    PubMed Central

    Steiner, Nadia; Carneiro, Lionel; Favrod, Céline; Preitner, Frédéric; Thorens, Bernard; Stehle, Jean-Christophe; Dix, Laure; Pralong, François; Magistretti, Pierre J.; Pellerin, Luc

    2013-01-01

    The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1+/− mice developed normally. However, when fed high fat diet (HFD), MCT1+/− mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1+/+ mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1+/− mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O2 consumption and CO2 production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1+/+ mice when fed HFD, were reduced in MCT1+/− mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1+/+ mice under high fat diet was prevented in the liver of MCT1+/− mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet. PMID:24367518

  16. Hepatocellular proliferation and hepatocarcinogen bioactivation in mice with diet-induced fatty liver and obesity.

    PubMed

    Iatropoulos, M J; Duan, J-D; Jeffrey, A M; Leach, M W; Hayes, A N; Stedman, N L; Williams, G M

    2013-05-01

    Human liver cancer is in part associated with obesity and related metabolic diseases. The present study was undertaken in a mouse model of diet-induced obesity (DIO) and hepatic steatosis, conditions which can be associated with hepatic neoplasia, to determine whether the rates of cell proliferation or hepatocarcinogen bioactivation were altered in ways which could facilitate hepatocarcinogenesis. DIO mice were generated by feeding C57BL/6 (B6) male mice a high-fat diet beginning at 4 weeks of age; age-matched conventional lean (LEAN) B6 mice fed a low fat diet (10% Kcal from fat) were used for comparison. Groups of 28 week old DIO and LEAN mice were dosed with the bioactivation-dependent DNA-reactive hepatocarcinogen 2-acetylaminofluorene (AAF), at 2.24 or 22.4 mg/kg, given by gavage 3 times per week for 31 days, or received no treatment (DIO and LEAN control groups). Compared with the LEAN control group, the DIO control group had a higher mean body weight (16.5 g), higher mean absolute (1.4 g) and mean relative (25.5%) liver weights, higher (394%) liver triglyceride concentrations, and an increased incidence and severity of hepatocellular steatosis at the end of the dosing phase. The DIO control group also had a higher mean hepatocellular replicating fraction (31% increase, determined by proliferating cell nuclear antigen immunohistochemistry). Hepatocarcinogen bioactivation, based on formation of AAF DNA adducts as measured by nucleotide (32)P-postlabeling, was similar in both DIO and LEAN AAF-dosed groups. Thus, hepatocellular proliferation, but not hepatocarcinogen bioactivation, was identified as an alteration in livers of DIO mice which could contribute to their susceptibility to hepatocarcinogenesis.

  17. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced obesity.

    PubMed

    Mwangi, Simon Musyoka; Nezami, Behtash Ghazi; Obukwelu, Blessing; Anitha, Mallappa; Marri, Smitha; Fu, Ping; Epperson, Monica F; Le, Ngoc-Anh; Shanmugam, Malathy; Sitaraman, Shanthi V; Tseng, Yu-Hua; Anania, Frank A; Srinivasan, Shanthi

    2014-03-01

    Obesity is a growing epidemic with limited effective treatments. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) was recently shown to enhance β-cell mass and improve glucose control in rodents. Its role in obesity is, however, not well characterized. In this study, we investigated the ability of GDNF to protect against high-fat diet (HFD)-induced obesity. GDNF transgenic (Tg) mice that overexpress GDNF under the control of the glial fibrillary acidic protein promoter and wild-type (WT) littermates were maintained on a HFD or regular rodent diet for 11 wk, and weight gain, energy expenditure, and insulin sensitivity were monitored. Differentiated mouse brown adipocytes and 3T3-L1 white adipocytes were used to study the effects of GDNF in vitro. Tg mice resisted the HFD-induced weight gain, insulin resistance, dyslipidemia, hyperleptinemia, and hepatic steatosis seen in WT mice despite similar food intake and activity levels. They exhibited significantly (P<0.001) higher energy expenditure than WT mice and increased expression in skeletal muscle and brown adipose tissue of peroxisome proliferator activated receptor-α and β1- and β3-adrenergic receptor genes, which are associated with increased lipolysis and enhanced lipid β-oxidation. In vitro, GDNF enhanced β-adrenergic-mediated cAMP release in brown adipocytes and suppressed lipid accumulation in differentiated 3T3L-1 cells through a p38MAPK signaling pathway. Our studies demonstrate a novel role for GDNF in the regulation of high-fat diet-induced obesity through increased energy expenditure. They show that GDNF and its receptor agonists may be potential targets for the treatment or prevention of obesity.

  18. Dilemmas in the process of weight reduction: Exploring how women experience training as a means of losing weight

    PubMed Central

    Groven, Karen Synne; Engelsrud, Gunn

    2010-01-01

    Patients diagnosed with obesity are usually offered group-based behavior interventions which include dietary advice and exercise programs. In particular, high-intensity training—combining weight lifting with aerobic exercising—has been proven effective for losing weight. Moreover, recent studies have shown that persons participating in high-intensity training are more likely to maintain their weight loss compared to persons with lower levels of physical activity. However, most of the research in the field has made use of quantitative methods focusing on the measurable effect of such interventions. Therefore, the aim of this study was to show how the training is experienced from a first-person perspective, namely the patients themselves. Our hope was to shed some new light on the process of weight loss that concerns more than the measurable “impacts” of the training. A qualitative approach was used based on interviews with five women selected from a primary healthcare clinic in Norway. Our results show that experiences of training are connected to the participants' general experience of being overweight. Both relationships to other people and earlier experiences are important for how the training is carried out and perceived. Five themes were identified supporting this line of argument: (1) the gaze of others; (2) a common ground; (3) dependence of close-follow up; (4) bodily discomfort as painful; and (5) aiming for results—an ambivalent experience. The results highlight the importance of finding the proper context and support for each patient's needs. PMID:20640017

  19. A high-fructose diet induces hippocampal insulin resistance and exacerbates memory deficits in male Sprague-Dawley rats.

    PubMed

    Wu, Hui-Wen; Ren, Lai-Feng; Zhou, Xing; Han, De-Wu

    2015-10-01

    The purpose of this study was to investigate the effects of a long-term high-fructose diet on the insulin-signaling pathway of the hippocampus. Sprague-Dawley rats were fed either on a control (0% fructose solution) or high-fructose diet (10% fructose solution). Food intake and body mass were measured regularly. Eight months later, peripheral insulin sensitivity, the activity of the hippocampal insulin pathway, and memory tasks were assessed. Compared to the control group, the high fructose group exhibited more weight gain, peripheral insulin resistance, metabolic disorders, and memory impairments. In addition, insulin signaling in the hippocampus was attenuated in the high fructose group. These results suggested that a high-fructose diet induced peripheral insulin resistance and an abnormal insulin-signaling pathway in the hippocampus which exacerbated memory deficits in the rats.

  20. Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice

    PubMed Central

    Seo, Eunhui; Oh, Yoon Sin; Jun, Hee-Sook

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver. PMID:26861390

  1. Cafeteria diet induce changes in blood flow that are more related with heat dissipation than energy accretion.

    PubMed

    Sabater, David; Agnelli, Silvia; Arriarán, Sofía; Romero, María Del Mar; Fernández-López, José Antonio; Alemany, Marià; Remesar, Xavier

    2016-01-01

    Background. A "cafeteria" diet is a self-selected high-fat diet, providing an excess of energy, which can induce obesity. Excess of lipids in the diet hampers glucose utilization eliciting insulin resistance, which, further limits amino acid oxidation for energy. Methods. Male Wistar rats were exposed for a month to "cafeteria" diet. Rats were cannulated and fluorescent microspheres were used to determine blood flow. Results. Exposure to the cafeteria diet did not change cardiac output, but there was a marked shift in organ irrigation. Skin blood flow decreased to compensate increases in lungs and heart. Blood flow through adipose tissue tended to increase in relation to controls, but was considerably increased in brown adipose tissue (on a weight basis). Discussion. The results suggest that the cafeteria diet-induced changes were related to heat transfer and disposal. PMID:27547590

  2. Cafeteria diet induce changes in blood flow that are more related with heat dissipation than energy accretion

    PubMed Central

    Sabater, David; Agnelli, Silvia; Arriarán, Sofía; Romero, María del Mar; Fernández-López, José Antonio; Alemany, Marià

    2016-01-01

    Background. A “cafeteria” diet is a self-selected high-fat diet, providing an excess of energy, which can induce obesity. Excess of lipids in the diet hampers glucose utilization eliciting insulin resistance, which, further limits amino acid oxidation for energy. Methods. Male Wistar rats were exposed for a month to “cafeteria” diet. Rats were cannulated and fluorescent microspheres were used to determine blood flow. Results. Exposure to the cafeteria diet did not change cardiac output, but there was a marked shift in organ irrigation. Skin blood flow decreased to compensate increases in lungs and heart. Blood flow through adipose tissue tended to increase in relation to controls, but was considerably increased in brown adipose tissue (on a weight basis). Discussion. The results suggest that the cafeteria diet-induced changes were related to heat transfer and disposal. PMID:27547590

  3. Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity

    PubMed Central

    Labonté, Eric D.; Pfluger, Paul T.; Cash, James G.; Kuhel, David G.; Roja, Juan C.; Magness, Daniel P.; Jandacek, Ronald J.; Tschöp, Matthias H.; Hui, David Y.

    2010-01-01

    Decrease in fat catabolic rate on consuming a high-fat diet contributes to diet-induced obesity. This study used group 1B phospholipase A2 (Pla2g1b)-deficient mice, which are resistant to hyperglycemia, to test the hypothesis that Pla2g1b and its lipolytic product lysophospholipid suppress hepatic fat utilization and energy metabolism in promoting diet-induced obesity. The metabolic consequences of hypercaloric diet, including body weight gain, energy expenditure, and fatty acid oxidation, were compared between Pla2g1b+/+ and Pla2g1b−/− mice. The Pla2g1b−/− mice displayed normal energy balance when fed chow, but were resistant to obesity when challenged with a hypercaloric diet. Obesity resistance in Pla2g1b−/− mice is due to their ability to maintain elevated energy expenditure and core body temperature when subjected to hypercaloric diet, which was not observed in Pla2g1b+/+ mice. The Pla2g1b−/− mice also displayed increased postprandial hepatic fat utilization due to increased expression of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-δ, PPAR-γ, cd36/Fat, and Ucp2, which coincided with reduced postprandial plasma lysophospholipid levels. Lysophospholipids produced by Pla2g1b hydrolysis suppress hepatic fat utilization and down-regulate energy expenditure, thereby preventing metabolically beneficial adaptation to a high-fat diet exposure in promoting diet-induced obesity and type 2 diabetes.—Labonté, E. D., Pfluger, P. T., Cash, J. G., Kuhel, D. G., Rojas, J. C., Magness, D. P., Jandacek, R. J., Tschöp, M. H., Hui, D. Y. Postprandial lysophospholipid suppresses hepatic fatty acid oxidation: the molecular link between group 1B phospholipase A2 and diet-induced obesity. PMID:20215528

  4. Reversion of steatosis by SREBP-1c antisense oligonucleotide did not improve hepatic insulin action in diet-induced obesity mice.

    PubMed

    Vitto, M F; Luz, G; Luciano, T F; Marques, S O; Souza, D R; Pinho, R A; Lira, F S; Cintra, D E; De Souza, C T

    2012-11-01

    The literature has associated hepatic insulin action with NAFLD. In this sense, treatments to revert steatosis and improve hepatic insulin action become important. Our group has demonstrated that inhibition of Sterol Regulatory Element Binding Proteins-1c (SREBP-1c) reverses hepatic steatosis. However, insulin signals after NAFLD reversion require better investigation. Thus, in this study, we investigated if the reversal of NAFLD by SREBP-1c inhibitor results in improvement in the hepatic insulin signal in obesity mice. After installation/achievement of diet-induced obesity and insulin resistance, Swiss mice were divided into 3 groups: i) Lean, ii) D-IHS, diet-induced hepatic steatosis [no treatment with antisense oligonucleotide (ASO)], and iii) RD-IHS, reversion of diet-induced hepatic steatosis (treated with ASO). The mice were treated with ASO SREBP-1c as previously described by our group. After ASO treatment, one set of animals was anesthetized and used for in vivo test, and another mice set was anesthetized and used for histology and Western blot analysis. Reversion of diet-induced hepatic steatosis did not change blood glucose, glucose decay constant (k(ITT)), body weight, or serum insulin levels. In addition, results showed that the protocol did not improve insulin pathway signaling, as confirmed by the absence of changes in IR, IRS1, Akt and Foxo1 phosphorylation in hepatic tissue. In parallel, no alterations were observed in proinflammatory molecules. Thus, our results suggest that the inhibition of SREBP-1c reverts steatosis, but without improving insulin hepatic resistance.

  5. Yerba mate extract (Ilex paraguariensis) attenuates both central and peripheral inflammatory effects of diet-induced obesity in rats.

    PubMed

    Pimentel, Gustavo D; Lira, Fábio S; Rosa, José C; Caris, Aline V; Pinheiro, Fernanda; Ribeiro, Eliane B; Oller do Nascimento, Cláudia M; Oyama, Lila M

    2013-05-01

    To clarify the effects of natural dietary components on the metabolic consequences of obesity, we examined the effects of yerba mate extract Ilex paraguariensis on both central and peripheral inflammatory effects of diet-induced obesity and correlated the hypothalamic tumor necrosis factor (TNF)-α level with adipose depot weight. Wistar rats were divided into four groups: a control group (CTL) fed with chow diet, a second group fed with chow diet plus yerba mate extract (CTL+E), a third group fed with a high-fat diet rich in saturated fatty acids (HFD) and a fourth group fed with HFD plus yerba mate extract (HFD+E). Enzyme-linked immunosorbent assay, Western blotting, colorimetric method and treatment by gavage were utilized as materials and methods. The HFD groups showed a significant increase in food intake (kcal), body weight, adipose tissue and leptin level in comparison to CTL and CTL+E. HFD leads to increase of both central and peripheral inflammatory effects, and deregulation of insulin pathway. In addition, yerba mate extract intake blunted the proinflammatory effects of diet-induced obesity in rats by reducing the phosphorylation of hypothalamic IKK and NFκBp65 expression and increasing the phosphorylation of IκBα, the expression of adiponectin receptor-1 and consequently the amount of IRS-2. Moreover, the increase in interleukin (IL)-6 levels in the liver and muscle and of the IL-10/TNF-α ratio in groups that received yerba mate extract showed the anti-inflammatory effects of this natural substance. Taken together, our data suggest that the use of yerba mate extract may be useful for reducing low-grade obesity-associated inflammation.

  6. Gut carbohydrate metabolism instead of fat metabolism regulated by gut microbes mediates high-fat diet-induced obesity.

    PubMed

    Li, M; Gu, D; Xu, N; Lei, F; Du, L; Zhang, Y; Xie, W

    2014-09-01

    The aim of this study was to investigate the mechanisms underlying the involvement of gut microbes in body weight gain of high-fat diet-fed obesity-prone (obese) and obesity-resistant (lean) mice. C57BL/6 mice were grouped into an obese group, a lean group and a normal control group. Both obese and lean mice were fed a high-fat diet while normal control mice were fed a normal diet; they were observed for six weeks. The results showed that lean mice had lower serum lipid levels, body fat and weight gain than obese mice. The ATPase, succinate dehydrogenase and malate dehydrogenase activities in liver as well as oxygen expenditure and rectal temperature of lean mice were significantly lower than in obese mice. As compared with obese mice, the absorption of intestinal carbohydrates but not of fats or proteins was significantly attenuated in lean mice. Furthermore, 16S rRNA abundances of faecal Firmicutes and Bacteroidetes were significantly reduced in lean mice. In addition, faecal β-D-galactosidase activity and short chain fatty acid levels were significantly decreased in lean mice. Expressions of peroxisome proliferator-activated receptor gamma 2 and CCAAT/enhancer binding protein-β in visceral adipose tissues were significantly downregulated in lean mice as compared with obese mice. Resistance to dyslipidaemia and high-fat diet-induced obesity was mediated by ineffective absorption of intestinal carbohydrates but not of fats or proteins, probably through reducing gut Bacteroidetes and Firmicutes contents and lowering of gut carbohydrate metabolism. The regulation of intestinal carbohydrates instead of fat absorption by gut microbes might be a potential treatment strategy for high-fat diet-induced obesity.

  7. Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats.

    PubMed

    Conde, Silvia V; Nunes da Silva, Tiago; Gonzalez, Constancio; Mota Carmo, Miguel; Monteiro, Emilia C; Guarino, Maria P

    2012-01-01

    We tested the hypothesis that long-term caffeine intake prevents the development of insulin resistance and hypertension in two pathological animal models: the high-fat (HF) and the high-sucrose (HSu) diet rat. We used six groups of animals: control; caffeine-treated (Caff; 1 g/l in drinking water during 15 d); HF; caffeine-treated HF (HFCaff); HSu; caffeine-treated HSu (HSuCaff). Insulin sensitivity was assessed using the insulin tolerance test. Blood pressure, weight gain, visceral fat, hepatic glutathione, plasma caffeine, insulin and NO, and serum NEFA and catecholamines were measured. Caffeine reversed insulin resistance and hypertension induced by both the HF and HSu diets. In the HF-fed animals caffeine treatment restored fasting insulin levels to control values and reversed increased weight gain and visceral fat mass. In the HSu group, caffeine reversed fasting hyperglycaemia and restored NEFA to control values. There were no changes either in plasma NO or in hepatic glutathione levels. In contrast, caffeine totally prevented the increase in serum catecholamines induced by HF and HSu diets. To test the hypothesis that inhibition of the sympathetic nervous system prevents the development of diet-induced insulin resistance we administered carvedilol, an antagonist of β1, β2 and also α1 adrenoceptors, to HF and HSu rats. Carvedilol treatment fully prevented diet-induced insulin resistance and hypertension, mimicking the effect of caffeine. We concluded that long-term caffeine intake prevented the development of insulin resistance and hypertension in HF and HSu models and that this effect was related to a decrease in circulating catecholamines.

  8. SR-BI in Bone Marrow Derived Cells Protects Mice from Diet Induced Coronary Artery Atherosclerosis and Myocardial Infarction

    PubMed Central

    Pei, Ying; Chen, Xing; Aboutouk, Dina; Fuller, Mark T.; Dadoo, Omid; Yu, Pei; White, Elizabeth J.; Igdoura, Suleiman A.; Trigatti, Bernardo L.

    2013-01-01

    SR-BI deficient mice that are also hypomorphic for apolipoprotein E expression develop diet induced occlusive coronary artery atherosclerosis, myocardial infarction and early death. To test the role of SR-BI in bone marrow derived cells, we used bone marrow transplantation to generate SR-BI-null; apoE-hypomorphic mice in which SR-BI expression was restored solely in bone marrow derived cells. SR-BI-null; apoE-hypomorphic mice were transplanted with SR-BI+/+apoE-hypomorphic, or control, autologous SR-BI-null; apoE-hypomorphic bone marrow. Four weeks later, mice were fed a high-fat, high-cholesterol, cholate-containing diet to induce coronary artery atherosclerosis. Mice transplanted with autologous bone marrow developed extensive aortic atherosclerosis and severe occlusive coronary artery atherosclerosis after 4 weeks of feeding. This was accompanied by myocardial fibrosis and increased heart weights. In contrast, restoration of SR-BI expression in bone marrow derived-cells reduced diet induced aortic and coronary artery atherosclerosis, myocardial fibrosis and the increase in heart weights in SR-BI-null; apoE-hypomorphic mice. Restoration of SR-BI in bone marrow derived cells did not, however, affect steady state lipoprotein cholesterol levels, but did reduce plasma levels of IL-6. Monocytes from SR-BI-null mice exhibited a greater capacity to bind to VCAM-1 and ICAM-1 than those from SR-BI+/+ mice. Furthermore, restoration of SR-BI expression in bone marrow derived cells attenuated monocyte recruitment into atherosclerotic plaques in mice fed high fat, high cholesterol cholate containing diet. These data demonstrate directly that SR-BI in bone marrow-derived cells protects against both aortic and CA atherosclerosis. PMID:23967310

  9. EMP acupoint stimulation conducive to increase the effect of weight reduction through aerobic exercise

    PubMed Central

    Jiao, Chun; Zhu, Ximei; Zhang, Hongyu; Du, Xiaowei

    2015-01-01

    Purpose: to observe whether weight reduction through aerobic exercise is more effective with the intervention of electromagnetic pulse (EMP) Acupoint stimulation. Method: based on the need of this study, we choose 48 young and middle-aged obese patients and randomly divide them into Experimental Group and Control Group with each group consisting of 24 of them. The Control Group has an aerobic endurance running each day with each running lasting for about 45 minutes and covering about 6 KM; the Experimental Group has the same exercise as the CG, but, after their running, stimulation by electromagnetic pulse meter is given to their Sanyinjiao Acupoint and Zushanli Acupoint. Then the content of body fat and the lipid indexes of the two groups before the treatment are compared with their counterparts after the said treatment. Result: after 6 weeks of treatment, the various indexes of the two groups are improved to different degrees (P<0.05); the effect on lipid indexes of the Experimental Group is obviously better than that of the Control Group (P<0.05), but the content of their body fat shows no conspicuous difference (P>0.05). Conclusion: after 6 weeks of treatment, the intervention of EMP acupoint stimulation can more evidently improve the lipid indexes than it has done to the group only having aerobic exercise; but it has little effect in terms of the improvement of the body fat content, which may be because of the short time of such intervention. PMID:26379942

  10. Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice

    PubMed Central

    Nagao, Koji; Inoue, Nao; Ujino, Yoko; Higa, Kouki; Shirouchi, Bungo; Wang, Yu-Ming; Yanagita, Teruyoshi

    2008-01-01

    Background Lipodystrophies are rare acquired and genetic disorders characterized by the complete or partial absence of body fat with a line of metabolic disorders. Previous studies demonstrated that dietary conjugated linoleic acid (CLA) induces hepatic steatosis and hyperinsulinemia through the drastic reduction of adipocytokine levels due to a paucity of adipose tissue in mice and the pathogenesis of these metabolic abnormalities in CLA-fed mice is similar to that in human lipodystrophy. The present study explores the effect of leptin infusion on the pathogenesis of diet-induced lipodystrophy in mice. C57BL/6N mice were assigned to three groups: (1) mice were fed a semisynthetic diet supplemented with 6% corn oil and infused PBS intraperitoneally (normal group), (2) mice were fed a semisynthetic diet supplemented with 4% corn oil plus 2% CLA and infused PBS intraperitoneally (lipodystrophy-control group), and (3) mice were fed a semisynthetic diet supplemented with 4% corn oil plus 2% CLA and infused recombinant murine leptin intraperitoneally (lipodystrophy-leptin group). All mice were fed normal or lipodystrophy model diets for 4 weeks and were infused intrapeneally 0 or 5 μg of leptin per day from third week of the feeding period for 1 week. Results The results indicate that leptin infusion can attenuate hepatic steatosis and hyperinsulinemia through the reduction of hepatic triglyceride synthesis and the improvement of insulin sensitivity in diet-induced lipodystrophy model mice. Conclusion We expect the use of this model for clarifying the pathophysiology of lipodystrophy-induced metabolic abnormalities and evaluating the efficacy and safety of drug and dietary treatment. PMID:18348717

  11. Aeronautical fuel conservation possibilities for advanced subsonic transports. [application of aeronautical technology for drag and weight reduction

    NASA Technical Reports Server (NTRS)

    Braslow, A. L.; Whitehead, A. H., Jr.

    1973-01-01

    The anticipated growth of air transportation is in danger of being constrained by increased prices and insecure sources of petroleum-based fuel. Fuel-conservation possibilities attainable through the application of advances in aeronautical technology to aircraft design are identified with the intent of stimulating NASA R and T and systems-study activities in the various disciplinary areas. The material includes drag reduction; weight reduction; increased efficiency of main and auxiliary power systems; unconventional air transport of cargo; and operational changes.

  12. Alterations in the hippocampal endocannabinoid system in diet-induced obese mice

    PubMed Central

    Massa, Federico; Mancini, Giacomo; Schmidt, Helmut; Steindel, Frauke; Mackie, Ken; Angioni, Carlo; Oliet, Stéphane H.R.; Geisslinger, Gerd; Lutz, Beat

    2010-01-01

    The endocannabinoid (eCB) system plays central roles in the regulation of food intake and energy expenditure. Its alteration in activity contributes to the development and maintenance of obesity. Stimulation of the cannabinoid receptor type 1 (CB1 receptor) increases feeding, enhances reward aspects of eating and promotes lipogenesis, while its blockade decreases appetite, sustains weight loss, increases insulin sensitivity, and alleviates dysregulation of lipid metabolism. The hypothesis has been put forward that the eCB system is over-active in obesity. Hippocampal circuits are not directly involved in the neuronal control of food intake and appetite, but they play important roles in hedonic aspects of eating. We investigated the possibility whether or not diet-induced obesity (DIO) alters the functioning of the hippocampal eCB system. We found that levels of the two eCBs, 2-arachidonoyl glycerol (2-AG) and anandamide, were increased in the hippocampus from DIO mice, with a concomitant increase of the 2-AG synthesizing enzyme diacylglycerol lipase-α and increased CB1 receptor immunoreactivity in CA1 and CA3 regions, while CB1 receptor agonist-induced GTPγS binding was unchanged. eCB-mediated synaptic plasticity was changed in the CA1 region, as depolarization-induced suppression of inhibition (DSI) and long-term depression of inhibitory synapses (I-LTD) were enhanced. Functionality of CB1 receptors in GABAergic neurons was furthermore revealed, as mice specifically lacking CB1 receptors on this neuronal population were partly resistant to DIO. Our results showed that DIO-induced changes in the eCB system does not affect only tissues directly involved in the metabolic regulation, but also brain regions mediating hedonic aspects of eating and influencing cognitive processes. PMID:20445053

  13. Yellow pea fiber improves glycemia and reduces Clostridium leptum in diet-induced obese rats.

    PubMed

    Eslinger, Amanda J; Eller, Lindsay K; Reimer, Raylene A

    2014-08-01

    Numerous studies have demonstrated the impact of functional fibers on gut microbiota and metabolic health, but some less well-studied fibers and/or fractions of foods known to be high in fiber still warrant examination. The aim of this study was to assess the effect of yellow pea-derived fractions varying in fiber and protein content on metabolic parameters and gut microbiota in diet-induced obese rats. We hypothesized that the yellow pea fiber (PF) fraction would improve glycemia and alter gut microbiota. Rats were randomized to 1 of 5 isoenergetic dietary treatments for 6 weeks: (1) control; (2) oligofructose (OFS); (3) yellow PF; (4) yellow pea flour (PFL); or (5) yellow pea starch (PS). Glycemia, plasma gut hormones, body composition, hepatic triglyceride content, gut microbiota, and messenger RNA expression of genes related to hepatic fat metabolism were examined. Pea flour attenuated weight gain compared with control, PF, and PS (P < .05). Pea flour, PS, and OFS had significantly lower final percent body fat compared with control. Oligofructose but not the pea fraction diets reduced food intake compared with control (P < .05). Pea fiber resulted in lower fasting glucose and glucose area under the curve compared with control. Changes in gut microbiota were fraction specific and included a decrease in Firmicutes (percent) for OFS, PF, and PFL compared with control (P < .05). The Firmicutes/Bacteroidetes ratio was reduced with OFS, PF, and PFL when compared with PS (P < .05). Taken together, this work suggests that yellow pea-derived fractions are able to distinctly modulate metabolic parameters and gut microbiota in obese rats.

  14. Western-style diet induces insulin insensitivity and hyperactivity in adolescent male rats.

    PubMed

    Marwitz, Shannon E; Woodie, Lauren N; Blythe, Sarah N

    2015-11-01

    The prevalence of obesity in children and adolescents has increased rapidly over the past 30 years, as has the incidence of attention deficit hyperactivity disorder (ADHD). In 2012, it was found that overweight children have a twofold higher chance of developing ADHD than their normal weight counterparts. Previous work has documented learning and memory impairments linked to consumption of an energy-dense diet in rats, but the relationship between diet and ADHD-like behaviors has yet to be explored using animal models. Therefore, the purpose of this study was to explore the role of diet in the etiology of attention and hyperactivity disorders using a rat model of diet-induced obesity. Male Sprague-Dawley rats were fed either a control diet or a Western-style diet (WSD) for ten weeks, and specific physiological and behavioral effects were examined. Tail blood samples were collected to measure fasting blood glucose and insulin levels in order to assess insulin insensitivity. Rats also performed several behavioral tasks, including the open field task, novel object recognition test, and attentional set-shifting task. Rats exposed to a WSD had significantly higher fasting insulin levels than controls, but both groups had similar glucose levels. The quantitative insulin sensitivity check index (QUICKI) indicated the development of insulin resistance in WSD rats. Performance in the open field test indicated that WSD induced pronounced hyperactivity and impulsivity. Further, control diet animals were able to discriminate between old and novel objects, but the WSD animals were significantly impaired in object recognition. However, regardless of dietary condition, rats were able to perform the attentional set-shifting paradigm. While WSD impaired episodic memory and induced hyperactivity, attentional set-shifting capabilities are unaffected. With the increasing prevalence of both obesity and ADHD, understanding the potential links between the two conditions is of clinical

  15. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    SciTech Connect

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, K. Monica; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung

  16. Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin

    SciTech Connect

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, Monika K.; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  17. Weight regain after sustained weight reduction is accompanied by suppressed oxidation of dietary fat and adipocyte hyperplasia.

    PubMed

    Jackman, Matthew R; Steig, Amy; Higgins, Janine A; Johnson, Ginger C; Fleming-Elder, Brooke K; Bessesen, Daniel H; MacLean, Paul S

    2008-04-01

    A dual-tracer approach (dietary 14C-palmitate and intraperitoneal 3H-H2O) was used to assess the trafficking of dietary fat and net retention of carbon in triglyceride depots during the first 24 h of weight regain. Obesity-prone male Wistar rats were allowed to mature under obesogenic conditions for 16 wk. One group was switched to ad libitum feeding of a low-fat diet for 10 wk (Obese group). The remaining rats were switched to an energy-restricted, low-fat diet for 10 wk that reduced body weight by 14% and were then assessed in energy balance (Reduced group), with free access to the low-fat diet (Relapse-Day1 group), or with a provision that induced a minor imbalance (+10 kcal) equivalent to that observed in obese rats (Gap-Matched group). Fat oxidation remained at a high, steady rate throughout the day in Obese rats, but was suppressed in Reduced, Gap-Matched, and Relapse-Day1 rats though 9, 18, and 24 h, respectively. The same caloric excess in Obese and Gap-Matched rats led to less fat oxidation over the day and greater trafficking of dietary fat to visceral depots in the latter. In addition to trafficking nutrients to storage, Relapse-Day1 rats had more small, presumably new, adipocytes at the end of 24 h. Dietary fat oxidation at 24 h was related to the phosphorylation of skeletal muscle acetyl-CoA carboxylase and fatty acid availability. These observations provide evidence of adaptations in the oxidation and trafficking of dietary fat that extend beyond the energy imbalance, which facilitate rapid, efficient regain during the relapse to obesity. PMID:18287221

  18. Mediobasal hypothalamic overexpression of DEPTOR protects against high-fat diet-induced obesity

    PubMed Central

    Caron, Alexandre; Labbé, Sébastien M.; Lanfray, Damien; Blanchard, Pierre-Gilles; Villot, Romain; Roy, Christian; Sabatini, David M.; Richard, Denis; Laplante, Mathieu

    2015-01-01

    Background/Objective The mechanistic target of rapamycin (mTOR) is a serine–threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulate energy homeostasis. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to dampen mTORC1 function, consequently reducing mTORC1 negative feedbacks and promoting insulin signaling and Akt/PKB activation in several models. Recently, we observed that DEPTOR is expressed in several structures of the brain including the mediobasal hypothalamus (MBH), a region that regulates energy balance. Whether DEPTOR in the MBH plays a functional role in regulating energy balance and hypothalamic insulin signaling has never been tested. Methods We have generated a novel conditional transgenic mouse model based on the Cre-LoxP system allowing targeted overexpression of DEPTOR. Mice overexpressing DEPTOR in the MBH were subjected to a metabolic phenotyping and MBH insulin signaling was evaluated. Results We first report that systemic (brain and periphery) overexpression of DEPTOR prevents high-fat diet-induced obesity, improves glucose metabolism and protects against hepatic steatosis. These phenotypes were associated with a reduction in food intake and feed efficiency and an elevation in oxygen consumption. Strikingly, specific overexpression of DEPTOR in the MBH completely recapitulated these phenotypes. DEPTOR overexpression was associated with an increase in hypothalamic insulin signaling, as illustrated by elevated Akt/PKB activation. Conclusion Altogether, these results support a role for MBH DEPTOR in the regulation of energy balance and metabolism. PMID:26909318

  19. Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance.

    PubMed

    Nawrocki, Andrea R; Rodriguez, Carlos G; Toolan, Dawn M; Price, Olga; Henry, Melanie; Forrest, Gail; Szeto, Daphne; Keohane, Carol Ann; Pan, Yie; Smith, Karen M; Raheem, Izzat T; Cox, Christopher D; Hwa, Joyce; Renger, John J; Smith, Sean M

    2014-01-01

    Phosphodiesterase 10A (PDE10A) is a novel therapeutic target for the treatment of schizophrenia. Here we report a novel role of PDE10A in the regulation of caloric intake and energy homeostasis. PDE10A-deficient mice are resistant to diet-induced obesity (DIO) and associated metabolic disturbances. Inhibition of weight gain is due to hypophagia after mice are fed a highly palatable diet rich in fats and sugar but not a standard diet. PDE10A deficiency produces a decrease in caloric intake without affecting meal frequency, daytime versus nighttime feeding behavior, or locomotor activity. We tested THPP-6, a small molecule PDE10A inhibitor, in DIO mice. THPP-6 treatment resulted in decreased food intake, body weight loss, and reduced adiposity at doses that produced antipsychotic efficacy in behavioral models. We show that PDE10A inhibition increased whole-body energy expenditure in DIO mice fed a Western-style diet, achieving weight loss and reducing adiposity beyond the extent seen with food restriction alone. Therefore, chronic THPP-6 treatment conferred improved insulin sensitivity and reversed hyperinsulinemia. These data demonstrate that PDE10A inhibition represents a novel antipsychotic target that may have additional metabolic benefits over current medications for schizophrenia by suppressing food intake, alleviating weight gain, and reducing the risk for the development of diabetes. PMID:24101672

  20. Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance.

    PubMed

    Nawrocki, Andrea R; Rodriguez, Carlos G; Toolan, Dawn M; Price, Olga; Henry, Melanie; Forrest, Gail; Szeto, Daphne; Keohane, Carol Ann; Pan, Yie; Smith, Karen M; Raheem, Izzat T; Cox, Christopher D; Hwa, Joyce; Renger, John J; Smith, Sean M

    2014-01-01

    Phosphodiesterase 10A (PDE10A) is a novel therapeutic target for the treatment of schizophrenia. Here we report a novel role of PDE10A in the regulation of caloric intake and energy homeostasis. PDE10A-deficient mice are resistant to diet-induced obesity (DIO) and associated metabolic disturbances. Inhibition of weight gain is due to hypophagia after mice are fed a highly palatable diet rich in fats and sugar but not a standard diet. PDE10A deficiency produces a decrease in caloric intake without affecting meal frequency, daytime versus nighttime feeding behavior, or locomotor activity. We tested THPP-6, a small molecule PDE10A inhibitor, in DIO mice. THPP-6 treatment resulted in decreased food intake, body weight loss, and reduced adiposity at doses that produced antipsychotic efficacy in behavioral models. We show that PDE10A inhibition increased whole-body energy expenditure in DIO mice fed a Western-style diet, achieving weight loss and reducing adiposity beyond the extent seen with food restriction alone. Therefore, chronic THPP-6 treatment conferred improved insulin sensitivity and reversed hyperinsulinemia. These data demonstrate that PDE10A inhibition represents a novel antipsychotic target that may have additional metabolic benefits over current medications for schizophrenia by suppressing food intake, alleviating weight gain, and reducing the risk for the development of diabetes.

  1. Anti-inflammatory and antiobesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity.

    PubMed

    Lim, Hyun Hwa; Lee, Sung Ok; Kim, Sun Yeou; Yang, Soo Jin; Lim, Yunsook

    2013-10-01

    The purpose of this study was to investigate the anti-inflammatory and antiobesity effect of combinational mulberry leaf extract (MLE) and mulberry fruit extract (MFE) in a high-fat (HF) diet-induced obese mice. Mice were fed a control diet or a HF diet for nine weeks. After obesity was induced, the mice were administered with single MLE at low dose (133 mg/kg/day, LMLE) and high dose (333 mg/kg/day, HMLE) or combinational MLE and MFE (MLFE) at low dose (133 mg MLE and 67 mg MFE/kg/day, LMLFE) and high dose (333 mg MLE and 167 mg MFE/kg/day, HMLFE) by stomach gavage for 12 weeks. The mulberry leaf and fruit extract treatment for 12 weeks did not show liver toxicity. The single MLE and combinational MLFE treatments significantly decreased plasma triglyceride, liver lipid peroxidation levels and adipocyte size and improved hepatic steatosis as compared with the HF group. The combinational MLFE treatment significantly decreased body weight gain, fasting plasma glucose and insulin, and homeostasis model assessment of insulin resistance. HMLFE treatment significantly improved glucose control during intraperitoneal glucose tolerance test compared with the HF group. Moreover, HMLFE treatment reduced protein levels of oxidative stress markers (manganese superoxide dismutase) and inflammatory markers (monocyte chemoattractant protein-1, inducible nitric oxide synthase, C-reactive protein, tumour necrosis factor-α and interleukin-1) in liver and adipose tissue. Taken together, combinational MLFE treatment has potential antiobesity and antidiabetic effects through modulation of obesity-induced inflammation and oxidative stress in HF diet-induced obesity.

  2. The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a mouse model of diet induced obesity.

    PubMed

    Rodríguez-Rodríguez, César; Torres, Nimbe; Gutiérrez-Uribe, Janet A; Noriega, Lilia G; Torre-Villalvazo, Iván; Leal-Díaz, Ana M; Antunes-Ricardo, Marilena; Márquez-Mota, Claudia; Ordaz, Guillermo; Chavez-Santoscoy, Rocío A; Serna-Saldivar, Sergio O; Tovar, Armando R

    2015-03-01

    A diet rich in polyphenols can ameliorate some metabolic alterations associated with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this research was to determine the metabolic effect of an OFI extract on a mouse model of diet-induced obesity and in isolated pancreatic islets. OFI extract was added to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract gained less body weight and exhibited significantly lower circulating total cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF diet alone. The HF-OFI diet fed mice presented lower glucose and insulin concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended to have higher insulin concentration than control mice. The OFI extract stimulated insulin secretion in vitro, associated with increased glucose transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA content. Furthermore, the OFI extract improved glucose tolerance, and additionally increased energy expenditure. These metabolic improvements were associated with reduced adipocyte size, increased hepatic IRS1 tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also diminished the hepatic lipid content associated with reduced mRNA expression of the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA expression of genes related to fatty acid oxidation. Overall, the OFI extract prevented the development of metabolic abnormalities associated with diet-induced obesity. PMID:25588195

  3. The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a mouse model of diet induced obesity.

    PubMed

    Rodríguez-Rodríguez, César; Torres, Nimbe; Gutiérrez-Uribe, Janet A; Noriega, Lilia G; Torre-Villalvazo, Iván; Leal-Díaz, Ana M; Antunes-Ricardo, Marilena; Márquez-Mota, Claudia; Ordaz, Guillermo; Chavez-Santoscoy, Rocío A; Serna-Saldivar, Sergio O; Tovar, Armando R

    2015-03-01

    A diet rich in polyphenols can ameliorate some metabolic alterations associated with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this research was to determine the metabolic effect of an OFI extract on a mouse model of diet-induced obesity and in isolated pancreatic islets. OFI extract was added to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract gained less body weight and exhibited significantly lower circulating total cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF diet alone. The HF-OFI diet fed mice presented lower glucose and insulin concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended to have higher insulin concentration than control mice. The OFI extract stimulated insulin secretion in vitro, associated with increased glucose transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA content. Furthermore, the OFI extract improved glucose tolerance, and additionally increased energy expenditure. These metabolic improvements were associated with reduced adipocyte size, increased hepatic IRS1 tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also diminished the hepatic lipid content associated with reduced mRNA expression of the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA expression of genes related to fatty acid oxidation. Overall, the OFI extract prevented the development of metabolic abnormalities associated with diet-induced obesity.

  4. Apple-Derived Pectin Modulates Gut Microbiota, Improves Gut Barrier Function, and Attenuates Metabolic Endotoxemia in Rats with Diet-Induced Obesity.

    PubMed

    Jiang, Tingting; Gao, Xuejin; Wu, Chao; Tian, Feng; Lei, Qiucheng; Bi, Jingcheng; Xie, Bingxian; Wang, Hong Yu; Chen, Shuai; Wang, Xinying

    2016-03-01

    This study was aimed at determining potential effects of apple-derived pectin on weight gain, gut microbiota, gut barrier and metabolic endotoxemia in rat models of diet-induced obesity. The rats received a standard diet (control; Chow group; n = 8) or a high-fat diet (HFD; n = 32) for eight weeks to induce obesity. The top 50th percentile of weight-gainers were selected as diet induced obese rats. Thereafter, the Chow group continued on chow, and the diet induced obese rats were randomly divided into two groups and received HFD (HF group; n = 8) or pectin-supplemented HFD (HF-P group; n = 8) for six weeks. Compared to the HF group, the HF-P group showed attenuated weight gain (207.38 ± 7.96 g vs. 283.63 ± 10.17 g, p < 0.01) and serum total cholesterol level (1.46 ± 0.13 mmol/L vs. 2.06 ± 0.26 mmol/L, p < 0.01). Compared to the Chow group, the HF group showed a decrease in Bacteroidetes phylum and an increase in Firmicutes phylum, as well as subordinate categories (p < 0.01). These changes were restored to the normal levels in the HF-P group. Furthermore, compared to the HF group, the HF-P group displayed improved intestinal alkaline phosphatase (0.57 ± 0.20 vs. 0.30 ± 0.19, p < 0.05) and claudin 1 (0.76 ± 0.14 vs. 0.55 ± 0.18, p < 0.05) expression, and decreased Toll-like receptor 4 expression in ileal tissue (0.76 ± 0.58 vs. 2.04 ± 0.89, p < 0.01). The HF-P group also showed decreased inflammation (TNFα: 316.13 ± 7.62 EU/mL vs. 355.59 ± 8.10 EU/mL, p < 0.01; IL-6: 51.78 ± 2.35 EU/mL vs. 58.98 ± 2.59 EU/mL, p < 0.01) and metabolic endotoxemia (2.83 ± 0.42 EU/mL vs. 0.68 ± 0.14 EU/mL, p < 0.01). These results suggest that apple-derived pectin could modulate gut microbiota, attenuate metabolic endotoxemia and inflammation, and consequently suppress weight gain and fat accumulation in diet induced obese rats. PMID:26938554

  5. Apple-Derived Pectin Modulates Gut Microbiota, Improves Gut Barrier Function, and Attenuates Metabolic Endotoxemia in Rats with Diet-Induced Obesity

    PubMed Central

    Jiang, Tingting; Gao, Xuejin; Wu, Chao; Tian, Feng; Lei, Qiucheng; Bi, Jingcheng; Xie, Bingxian; Wang, Hong Yu; Chen, Shuai; Wang, Xinying

    2016-01-01

    This study was aimed at determining potential effects of apple-derived pectin on weight gain, gut microbiota, gut barrier and metabolic endotoxemia in rat models of diet-induced obesity. The rats received a standard diet (control; Chow group; n = 8) or a high-fat diet (HFD; n = 32) for eight weeks to induce obesity. The top 50th percentile of weight-gainers were selected as diet induced obese rats. Thereafter, the Chow group continued on chow, and the diet induced obese rats were randomly divided into two groups and received HFD (HF group; n = 8) or pectin-supplemented HFD (HF-P group; n = 8) for six weeks. Compared to the HF group, the HF-P group showed attenuated weight gain (207.38 ± 7.96 g vs. 283.63 ± 10.17 g, p < 0.01) and serum total cholesterol level (1.46 ± 0.13 mmol/L vs. 2.06 ± 0.26 mmol/L, p < 0.01). Compared to the Chow group, the HF group showed a decrease in Bacteroidetes phylum and an increase in Firmicutes phylum, as well as subordinate categories (p < 0.01). These changes were restored to the normal levels in the HF-P group. Furthermore, compared to the HF group, the HF-P group displayed improved intestinal alkaline phosphatase (0.57 ± 0.20 vs. 0.30 ± 0.19, p < 0.05) and claudin 1 (0.76 ± 0.14 vs. 0.55 ± 0.18, p < 0.05) expression, and decreased Toll-like receptor 4 expression in ileal tissue (0.76 ± 0.58 vs. 2.04 ± 0.89, p < 0.01). The HF-P group also showed decreased inflammation (TNFα: 316.13 ± 7.62 EU/mL vs. 355.59 ± 8.10 EU/mL, p < 0.01; IL-6: 51.78 ± 2.35 EU/mL vs. 58.98 ± 2.59 EU/mL, p < 0.01) and metabolic endotoxemia (2.83 ± 0.42 EU/mL vs. 0.68 ± 0.14 EU/mL, p < 0.01). These results suggest that apple-derived pectin could modulate gut microbiota, attenuate metabolic endotoxemia and inflammation, and consequently suppress weight gain and fat accumulation in diet induced obese rats. PMID:26938554

  6. Toll Like Receptor-4 Mediates Vascular Inflammation and Insulin Resistance in Diet-Induced Obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular dysfunction is a major complication of metabolic disorders such as diabetes and obesity. The current studies were undertaken to determine if inflammatory responses are activated in the vasculature of mice with diet-induced obesity (DIO), and if so, whether Toll Like Receptor-4 (TLR4), a ke...

  7. Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid tran...

  8. Appropriateness of the hamster as a model to study diet-induced atherosclerosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apo...

  9. Gamma delta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gamma delta T cells are resident in adipose tissue and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5-10 week high milk fat diet. The high milk fat diet resulted in significant in...

  10. Is Western Diet-Induced Nonalcoholic Steatohepatitis in Ldlr-/- Mice Reversible?

    PubMed Central

    Lytle, Kelli A.; Jump, Donald B.

    2016-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is a major public health burden in western societies. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), is characterized by hepatosteatosis, inflammation, oxidative stress, and hepatic damage that can progress to fibrosis and cirrhosis; risk factors for hepatocellular carcinoma. Given the scope of NASH, validating treatment protocols (i.e., low fat diets and weight loss) is imperative. Methods We evaluated the efficacy of two diets, a non-purified chow (NP) and purified (low-fat low-cholesterol, LFLC) diet to reverse western diet (WD)-induced NASH and fibrosis in Ldlr-/- mice. Results Mice fed WD for 22–24 weeks developed robust hepatosteatosis with mild fibrosis, while mice maintained on the WD an additional 7–8 weeks developed NASH with moderate fibrosis. Returning WD-fed mice to the NP or LFLC diets significantly reduced body weight and plasma markers of metabolic syndrome (dyslipidemia, hyperglycemia) and hepatic gene expression markers of inflammation (Mcp1), oxidative stress (Nox2), fibrosis (Col1A, LoxL2, Timp1) and collagen crosslinking (hydroxyproline). Time course analyses established that plasma triglycerides and hepatic Col1A1 mRNA were rapidly reduced following the switch from the WD to the LFLC diet. However, hepatic triglyceride content and fibrosis did not return to normal levels 8 weeks after the change to the LFLC diet. Time course studies further revealed a strong association (r2 ≥ 0.52) between plasma markers of inflammation (TLR2 activators) and hepatic fibrosis markers (Col1A, Timp1, LoxL2). Inflammation and fibrosis markers were inversely associated (r2 ≥ 0.32) with diet-induced changes in hepatic ω3 and ω6 polyunsaturated fatty acids (PUFA) content. Conclusion These studies establish a temporal link between plasma markers of inflammation and hepatic PUFA and fibrosis. Low-fat low-cholesterol diets promote reversal of many, but not all, features associated with WD

  11. Curcumin ameliorates high-fat diet-induced spermatogenesis dysfunction

    PubMed Central

    Mu, Yang; Yan, Wen-Jie; Yin, Tai-Lang; Yang, Jing

    2016-01-01

    Curcumin, a type of natural active ingredient, is derived from rhizoma of Curcuma, which possesses antioxidant, antitumorigenic and anti-inflammatory activities. The present study aimed to investigate whether treatment with curcumin reduced high-fat diet (HFD)-induced spermatogenesis dysfunction. Sprague-Dawley rats fed a HFD were treated with or without curcumin for 8 weeks. The testis/body weight, histological analysis and serum hormone levels were used to evaluate the effects of curcumin treatment on spermatogenesis dysfunction induced by the HFD. In addition, the expression levels of apoptosis associated proteins, Fas, B-cell lymphoma (Bcl)-xl, Bcl-associated X protein (Bax) and cleaved-caspase 3, were determined in the testis. The results of the present study suggested that curcumin treatment attenuated decreased testis/body weight and abnormal hormone levels. Morphological changes induced by a HFD were characterized as atrophied seminiferous tubules, decreased spermatogenetic cells and interstitial cells were improved by curcumin treatment. In addition, curcumin treatment reduced apoptosis in the testis, and decreased expression of Fas, Bax and cleaved-caspase 3, as well as increased expression of Bcl-xl. In conclusion, the present study revealed that curcumin treatment reduced HFD-induced spermatogenesis dysfunction in male rats. PMID:27600729

  12. IL-33 treatment attenuated diet-induced hepatic steatosis but aggravated hepatic fibrosis

    PubMed Central

    Gao, Yinjie; Liu, Yuan; Yang, Mei; Guo, Xiaodong; Zhang, Min; Li, Hanwei; Li, Jin; Zhao, Jingmin

    2016-01-01

    The aim of our work was to investigate the role of interleukin-33 (IL-33) and its receptor ST2 in the progression of diet-induced nonalcoholic steatohepatitis (NASH) in mice, and the characteristic expression in livers of patients with NASH. Mice were fed with high-fat diet (HFD) or methionine-choline 4-deficient diet (MCD) and injected intraperitoneally with IL-33. Both mRNA and protein expression levels of IL-33 and ST2 were up-regulated in the livers of mice fed with HFD or MCD. Treatment with IL-33 attenuated diet-induced hepatic steatosis and reduced activities of ALT in serum, as well as ameliorated HFD-induced systemic insulin resistance and glucose intolerance, while aggravated hepatic fibrosis in diet-induced NASH. Furthermore, treatment with IL-33 can also promote Th2 response and M2 macrophage activation and beneficial modulation on expression profiles of fatty acid metabolism genes in livers. ST2 deficiency did not affect hepatic steatosis and fibrosis when fed with controlling diet. IL-33 did not affect diet-induced hepatic steatosis and fibrosis in ST2 knockout mice. Meanwhile, in the livers of patients with NASH, IL-33 was mainly located in hepatic sinusoid, endothelial cells, and hepatic stellate cells. The mRNA expression level of IL-33 and ST2 was elevated with the progression of NASH. In conclusion, treatment with IL-33 attenuated diet-induced hepatic steatosis, but aggravated hepatic fibrosis, in a ST2-dependent manner. PMID:27172901

  13. Anti-obesity effect of extract from fermented Curcuma longa L. through regulation of adipogenesis and lipolysis pathway in high-fat diet-induced obese rats

    PubMed Central

    Kim, Ji Hye; Kim, Ok-Kyung; Yoon, Ho-Geun; Park, Jeongjin; You, Yanghee; Kim, Kyungmi; Lee, Yoo-Hyun; Choi, Kyung-Chul; Lee, Jeongmin; Jun, Woojin

    2016-01-01

    Background Even though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food. Objective The present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis. Design Rats were divided into four groups (n=6 per group) after 1 week of acclimatization: a normal diet group comprised rats fed the AIN76A rodent diet; a high-fat diet-induced obese group with rats fed a 60% high-fat diet; a Garcinia cambogia treated group (positive control) with rats fed a 60% high-fat diet with G. cambogia 500 g/kg body weight (b.w.)/day; and an fermented C. longa L. 50% ethanolic extract treated group (FCE50) with rats fed a 60% high-fat diet with FCE50 500 g/kg b.w./day. Each group received the appropriate vehicle or sample daily by gastric intubation for 12 weeks. Results We found that FCE50 administration suppressed b.w. gain and reduced white adipose tissue weight, serum triglyceride (TG), and cholesterol in high-fat diet-induced obese rats. These results can be associated with the suppression of adipocyte differentiation and lipogenesis with a decrease in the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, adipocyte protein 2, and lipoprotein lipase induced by FCE50 administration. In addition, FCE50 increased lipolysis and β-oxidation by up-regulating the expression of lipases such as adipose triglyceride lipase, hormone-sensitive lipase, adiponectin, and AMP-activated protein kinase. Conclusions These results suggest that FCE50 can be a candidate for the prevention of obesity via suppressing adipogenesis and promoting lipolysis. PMID:26822962

  14. Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without Type 2 diabetes.

    PubMed

    Lee, SoJung; Kuk, Jennifer L; Davidson, Lance E; Hudson, Robert; Kilpatrick, Katherine; Graham, Terry E; Ross, Robert

    2005-09-01

    It is unclear whether chronic exercise without caloric restriction or weight loss is a useful strategy for obesity reduction in obese men with and without Type 2 diabetes (T2D). We examined the effects of exercise without weight loss on total and regional adiposity and skeletal muscle mass and composition in lean men and in obese men with and without T2D. Twenty-four men participated in 13 wk of supervised aerobic exercise, five times per week for 60 min at a moderate intensity (approximately 60% peak oxygen uptake). Total and regional body composition was measured by magnetic resonance imaging. Skeletal muscle composition was determined using computed tomography. Cardiorespiratory fitness was assessed using a graded maximal treadmill test. Body weight did not change within any group in response to exercise (P > 0.1). Significant reductions in total, abdominal subcutaneous, and visceral fat were observed within each group (P < 0.01). The reduction in total and abdominal subcutaneous fat was not different (P > 0.1) between groups; however, the reduction in visceral fat was greater (P < 0.01) in the obese and T2D groups by comparison to the lean group. A significant (P < 0.01) increase in total skeletal muscle, high-density muscle area, and mean muscle attenuation was observed independent of group, and these changes were not different between groups (P > 0.1). Accordingly, whole body fat-to-muscle ratio was increased (P < 0.01) independent of groups. In conclusion, regular exercise without weight loss is associated with a substantial reduction in total and visceral fat and in skeletal muscle lipid in both obesity and T2D.

  15. Pharmacological glycerol-3-phosphate acyltransferase inhibition decreases food intake and adiposity and increases insulin sensitivity in diet-induced obesity.

    PubMed

    Kuhajda, Francis P; Aja, Susan; Tu, Yajun; Han, Wan Fang; Medghalchi, Susan M; El Meskini, Rajaa; Landree, Leslie E; Peterson, Jonathan M; Daniels, Khadija; Wong, Kody; Wydysh, Edward A; Townsend, Craig A; Ronnett, Gabriele V

    2011-07-01

    Storage of excess calories as triglycerides is central to obesity and its associated disorders. Glycerol-3-phosphate acyltransferases (GPATs) catalyze the initial step in acylglyceride syntheses, including triglyceride synthesis. We utilized a novel small-molecule GPAT inhibitor, FSG67, to investigate metabolic consequences of systemic pharmacological GPAT inhibition in lean and diet-induced obese (DIO) mice. FSG67 administered intraperitoneally decreased body weight and energy intake, without producing conditioned taste aversion. Daily FSG67 (5 mg/kg, 15.3 μmol/kg) produced gradual 12% weight loss in DIO mice beyond that due to transient 9- to 10-day hypophagia (6% weight loss in pair-fed controls). Continued FSG67 maintained the weight loss despite return to baseline energy intake. Weight was lost specifically from fat mass. Indirect calorimetry showed partial protection by FSG67 against decreased rates of oxygen consumption seen with hypophagia. Despite low respiratory exchange ratio due to a high-fat diet, FSG67-treated mice showed further decreased respiratory exchange ratio, beyond pair-fed controls, indicating enhanced fat oxidation. Chronic FSG67 increased glucose tolerance and insulin sensitivity in DIO mice. Chronic FSG67 decreased gene expression for lipogenic enzymes in white adipose tissue and liver and decreased lipid accumulation in white adipose, brown adipose, and liver tissues without signs of damage. RT-PCR showed decreased gene expression for orexigenic hypothalamic neuropeptides AgRP or NPY after acute and chronic systemic FSG67. FSG67 given intracerebroventricularly (100 and 320 nmol icv) produced 24-h weight loss and feeding suppression, indicating contributions from direct central nervous system sites of action. Together, these data point to GPAT as a new potential therapeutic target for the management of obesity and its comorbidities. PMID:21490364

  16. Serotonin Improves High Fat Diet Induced Obesity in Mice.

    PubMed

    Watanabe, Hitoshi; Nakano, Tatsuya; Saito, Ryo; Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

    2016-01-01

    There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle. PMID:26766570

  17. Serotonin Improves High Fat Diet Induced Obesity in Mice

    PubMed Central

    Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T.; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

    2016-01-01

    There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle. PMID:26766570

  18. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.

    PubMed

    Schafer, Marissa J; White, Thomas A; Evans, Glenda; Tonne, Jason M; Verzosa, Grace C; Stout, Michael B; Mazula, Daniel L; Palmer, Allyson K; Baker, Darren J; Jensen, Michael D; Torbenson, Michael S; Miller, Jordan D; Ikeda, Yasuhiro; Tchkonia, Tamara; van Deursen, Jan M; Kirkland, James L; LeBrasseur, Nathan K

    2016-06-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span. PMID:26983960

  19. Body image in obese patients before and after stable weight reduction following bariatric surgery.

    PubMed

    Adami, G F; Meneghelli, A; Bressani, A; Scopinaro, N

    1999-03-01

    The role of possessing an abnormal body weight in the body image alterations of obese patients was evaluated in bariatric surgery subjects prior to and at long term after operation, when body weight and shape had become steadily normalized. Body image was assessed by the body dissatisfaction scale of the Eating Disorders Inventory, the Body Shape Questionnaire, and the Body Attitude Questionnaire. When the individuals were obese, a sharply impaired body image was observed; following operation, weight loss corresponded to normalization of body dissatisfaction, feeling of fatness, and physical attractiveness, whereas body disparagement and salience of shape, although improved in comparison to preoperative data, remained significantly different from that of controls. In the obese patients, some aspects of body image alterations are substantially accounted for by overweight status; other aspects reflect inner feelings, which are partially independent of the actual body weight and shape. PMID:10193918

  20. Effect of recovery from muscle strength imbalance in lower limb using four point weight bearing reduction system.

    PubMed

    Yu, Chang Ho; Kang, Seung Rok; Jeong, Ho Choon; Kim, Kyung; Kwon, Tae Kyu

    2014-01-01

    This study was performed to assess the improvement of muscle strength imbalance in the lower limbs using a four point weight bearing reduction system with a two-belt treadmill. Participants, each having differences in muscle function of the left and right legs of over 20%, were divided into two groups of ten. The participants were involved in experiments progressing 40 minutes per day, 3 days per week, during a period of 4 weeks. The maximal peak torque and average power were measured for testing joint torque in the hip, knee and ankle. The results showed the improvement of muscle imbalance as assessed by the maximal muscle strength was the most effective in the hip joint, while the improvement of muscular reaction was the most effective in the knee joint. We suggest that the method of weight bearing reduction could be sufficient to reduce muscle imbalance in the lower limbs.

  1. Radiation dose reduction in CBCT imaging using K-edge filtering and energy weighting.

    PubMed

    Kang, Se-Ryong; Lee, Woo-Jin; Woo, Sang-Yoon; Kim, Dae-Seung; Yi, Won-Jin

    2014-01-01

    This paper presents K-edge filtering and energy weighting methods which enhance the contrast with less radiation does. Usually, energy weighting methods are used with photon-counting detector based CT for each energy bin data obtained to enhance the quality of image. However, we used these methods combine with K-edge filtering in energy-integrating detector. Using K-edge filtering, different energy bin data for energy weighting methods were obtained, and then energy weighting factors were calculated to enhance the contrast of image. We report an evaluation of the contrast-to-noise ratio (CNR) of reconstructed image with and without these two methods. This evaluation was proceeded with two phantoms; one is the phantom created personally, and the other is Sendentexct IQ dental CBCT (SENDENTEXCT, EU). As for the phantom created personally, the CNR of images reconstructed with these methods were increased than CNR of standard images. It was seen that 31% to 81% in each energy weighting method for optimizing each material (cortical bone, inner bone, soft tissue, iodine (18.5 g/l), iodine (37 g/l)). In conclusion, we can enhance the contrast of CT images with less radiation dose using K-edge filtering and energy weighting method. PMID:25571149

  2. Long-Term Follow-Up of the Telemonitoring Weight-Reduction Program “Active Body Control”

    PubMed Central

    Stumm, Gabriele; Blaik, Alexandra; Kropf, Siegfried; Westphal, Sabine; Hantke, Tanja Katrin; Luley, Claus

    2016-01-01

    The Active Body Control (ABC) weight-reduction program is based on telemonitoring of physical activity and nutrition together with telecoaching by weekly counseling letters sent by post or by e-mail. The study presented here reports the results of a 1-year follow-up of 49 patients with the metabolic syndrome who had lost weight with the aid of the ABC program in the preceding year. The weight regain after the second year in patients not receiving any further care (“ABC discontinued” group; n = 24) and the potential benefit of continuing with the ABC program with monthly counseling letters (“ABC continued” group; n = 25) were investigated. The relative weight changes after the first year had been, respectively, −13.4% and −11.4% in the “ABC discontinued” and “ABC continued” groups, and after the second year they decreased by, respectively, 4.4 and 2.8%. However, this difference in weight regains between the two groups was not statistically significant. It is concluded that three-quarters of the weight loss after 1 year is maintained after the second year. The decision whether to continue with the ABC program after 1 year should be made individually. PMID:27088096

  3. Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation in Diet-Induced Nonalcoholic Fatty Liver Disease.

    PubMed

    Pacana, Tommy; Cazanave, Sophie; Verdianelli, Aurora; Patel, Vaishali; Min, Hae-Ki; Mirshahi, Faridoddin; Quinlivan, Eoin; Sanyal, Arun J

    2015-01-01

    Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, p< 0.01) while s-adenosylmethionine (SAM)/methionine ratio (p< 0.05), s-adenosylhomocysteine (SAH) (35%, p< 0.01) and homocysteine (25%, p< 0.01) were increased significantly. SAH hydrolase protein levels decreased significantly (p <0.01). Serine, a substrate for both homocysteine remethylation and transsulfuration, was depleted (45%, p< 0.01). In the transsulfuration pathway, cystathionine and cysteine trended upward while glutathione decreased significantly (p< 0.05). In the transmethylation pathway, levels of glycine N-methyltransferase (GNMT), the most abundant methyltransferase in the liver, decreased. The phosphatidylcholine (PC)/ phosphatidylethanolamine (PE) ratio increased significantly (p< 0.01), indicative of increased phosphatidylethanolamine methyltransferase (PEMT) activity. The protein levels of protein arginine methytransferase 1 (PRMT1) increased significantly, but its products, monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), decreased significantly. Circulating ADMA increased and approached significance (p< 0.06). Protein expression of methionine adenosyltransferase 1A, cystathionine β-synthase, γ-glutamylcysteine synthetase, betaine-homocysteine methyltransferase, and methionine synthase remained unchanged. Although gene expression of the DNA

  4. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality

    PubMed Central

    Boon, Mariëtte R.; van den Berg, Sjoerd A. A.; Wang, Yanan; van den Bossche, Jan; Karkampouna, Sofia; Bauwens, Matthias; De Saint-Hubert, Marijke; van der Horst, Geertje; Vukicevic, Slobodan; de Winther, Menno P. J.; Havekes, Louis M.; Jukema, J. Wouter; Tamsma, Jouke T.; van der Pluijm, Gabri; van Dijk, Ko Willems; Rensen, Patrick C. N.

    2013-01-01

    Background/Aims Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity. Methods and Results High-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21°C or 28°C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21°C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28°C. Additionally, BMP7 resulted in extensive ‘browning’ of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia. Conclusion Together, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to

  5. Black tea polyphenols and polysaccharides improve body composition, increase fecal fatty acid, and regulate fat metabolism in high-fat diet-induced obese rats.

    PubMed

    Wu, Tao; Guo, Yu; Liu, Rui; Wang, Kuan; Zhang, Min

    2016-05-18

    With the current changes in diet and living habits, obesity has become a global health problem. Thus, the weight-reducing function of tea has attracted considerable attention. This study investigated the anti-obesity effect and the mechanism of black tea (BT) polyphenols and polysaccharides in male Sprague-Dawley rats. The BT polyphenols and polysaccharides reduced the body weight, Lee's index, visceral fat weight, and fat cell size but improved the biochemical profile and increased the fecal fatty acid content, thereby preventing high-fat diet-induced obesity. A gene expression profile array was used to screen eight upregulated and five downregulated differentially expressed genes that affect fat metabolic pathways, such as glycerolipid and glycerophospholipid metabolism, fatty acid degradation, glycolysis and gluconeogenesis, bile and pancreatic secretion, the insulin signaling pathway, and steroid hormone secretion. The BT polyphenols and polysaccharides suppressed the formation and accumulation of fat and promoted its decomposition to prevent obesity.

  6. Lifestyle modification and weight reduction among low-income patients with the metabolic syndrome: the CHARMS randomized controlled trial.

    PubMed

    Chirinos, Diana A; Goldberg, Ronald B; Llabre, Maria M; Gellman, Marc; Gutt, Miriam; McCalla, Judith; Mendez, Armando; Schneiderman, Neil

    2016-06-01

    Although weight is an important intervention target among patients with metabolic syndrome, few trials have recruited low-income minority populations. The Community Health and Risk-reduction for Metabolic Syndrome randomized controlled trial aimed to examine the effects of a lifestyle intervention on weight and metabolic syndrome components among low-income minority adults. We randomized 120 adults with metabolic syndrome to standard medical care (N = 60) or a lifestyle intervention (N = 60). Using an intent-to-treat approach, we found significant intervention effects on weight [B = -0.452; SE = 0.122; 95 % confidence intervals (CI) -0.653 to -0.251) and glucose levels at 6-months (B = -0.522, SE = 0.234, 95 % CI -0.907 to -0.138). These changes were maintained through the 12-month assessment. No significant effects were observed on insulin resistance or other metabolic syndrome components. Our intervention was successful in achieving modest but significant weight loss and reduction in fasting glucose among low-income minority subjects with metabolic syndrome.

  7. Anti-Obese Effect of Glucosamine and Chitosan Oligosaccharide in High-Fat Diet-Induced Obese Rats

    PubMed Central

    Huang, Lanlan; Chen, Jian; Cao, Peiqiu; Pan, Haitao; Ding, Chen; Xiao, Tiancun; Zhang, Pengfei; Guo, Jiao; Su, Zhengquan

    2015-01-01

    Objective: This study is to evaluate the anti-obese effects of glucosamine (GLC) and chitosan oligosaccharide (COS) on high-fat diet-induced obese rats. Methods: The rats were randomly divided into twelve groups: a normal diet group (NF), a high-fat diet group (HF), Orlistat group, GLC high-, middle-, and low-dose groups (GLC-H, GLC-M, GLC-L), COS1 (COS, number-average molecular weight ≤1000) high-, middle-, and low-dose groups (COS1-H, COS1-M, COS1-L), and COS2 (COS, number-average molecular weight ≤3000) high-, middle-, and low-dose groups (COS2-H, COS2-M, COS2-L). All groups received oral treatment by gavage once daily for a period of six weeks. Results: Rats fed with COS1 gained the least weight among all the groups (P < 0.01), and these rats lost more weight than those treated with Orlistat. In addition to the COS2-H and Orlistat groups, the serum total cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced in all treatment groups compared to the HF group (P < 0.01). The various doses of GLC, COS1 and COS2 reduced the expression levels of PPARγ and LXRα mRNA in the white adipose tissue. Conclusions: The results above demonstrated that GLC, COS1, and COS2 improved dyslipidemia and prevented body weight gains by inhibiting the adipocyte differentiation in obese rats induced by a high-fat diet. Thus, these agents may potentially be used to treat obesity. PMID:25942093

  8. Cashew apple extract inhibition of fat storage and insulin resistance in the diet-induced obesity mouse model.

    PubMed

    Beejmohun, Vickram; Mignon, Cyril; Mazollier, Aude; Peytavy-Izard, Marie; Pallet, Dominique; Dornier, Manuel; Chapal, Nicolas

    2015-01-01

    The cashew apple is an unvalued by-product from the cashew nut industry, of which millions of tonnes are simply discarded globally. Interestingly, however, cashew apple nutrients may have beneficial effects for health even if these are still poorly described. The present study was designed to evaluate the effect of a hydro-alcoholic extract of cashew apple (cashew apple extract; CAE; Cashewin(™)) on obesity and diabetes, in two experimental designs using the diet-induced obesity (DIO) mouse model. First, in the preventive design, mice were treated orally with the CAE at the dose of 200 mg/kg body weight from the first day under a high-fat diet (HFD) and during 8 weeks thereafter. Second, in the curative design, the animals were first maintained under the HFD for 4 weeks and then treated with the CAE for a further 4 weeks under the same regimen. For both experimental designs, body weight, peri-epididymal adipose tissue, liver weight, food consumption, glycaemia, insulinaemia and insulin resistance were assessed. In both designs, the CAE significantly reduced body-weight gain and fat storage in both the peri-epididymal adipose tissue and the liver for mice under the HFD. This was achieved without modifying their energy consumption. Furthermore, glycaemia, insulinaemia and insulin resistance (homeostasis model assessment-insulin resistance) of the DIO mice were significantly lowered compared with the control group. Thus, a well-designed hydro-alcoholic extract of cashew apple could provide an attractive nutritional food ingredient to help support the management of body weight and associated metabolic parameters such as blood glucose and insulin levels.

  9. Cashew apple extract inhibition of fat storage and insulin resistance in the diet-induced obesity mouse model.

    PubMed

    Beejmohun, Vickram; Mignon, Cyril; Mazollier, Aude; Peytavy-Izard, Marie; Pallet, Dominique; Dornier, Manuel; Chapal, Nicolas

    2015-01-01

    The cashew apple is an unvalued by-product from the cashew nut industry, of which millions of tonnes are simply discarded globally. Interestingly, however, cashew apple nutrients may have beneficial effects for health even if these are still poorly described. The present study was designed to evaluate the effect of a hydro-alcoholic extract of cashew apple (cashew apple extract; CAE; Cashewin(™)) on obesity and diabetes, in two experimental designs using the diet-induced obesity (DIO) mouse model. First, in the preventive design, mice were treated orally with the CAE at the dose of 200 mg/kg body weight from the first day under a high-fat diet (HFD) and during 8 weeks thereafter. Second, in the curative design, the animals were first maintained under the HFD for 4 weeks and then treated with the CAE for a further 4 weeks under the same regimen. For both experimental designs, body weight, peri-epididymal adipose tissue, liver weight, food consumption, glycaemia, insulinaemia and insulin resistance were assessed. In both designs, the CAE significantly reduced body-weight gain and fat storage in both the peri-epididymal adipose tissue and the liver for mice under the HFD. This was achieved without modifying their energy consumption. Furthermore, glycaemia, insulinaemia and insulin resistance (homeostasis model assessment-insulin resistance) of the DIO mice were significantly lowered compared with the control group. Thus, a well-designed hydro-alcoholic extract of cashew apple could provide an attractive nutritional food ingredient to help support the management of body weight and associated metabolic parameters such as blood glucose and insulin levels. PMID:26688724

  10. Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice.

    PubMed

    Miranda, Cristobal L; Elias, Valerie D; Hay, Joshua J; Choi, Jaewoo; Reed, Ralph L; Stevens, Jan F

    2016-06-01

    Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals. The mice were fed a high-fat diet (60% kcal as fat) supplemented with XN at dose levels of 0, 30, or 60 mg/kg body weight/day, for 12 weeks. Dietary XN caused a dose-dependent decrease in body weight gain. Plasma levels of glucose, total triglycerides, total cholesterol, and MCP-1 were significantly decreased in mice on the 60 mg/kg/day treatment regimen. Treatment with XN at 60 mg/kg/day resulted in reduced plasma LDL-cholesterol (LDL-C), IL-6, insulin and leptin levels by 80%, 78%, 42%, and 41%, respectively, compared to the vehicle control group. Proprotein Convertase Subtilisin Kexin 9 (PCSK-9) levels were 44% lower in the 60 mg/kg dose group compared to the vehicle control group (p ≤ 0.05) which may account for the LDL-C lowering activity of XN. Our results show that oral administration of XN improves markers of systemic inflammation and metabolic syndrome in diet-induced obese C57BL/6J mice. PMID:26976708

  11. Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress.

    PubMed

    Vijayakumar, R S; Surya, D; Nalini, N

    2004-01-01

    The present study was aimed to explore the effect of black pepper (Piper nigrum L.) on tissue lipid peroxidation, enzymic and non-enzymic antioxidants in rats fed a high-fat diet. Thirty male Wistar rats (95-115 g) were divided into 5 groups. They were fed standard pellet diet, high-fat diet (20% coconut oil, 2% cholesterol and 0.125% bile salts), high-fat diet plus black pepper (0.25 g or 0.5 g/kg body weight), high-fat diet plus piperine (0.02 g/kg body weight) for a period of 10 weeks. Significantly elevated levels of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and significantly lowered activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) in the liver, heart, kidney, intestine and aorta were observed in rats fed the high fat diet as compared to the control rats. Simultaneous supplementation with black pepper or piperine lowered TBARS and CD levels and maintained SOD, CAT, GPx, GST, and GSH levels to near those of control rats. The data indicate that supplementation with black pepper or the active principle of black pepper, piperine, can reduce high-fat diet induced oxidative stress to the cells.

  12. Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases leptin receptor signaling and prevents diet-induced obesity

    PubMed Central

    Couturier, Cyril; Sarkis, Chamsy; Séron, Karin; Belouzard, Sandrine; Chen, Patty; Lenain, Aude; Corset, Laetitia; Dam, Julie; Vauthier, Virginie; Dubart, Anne; Mallet, Jacques; Froguel, Philippe; Rouillé, Yves; Jockers, Ralf

    2007-01-01

    Obesity is a major public health problem and is often associated with type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome. Leptin is the crucial adipostatic hormone that controls food intake and body weight through the activation of specific leptin receptors (OB-R) in the hypothalamic arcuate nucleus (ARC). However, in most obese patients, high circulating levels of leptin fail to bring about weight loss. The prevention of this “leptin resistance” is a major goal for obesity research. We report here a successful prevention of diet-induced obesity (DIO) by silencing a negative regulator of OB-R function, the OB-R gene-related protein (OB-RGRP), whose transcript is genetically linked to the OB-R transcript. We provide in vitro evidence that OB-RGRP controls OB-R function by negatively regulating its cell surface expression. In the DIO mouse model, obesity was prevented by silencing OB-RGRP through stereotactic injection of a lentiviral vector encoding a shRNA directed against OB-RGRP in the ARC. This work demonstrates that OB-RGRP is a potential target for obesity treatment. Indeed, regulators of the receptor could be more appropriate targets than the receptor itself. This finding could serve as the basis for an approach to identifying potential new therapeutic targets for a variety of diseases, including obesity. PMID:18042720

  13. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms.

    PubMed

    Lin, Hua V; Frassetto, Andrea; Kowalik, Edward J; Nawrocki, Andrea R; Lu, Mofei M; Kosinski, Jennifer R; Hubert, James A; Szeto, Daphne; Yao, Xiaorui; Forrest, Gail; Marsh, Donald J

    2012-01-01

    Short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, are metabolites formed by gut microbiota from complex dietary carbohydrates. Butyrate and acetate were reported to protect against diet-induced obesity without causing hypophagia, while propionate was shown to reduce food intake. However, the underlying mechanisms for these effects are unclear. It was suggested that SCFAs may regulate gut hormones via their endogenous receptors Free fatty acid receptors 2 (FFAR2) and 3 (FFAR3), but direct evidence is lacking. We examined the effects of SCFA administration in mice, and show that butyrate, propionate, and acetate all protected against diet-induced obesity and insulin resistance. Butyrate and propionate, but not acetate, induce gut hormones and reduce food intake. As FFAR3 is the common receptor activated by butyrate and propionate, we examined these effects in FFAR3-deficient mice. The effects of butyrate and propionate on body weight and food intake are independent of FFAR3. In addition, FFAR3 plays a minor role in butyrate stimulation of Glucagon-like peptide-1, and is not required for butyrate- and propionate-dependent induction of Glucose-dependent insulinotropic peptide. Finally, FFAR3-deficient mice show normal body weight and glucose homeostasis. Stimulation of gut hormones and food intake inhibition by butyrate and propionate may represent a novel mechanism by which gut microbiota regulates host metabolism. These effects are largely intact in FFAR3-deficient mice, indicating additional mediators are required for these beneficial effects.

  14. The Crude Extract from Puerariae Flower Exerts Antiobesity and Antifatty Liver Effects in High-Fat Diet-Induced Obese Mice

    PubMed Central

    Kamiya, Tomoyasu; Sameshima-Kamiya, Mayu; Nagamine, Rika; Tsubata, Masahito; Ikeguchi, Motoya; Takagaki, Kinya; Shimada, Tsutomu; Aburada, Masaki

    2012-01-01

    Kudzu, a leguminous plant, has long been used in folk medicine. In particular, its flowers are used in Japanese and Chinese folk medicine for treating hangovers. We focused on the flower of Kudzu (Puerariae thomsonii), and we previously reported the antiobesity effect of Puerariae thomsonii flower extract (PFE) in humans. In this study, we conducted an animal study to investigate the effect of PFE on visceral fat and hepatic lipid levels in mice with diet-induced obesity. In addition, we focused on gene expression profiles to investigate the antiobesity mechanism of PFE. Male C57BL/6J mice were fed a high-fat diet (HFD) or an HFD supplemented with 5% PFE for 14 days. PFE supplementation significantly reduced body weight and white adipose tissue (WAT) weight. Moreover, in the histological analysis, PFE supplementation improved fatty liver. Hepatic reverse transcription-polymerase chain reaction revealed that PFE supplementation downregulated acetyl-CoA carboxylase expression. For adipose tissue, the expressions of hormone-sensitive lipase in WAT and uncoupling protein 1 in brown adipose tissue (BAT) were significantly upregulated. These results suggest that PFE exerts antiobesity and antifatty liver effects in high-fat diet-induced obese mice through suppressing lipogenesis in the liver, stimulating lipolysis in WAT, and promoting thermogenesis in BAT. PMID:22685484

  15. The combined action of omega-3 polyunsaturated fatty acids and grape proanthocyanidins on a rat model of diet-induced metabolic alterations.

    PubMed

    Ramos-Romero, Sara; Molinar-Toribio, Eunice; Pérez-Jiménez, Jara; Taltavull, Núria; Dasilva, Gabriel; Romeu, Marta; Medina, Isabel; Torres, Josep Lluís

    2016-08-10

    It has been suggested that food components such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and (poly)phenols counteract diet-induced metabolic alterations by common or complementary mechanisms. To examine the effects of a combination of ω-3 PUFAs and (poly)phenols on such alterations, adult Wistar-Kyoto rats were fed an obesogenic high-fat high-sucrose diet supplemented, or not, for 24 weeks with: eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) 1 : 1 (16.6 g kg(-1) feed); proanthocyanidin-rich grape seed extract (GSE, 0.8 g kg(-1) feed); or EPA/DHA 1 : 1 + GSE. Body weight, feed intake, and plasma glucose were evaluated every 6 weeks, while adipose tissue weight, insulin, glucagon, ghrelin, leptin, adiponectin, cholesterol, and triglycerides were evaluated at the end of the experiment. ω-3 PUFAs reduced plasma leptin and cholesterol levels, but did not modify diet-induced perigonadal fat or plasma insulin levels; while GSE increased plasma triglyceride levels. The combined action of ω-3 PUFAs and the proanthocyanidins reduced plasma insulin and leptin, as well as partially prevented perigonadal fat accumulation. While separate supplementation with ω-3 PUFAs or grape proanthocyanidins may not counteract all the key metabolic changes induced by a high-energy-dense diet, the combination of both supplements reverts altered insulin, leptin and triglyceride levels to normal. PMID:27418399

  16. Purple Tea and Its Extract Suppress Diet-induced Fat Accumulation in Mice and Human Subjects by Inhibiting Fat Absorption and Enhancing Hepatic Carnitine Palmitoyltransferase Expression

    PubMed Central

    Shimoda, Hiroshi; Hitoe, Shoketsu; Nakamura, Seikou; Matsuda, Hisashi

    2015-01-01

    A number of clinical trials have been completed using green tea and black tea to investigate their effect in controlling weight in overweight adults. The results of these investigations, however, have often been contradictory, with some trials reporting positive effects of tea supplementation and some trials reporting no effect. As a result, the use of these teas for weight loss is controversial. Purple tea is a variety of green tea developed in Kenya (called TRFK306), which in addition to certain tea constituents found in green tea, also contains anthocyanins. The major constituents in the leaves of purple tea are caffeine, theobromine, epigallocatechin (ECG), epigallocatechin gallate (EGCG) and 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-β-D-glucose (GHG). We investigated the efficacy of purple tea extract (PTE) on diet-induced fat accumulation in mice. PTE administration (200 mg/kg) significantly suppressed body weight gain, liver weight, abdominal fat and triglycerides in serum and liver. Protein expression of carnitine palmitoyltransferase (CPT) 1A was also enhanced. In olive oil loaded mice, PTE (100 mg/kg) and caffeine (25 mg/kg) suppressed fat absorption. PTE (10 μg/mL) and GHG (10 μg/mL) also enhanced protein expression of CPT1A in HepG2 hepatoma. Moreover, 4-week daily consumption of purple tea drink in humans improved obesity parameters compared to baseline, including body weight (79.9 ± 3.1 kg vs 80.8 ± 3.2, p<0.05), body mass index (BMI) (26.8 ± 0.6 vs 27.0 ± 0.6, p<0.05) and body fat mass (21.0 ± 1.4 kg vs 21.8 ± 1.5, p<0.01). In conclusion, PTE could control diet-induced weight gain by suppression of fat absorption and enhancement of hepatic fat metabolism PMID:26199579

  17. Purple Tea and Its Extract Suppress Diet-induced Fat Accumulation in Mice and Human Subjects by Inhibiting Fat Absorption and Enhancing Hepatic Carnitine Palmitoyltransferase Expression.

    PubMed

    Shimoda, Hiroshi; Hitoe, Shoketsu; Nakamura, Seikou; Matsuda, Hisashi

    2015-06-01

    A number of clinical trials have been completed using green tea and black tea to investigate their effect in controlling weight in overweight adults. The results of these investigations, however, have often been contradictory, with some trials reporting positive effects of tea supplementation and some trials reporting no effect. As a result, the use of these teas for weight loss is controversial. Purple tea is a variety of green tea developed in Kenya (called TRFK306), which in addition to certain tea constituents found in green tea, also contains anthocyanins. The major constituents in the leaves of purple tea are caffeine, theobromine, epigallocatechin (ECG), epigallocatechin gallate (EGCG) and 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-β-D-glucose (GHG). We investigated the efficacy of purple tea extract (PTE) on diet-induced fat accumulation in mice. PTE administration (200 mg/kg) significantly suppressed body weight gain, liver weight, abdominal fat and triglycerides in serum and liver. Protein expression of carnitine palmitoyltransferase (CPT) 1A was also enhanced. In olive oil loaded mice, PTE (100 mg/kg) and caffeine (25 mg/kg) suppressed fat absorption. PTE (10 μg/mL) and GHG (10 μg/mL) also enhanced protein expression of CPT1A in HepG2 hepatoma. Moreover, 4-week daily consumption of purple tea drink in humans improved obesity parameters compared to baseline, including body weight (79.9 ± 3.1 kg vs 80.8 ± 3.2, p<0.05), body mass index (BMI) (26.8 ± 0.6 vs 27.0 ± 0.6, p<0.05) and body fat mass (21.0 ± 1.4 kg vs 21.8 ± 1.5, p<0.01). In conclusion, PTE could control diet-induced weight gain by suppression of fat absorption and enhancement of hepatic fat metabolism. PMID:26199579

  18. Weight reduction in the management of hypertension: epidemiologic and mechanistic evidence.

    PubMed

    Reisin, E

    1986-06-01

    A number of studies have established a close association between increased body mass and elevated blood pressure. The presence of obesity in hypertensive subjects is associated with some hemodynamic, metabolic, and endocrinic characteristics: an increased intravascular volume with a high intracellular body water/interstitial fluid volume ratio, increased cardiac output, stroke volume, and left ventricular work while peripheral resistance was reduced or normal. Weight loss of at least 10 kg can reduce blood pressure independently of changes in sodium intake in obese persons of both sexes with mild, moderate, or severe high blood pressure. The fall in arterial pressure in obese hypertensives after weight loss may reverse many of the previously mentioned altered findings and underscore previous epidemiological studies that have shown that weight control could be an important measure in the treatment of hypertension. PMID:3756637

  19. Cardiovascular and Renal Effects of Weight Reduction in Obesity and the Metabolic Syndrome

    PubMed Central

    Cohen, Jordana B.; Cohen, Debbie L.

    2015-01-01

    Obesity is a critical public health issue worldwide. Patients with obesity have markedly increased morbidity and mortality compared to the general population. The increased health risks of obesity in part are due to its close association with each of the other components of the metabolic syndrome, including hypertension, dyslipidemia, and insulin resistance. Accordingly, obese individuals are at particularly increased risk of cardiovascular disease and chronic kidney disease. Modest weight loss results in improvements in serum cholesterol levels, blood pressure, and glycemic profiles. Lifestyle interventions for weight loss have long been the mainstay of treatment in obesity. However, the existing literature demonstrates limited weight loss sustainability and inconsistent cardiovascular and renal benefits using these modalities. In addition to improvements in intermediate risk factors, surgical interventions provide a more lasting impact on long-term cardiovascular and renal outcomes, though carry higher short-term risks due to perioperative complications. PMID:25833456

  20. Cardiovascular and renal effects of weight reduction in obesity and the metabolic syndrome.

    PubMed

    Cohen, Jordana B; Cohen, Debbie L

    2015-05-01

    Obesity is a critical public health issue worldwide. Patients with obesity have markedly increased morbidity and mortality compared to the general population. The increased health risks of obesity in part are due to its close association with each of the other components of the metabolic syndrome, including hypertension, dyslipidemia, and insulin resistance. Accordingly, obese individuals are at particularly increased risk of cardiovascular disease and chronic kidney disease. Modest weight loss results in improvements in serum cholesterol levels, blood pressure, and glycemic profiles. Lifestyle interventions for weight loss have long been the mainstay of treatment in obesity. However, the existing literature demonstrates limited weight loss sustainability and inconsistent cardiovascular and renal benefits using these modalities. In addition to improvements in intermediate risk factors, surgical interventions provide a more lasting impact on long-term cardiovascular and renal outcomes, though carry higher short-term risks due to perioperative complications. PMID:25833456

  1. Evaluation of intervention research in weight reduction in post menopausal women.

    PubMed

    Al-Zadjali, Manal; Keller, Colleen; Larkey, Linda K; Albertini, Lauren

    2010-01-01

    To describe the evidence that has accrued for interventions targeting weight loss in postmenopausal women, and to assess the strengths and limitations of weight loss interventions in postmenopausal women using the framework of evaluation theory, including definition of the problem and the use of theoretical framework and mediators. Electronic databases were used, including CINAHL, EBSCO Host, Google scholar, Medline, and the Science Citation Index, Expanded, in the Web of Science from 1995 to December 2009. Keyword searches included the terms obesity, obese, overweight, menopause, and weight management interventions. Searches were combined to find reports addressing 1 or more keywords. Experimental design studies that examined physical activity or dietary intervention effects on weight loss or body composition changes in postmenopausal women were selected for review. Reports of 15 intervention studies met inclusion criteria from the list of 120 generated through the database searches. Each article was evaluated for 1) effects produced as a result of the intervention, 2) the characteristics of the problem of postmenopausal obesity, 3) specification of theoretical constructs and critical inputs that guide the design of an intervention, and 4) link of the theoretical predictors and the outcome measures selected. Four types of interventions were tested in the 15 research reports. Only 5 of the 15 used theories or models to guide the interventions. All of the interventions resulted in some positive weight management outcome, such as lowered body mass index, fat mass, waist circumference, systolic blood pressure, glucose, and cholesterol. Overall, the reviewed research showed efficacy of varying intensities of exercise when combined with hypocaloric diet or meal replacement therapy in producing low body weight, low fat, improved insulin sensitivity, glycemic control, and cardio-respiratory fitness. The external validity of the 15 studies was limited in reporting of a

  2. Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity.

    PubMed

    Higgins, Guy A; Desnoyer, Jill; Van Niekerk, Annalise; Silenieks, Leo B; Lau, Winnie; Thevarkunnel, Sandy; Izhakova, Julia; DeLannoy, Ines Am; Fletcher, Paul J; DeLay, Josepha; Dobson, Howard

    2015-02-01

    The 5-HT2C receptor agonist lorcaserin (Belviq®) has been Food and Drug Administration (FDA) approved for the treatment of obesity. The present study is a back translational investigation into the effect of 28-day lorcaserin treatment in a diet-induced obesity (DIO) model using male, Sprague-Dawley rats. An assessment of drug effect on efficacy and multiple safety endpoints including cardiac function was undertaken. Lorcaserin (1-2 mg/kg SC b.i.d.) significantly reduced percentage body weight gain compared to vehicle-treated controls (VEH: 10.6 ± 0.4%; LOR 1: 7.6 ± 1.2%; LOR 2: 5.4 ± 0.6%). Measurement of body composition using quantitative magnetic resonance (QMR) imaging indicated this change was due to the selective reduction in body fat mass. Modest effects on food intake were recorded. At the completion of the treatment phase, echocardiography revealed no evidence for valvulopathy, that is, no aortic or mitral valve regurgitation. The pharmacokinetics of the present treatment regimen was determined over a 7-day treatment period; plasma C min and C max were in the range 13-160 ng/mL (1 mg/kg b.i.d.) and 34-264 ng/mL (2 mg/kg b.i.d.) with no evidence for drug accumulation. In sum, these studies show an effect of lorcaserin in the DIO model, that in the context of the primary endpoint measure of % body weight change was similar to that reported clinically (i.e., 3.0-5.2% vs. 3.2%). The present studies highlight the translational value of obesity models such as DIO, and suggest that assuming consideration is paid to nonspecific drug effects such as malaise, the DIO model has reasonable forward translational value to help predict clinical outcomes of a new chemical entity.

  3. Reduction of bias in neutron multiplicity assay using a weighted point model

    SciTech Connect

    Geist, W. H.; Krick, M. S.; Mayo, D. R.

    2004-01-01

    Accurate assay of most common plutonium samples was the development goal for the nondestructive assay technique of neutron multiplicity counting. Over the past 20 years the technique has been proven for relatively pure oxides and small metal items. Unfortunately, the technique results in large biases when assaying large metal items. Limiting assumptions, such as unifoh multiplication, in the point model used to derive the multiplicity equations causes these biases for large dense items. A weighted point model has been developed to overcome some of the limitations in the standard point model. Weighting factors are detemiined from Monte Carlo calculations using the MCNPX code. Monte Carlo calculations give the dependence of the weighting factors on sample mass and geometry, and simulated assays using Monte Carlo give the theoretical accuracy of the weighted-point-model assay. Measured multiplicity data evaluated with both the standard and weighted point models are compared to reference values to give the experimental accuracy of the assay. Initial results show significant promise for the weighted point model in reducing or eliminating biases in the neutron multiplicity assay of metal items. The negative biases observed in the assay of plutonium metal samples are caused by variations in the neutron multiplication for neutrons originating in various locations in the sample. The bias depends on the mass and shape of the sample and depends on the amount and energy distribution of the ({alpha},n) neutrons in the sample. When the standard point model is used, this variable-multiplication bias overestimates the multiplication and alpha values of the sample, and underestimates the plutonium mass. The weighted point model potentially can provide assay accuracy of {approx}2% (1 {sigma}) for cylindrical plutonium metal samples < 4 kg with {alpha} < 1 without knowing the exact shape of the samples, provided that the ({alpha},n) source is uniformly distributed throughout the

  4. Weight loss for reduction of proteinuria in diabetic nephropathy: Comparison with angiotensin-converting enzyme inhibitor therapy

    PubMed Central

    Patil, M. R.; Mishra, A.; Jain, N.; Gutch, M.; Tewari, R.

    2013-01-01

    Reduction of weight in obese type 2 diabetes mellitus (T2DM) individuals is emerging as a significant strategy in the reduction of proteinuria in diabetic nephropathy along with control of hyperglycemia, hypertension, and dyslipidemia. The objective was to evaluate the reduction in 24-h proteinuria in T2DM patients with nephropathy by weight loss, with conventional therapy (angiotensin-converting enzyme [ACE] inhibitors) as the control arm. A prospective, randomized controlled trial was conducted between June 2010 and May 2011. T2DM patients with confirmed nephropathy by 24-h urinary protein estimation with a body mass index (BMI) of >25 kg/m2 were studied. Patients who had nondiabetic nephropathy, uncontrolled hypertension (>125/75 mmHg) irrespective of antihypertensive drugs, excess weight due to edema or obesity due to other specific diseases, alcoholics, smokers, and patients who were on hemodialysis were excluded from the study. The patients were divided into three groups, namely, group A, patients on ACE inhibitor therapy; group B, patients on lifestyle modifications for weight loss; and group C, patients on an antiobesity drug (orlistat) and lifestyle modifications. At the end of 6 months, all the three groups were compared. Data were analyzed using software SPSS version 15.0. This study encompassed a total of 88 patients; 12 patients were dropped during the study period and 76 (group A: 22, group B: 23, and group C: 31) patients remained. The mean age of the patients was 58.36 ± 10.87 years (range: 30-70 years). At baseline, age, gender, mean BMI, waist-to-hip ratio (WHR), and 24-h proteinuria did not vary significantly among the three groups. At 6 months, the mean BMI significantly decreased in group C (P < 0.001) compared to that in the other two groups. Among the parameters BMI and WHR, the proportional form of BMI correlated well with the degree of reduction in proteinuria (r = 0.397, P = 0.01). Reduction in weight using lifestyle modifications and

  5. Weight-bearing, aerobic exercise increases markers of bone formation during short-term weight loss in overweight and obese men and women.

    PubMed

    Hinton, Pamela S; Rector, R Scott; Thomas, Tom R

    2006-12-01

    We investigated the impact of weight-bearing, aerobic exercise- and diet-induced weight loss on markers of bone turnover during a larger study of changes in metabolic fitness during short-term weight reduction using a repeated-measures, within-subject experimental design. Subjects (N = 19) underwent 6 weeks of energy restriction (reduced by approximately 3140 kJ/d) and aerobic exercise ( approximately 1675 kJ/d, walking or jogging at 60% maximum oxygen consumption) to induce a 5% reduction in body weight. Bone turnover markers and hormones were measured in serum collected at baseline and after 6 weeks of weight loss. Despite a 5% reduction in body weight at week 6, markers of bone formation, osteocalcin, and bone alkaline phosphatase, were significantly increased, and resorption markers, C-terminal cross-links of type I collagen and soluble receptor activator of nuclear factor kappaB ligand, were unchanged after 6 weeks of energy restriction and exercise. The concentration of leptin was significantly reduced after weight loss, but insulin-like growth factor I (IGF-I) and cortisol levels were unaffected. In conclusion, weight-bearing, aerobic exercise training may favorably affect the balance between bone resorption and formation during weight loss.

  6. Weight Reduction and Maintenance for Overweight, Mentally Retarded Students, Ages 9-17.

    ERIC Educational Resources Information Center

    Nelson, Evelyn C.; And Others

    1983-01-01

    This article reports on a study undertaken to determine if overweight, mentally retarded students could safely lose weight and maintain their individual losses through a given time period (six months). School personnel and parents instituted minor changes in nutrition and a simple activity program. (Authors/JMK)

  7. Baseline Adherence as a Predictor of Dropout in a Children's Weight-Reduction Program.

    ERIC Educational Resources Information Center

    Israel, Allen C.; And Others

    1987-01-01

    Examined relationship between baseline adherence and attrition among families involved in a children's weight-loss program. Evaluated overall baseline adherence by the degree of families' completion of food intake and activity records. Anything but high adherence during baseline was predictive of dropout, suggesting that this is a useful index for…

  8. The Impact of a Long-Term Reduction in Dietary Energy Density on Body Weight Within a Randomized Diet Trial

    PubMed Central

    Saquib, Nazmus; Natarajan, Loki; Rock, Cheryl L.; Flatt, Shirley W.; Madlensky, Lisa; Kealey, Sheila; Pierce, John P.

    2008-01-01

    We examined the effect of dietary energy density change on body weight in participants of a randomized trial. Intervention participants markedly increased fruit and vegetable intake while reducing energy intake from fat. Participants were 2,718 breast cancer survivors, aged 26−74 yr, with baseline mean body mass index of 27.3 kg/m2 (SD = 6.3). We assessed dietary intake by sets of four 24-h dietary recalls and validated with plasma carotenoid concentrations. Weight and height were measured at baseline, 1 yr, and 4 yr. Dietary energy density was calculated using food but excluding beverages. Intervention participants significantly reduced dietary energy density compared to controls and maintained it over 4 yr—both in cross-sectional (P < 0.0001) and longitudinal (Group × Time interaction, P < 0.0001) analyses. Total energy intake or physical activity did not vary between groups. The intervention group had a small but significant weight loss at 1 yr (Group × Time interaction, P < 0.0001), but no between-group weight difference was observed at 4 yr. Our study showed that reducing dietary energy density did not result in a reduction in total energy intake and suggests that this strategy alone is not sufficient to promote long-term weight loss in a free-living population. PMID:18444133

  9. The impact of a long-term reduction in dietary energy density on body weight within a randomized diet trial.

    PubMed

    Saquib, Nazmus; Natarajan, Loki; Rock, Cheryl L; Flatt, Shirley W; Madlensky, Lisa; Kealey, Sheila; Pierce, John P

    2008-01-01

    We examined the effect of dietary energy density change on body weight in participants of a randomized trial. Intervention participants markedly increased fruit and vegetable intake while reducing energy intake from fat. Participants were 2,718 breast cancer survivors, aged 26-74 yr, with baseline mean body mass index of 27.3 kg/m(2) (SD = 6.3). We assessed dietary intake by sets of four 24-h dietary recalls and validated with plasma carotenoid concentrations. Weight and height were measured at baseline, 1 yr, and 4 yr. Dietary energy density was calculated using food but excluding beverages. Intervention participants significantly reduced dietary energy density compared to controls and maintained it over 4 yr -- both in cross-sectional (P < 0.0001) and longitudinal (Group x Time interaction, P < 0.0001) analyses. Total energy intake or physical activity did not vary between groups. The intervention group had a small but significant weight loss at 1 yr (Group x Time interaction, P < 0.0001), but no between-group weight difference was observed at 4 yr. Our study showed that reducing dietary energy density did not result in a reduction in total energy intake and suggests that this strategy alone is not sufficient to promote long-term weight loss in a free-living population. PMID:18444133

  10. Diet-Induced Obesity in Mice Reduces the Maintenance of Influenza-Specific CD8+ Memory T Cells12

    PubMed Central

    Karlsson, Erik A.; Sheridan, Patricia A.; Beck, Melinda A.

    2010-01-01

    Obesity has been associated with increasing the risk for type 2 diabetes and heart disease, but its influence on the immune response to viral infection is understudied. Memory T cells generated during a primary influenza infection are important for protection against subsequent influenza exposures. Previously, we have demonstrated that diet-induced obese (DIO) mice have increased morbidity and mortality following secondary influenza infection compared with lean mice. To determine whether the problem resided in a failure to maintain functional, influenza-specific CD8+ memory T cells, male DIO and lean mice were infected with influenza X-31. At 84 d postinfection, DIO mice had a 10% reduction in memory T cell numbers. This reduction may have resulted from significantly reduced memory T cell expression of interleukin 2 receptor β (IL-2R β, CD122), but not IL-7 receptor α (CD127), which are both required for memory cell maintenance. Peripheral leptin resistance in the DIO mice may be a contributing factor to the impairment. Indeed, leptin receptor mRNA expression was significantly reduced in the lungs of obese mice, whereas suppressor of cytokine signaling (Socs)1 and Socs3 mRNA expression were increased. It is imperative to understand how the obese state alters memory T cells, because impairment in maintenance of functional memory responses has important implications for vaccine efficacy in an obese population. PMID:20592105

  11. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    PubMed Central

    da Silva, Danielle Cristina Tomaz; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; de Campos, Dijon Henrique Salomé; do Nascimento, André Ferreira; de Oliveira, Sílvio Assis; Padovani, Carlos Roberto; Cicogna, Antonio Carlos

    2014-01-01

    Background Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Objective Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Methods Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C15 and Ob15) and 30 (C30 and Ob30) consecutive weeks. Obesity was determined by adiposity index. Results The Ob15 group was similar to the C15 group regarding the expression of myocardial collagen type I; however, expression in the Ob30 group was less than C30 group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob30 when compared with Ob15. Obesity did not affect collagen type III expression. Conclusion This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression. PMID:24676371

  12. Influence of beta(2)-adrenoceptor gene polymorphisms on diet-induced thermogenesis.

    PubMed

    Oomen, J M; Waijers, P M C M; van Rossum, C; Hoebee, B; Saris, W H M; van Baak, M A

    2005-11-01

    The sympathetic nervous system is involved in the control of energy metabolism and expenditure. Diet-induced thermogenesis is mediated partly by the ss-adrenergic component of this system. The aim of the present study was to investigate the role of genetic variation in the beta(2)-adrenoceptor in diet-induced thermogenesis. Data from twenty-four subjects (fourteen men and ten women; BMI 26.7(sem 0.8) kg/m(2); age 45.2(sem1.4) years) with different polymorphisms of the beta(2)-adrenoceptor at codon 16 (Gly16Gly, Gly16Arg or Arg16Arg) were recruited for this study. Subjects were given a high-carbohydrate liquid meal, and the energy expenditure, respiratory exchange ratio, and plasma concentrations of NEFA, glycerol, glucose, insulin and catecholamines were measured before and over 4 h after the meal. The AUC of energy expenditure (diet-induced thermogenesis) was not significantly different between polymorphism groups, nor was the response of any of the other measured variables to the meal. In a multiple regression model, the only variable that explained a significant proportion (32 %) of the variation in diet-induced thermogenesis was the increase in plasma adrenaline in response to the meal (P<0.05). The beta(2)-adrenoceptor codon16 polymorphisms did not contribute significantly. In conclusion, an independent contribution of the codon 16 polymorphism of the beta(2)-adrenoceptor gene to the variation in thermogenic response to a high-carbohydrate meal could not be demonstrated. The interindividual variation in thermogenic response to the meal was correlated with variations in the plasma adrenaline response to the meal.

  13. Long-term voluntary running improves diet-induced adiposity in young adult mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of long-term voluntary running on diet-induced adiposity in male C57BL/6 mice. Four-week old mice (n = 15 per group) were fed the AIN93G diet or a 45% high-fat diet (% kcal.) with or without access to in-cage activity wheels for 14 weeks. The high-fat die...

  14. 3,5-Diiodo-L-Thyronine (3,5-T2) Exerts Thyromimetic Effects on Hypothalamus-Pituitary-Thyroid Axis, Body Composition, and Energy Metabolism in Male Diet-Induced Obese Mice

    PubMed Central

    Lietzow, Julika; Wohlgemuth, Franziska; Hoefig, Carolin S.; Wiedmer, Petra; Schweizer, Ulrich; Köhrle, Josef; Schürmann, Annette

    2015-01-01

    Effective and safe antiobesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with T3 administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2-treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase activity after application of 3,5-T2 (2.5 μg/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether, the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity. PMID:25322465

  15. Improved Function With Enhanced Protein Intake per Meal: A Pilot Study of Weight Reduction in Frail, Obese Older Adults

    PubMed Central

    Pieper, Carl F.; Orenduff, Melissa C.; McDonald, Shelley R.; McClure, Luisa B.; Zhou, Run; Payne, Martha E.; Bales, Connie W.

    2016-01-01

    Background: Obesity is a significant cause of functional limitations in older adults; yet, concerns that weight reduction could diminish muscle along with fat mass have impeded progress toward an intervention. Meal-based enhancement of protein intake could protect function and/or lean mass but has not been studied during geriatric obesity reduction. Methods: In this 6-month randomized controlled trial, 67 obese (body mass index ≥30kg/m2) older (≥60 years) adults with a Short Physical Performance Battery score of 4–10 were randomly assigned to a traditional (Control) weight loss regimen or one with higher protein intake (>30g) at each meal (Protein). All participants were prescribed a hypo-caloric diet, and weighed and provided dietary guidance weekly. Physical function (Short Physical Performance Battery) and lean mass (BOD POD), along with secondary measures, were assessed at 0, 3, and 6 months. Results: At the 6-month endpoint, there was significant (p < .001) weight loss in both the Control (−7.5±6.2kg) and Protein (−8.7±7.4kg) groups. Both groups also improved function but the increase in the Protein (+2.4±1.7 units; p < .001) was greater than in the Control (+0.9±1.7 units; p < .01) group (p = .02). Conclusion: Obese, functionally limited older adults undergoing a 6-month weight loss intervention with a meal-based enhancement of protein quantity and quality lost similar amounts of weight but had greater functional improvements relative to the Control group. If confirmed, this dietary approach could have important implications for improving the functional status of this vulnerable population (ClinicalTrials.gov identifier: NCT01715753). PMID:26786203

  16. Soluble Fermentable Dietary Fibre (Pectin) Decreases Caloric Intake, Adiposity and Lipidaemia in High-Fat Diet-Induced Obese Rats.

    PubMed

    Adam, Clare L; Thomson, Lynn M; Williams, Patricia A; Ross, Alexander W

    2015-01-01

    Consumption of a high fat diet promotes obesity and poor metabolic health, both of which may be improved by decreasing caloric intake. Satiety-inducing ingredients such as dietary fibre may be beneficial and this study investigates in diet-induced obese (DIO) rats the effects of high or low fat diet with or without soluble fermentable fibre (pectin). In two independently replicated experiments, young adult male DIO rats that had been reared on high fat diet (HF; 45% energy from fat) were given HF, low fat diet (LF; 10% energy from fat), HF with 10% w/w pectin (HF+P), or LF with 10% w/w pectin (LF+P) ad libitum for 4 weeks (n = 8/group/experiment). Food intake, body weight, body composition (by magnetic resonance imaging), plasma hormones, and plasma and liver lipid concentrations were measured. Caloric intake and body weight gain were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Body fat mass increased in HF, was maintained in LF, but decreased significantly in LF+P and HF+P groups. Final plasma leptin, insulin, total cholesterol and triglycerides were lower, and plasma satiety hormone PYY concentrations were higher, in LF+P and HF+P than in LF and HF groups, respectively. Total fat and triglyceride concentrations in liver were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Therefore, the inclusion of soluble fibre in a high fat (or low fat) diet promoted increased satiety and decreased caloric intake, weight gain, adiposity, lipidaemia, leptinaemia and insulinaemia. These data support the potential of fermentable dietary fibre for weight loss and improving metabolic health in obesity.

  17. Soluble Fermentable Dietary Fibre (Pectin) Decreases Caloric Intake, Adiposity and Lipidaemia in High-Fat Diet-Induced Obese Rats

    PubMed Central

    Adam, Clare L.; Thomson, Lynn M.; Williams, Patricia A.; Ross, Alexander W.

    2015-01-01

    Consumption of a high fat diet promotes obesity and poor metabolic health, both of which may be improved by decreasing caloric intake. Satiety-inducing ingredients such as dietary fibre may be beneficial and this study investigates in diet-induced obese (DIO) rats the effects of high or low fat diet with or without soluble fermentable fibre (pectin). In two independently replicated experiments, young adult male DIO rats that had been reared on high fat diet (HF; 45% energy from fat) were given HF, low fat diet (LF; 10% energy from fat), HF with 10% w/w pectin (HF+P), or LF with 10% w/w pectin (LF+P) ad libitum for 4 weeks (n = 8/group/experiment). Food intake, body weight, body composition (by magnetic resonance imaging), plasma hormones, and plasma and liver lipid concentrations were measured. Caloric intake and body weight gain were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Body fat mass increased in HF, was maintained in LF, but decreased significantly in LF+P and HF+P groups. Final plasma leptin, insulin, total cholesterol and triglycerides were lower, and plasma satiety hormone PYY concentrations were higher, in LF+P and HF+P than in LF and HF groups, respectively. Total fat and triglyceride concentrations in liver were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Therefore, the inclusion of soluble fibre in a high fat (or low fat) diet promoted increased satiety and decreased caloric intake, weight gain, adiposity, lipidaemia, leptinaemia and insulinaemia. These data support the potential of fermentable dietary fibre for weight loss and improving metabolic health in obesity. PMID:26447990

  18. Effects of auricular acupressure on weight reduction and abdominal obesity in Asian young adults: a randomized controlled trial.

    PubMed

    Hsieh, Ching Hsiu; Su, Tsann-Jnn; Fang, Yu-Wen; Chou, Pei-Hsuan

    2011-01-01

    The current study was designed to test the efficacy of auricular acupressure on weight reduction and changes of waist circumference and waist-to-hip ratio. This study used a randomized design with one control group and one experimental group consisting of Asian young adults with a waist circumference ≥80 cm in the females and ≥90cm in the males. At completion of eight weeks of auricular therapy, the total sample size was 55 young adults who ranged in age from 18 to 20 years old. Each participant was treated weekly for ear acupressure in ten-minute sessions. Sessions continued for eight weeks wherein the control group received acupressure only while the experimental group received acupressure with the Japanese Magnetic Pearl on the ear acupoints. While both the control and treatment groups showed significant reduction (p ≤ 0.05) to body weight and waist circumference after eight weeks of treatment, only the group treated with Japanese Magnetic Pearls showed decreased waist to hip ratio. Thus, auricular acupressure may be a beneficial addition to weight loss programs for young adults. Auricular acupressure is thus a reasonable option in the treatment of overweight and obesity in young adults. PMID:21598412

  19. Weight reduction among people with severe and persistent mental illness after health behavior counseling and monitoring.

    PubMed

    Katekaru, Matthew; Minn, Carol E; Pobutsky, Ann M

    2015-04-01

    The high prevalence of obesity and associated chronic conditions in persons with severe and persistent mental illness has contributed to a mortality rate that is nearly two times higher than the overall population. In 2008, the Central O'ahu Community Mental Health Center of the Hawai'i State Department of Health, Adult Mental Health Division began an unfunded, health counseling intervention pilot project to address such concerns for the health of persons with severe and persistent mental illness. This article reviews the results of this intervention. Forty-seven persons with schizophrenia or related disorders were included in the intervention which involved health counseling and monitoring of weight as a risk factor for chronic disease. After five years of counseling and monitoring, medical chart reviews were conducted for each person for data on weight change. Analysis showed weight loss and improvements in body mass index. The results of this project show potential for long-term counseling and monitoring as an intervention for obesity in persons with severe and persistent mental illness.

  20. Weight loss and brown adipose tissue reduction in rat model of sleep apnea

    PubMed Central

    Martinez, Denis; Vasconcellos, Luiz FT; de Oliveira, Patricia G; Konrad, Signorá P

    2008-01-01

    Background - Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS), but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH) is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT) of Wistar rats. Methods Nine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle. Results Body weight of the hypoxia group decreased 17 ± 7 grams, significantly different from the variation observed in the control group (p = 0,001). The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054). Conclusion Our preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT. PMID:18671859

  1. Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects

    PubMed Central

    Lopez-Legarrea, P; de la Iglesia, R; Crujeiras, A B; Pardo, M; Casanueva, F F; Zulet, M A; Martinez, J A

    2014-01-01

    Irisin is assumed to be a relevant link between muscle and weight maintenance as well as to mediate exercise benefits on health. The aim of this study was to assess the possible associations between irisin levels and glucose homeostasis in obese subjects with metabolic syndrome (MetS) following an energy-restricted treatment. Ninety-six adults with excessive body weight and MetS features underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA randomized controlled trial (www.clinicaltrials.gov; NCT01087086). After the intervention, dietary restriction significantly reduced body weight and evidenced a dietary-induced decrease in circulating levels of irisin in parallel with improvements on glucose homeostasis markers. Interestingly, participants with higher irisin values at baseline (above the median) showed a greater reduction on glucose (P=0.022) and insulin (P=0.021) concentrations as well as on the homeostasis model assessment index (P=0.008) and triglycerides (P=0.006) after the dietary intervention, compared with those presenting low-irisin baseline values (below the median). Interestingly, a positive correlation between irisin and carbohydrate intake was found at the end of the experimental period. In conclusion, irisin appears to be involved in glucose metabolism regulation after a dietary-induced weight loss. PMID:24567125

  2. Reduction of speckle noise from optical coherence tomography images using multi-frame weighted nuclear norm minimization method

    NASA Astrophysics Data System (ADS)

    Thapa, Damber; Raahemifar, Kaamran; Lakshminarayanan, Vasudevan

    2015-12-01

    In this paper, we propose a speckle noise reduction method for spectral-domain optical coherence tomography (SD-OCT) images called multi-frame weighted nuclear norm minimization (MWNNM). This method is a direct extension of weighted nuclear norm minimization (WNNM) in the multi-frame framework since an adequately denoised image could not be achieved with single-frame denoising methods. The MWNNM method exploits multiple B-scans collected from a small area of a SD-OCT volumetric image, and then denoises and averages them together to obtain a high signal-to-noise ratio B-scan. The results show that the image quality metrics obtained by denoising and averaging only five nearby B-scans with MWNNM method is considerably better than those of the average image obtained by registering and averaging 40 azimuthally repeated B-scans.

  3. Lifestyle interventions for cardiovascular disease risk reduction: a systematic review of the effects of diet composition, food provision, and treatment modality on weight loss.

    PubMed

    Dutton, Gareth R; Laitner, Melissa H; Perri, Michael G

    2014-10-01

    The purpose of this systematic review was to evaluate, synthesize, and interpret findings from recent randomized controlled trials (RCTs) of dietary and lifestyle weight loss interventions examining the effects of (1) diet composition, (2) use of food provision, and (3) modality of treatment delivery on weight loss. Trials comparing different dietary approaches indicated that reducing carbohydrate intake promoted greater initial weight loss than other approaches but did not appear to significantly improve long-term outcomes. Food provision appears to enhance adherence to reduction in energy intake and produce greater initial weight losses. The long-term benefits of food provision are less clear. Trials comparing alternative treatment modalities suggest that phone-based treatment produce short- and long-term weight reductions equivalent to face-to-face interventions. The use of Internet and mobile technologies are associated with smaller reductions in body weight than face-to-face interventions. Based on this review, clinical implications and future research directions are provided.

  4. Effect of the supplementation of dietary rich phytoestrogens in altering the vitamin D levels in diet induced osteoporotic rat model.

    PubMed

    Chennaiah, S; Vijayalakshmi, V; Suresh, C

    2010-07-01

    Plant-derived estrogen-like compounds such as isoflavones (IF) especially daidzein and genistein are said to be preserving the bone in the osteoporotic conditions. However, it is not known whether a combination of IF and calcium (Ca) supplementation attenuates losses in bone mass and prevents the loss of vitamin D (VD). The present study addresses the role of phytoestrogens (PE) and Ca supplementation in low Ca and low VD diet induced osteoporosis (OSP). Cowpea (CP) which has high amount of the IF was selected to study its effect on diet induced osteoporotic conditions. Female weanling WNIN rats (total of 68) were divided into five groups and fed for five weeks on semisynthetic diet with low Ca (0.15%) and low VD (0.1IU/day/rat) in combination with low (10 mg/kg) or high (25 mg/kg) concentrations of PEs derived from CPIF. The study groups are: (I) normal Ca(0.47%) and normal VD (25IU/day/rat), (II) low Ca+low VD, (III) low Ca+low VD+low CPIF (10 mg/kg diet), (IV) low Ca+low VD+high CPIF (25 mg/kg diet) and (V) low Ca+low VD+17-(-estradiol (3.2 mg/kg diet). After the development of OSP the group II was subgrouped into: (SG I) continued on low Ca+VD, (SG II) low CPIF, (SG III) high CPIF, (SG IV) 17-beta-estradiol and (SG V) normal Ca and VD. Serum 25-VD levels were in the range of 14-38 ng/ml in groups I, III, IV and V, where as the values were very low in the group II (5.8 ng/ml). These were partially reversed upon supplementation of CPIF. The results correlated with altered Ca levels, body weight, bone mineral density and content and other related biochemical parameters. The paper further explains the possibility of protective and therapeutic role of VD in the presence of CPIF in osteoporotic health manifestations. PMID:20362669

  5. Effect of at-the-source noise reduction on performance and weights of a tilt-rotor aircraft

    NASA Technical Reports Server (NTRS)

    Gibs, J.; Stepniewski, W. Z.; Spencer, R.

    1975-01-01

    Reduction of far-field acoustic signature through modification of basic design parameters (tip speed, number of blades, disc loading and rotor blade area) was examined, using a tilt-rotor flight research aircraft as a baseline configuration. Of those design parameters, tip speed appeared as the most important. Next, preliminary design of two aircraft was performed, postulating the following reduction of noise level from that of the baseline machine, at 500 feet from the spot of OGE hover. In one aircraft, the PNL was lowered by 10 PNdB and in the other, OASPL decreased by 10 dB. The resulting weight and performance penalties were examined. Then, PNL and EPNL aspects of terminal operation were compared for the baseline and quieter aircraft.

  6. White adipose tissue re-growth after partial lipectomy in high fat diet induced obese wistar rats.

    PubMed

    Bueno, Allain Amador; Habitante, Carlos Alexandre; Oyama, Lila Missae; Estadella, Débora; Ribeiro, Eliane Beraldi; Oller do Nascimento, Cláudia Maria

    2011-01-01

    The effects of partial removal of epididymal (EPI) and retroperitoneal (RET) adipose tissues (partial lipectomy) on the triacylglycerol deposition of high fat diet induced obese rats were analyzed, aiming to challenge the hypothesized body fat regulatory system. Male 28-day-old wistar rats received a diet enriched with peanuts, milk chocolate and sweet biscuits during the experimental period. At the 90th day of life, rats were submitted to either lipectomy (L) or sham surgery. After 7 or 30 days, RET, EPI, liver, brown adipose tissue (BAT), blood and carcass were obtained and analyzed. Seven days following surgery, liver lipogenesis rate and EPI relative weight were increased in L. After 30 days, L, RET and EPI presented increased lipogenesis, lipolysis and percentage of small area adipocytes. L rats also presented increased liver malic enzyme activity, BAT lipogenesis, and triacylglycerol and corticosterone serum levels. The partial removal of visceral fat pads affected the metabolism of high fat diet obese rats, which leads to excised tissue re-growth and possibly compensatory growth of non-excised depots at a later time.

  7. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.

    PubMed

    Paul, Heather A; Bomhof, Marc R; Vogel, Hans J; Reimer, Raylene A

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy.

  8. Antiobesity Effect of Garlic Extract Fermented by Lactobacillus plantarum BL2 in Diet-Induced Obese Mice.

    PubMed

    Lee, Hee-Seop; Lim, Won-Chul; Lee, Sung-Jin; Lee, Seung-Hyun; Lee, Jin-Hyup; Cho, Hong-Yon

    2016-09-01

    Obesity is viewed as a serious public health problem. This study aimed to investigate the antiobesity effects of fermented garlic extract by lactic acid bacteria (LAFGE) on obesity. Male C57BL/6J mice were fed with high-fat diet (HFD) to induce obesity. The HFD-induced obese mice were orally administrated with 250 or 500 mg/kg LAFGE for 8 weeks. Feeding HFD-fed mice with 250 or 500 mg/kg LAFGE reduced body weight by 14% and 18%, respectively, compared to HFD. HFD-fed mice with 500 mg/kg LAFGE administration had lower epididymal, retroperitoneal, and mesenteric adipose tissue mass by 36%, 44%, and 63%, respectively, compared to HFD. The concentration of plasma triacylglyceride and total cholesterol was significantly lower in the HFD-fed mice with LAFGE administration. Moreover, LAFGE supplementation suppressed adipogenesis by downregulation in mRNA and protein expression of PPARγ, C/EBPα, and lipogenic proteins, including SREBP-1c, FAS, and SCD-1. Based on these findings, LAFGE may ameliorate diet-induced obesity by inhibiting adipose tissue hypertrophy by suppressing adipogenesis. PMID:27627701

  9. Hypolipidaemic effects of methanol extract of Holoptelea integrifolia (Roxb.) Planchon bark in diet-induced obese rats.

    PubMed

    Subash, Arun Koorappally; Augustine, Anu

    2013-01-01

    The leaf and bark paste of Holoptelea integrifolia is traditionally used for the treatment of obesity in Asian countries. However, no scientific studies have been undertaken to reveal the actual mechanism of action. The present study aimed to investigate the hypolipidaemic effect of H. integrifolia and its mechanism in diet-induced obese rat model. After 4 weeks of oral administration, blood samples were collected for the estimation of serum lipids, lecithin: cholesterolacyltransferase (LCAT) apolipoproteins (apo) and liver for HMG-CoA reductase (HMGR) assay. The faecal samples were also collected to estimate the faecal fat content. The H. integrifolia treatment markedly lowered body weight, serum lipids and apo B and increase high-density lipoprotein-cholesterol and apo A1 concentrations. In this study, HMGR activity was enormously reduced, which helps to reduce cholesterol biosynthesis and an increase in LCAT activity was also observed. The detailed faecal analysis showed a remarkable increase in faecal lipids, which indicates the ability to inhibit intestinal fat absorption. The methanol fraction of H. integrifolia on LC-MS and tandem mass spectrometry analysis shows the presence of a compound, 3-(7-ethoxy-4-methyl-2-oxo-2H-chromen-3-yl)propanoate (C1). The result showed that the significant hypolipidaemic effect of H. integrifolia may be linked to its ability to inhibit HMGR activity and block intestinal fat absorption.

  10. The Anti-Inflammatory Effect of Prunus yedoensis Bark Extract on Adipose Tissue in Diet-Induced Obese Mice

    PubMed Central

    Kang, Hee; Kwak, Tae-Kyung; Kim, Bo-Geun; Lee, Kyung-Jin

    2015-01-01

    Chronic, low-grade inflammatory responses occur in obese adipose tissue and play a crucial role in the development of insulin resistance. Macrophages exposed to high glucose upregulate the expression of SRA, a macrophage-specific scavenger receptor. The present study investigated whether Prunus yedoensis (PY) bark extract affects the inflammatory response and scavenger receptor gene expression observed in a diet-induced obesity model in vivo. Oral administration of PY extract significantly reduced fasting blood glucose levels without a change in body weight in mice fed a high fat diet for 17 weeks. PY extract significantly suppressed expression of inflammatory and macrophage genes such as tumor necrosis factor-α, interleukin-6, and F4/80 in epididymal adipose tissue. Among scavenger receptor genes, SRA expression was significantly reduced. The inhibitory responses of PY extract and its fractions were determined through evaluation of scavenger receptor expression in THP-1 cells. PY extract and its ethyl acetate fraction decreased the levels of SRA mRNA and phospho-ERK1/2 during monocyte differentiation. Our data indicate that the anti-inflammatory effects of PY extract and its downregulation of SRA seem to account for its hypoglycemic effects. PMID:26413130

  11. Dual melanocortin-4 receptor and GLP-1 receptor agonism amplifies metabolic benefits in diet-induced obese mice

    PubMed Central

    Clemmensen, Christoffer; Finan, Brian; Fischer, Katrin; Tom, Robby Zachariah; Legutko, Beata; Sehrer, Laura; Heine, Daniela; Grassl, Niklas; Meyer, Carola W; Henderson, Bart; Hofmann, Susanna M; Tschöp, Matthias H; Van der Ploeg, Lex HT; Müller, Timo D

    2015-01-01

    We assessed the efficacy of simultaneous agonism at the glucagon-like peptide-1 receptor (GLP-1R) and the melanocortin-4 receptor (MC4R) for the treatment of obesity and diabetes in rodents. Diet-induced obese (DIO) mice were chronically treated with either the long-acting GLP-1R agonist liraglutide, the MC4R agonist RM-493 or a combination of RM-493 and liraglutide. Co-treatment of DIO mice with RM-493 and liraglutide improves body weight loss and enhances glycemic control and cholesterol metabolism beyond what can be achieved with either mono-therapy. The superior metabolic efficacy of this combination therapy is attributed to the anorectic and glycemic actions of both drugs, along with the ability of RM-493 to increase energy expenditure. Interestingly, compared to mice treated with liraglutide alone, hypothalamic Glp-1r expression was higher in mice treated with the combination therapy after both acute and chronic treatment. Further, RM-493 enhanced hypothalamic Mc4r expression. Hence, co-dosing with MC4R and GLP-1R agonists increases expression of each receptor, indicative of minimized receptor desensitization. Together, these findings suggest potential opportunities for employing combination treatments that comprise parallel MC4R and GLP-1R agonism for the treatment of obesity and diabetes. PMID:25652173

  12. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

    PubMed Central

    Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.

    2015-01-01

    Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

  13. Differences in Hematopoietic Stem Cells Contribute to Sexually Dimorphic Inflammatory Responses to High Fat Diet-induced Obesity.

    PubMed

    Singer, Kanakadurga; Maley, Nidhi; Mergian, Taleen; DelProposto, Jennifer; Cho, Kae Won; Zamarron, Brian F; Martinez-Santibanez, Gabriel; Geletka, Lynn; Muir, Lindsey; Wachowiak, Phillip; Demirjian, Chaghig; Lumeng, Carey N

    2015-05-22

    Women of reproductive age are protected from metabolic disease relative to postmenopausal women and men. Most preclinical rodent studies are skewed toward the use of male mice to study obesity-induced metabolic dysfunction because of a similar protection observed in female mice. How sex differences in obesity-induced inflammatory responses contribute to these observations is unknown. We have compared and contrasted the effects of high fat diet-induced obesity on glucose metabolism and leukocyte activation in multiple depots in male and female C57Bl/6 mice. With both short term and long term high fat diet, male mice demonstrated increased weight gain and CD11c(+) adipose tissue macrophage content compared with female mice despite similar degrees of adipocyte hypertrophy. Competitive bone marrow transplant studies demonstrated that obesity induced a preferential contribution of male hematopoietic cells to circulating leukocytes and adipose tissue macrophages compared with female cells independent of the sex of the recipient. Sex differences in macrophage and hematopoietic cell in vitro activation in response to obesogenic cues were observed to explain these results. In summary, this report demonstrates that male and female leukocytes and hematopoietic stem cells have cell-autonomous differences in their response to obesity that contribute to an amplified response in males compared with females.

  14. Nedd4 haploinsufficient mice display moderate insulin resistance, enhanced lipolysis, and protection against high-fat diet-induced obesity.

    PubMed

    Li, Jing Jing; Ferry, Robert J; Diao, Shiyong; Xue, Bingzhong; Bahouth, Suleiman W; Liao, Francesca-Fang

    2015-04-01

    Neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) is the prototypical protein in the Nedd4 ubiquitin ligase (E3) family, which governs ubiquitin-dependent endocytosis and/or degradation of plasma membrane proteins. Loss of Nedd4 results in embryonic or neonatal lethality in mice and reduced insulin/IGF-1 signaling in embryonic fibroblasts. To delineate the roles of Nedd4 in vivo, we examined the phenotypes of heterozygous knockout mice using a high-fat diet-induced obesity (HFDIO) model. We observed that Nedd4+/- mice are moderately insulin resistant but paradoxically protected against HFDIO. After high-fat diet feeding, Nedd4+/- mice showed less body weight gain, less fat mass, and smaller adipocytes vs the wild type. Despite ameliorated HFDIO, Nedd4+/- mice did not manifest improvement in glucose tolerance vs the wild type in both genders. Nedd4+/- male, but not female, mice displayed significantly lower fasting blood glucose levels and serum insulin levels. Under obesogenic conditions, Nedd4+/- mice displayed elevated stimulated lipolytic activity, primarily through a β2-adrenergic receptor. Combined, these data support novel complex roles for Nedd4 in metabolic regulation involving altered insulin and β-adrenergic signaling pathways.

  15. RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice.

    PubMed

    Cui, Xiao-Bing; Luan, Jun-Na; Ye, Jianping; Chen, Shi-You

    2015-02-01

    Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32(-/-) (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32(-/-) mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32(-/-) induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.

  16. Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs.

    PubMed

    Bruin, Jennifer E; Saber, Nelly; Braun, Natalie; Fox, Jessica K; Mojibian, Majid; Asadi, Ali; Drohan, Campbell; O'Dwyer, Shannon; Rosman-Balzer, Diana S; Swiss, Victoria A; Rezania, Alireza; Kieffer, Timothy J

    2015-04-14

    Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs.

  17. Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice*

    PubMed Central

    Su, Hong-ming; Feng, Li-na; Zheng, Xiao-dong; Chen, Wei

    2016-01-01

    Background: Myricetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. Objective: This study was undertaken to investigate the effect of myricetin on high-fat diet (HFD)-induced obesity in C57BL/6 mice. Results: Administration of myricetin dramatically reduced the body weight of diet-induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly decreased in myricetin-treated mice. Moreover, obesity-associated oxidative stress (glutathione peroxidase (GPX) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA)) and inflammation (tumor necrosis factor-α (TNF-α)) were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of myricetin against HFD-induced obesity in mice appeared to be partially mediated through the down-regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP-1c). Conclusions: Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications. PMID:27256677

  18. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    PubMed Central

    Bruin, Jennifer E.; Saber, Nelly; Braun, Natalie; Fox, Jessica K.; Mojibian, Majid; Asadi, Ali; Drohan, Campbell; O’Dwyer, Shannon; Rosman-Balzer, Diana S.; Swiss, Victoria A.; Rezania, Alireza; Kieffer, Timothy J.

    2015-01-01

    Summary Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs. PMID:25801507

  19. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats

    PubMed Central

    Paul, Heather A.; Bomhof, Marc R.; Vogel, Hans J.; Reimer, Raylene A.

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID:26868870

  20. Thrombospondin 1 mediates high-fat diet-induced muscle fibrosis and insulin resistance in male mice.

    PubMed

    Inoue, Mayumi; Jiang, Yibin; Barnes, Richard H; Tokunaga, Masakuni; Martinez-Santibañez, Gabriel; Geletka, Lynn; Lumeng, Carey N; Buchner, David A; Chun, Tae-Hwa

    2013-12-01

    Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression. PMID:24140711

  1. Hypolipidaemic effects of methanol extract of Holoptelea integrifolia (Roxb.) Planchon bark in diet-induced obese rats.

    PubMed

    Subash, Arun Koorappally; Augustine, Anu

    2013-01-01

    The leaf and bark paste of Holoptelea integrifolia is traditionally used for the treatment of obesity in Asian countries. However, no scientific studies have been undertaken to reveal the actual mechanism of action. The present study aimed to investigate the hypolipidaemic effect of H. integrifolia and its mechanism in diet-induced obese rat model. After 4 weeks of oral administration, blood samples were collected for the estimation of serum lipids, lecithin: cholesterolacyltransferase (LCAT) apolipoproteins (apo) and liver for HMG-CoA reductase (HMGR) assay. The faecal samples were also collected to estimate the faecal fat content. The H. integrifolia treatment markedly lowered body weight, serum lipids and apo B and increase high-density lipoprotein-cholesterol and apo A1 concentrations. In this study, HMGR activity was enormously reduced, which helps to reduce cholesterol biosynthesis and an increase in LCAT activity was also observed. The detailed faecal analysis showed a remarkable increase in faecal lipids, which indicates the ability to inhibit intestinal fat absorption. The methanol fraction of H. integrifolia on LC-MS and tandem mass spectrometry analysis shows the presence of a compound, 3-(7-ethoxy-4-methyl-2-oxo-2H-chromen-3-yl)propanoate (C1). The result showed that the significant hypolipidaemic effect of H. integrifolia may be linked to its ability to inhibit HMGR activity and block intestinal fat absorption. PMID:23239412

  2. Diet-induced obesity alters behavior as well as serum levels of corticosterone in F344 rats.

    PubMed

    Buchenauer, T; Behrendt, P; Bode, F J; Horn, R; Brabant, G; Stephan, M; Nave, H

    2009-12-01

    Obesity is an increasing socio-economic health problem. Diet-induced obese (DIO) rodents are widely used as a model of obesity in humans. However, there is no comprehensive data about the behavioral phenotype of DIO rodents. Therefore, the aim of the present study was to determine whether a high-fat-diet changes behavioral patterns of DIO Fischer 344 (F344) rats in comparison with lean littermates. The behavioral tests (homecage, holeboard, social interaction, and hotplate) were performed in 28 normal-weight and 28 male DIO F344 rats (mean age: 16 weeks) and revealed a significantly higher level of anxiety- and aggression-related parameters in obese rats, whereas their pain threshold was significantly lower. Fitting to a different behavioral response, basal corticosterone levels (measured by RIA) of obese animals were significantly elevated (16.0ng/ml vs. 12.5ng/ml; p<0.01). We conclude that obese rats differ in various aspects from their lean littermates. The altered behavioral characteristics displayed by DIO F344 rats have to be considered in further experiments involving DIO rodents. PMID:19751751

  3. Phlorizin Supplementation Attenuates Obesity, Inflammation, and Hyperglycemia in Diet-Induced Obese Mice Fed a High-Fat Diet.

    PubMed

    Shin, Su-Kyung; Cho, Su-Jung; Jung, Un Ju; Ryu, Ri; Choi, Myung-Sook

    2016-02-16

    Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w), high-fat diet (HFD, 20% fat, w/w), or HFD supplemented with phlorizin (PH, 0.02%, w/w). The findings revealed that the PH group had significantly decreased visceral and total white adipose tissue (WAT) weights, and adipocyte size compared to the HFD. Plasma and hepatic lipids profiles also improved in the PH group. The decreased levels of hepatic lipids in PH were associated with decreased activities of enzymes involved in hepatic lipogenesis, cholesterol synthesis and esterification. The PH also suppressed plasma pro-inflammatory adipokines levels such as leptin, adipsin, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon-γ, and interleukin-6, and prevented HFD-induced collagen accumulation in the liver and WAT. Furthermore, the PH supplementation also decreased plasma glucose, insulin, glucagon, and homeostasis model assessment of insulin resistance levels. In conclusion, phlorizin is beneficial for preventing diet-induced obesity, hepatic steatosis, inflammation, and fibrosis, as well as insulin resistance.

  4. Intestine-specific Deletion of Acyl-CoA:Monoacylglycerol Acyltransferase (MGAT) 2 Protects Mice from Diet-induced Obesity and Glucose Intolerance*

    PubMed Central

    Nelson, David W.; Gao, Yu; Yen, Mei-I; Yen, Chi-Liang Eric

    2014-01-01

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2−/−) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2IKO). We found that, like Mogat2−/− mice, Mogat2IKO mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2IKO mice increased energy expenditure although to a lesser degree than Mogat2−/− mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism. PMID:24784138

  5. Intestine-specific deletion of acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 protects mice from diet-induced obesity and glucose intolerance.

    PubMed

    Nelson, David W; Gao, Yu; Yen, Mei-I; Yen, Chi-Liang Eric

    2014-06-20

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2(-/-)) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2(IKO)). We found that, like Mogat2(-/-) mice, Mogat2(IKO) mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2(IKO) mice increased energy expenditure although to a lesser degree than Mogat2(-/-) mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism.

  6. The Effect of Weight Reduction on Ultrasonographic Findings of Nonalcoholic Fatty Liver

    PubMed Central

    Tahaei, SA; Sedighi, N; Derogar, R; Aslani, A; Malekzadeh, R; Merat, S

    2010-01-01

    BACKGROUND Non-alcoholic fatty liver (NAFL) includes a spectrum of diseases ranging from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NAFL is typically seen in association with obesity, diabetes and hypertriglyceridaemia. In order to seek the role of diet therapy in treatment of NAFL, we compared the ultrasonographic findings of patients with fatty liver disease before and after standard diet therapy. METHODS Twenty-three overweight or obese subjects with incidental fatty liver discovered during ultrasonography were included. Subjects underwent 3 months of diet therapy, and anthropometric data including weight, height, BMI, waist circumference, and hip circumference were measured. Ultrasonographic findings were graded from 0 to 3. Changes in ultrasonographic findings and anthropometric data were studied. RESULTS After three months of dieting, the ultrasonographic grade of all patients decreased by one or two grades. Fifteen patients decreased one grade while 8 others decreased by 2 grades. We observed a significant correlation between the decrease in ultrasonographic grade and the decrease in weight and BMI. CONCLUSION Our study indicates that standard diet therapy could be used as an effective treatment for NAFL patients. PMID:25197505

  7. Antiobesity effects of yerba maté extract (Ilex paraguariensis) in high-fat diet-induced obese mice.

    PubMed

    Arçari, Demétrius P; Bartchewsky, Waldemar; dos Santos, Tanila W; Oliveira, Karim A; Funck, Alexandre; Pedrazzoli, José; de Souza, Marina F F; Saad, Mario J; Bastos, Deborah H M; Gambero, Alessandra; Carvalho, Patricia de O; Ribeiro, Marcelo L

    2009-12-01

    Because the potential of yerba maté (Ilex paraguariensis) has been suggested in the management of obesity, the aim of the present study was to evaluate the effects of yerba maté extract on weight loss, obesity-related biochemical parameters, and the regulation of adipose tissue gene expression in high-fat diet-induced obesity in mice. Thirty animals were randomly assigned to three groups. The mice were introduced to standard or high-fat diets. After 12 weeks on a high-fat diet, mice were randomly assigned according to the treatment (water or yerba maté extract 1.0 g/kg). After treatment intervention, plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and glucose were evaluated. Adipose tissue was examined to determine the mRNA levels of several genes such as tumor necrosis factor-alpha (TNF-alpha), leptin, interleukin-6 (IL-6), C-C motif chemokine ligand-2 (CCL2), CCL receptor-2 (CCR2), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), adiponectin, resistin, peroxisome proliferator-activated receptor-gamma(2) (PPAR-gamma(2)), uncoupling protein-1 (UCP1), and PPAR-gamma coactivator-1 alpha (PGC-1 alpha). The F4/80 levels were determined by immunoblotting. We found that obese mice treated with yerba maté exhibited marked attenuation of weight gain, adiposity, a decrease in epididymal fat-pad weight, and restoration of the serum levels of cholesterol, triglycerides, LDL cholesterol, and glucose. The gene and protein expression levels were directly regulated by the high-fat diet. After treatment with yerba maté extract, we observed a recovery of the expression levels. In conclusion, our data show that yerba maté extract has potent antiobesity activity in vivo. Additionally, we observed that the treatment had a modulatory effect on the expression of several genes related to obesity.

  8. Differential effects of prenatal stress on metabolic programming in diet-induced obese and dietary-resistant rats.

    PubMed

    Balasubramanian, Priya; Varde, Pratibha A; Abdallah, Simon Labib; Najjar, Sonia M; MohanKumar, P S; MohanKumar, Sheba M J

    2015-09-15

    Stress during pregnancy is a known contributing factor for the development of obesity in the offspring. Since maternal obesity is on the rise, we wanted to identify the effects of prenatal stress in the offspring of diet-induced obese (DIO) rats and compare them with the offspring of dietary-resistant (DR) rats. We hypothesized that prenatal stress would make both DIO and DR offspring susceptible to obesity, but the effect would be more pronounced in DIO rats. Pregnant DIO and DR rats were divided into two groups: nonstressed controls (control) and prenatal stress (subjected to restraint stress, three times/day from days 14 to 21 of gestation). After recording birth weight and weaning weight, male offspring were weaned onto a chow diet for 9 wk and shifted to a high-fat (HF) diet for 1 wk. At the end of the 10th wk the animals were euthanized, and visceral adipose mass, blood glucose, serum insulin, and C-peptide levels were measured. Prenatal stress resulted in hyperinsulinemia and higher C-peptide levels without altering caloric intake, body weight gain, or fat mass in the DIO offspring after 1 wk of HF intake, but not in DR offspring. To determine the mechanism underlying the hyperinsulinemia, we measured the levels of CEACAM1 that are responsible for insulin clearance. CEACAM1 levels in the liver were reduced in prenatally stressed DIO offspring after the HF challenge, suggesting that preexisting genetic predisposition in combination with prenatal stress increases the risk for obesity in adulthood, especially when offspring are fed a HF diet.

  9. Differential effects of prenatal stress on metabolic programming in diet-induced obese and dietary-resistant rats

    PubMed Central

    Balasubramanian, Priya; Varde, Pratibha A.; Abdallah, Simon Labib; Najjar, Sonia M.; MohanKumar, P. S.

    2015-01-01

    Stress during pregnancy is a known contributing factor for the development of obesity in the offspring. Since maternal obesity is on the rise, we wanted to identify the effects of prenatal stress in the offspring of diet-induced obese (DIO) rats and compare them with the offspring of dietary-resistant (DR) rats. We hypothesized that prenatal stress would make both DIO and DR offspring susceptible to obesity, but the effect would be more pronounced in DIO rats. Pregnant DIO and DR rats were divided into two groups: nonstressed controls (control) and prenatal stress (subjected to restraint stress, three times/day from days 14 to 21 of gestation). After recording birth weight and weaning weight, male offspring were weaned onto a chow diet for 9 wk and shifted to a high-fat (HF) diet for 1 wk. At the end of the 10th wk the animals were euthanized, and visceral adipose mass, blood glucose, serum insulin, and C-peptide levels were measured. Prenatal stress resulted in hyperinsulinemia and higher C-peptide levels without altering caloric intake, body weight gain, or fat mass in the DIO offspring after 1 wk of HF intake, but not in DR offspring. To determine the mechanism underlying the hyperinsulinemia, we measured the levels of CEACAM1 that are responsible for insulin clearance. CEACAM1 levels in the liver were reduced in prenatally stressed DIO offspring after the HF challenge, suggesting that preexisting genetic predisposition in combination with prenatal stress increases the risk for obesity in adulthood, especially when offspring are fed a HF diet. PMID:26219866

  10. Differences in Birth Weight Associated with the 2008 Beijing Olympics Air Pollution Reduction: Results from a Natural Experiment

    PubMed Central

    Liu, Kaibo; Zhang, Jinliang; Thurston, Sally W.; Stevens, Timothy P.; Pan, Ying; Kane, Cathleen; Weinberger, Barry; Ohman-Strickland, Pamela; Woodruff, Tracey J.; Duan, Xiaoli; Assibey-Mensah, Vanessa; Zhang, Junfeng

    2015-01-01

    , Thurston SW, Stevens TP, Pan Y, Kane C, Weinberger B, Ohman-Strickland P, Woodruff TJ, Duan X, Assibey-Mensah V, Zhang J. 2015. Differences in birth weight associated with the 2008 Beijing Olympics air pollution reduction: results from a natural experiment. Environ Health Perspect 123:880–887; http://dx.doi.org/10.1289/ehp.1408795 PMID:25919693

  11. Blended-Wing-Body (BWB) Fuselage Structural Design for Weight Reduction

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, V.

    2005-01-01

    Structural analysis and design of efficient pressurized fuselage configurations for the advanced Blended-Wing-Body (BWB) flight vehicle is a challenging problem. Unlike a conventional cylindrical pressurized fuselage, stress level in a box type BWB fuselage is an order of magnitude higher, because internal pressure primarily results in bending stress instead of skin-membrane stress. In addition, resulting deformation of aerodynamic surface could significantly affect performance advantages provided by lifting body. The pressurized composite conformal multi-lobe tanks of X-33 type space vehicle also suffered from similar problem. In the earlier BWB design studies, Vaulted Ribbed Shell (VLRS), Flat Ribbed Shell (FRS); Vaulted shell Honeycomb Core (VLHC) and Flat sandwich shell Honeycomb Core (FLHC) concepts were studied. The flat and vaulted ribbed shell concepts were found most efficient. In a recent study, a set of composite sandwich panel and cross-ribbed panel were analyzed. Optimal values of rib and skin thickness, rib spacing, and panel depth were obtained for minimal weight under stress and buckling constraints. In addition, a set of efficient multi-bubble fuselage (MBF) configuration concept was developed. The special geometric configuration of this concept allows for balancing internal cabin pressure load efficiently, through membrane stress in inner-stiffened shell and inter-cabin walls, while the outer-ribbed shell prevents buckling due to external resultant compressive loads. The initial results from these approximate finite element analyses indicate progressively lower maximum stresses and deflections compared to the earlier study. However, a relative comparison of the FEM weight per unit floor area of the segment unit indicates that the unit weights are still relatively higher that the conventional B777 type cylindrical or A380 type elliptic fuselage design. Due to the manufacturing concern associated with multi-bubble fuselage, a Y braced box

  12. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity

    PubMed Central

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-01-01

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction. PMID:27686325

  13. Xanthohumol Improves Diet-induced Obesity and Fatty Liver by Suppressing Sterol Regulatory Element-binding Protein (SREBP) Activation*

    PubMed Central

    Miyata, Shingo; Inoue, Jun; Shimizu, Makoto; Sato, Ryuichiro

    2015-01-01

    Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that stimulate the expression of genes involved in fatty acid and cholesterol biosynthesis. Here, we demonstrate that a prenylated flavonoid in hops, xanthohumol (XN), is a novel SREBP inactivator that reduces the de novo synthesis of fatty acid and cholesterol. XN independently suppressed the maturation of SREBPs of insulin-induced genes in a manner different from sterols. Our results suggest that XN impairs the endoplasmic reticulum-to-Golgi translocation of the SREBP cleavage-activating protein (SCAP)-SREBP complex by binding to Sec23/24 and blocking SCAP/SREBP incorporation into common coated protein II vesicles. Furthermore, in diet-induced obese mice, dietary XN suppressed SREBP-1 target gene expression in the liver accompanied by a reduction of the mature form of hepatic SREBP-1, and it inhibited the development of obesity and hepatic steatosis. Altogether, our data suggest that XN attenuates the function of SREBP-1 by repressing its maturation and that it has the potential of becoming a nutraceutical food or pharmacological agent for improving metabolic syndrome. PMID:26140926

  14. 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

  15. Cinnamomum camphora Seed Kernel Oil Improves Lipid Metabolism and Enhances β3-Adrenergic Receptor Expression in Diet-Induced Obese Rats.

    PubMed

    Fu, Jing; Zeng, Cheng; Zeng, Zheling; Wang, Baogui; Wen, Xuefang; Yu, Ping; Gong, Deming

    2016-06-01

    The effects of dietary Cinnamomum camphora seed kernel oil (CCSKO) containing medium-chain triacylglycerols on lipid metabolism and mRNA and protein expression of β-3 adrenergic receptor in adipose tissue were studied in diet-induced obese rats. High fat food-induced obese rats were randomly divided into CCSKO group, Lard group, Soybean oil (SOY) group and naturally restoring group (n = 10). Rats fed with low fat food were used as a normal control group. Significant decreases in body mass and abdominal fat mass/body mass after 12 weeks were found in CCSKO group as compared with Lard and SOY groups (p < 0.05). Levels of blood total cholesterol (TC), triglyceride, free fatty acid, fasting insulin and insulin resistance in the CCSKO group were decreased significantly, and noradrenaline level and insulin sensitivity index in the CCSKO group were significantly higher than other groups. Meanwhile liver TC and triglyceride levels in the CCSKO group were also decreased markedly. Expression levels of β3-adrenergic receptor mRNA and protein were higher in CCSKO group than in Lard and SOY groups. These results suggest that CCSKO may contribute to reduction of the body fat mass, promote lipid metabolism and up-regulate β3-adrenergic receptor expression in high fat diet-induced obese rats. PMID:27068065

  16. Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE−/− mice

    PubMed Central

    Kumar, Saran; Chen, Mo; Li, Yan; Wong, Fiona H. S.; Thiam, Chung Wee; Hossain, Md Zakir; Poh, Kian Keong; Hirohata, Satoshi; Ogawa, Hiroko; Angeli, Véronique; Ge, Ruowen

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease characterized by formation of lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that regulates versican turnover in the arterial wall and atherosclerotic plaques. Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques and in the plasma of acute coronary syndrome patients. Nevertheless, whether increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal role in atherogenesis remains unknown. In this work, we investigated the role of ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE−/−) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in plaques as atherosclerosis progresses in ApoE−/− mice. ApoE−/−Adamts4−/− double knockout mice presented a significant reduction in plaque burden at 18 weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a significantly reduced plaque vulnerability index characterized by reduced lipid content and macrophages accompanied with a significant increase in smooth muscle cells, collagen deposition and fibrotic cap thickness. The reduced atherosclerosis is accompanied by an altered plasma inflammatory cytokine profile. These results demonstrate for the first time that ADAMTS4 contributes to diet induced atherosclerosis in ApoE−/− mice. PMID:27491335

  17. Ablation of the cholesterol transporter adenosine triphosphate-binding cassette transporter G1 reduces adipose cell size and protects against diet-induced obesity.

    PubMed

    Buchmann, Jana; Meyer, Christoph; Neschen, Susanne; Augustin, Robert; Schmolz, Katja; Kluge, Reinhart; Al-Hasani, Hadi; Jürgens, Hella; Eulenberg, Karsten; Wehr, Roland; Dohrmann, Cord; Joost, Hans-Georg; Schürmann, Annette

    2007-04-01

    The ATP-binding cassette transporter G1 (ABCG1) catalyzes export of cellular cholesterol from macrophages and hepatocytes. Here we identify an additional function of ABCG1 in the regulation of adiposity in screens of the Drosophila melanogaster and the New Zealand obese (NZO) mouse genomes. Insertion of modified transposable elements of the P-family upstream of CG17646, the Drosophila ortholog of Abcg1, generated lines of flies with increased triglyceride stores. In NZO mice, an Abcg1 variant was identified in a suggestive adiposity quantitative trait locus and was associated with higher expression of the gene in white adipose tissue. Targeted disruption of Abcg1 in mice resulted in reduced body weight gain (8.42+/-0.6 g in Abcg1-/- vs. 13.07+/-1.1 g in Abcg1+/+ mice) and adipose tissue mass gain (3.78+/-1.3 g in Abcg1-/- vs. 9.39+/-1.6 g in Abcg1+/+ mice) detected over a period of 12 wk. The reduction of adipose tissue mass in Abcg1-/- mice was associated with markedly decreased size of the adipocytes. In contrast to their wild-type littermates, male Abcg1-/- mice exhibited no high-fat diet-induced impairment of glucose tolerance and fatty liver. Furthermore, Abcg1-/- mice possess decreased food intake and elevated total energy expenditure (Abcg1-/- mice, 748.1+/-5.4 kJ/kg metabolic body mass; Abcg1+/+ mice, 684.3+/-5.0 kJ/kg metabolic body mass; P=0.011), body temperature (Abcg1-/- mice, 37.82+/-0.29 C; Abcg1+/+ mice, 36.83+/-0.24 C; P<0.05), and locomotor activity (Abcg1-/- mice, 3655+/-189 counts/12 h during dark phase; Abcg1+/+ mice, 2445+/-235 counts/12 h during dark phase; P<0.01). Our data indicate a previously unrecognized role of ABCG1 in the regulation of energy balance and triglyceride storage.

  18. Development of Novel Methods for the Reduction of Noise and Weight in Helicopter Transmissions

    NASA Technical Reports Server (NTRS)

    Dimofte, Florin; Keith, Theo G., Jr.

    2003-01-01

    Over the 70-year evolution of the helicopter, man's understanding of vibration control has greatly increased. However, in spite of the increased performance, the extent of helicopter vibration problems has not significantly diminished. Crew vibration and noise remains important factors in the design of all current helicopters. With more complex and critical demands being placed on aircrews, it is essential that vibration and noise not impair their performance. A major source of helicopter cabin noise (which has been measured at a sound pressure level of over 100 dB) is the gearbox. Reduction of this noise has been a goal of NASA and the U.S. Army. Gear mesh noise is typically in the frequency range of 1000 to 3000 Hz, a range important for speech. A requirement for U.S. Army/NASA Advanced Rotorcraft Transmission project has been a 10-dB reduction compared to current designs. A combined analytical/experimental effort has been underway, since the end of the 80's, to study effects of design parameters on noise production. The noise generated by the gear mesh can be transmitted to the surrounding media through the bearings that support the gear shaft. Therefore, the use of fluid film bearings instead of rolling element bearings could reduce the transmission noise by 10 dB. In addition, the fluid film bearings that support the gear shaft can change the dynamics of the gear assembly by providing damping to the system and by being softer than rolling element bearings. Wave bearings can attenuate, and filter, the noise generated by a machine component due to the dynamic stiffness and damping coefficients. The attenuation ratio could be as large as 35-40 dB. The noise components at higher frequencies than a synchronous frequency can be almost eliminated.

  19. Identification of Predictors for Weight Reduction in Children and Adolescents with Overweight and Obesity (IDA-Insel Survey)

    PubMed Central

    Schiel, Ralf; Kaps, Alexander; Stein, Günter; Steveling, Antje

    2016-01-01

    Introduction: Worldwide, overweight and obesity are known as posing serious health risks. Successful methods of prevention and therapy for overweight and obesity have remained elusive. It was the aim of the present trial to identify parameters and determinants to guarantee long-term weight reduction. Patients and methods: In total 143/159 children and adolescents (90%) with overweight and obesity completed the prospective, multicenter trial (age 13.9 ± 2.4 years, BMI 31.2 ± 5.4 kg/m2, BMI-SDS 2.51 ± 0.57). During a six-week rehabilitation patients participated in a structured treatment and teaching program (STTP). Following the inpatient treatment the children and adolescents were monitored over a period of 24 months (physical examination, measurements of BMI, BMI-SDS, body composition, carotid intima-media thickness, laboratory parameters, blood pressure, and standardized questionnaires to assess socio-demographic, socio-economic parameters, eating behavior, well-being, quality of life, intelligence, intrafamilial conflicts, self-efficacy, resilience, sense of coherence, stress-management, social support, and actual body shape). Results: 66% of the children and adolescents showed non-normal laboratory parameters as well as higher blood pressure and/or an increased carotid intima-media thickness. Mean thickness of carotid intima-media was 0.53 ± 0.09 mm (range, 0.40–0.80); 15% of the patients showed a normal range (<0.45 mm), 40% slightly elevated (0.45–0.50 mm) and 45% an elevated (>0.50 mm) thickness. After an inpatient treatment lasting 40.4 ± 4.1 (range, 28–49) days, children and adolescents reached a mean weight reduction of 5.52 ± 3.94 (0.4–13.3) kg (p < 0.01) accompanied by a reduction of body fat mass. Performing multivariate analyses, the most important psychological factors associated with long-term weight reduction were identified (R-square = 0.53): Well-being (β = −0.543), resilience (β = 0.434) and intrafamilial conflicts (β = 0

  20. Demonstration of improved vehicle fuel efficiency through innovative tire design, materials, and weight reduction technologies

    SciTech Connect

    Donley, Tim

    2014-12-31

    Cooper completed an investigation into new tire technology using a novel approach to develop and demonstrate a new class of fuel efficient tires using innovative materials technology and tire design concepts. The objective of this work was to develop a new class of fuel efficient tires, focused on the “replacement market” that would improve overall passenger vehicle fuel efficiency by 3% while lowering the overall tire weight by 20%. A further goal of this project was to accomplish the objectives while maintaining the traction and wear performance of the control tire. This program was designed to build on what has already been accomplished in the tire industry for rolling resistance based on the knowledge and general principles developed over the past decades. Cooper’s CS4 (Figure #1) premium broadline tire was chosen as the control tire for this program. For Cooper to achieve the goals of this project, the development of multiple technologies was necessary. Six technologies were chosen that are not currently being used in the tire industry at any significant level, but that showed excellent prospects in preliminary research. This development was divided into two phases. Phase I investigated six different technologies as individual components. Phase II then took a holistic approach by combining all the technologies that showed positive results during phase one development.

  1. Electromagnet Weight Reduction in a Magnetic Levitation System for Contactless Delivery Applications

    PubMed Central

    Hong, Do-Kwan; Woo, Byung-Chul; Koo, Dae-Hyun; Lee, Ki-Chang

    2010-01-01

    This paper presents an optimum design of a lightweight vehicle levitation electromagnet, which also provides a passive guide force in a magnetic levitation system for contactless delivery applications. The split alignment of C-shaped electromagnets about C-shaped rails has a bad effect on the lateral deviation force, therefore, no-split positioning of electromagnets is better for lateral performance. This is verified by simulations and experiments. This paper presents a statistically optimized design with a high number of the design variables to reduce the weight of the electromagnet under the constraint of normal force using response surface methodology (RSM) and the kriging interpolation method. 2D and 3D magnetostatic analysis of the electromagnet are performed using ANSYS. The most effective design variables are extracted by a Pareto chart. The most desirable set is determined and the influence of each design variable on the objective function can be obtained. The generalized reduced gradient (GRG) algorithm is adopted in the kriging model. This paper’s procedure is validated by a comparison between experimental and calculation results, which shows that the predicted performance of the electromagnet designed by RSM is in good agreement with the simulation results. PMID:22163572

  2. Effect of aging and drug-induced weight reduction on rat vascular reactivity.

    PubMed

    Feletou, M; Moreau, N; Boulanger, M; Duhault, J

    1993-01-01

    We determined the effects of D-fenfluramine treatment on the changes in vascular reactivity induced by aging. Nine- and 49-week-old Sprague-Dawley rats (a strain known to develop hyperinsulinemia and glucose intolerance during the aging process) were treated for 3 weeks either with D-fenfluramine 2.5 mg/kg twice daily orally or with vehicle. The rats were then exsanguinated and the abdominal aorta was carefully removed, cut into rings, and suspended in organ chambers for isometric tension recording. Control old rats (vehicle) had a significantly lower glucose infusion rate (an index of insulin resistance), and higher blood pressure (BP), glycemia, and insulinemia than young rats. The D-fenfluramine treatment in the aged animals produced a significant decrease in insulinemia and body weight. In aorta from the older treated and nontreated animals, the contraction to alpha-adrenergic stimulation and to the thromboxane analogue U46619 was significantly reduced as compared with that in young animals, but the response to KCl was unaffected. In contrast, in the old nontreated rats, the aorta was hyperresponsive to serotonin. D-Fenfluramine abolished this hyperreactivity. The response to beta-adrenergic stimulation and to forskolin was inhibited in the older animals but was not influenced by the treatment. Endothelium-dependent relaxations to acetylcholine were not statistically different in the various groups, but the endothelium-dependent relaxation to ADP was reduced in the control group of older animals. D-Fenfluramine treatment restored the response to ADP. PMID:7678666

  3. Electromagnet weight reduction in a magnetic levitation system for contactless delivery applications.

    PubMed

    Hong, Do-Kwan; Woo, Byung-Chul; Koo, Dae-Hyun; Lee, Ki-Chang

    2010-01-01

    This paper presents an optimum design of a lightweight vehicle levitation electromagnet, which also provides a passive guide force in a magnetic levitation system for contactless delivery applications. The split alignment of C-shaped electromagnets about C-shaped rails has a bad effect on the lateral deviation force, therefore, no-split positioning of electromagnets is better for lateral performance. This is verified by simulations and experiments. This paper presents a statistically optimized design with a high number of the design variables to reduce the weight of the electromagnet under the constraint of normal force using response surface methodology (RSM) and the kriging interpolation method. 2D and 3D magnetostatic analysis of the electromagnet are performed using ANSYS. The most effective design variables are extracted by a Pareto chart. The most desirable set is determined and the influence of each design variable on the objective function can be obtained. The generalized reduced gradient (GRG) algorithm is adopted in the kriging model. This paper's procedure is validated by a comparison between experimental and calculation results, which shows that the predicted performance of the electromagnet designed by RSM is in good agreement with the simulation results.

  4. Six-week Diet Correction for Body Weight Reduction and Its Subsequent Changes of Gut Microbiota: A Case Report.

    PubMed

    Oh, Bumjo; Kim, Jong Seung; Kweon, Meera; Kim, Bong-Soo; Huh, In Sil

    2016-04-01

    Impact of intestinal microbes on obesity and health is a new topic recently started to get attention. Comparing to the global concern and research trends, there are few research on the association between intestinal bacteria and life style disease in Korean. One voluntary case (female) was reported to show the change in gut microbiota and weight by diet intervention. She was overweight (BMI 23.2 kg/m(2)) and has abnormal liver function, and the causes of overweight were frequent drinking and meat consumption at the late evening hours. For 47 days, she was administered an improved diet on breakfast and dinner with reduction of meat consumption frequency by 50%. Alcohol consumption was reduced to once a week. As a result, she lost 3 kilograms of body weight. Her fecal sample was collected before and after the intervention, and gut microbiota change was compared using a high-throughput sequencing technique. After diet correction, the shift of gut microbiota was clearly observed with decreased proportion of Firmicutes (from 75.7% to 47.3% in total microbiota) but increased proportion of Bacteroidetes upto 47.7%. After incorporating the diet intervention, it is meaningful to confirm the changes in dominant gut microbiota and weight loss.

  5. Six-week Diet Correction for Body Weight Reduction and Its Subsequent Changes of Gut Microbiota: A Case Report

    PubMed Central

    2016-01-01

    Impact of intestinal microbes on obesity and health is a new topic recently started to get attention. Comparing to the global concern and research trends, there are few research on the association between intestinal bacteria and life style disease in Korean. One voluntary case (female) was reported to show the change in gut microbiota and weight by diet intervention. She was overweight (BMI 23.2 kg/m2) and has abnormal liver function, and the causes of overweight were frequent drinking and meat consumption at the late evening hours. For 47 days, she was administered an improved diet on breakfast and dinner with reduction of meat consumption frequency by 50%. Alcohol consumption was reduced to once a week. As a result, she lost 3 kilograms of body weight. Her fecal sample was collected before and after the intervention, and gut microbiota change was compared using a high-throughput sequencing technique. After diet correction, the shift of gut microbiota was clearly observed with decreased proportion of Firmicutes (from 75.7% to 47.3% in total microbiota) but increased proportion of Bacteroidetes upto 47.7%. After incorporating the diet intervention, it is meaningful to confirm the changes in dominant gut microbiota and weight loss. PMID:27152303

  6. Six-week Diet Correction for Body Weight Reduction and Its Subsequent Changes of Gut Microbiota: A Case Report.

    PubMed

    Oh, Bumjo; Kim, Jong Seung; Kweon, Meera; Kim, Bong-Soo; Huh, In Sil

    2016-04-01

    Impact of intestinal microbes on obesity and health is a new topic recently started to get attention. Comparing to the global concern and research trends, there are few research on the association between intestinal bacteria and life style disease in Korean. One voluntary case (female) was reported to show the change in gut microbiota and weight by diet intervention. She was overweight (BMI 23.2 kg/m(2)) and has abnormal liver function, and the causes of overweight were frequent drinking and meat consumption at the late evening hours. For 47 days, she was administered an improved diet on breakfast and dinner with reduction of meat consumption frequency by 50%. Alcohol consumption was reduced to once a week. As a result, she lost 3 kilograms of body weight. Her fecal sample was collected before and after the intervention, and gut microbiota change was compared using a high-throughput sequencing technique. After diet correction, the shift of gut microbiota was clearly observed with decreased proportion of Firmicutes (from 75.7% to 47.3% in total microbiota) but increased proportion of Bacteroidetes upto 47.7%. After incorporating the diet intervention, it is meaningful to confirm the changes in dominant gut microbiota and weight loss. PMID:27152303

  7. Nordihydroguaiaretic acid protects against high-fat diet-induced fatty liver by activating AMP-activated protein kinase in obese mice

    SciTech Connect

    Lee, Myoung-Su; Kim, Daeyoung; Jo, Keunae; Hwang, Jae-Kwan

    2010-10-08

    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 hepatic 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.

  8. Effects of diet-induced obesity on motivation and pain behavior in an operant assay.

    PubMed

    Rossi, H L; Luu, A K S; Kothari, S D; Kuburas, A; Neubert, J K; Caudle, R M; Recober, A

    2013-04-01

    Obesity has been associated with multiple chronic pain disorders, including migraine. We hypothesized that diet-induced obesity would be associated with a reduced threshold for thermal nociception in the trigeminal system. In this study, we sought to examine the effect of diet-induced obesity on facial pain behavior. Mice of two different strains were fed high-fat or regular diet (RD) and tested using a well-established operant facial pain assay. We found that the effects of diet on behavior in this assay were strain and reward dependent. Obesity-prone C57BL/6J mice fed a high-fat diet (HFD) display lower number of licks of a caloric, palatable reward (33% sweetened condensed milk or 30% sucrose) than control mice. This occurred at all temperatures, in both sexes, and was evident even before the onset of obesity. This diminished reward-seeking behavior was not observed in obesity-resistant SKH1-E (SK) mice. These findings suggest that diet and strain interact to modulate reward-seeking behavior. Furthermore, we observed a difference between diet groups in operant behavior with caloric, palatable rewards, but not with a non-caloric neutral reward (water). Importantly, we found no effect of diet-induced obesity on acute thermal nociception in the absence of inflammation or injury. This indicates that thermal sensation in the face is not affected by obesity-associated peripheral neuropathy as it occurs when studying pain behaviors in the rodent hindpaw. Future studies using this model may reveal whether obesity facilitates the development of chronic pain after injury or inflammation.

  9. Anti-inflammatory and anti-diabetic effects of brown seaweeds in high-fat diet-induced obese mice

    PubMed Central

    Oh, Ji-Hyun; Kim, Jaehoon

    2016-01-01

    BACKGROUND/OBJECTIVES Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-1β and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells. PMID:26865915

  10. Ghrelin, Sleep Reduction and Evening Preference: Relationships to CLOCK 3111 T/C SNP and Weight Loss

    PubMed Central

    Garaulet, Marta; Sánchez-Moreno, Carmen; Smith, Caren E.; Lee, Yu-Chi; Nicolás, Francisco; Ordovás, Jose M.

    2011-01-01

    Background Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation. The aim was to investigate the behavioral (sleep duration, eating patterns and chronobiological characteristics) and hormonal (plasma ghrelin and leptin concentrations) factors which could explain the previously reported association between the CLOCK 3111T/C SNP and weight loss. Methodology/Principal Findings We recruited 1495 overweight/obese subjects (BMI: 25–40 kg/m2) of 20–65 y. who attended outpatient obesity clinics in Murcia, in southeastern Spain. We detected an association between the CLOCK 3111T/C SNP and weight loss, which was particularly evident after 12–14 weeks of treatment (P = 0.038). Specifically, carriers of the minor C allele were more resistant to weight loss than TT individuals (Mean±SEM) (8.71±0.59 kg vs 10.4±0.57 kg) C and TT respectively. In addition, our data show that minor C allele carriers had: 1. shorter sleep duration Mean ± SEM (7.0±0.05 vs 7.3±0.05) C and TT respectively (P = 0.039), 2. higher plasma ghrelin concentrations Mean ± SEM (pg/ml) (1108±49 vs 976±47)(P = 0.034); 3. delayed breakfast time; 4. evening preference and 5. less compliance with a Mediterranean Diet pattern, as compared with TT homozygotes. Conclusions/Significance Sleep reduction, changes in ghrelin values, alterations of eating behaviors and evening preference that characterized CLOCK 3111C carriers could be affecting weight loss. Our results support the hypothesis that the influence of the CLOCK gene may extend to a broad range of variables linked with human behaviors. PMID:21386998

  11. Psychological and sociodemographic predictors of premature discontinuation of a 1-year multimodal outpatient weight-reduction program: an attrition analysis

    PubMed Central

    Ahnis, Anne; Riedl, Andrea; Figura, Andrea; Steinhagen-Thiessen, Elisabeth; Liebl, Max E; Klapp, Burghard F

    2012-01-01

    Objective Attrition rates of up to 77% have been reported in conservative weight-reduction programs for the treatment of obesity. In view of the cost of such programs to the health system, there is a need to identify the variables that predict premature discontinuation of treatment. Previous studies have focused mainly on somatic and sociodemographic parameters. The prospective influence of psychological factors has not been systematically investigated to date. Methods A total of 164 patients (138 of whom were women) with a mean age of 45 years and a mean body mass index of 39.57 participated in a 1-year outpatient weight-reduction program at the Charité – Universitätsmedizin Berlin University Hospital. The program included movement therapy, dietary advice, psychoeducational and behavioral interventions, relaxation procedures, and consultations with a specialist in internal medicine and a psychologist. Patients also underwent regular laboratory and psychological testing. The results were evaluated using a t-test, χ2-test, and logistic regression analysis. Results Seventy-one of the 164 patients (61 women, mean age = 43 years, mean body mass index = 39.53) withdrew before the end of the program (attrition rate = 43.3%). While there were no differences between the somatic and metabolic characteristics of those who withdrew and those who remained, the sociodemographic and psychological factors had some relevance. In particular, “expectation of self-efficacy” (Fragebogen zu Selbstwirksamkeit, Optimismus und Pessimismus [SWOP]), “not working,” “tiredness” (Berliner Stimmungsfragebogen [BSF]), “pessimism” (SWOP) and “positive reframing” (Brief-COPE) were found to play a role in whether participants subsequently dropped out of the treatment. “Support coping” (Brief-COPE) and “older age” prior to the start of treatment were identified as variables that promoted treatment adherence. Conclusion The results are discussed in light of previous

  12. Reversal of Nonalcoholic Hepatic Steatosis, Hepatic Insulin Resistance, and Hyperglycemia by Moderate Weight Reduction in Patients With Type 2 Diabetes

    PubMed Central

    Petersen, Kitt Falk; Dufour, Sylvie; Befroy, Douglas; Lehrke, Michael; Hendler, Rosa E.; Shulman, Gerald I.

    2010-01-01

    To examine the mechanism by which moderate weight reduction improves basal and insulin-stimulated rates of glucose metabolism in patients with type 2 diabetes, we used 1H magnetic resonance spectroscopy to assess intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) content in conjunction with hyperinsulinemic-euglycemic clamps using [6,6-2H2]glucose to assess rates of glucose production and insulin-stimulated peripheral glucose uptake. Eight obese patients with type 2 diabetes were studied before and after weight stabilization on a moderately hypocaloric very-low-fat diet (3%). The diabetic patients were markedly insulin resistant in both liver and muscle compared with the lean control subjects. These changes were associated with marked increases in IHL (12.2 ± 3.4 vs. 0.6 ± 0.1%; P = 0.02) and IMCL (2.0 ± 0.3 vs. 1.2 ± 0.1%; P = 0.02) compared with the control subjects. A weight loss of only ~8 kg resulted in normalization of fasting plasma glucose concentrations (8.8 ± 0.5 vs. 6.4 ± 0.3 mmol/l; P < 0.0005), rates of basal glucose production (193 ± 7 vs. 153 ± 10 mg/min; P < 0.0005), and the percentage suppression of hepatic glucose production during the clamp (29 ± 22 vs. 99 ± 3%; P = 0.003). These improvements in basal and insulin-stimulated hepatic glucose metabolism were associated with an 81 ± 4% reduction in IHL (P = 0.0009) but no significant change in insulin-stimulated peripheral glucose uptake or IMCL (2.0 ± 0.3 vs. 1.9 ± 0.3%; P = 0.21). In conclusion, these data support the hypothesis that moderate weight loss normalizes fasting hyperglycemia in patients with poorly controlled type 2 diabetes by mobilizing a relatively small pool of IHL, which reverses hepatic insulin resistance and normalizes rates of basal glucose production, independent of any changes in insulin-stimulated peripheral glucose metabolism. PMID:15734833

  13. Soy Isoflavones Regulate Lipid Metabolism through an AKT/mTORC1 Pathway in Diet-Induced Obesity (DIO) Male Rats.

    PubMed

    Huang, Chao; Pang, Dejiang; Luo, Qihui; Chen, Xiaolin; Gao, Qi; Shi, Liangqin; Liu, Wentao; Zou, Yuanfeng; Li, Lixia; Chen, Zhengli

    2016-05-03

    The pandemic tendency of obesity and its strong association with serious co-morbidities have elicited interest in the underlying mechanisms of these pathologies. Lipid homeostasis, closely involved in obesity, has been reported to be regulated by multiple pathways. mTORC1 is emerging as a critical regulator of lipid metabolism. Here, we describe that the consumption of soy isoflavones, with a structural similarity to that of estradiol, could mitigate obesity through an AKT/mTORC1 pathway. Fed with soy isoflavones, the diet-induced obesity (DIO) male rats exhibited decreased body weight, accompanied with suppressed lipogenesis and adipogenesis, as well as enhanced lipolysis and β‑oxidation. The phosphorylation of AKT and S6 were decreased after soy isoflavone treatment in vivo and in vitro, suggesting an inhibition effect of soy isoflavones on mTORC1 activity. Our study reveals a potential mechanism of soy isoflavones regulating lipid homeostasis, which will be important for obesity treatment.

  14. Supplementation of a Fermented Soybean Extract Reduces Body Mass and Prevents Obesity in High Fat Diet-Induced C57BL/6J Obese Mice

    PubMed Central

    Lee, Jae Yeon; Aravinthan, Adithan; Park, Young Shik; Hwang, Kyo Yeol; Seong, Su-Il; Hwang, Kwontack

    2016-01-01

    Obesity is a growing health problem that many countries face, mostly due to the consumption of a Westernized diet. In this present study we observed the effects of a soybean extract fermented by Bacillus subtilis MORI (BTD-1) containing 1-deoxynojirimycin against high fat diet-induced obesity. The results obtained from this study indicated that BTD-1 reduced body weight, regulated hepatic lipid content and adipose tissue, and also affected liver antioxidant enzymes and glucose metabolism. These results suggest that administration of BTD-1 affects obesity by inhibiting hyperglycemia and free radical-mediated stress; it also reduces lipid accumulation. Therefore, BTD-1 may be potentially useful for the prevention of obesity and its related secondary complications. PMID:27752494

  15. Persistence of diet-induced obesity despite access to voluntary activity in mice lacking sarcolipin

    PubMed Central

    Gamu, Daniel; Trinh, Anton; Bombardier, Eric; Tupling, A Russell

    2015-01-01

    Several rodent models of obesity have been shown to develop excessive adiposity only when voluntary cage ambulation is restricted. We have previously shown that mice lacking the sarco(endo)plasmic reticulum Ca2+-ATPase pump regulatory protein sarcolipin (Sln–/–), an uncoupler of Ca2+ uptake, develop excessive diet-induced obesity under standard housing conditions. However, it is unclear whether this phenotype is due, in part, to the sedentary housing environment in which these animals are kept. To address this, we allowed wild-type and Sln–/– animals ad libitum access to voluntary wheel running while consuming a standard chow or high-fat diet for 8 weeks. During this period, wheel revolutions were monitored along with weekly mass gain. Postdiet glucose tolerance and visceral adiposity were also taken. The volume of wheel running completed was similar between genotype, regardless of diet. Although voluntary activity reduced mass gain relative to sedentary controls within each diet (P < 0.05), visceral adiposity was surprisingly unaltered with activity. However, Sln–/– mice developed excessive obesity (P < 0.05) and glucose intolerance (P < 0.05) with high-fat feeding relative to wild-type controls. These findings indicate that the excessive diet-induced obese phenotype previously observed in Sln–/– mice is not the result of severely restricted daily ambulation, but in fact the inability to recruit uncoupling of the Ca2+-ATPase pump. PMID:26400985

  16. Inactivation of hypothalamic FAS protects mice from diet-induced obesity and inflammation.

    PubMed

    Chakravarthy, Manu V; Zhu, Yimin; Yin, Li; Coleman, Trey; Pappan, Kirk L; Marshall, Connie A; McDaniel, Michael L; Semenkovich, Clay F

    2009-04-01

    Obesity promotes insulin resistance and chronic inflammation. Disrupting any of several distinct steps in lipid synthesis decreases adiposity, but it is unclear if this approach coordinately corrects the environment that propagates metabolic disease. We tested the hypothesis that inactivation of FAS in the hypothalamus prevents diet-induced obesity and systemic inflammation. Ten weeks of high-fat feeding to mice with inactivation of FAS (FASKO) limited to the hypothalamus and pancreatic beta cells protected them from diet-induced obesity. Though high-fat fed FASKO mice had no beta-cell phenotype, they were hypophagic and hypermetabolic, and they had increased insulin sensitivity at the liver but not the periphery as demonstrated by hyperinsulinemic-euglycemic clamps, and biochemically by increased phosphorylated Akt, glycogen synthase kinase-3beta, and FOXO1 compared with wild-type mice. High-fat fed FASKO mice had decreased excretion of urinary isoprostanes, suggesting less oxidative stress and blunted tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) responses to endotoxin, suggesting less systemic inflammation. Pair-feeding studies demonstrated that these beneficial effects were dependent on central FAS disruption and not merely a consequence of decreased adiposity. Thus, inducing central FAS deficiency may be a valuable integrative strategy for treating several components of the metabolic syndrome, in part by correcting hepatic insulin resistance and suppressing inflammation.

  17. Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes.

    PubMed

    Igosheva, Natalia; Abramov, Andrey Y; Poston, Lucilla; Eckert, Judith J; Fleming, Tom P; Duchen, Michael R; McConnell, Josie

    2010-01-01

    The negative impact of obesity on reproductive success is well documented but the stages at which development of the conceptus is compromised and the mechanisms responsible for the developmental failure still remain unclear. Recent findings suggest that mitochondria may be a contributing factor. However to date no studies have directly addressed the consequences of maternal obesity on mitochondria in early embryogenesis.Using an established murine model of maternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology we have investigated the underlying mechanisms of obesity-induced reduced fertility. Our study is the first to show that maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and zygotes. Specifically, maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content and biogenesis. Generation of reactive oxygen species (ROS) was raised while glutathione was depleted and the redox state became more oxidised, suggestive of oxidative stress. These altered mitochondrial properties were associated with significant developmental impairment as shown by the increased number of obese mothers who failed to support blastocyst formation compared to lean dams. We propose that compromised oocyte and early embryo mitochondrial metabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductive outcomes frequently reported in obese women.

  18. Effect of diet-induced obesity on kinetic parameters of amino acid uptake by rat erythrocytes.

    PubMed

    Picó, C; Pons, A; Palou, A

    1992-11-01

    The effects of cafeteria diet-induced obesity upon in vitro uptake of L-Alanine, Glycine, L-Lysine, L-Glutamine, L-Glutamic acid, L-Phenylalanine and L-Leucine by isolated rat erythrocytes have been studied. The total Phe and Leu uptakes followed Michaelis-Menten kinetics. The Glu uptake was fitted to diffusion kinetics. The uptakes of Ala, Gly, Lys and Gln were best explained by a two-component transport: one saturable and one diffusion. Obesity increased the Km value for Ala, Gln and Leu, and the Vmax value for Ala, but decreased the Vmax for Lys. Kinetic parameters of Phe uptake were unaffected by obesity. In addition, the pseudo-first order rate constant (Vmax/Km) for Ala, Gly, Gln, Lys and Leu uptake decreased as a result of cafeteria diet-induced obesity. The Kd value for Ala, Gly, Gln and Glu decreased and that of Lys increased as result of obesity. These adaptations could, at least in part, explain alterations in amino acid distribution between blood cells and plasma related to overfeeding or obesity.

  19. Retinoic Acid Upregulates Preadipocyte Genes to Block Adipogenesis and Suppress Diet-Induced Obesity

    PubMed Central

    Berry, Daniel C.; DeSantis, David; Soltanian, Hooman; Croniger, Colleen M.; Noy, Noa

    2012-01-01

    Retinoic acid (RA) protects mice from diet-induced obesity. The activity is mediated in part through activation of the nuclear receptors RA receptors (RARs) and peroxisome proliferator–activated receptor β/δ and their associated binding proteins cellular RA binding protein type II (CRABP-II) and fatty acid binding protein type 5 in adipocytes and skeletal muscle, leading to enhanced lipid oxidation and energy dissipation. It was also reported that RA inhibits differentiation of cultured preadipocytes. However, whether the hormone suppresses adipogenesis in vivo and how the activity is propagated remained unknown. In this study, we show that RA inhibits adipocyte differentiation by activating the CRABP-II/RARγ path in preadipose cells, thereby upregulating the expression of the adipogenesis inhibitors Pref-1, Sox9, and Kruppel-like factor 2 (KLF2). In turn, KLF2 induces the expression of CRABP-II and RARγ, further potentiating inhibition of adipocyte differentiation by RA. The data also indicate that RA suppresses adipogenesis in vivo and that the activity significantly contributes to the ability of the hormone to counteract diet-induced obesity. PMID:22396202

  20. Stress- and diet-induced fat gain is controlled by NPY in catecholaminergic neurons.

    PubMed

    Zhang, Lei; Lee, I-Chieh J; Enriquez, Rondaldo F; Lau, Jackie; Vähätalo, Laura H; Baldock, Paul A; Savontaus, Eriika; Herzog, Herbert

    2014-08-01

    Neuropeptide Y (NPY) and noradrenaline are commonly co-expressed in sympathetic neurons. Both are key regulators of energy homeostasis and critical for stress-coping. However, little is known about the specific function of NPY in the catecholaminergic system in these regulations. Here we show that mice with NPY expression only in the noradrenergic and adrenergic cells of the catecholaminergic system (catNPY) exhibited exacerbated diet-induced obesity, lower body and brown adipose tissue temperatures compared to WT and NPY(-/-) mice under a HFD. Furthermore, chronic stress increased adiposity and serum corticosterone level in WT but not NPY(-/-) mice. Re-introducing NPY specifically to the catecholaminergic system in catNPY mice restored stress responsiveness associated with increased respiratory exchange ratio and decreased liver pACC to tACC ratio. These results demonstrate catecholaminergic NPY signalling is critical in mediating diet- and chronic stress-induced fat gain via effects on diet-induced thermogenesis and stress-induced increases in corticosterone levels and lipogenic capacity.

  1. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome.

    PubMed

    Bhaswant, Maharshi; Poudyal, Hemant; Mathai, Michael L; Ward, Leigh C; Mouatt, Peter; Brown, Lindsay

    2015-09-01

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom. PMID:26378573

  2. RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders

    PubMed Central

    Grandjean, Valérie; Fourré, Sandra; De Abreu, Diana Andrea Fernandes; Derieppe, Marie-Alix; Remy, Jean-Jacques; Rassoulzadegan, Minoo

    2015-01-01

    The paternal heredity of obesity and diabetes induced by a high-fat and/or high-sugar diet (Western-like diet) has been demonstrated through epidemiological analysis of human cohorts and experimental analysis, but the nature of the hereditary vector inducing this newly acquired phenotype is not yet well defined. Here, we show that microinjection of either testis or sperm RNA of male mice fed a Western-like diet into naive one-cell embryos leads to the establishment of the Western-like diet-induced metabolic phenotype in the resulting progenies, whereas RNAs prepared from healthy controls did not. Among multiple sequence differences between the testis transcriptomes of the sick and healthy fathers, we noted that several microRNAs had increased expression, which was of interest because this class of noncoding RNA is known to be involved in epigenetic control of gene expression. When microinjected into naive one-cell embryos, one of these small RNA, i.e., the microRNA miR19b, induced metabolic alterations that are similar to the diet-induced phenotype. Furthermore, this pathological phenotype was inherited by the offspring after crosses with healthy partners. Our results indicate that acquired food-induced trait inheritance might be enacted by RNA signalling. PMID:26658372

  3. Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis.

    PubMed

    Hiramitsu, Masanori; Shimada, Yasuhito; Kuroyanagi, Junya; Inoue, Takashi; Katagiri, Takao; Zang, Liqing; Nishimura, Yuhei; Nishimura, Norihiro; Tanaka, Toshio

    2014-01-15

    Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a rat model of high-fat diet. To investigate the mechanism of action of eriocitrin, we conducted feeding experiments on zebrafish with diet-induced obesity. Oral administration of eriocitrin (32 mg/kg/day for 28 days) improved dyslipidaemia and decreased lipid droplets in the liver. DNA microarray analysis revealed that eriocitrin increased mRNA of mitochondrial biogenesis genes, such as mitochondria transcription factor, nuclear respiratory factor 1, cytochrome c oxidase subunit 4, and ATP synthase. In HepG2 cells, eriocitrin also induced the corresponding orthologues, and reduced lipid accumulation under conditions of lipid loading. Eriocitrin increased mitochondrial size and mtDNA content, which resulted in ATP production in HepG2 cells and zebrafish. In summary, dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis.

  4. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome.

    PubMed

    Bhaswant, Maharshi; Poudyal, Hemant; Mathai, Michael L; Ward, Leigh C; Mouatt, Peter; Brown, Lindsay

    2015-09-11

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom.

  5. The Amplifying Pathway of the β-Cell Contributes to Diet-induced Obesity.

    PubMed

    Vetterli, Laurène; Carobbio, Stefania; Frigerio, Francesca; Karaca, Melis; Maechler, Pierre

    2016-06-17

    Efficient energy storage in adipose tissues requires optimal function of the insulin-producing β-cell, whereas its dysfunction promotes diabetes. The associated paradox related to β-cell efficiency is that excessive accumulation of fat in adipose tissue predisposes for type 2 diabetes. Insulin exocytosis is regulated by intracellular metabolic signal transduction, with glutamate dehydrogenase playing a key role in the amplification of the secretory response. Here, we used mice with β-cell-selective glutamate dehydrogenase deletion (βGlud1(-/-)), lacking an amplifying pathway of insulin secretion. As opposed to control mice, βGlud1(-/-) animals fed a high calorie diet maintained glucose tolerance and did not develop diet-induced obesity. Islets of βGlud1(-/-) mice did not increase their secretory response upon high calorie feeding, as did islets of control mice. Inhibited adipose tissue expansion observed in knock-out mice correlated with lower expression of genes responsible for adipogenesis. Rather than being efficiently stored, lipids were consumed at a higher rate in βGlud1(-/-) mice compared with controls, in particular during food intake periods. These results show that reduced β-cell function prior to high calorie feeding prevented diet-induced obesity. PMID:27137930

  6. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome

    PubMed Central

    Bhaswant, Maharshi; Poudyal, Hemant; Mathai, Michael L.; Ward, Leigh C.; Mouatt, Peter; Brown, Lindsay

    2015-01-01

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom. PMID:26378573

  7. Cinnamomum camphora Seed Kernel Oil Ameliorates Oxidative Stress and Inflammation in Diet-Induced Obese Rats.

    PubMed

    Fu, Jing; Zeng, Cheng; Zeng, Zheling; Wang, Baogui; Gong, Deming

    2016-05-01

    Cinnamomum camphora seed kernel oil (CCSKO) was found to reduce body fat deposition and improve blood lipid in both healthy and obese rats. The study was aimed to investigate the antioxidative stress and anti-inflammatory effects of CCSKO in high-fat-diet-induced obese rats. The obese rats were treated with CCSKO, lard, and soybean oil, respectively, for 12 wk. The level of total antioxidant capacity (T-AOC), activities of superoxide dismutase (SOD), glutathione peroxidase, and catalase, and levels of malondialdehyde (MDA), tumor necrosis factor (TNF)-α, peroxisome proliferator-activated receptor (PPAR)-γ, interleukin (IL)-6, and P65 were compared among CCSKO, lard, and soybean oil groups. Our results showed that the level of T-AOC and activities of SOD and catalase were significantly increased and the level of MDA was significantly decreased in CCSKO group. In addition, CCSKO treatment reduced the activities of serum glutamic oxaloacetic transaminase and glutamate-pyruvate transaminase, and levels of serum TNF-α, IL-6, and P65 through raising the level of PPAR-γ. In conclusion, CCSKO has, for the first time, been found to ameliorate oxidative stress and inflammation in high-fat-diet-induced obese rats. PMID:27003858

  8. RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders.

    PubMed

    Grandjean, Valérie; Fourré, Sandra; De Abreu, Diana Andrea Fernandes; Derieppe, Marie-Alix; Remy, Jean-Jacques; Rassoulzadegan, Minoo

    2015-12-14

    The paternal heredity of obesity and diabetes induced by a high-fat and/or high-sugar diet (Western-like diet) has been demonstrated through epidemiological analysis of human cohorts and experimental analysis, but the nature of the hereditary vector inducing this newly acquired phenotype is not yet well defined. Here, we show that microinjection of either testis or sperm RNA of male mice fed a Western-like diet into naive one-cell embryos leads to the establishment of the Western-like diet-induced metabolic phenotype in the resulting progenies, whereas RNAs prepared from healthy controls did not. Among multiple sequence differences between the testis transcriptomes of the sick and healthy fathers, we noted that several microRNAs had increased expression, which was of interest because this class of noncoding RNA is known to be involved in epigenetic control of gene expression. When microinjected into naive one-cell embryos, one of these small RNA, i.e., the microRNA miR19b, induced metabolic alterations that are similar to the diet-induced phenotype. Furthermore, this pathological phenotype was inherited by the offspring after crosses with healthy partners. Our results indicate that acquired food-induced trait inheritance might be enacted by RNA signalling.

  9. CRP, but not TNF-α or IL-6, decreases after weight loss in patients with morbid obesity exposed to intensive weight reduction and balneological treatment*

    PubMed Central

    Rość, Danuta; Adamczyk, Przemysław; Boinska, Joanna; Szafkowski, Robert; Ponikowska, Irena; Stankowska, Katarzyna; Góralczyk, Barbara; Ruszkowska-Ciastek, Barbara

    2015-01-01

    Objective: The aim of this study was to evaluate the concentrations of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the degree of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with morbid obesity exposed to a three-week low-calorie diet and balneotherapy. Methods: The study included 33 patients (25 females and 8 males; mean age 46 years) with body mass index (BMI) values of >40 kg/m2. Evaluations of CRP, IL-6, TNF-α, lipid profile, HOMA-IR, and fasting glucose were carried out before (baseline data) and three weeks after the treatment. The control group consisted of 20 healthy volunteers (15 females and 5 males) with a mean age of 39 years and BMI values of ≤24.9 kg/m2. Results: In the blood of patients with morbid obesity we found significantly elevated levels of CRP, TNF-α, triglycerides, HOMA-IR and fasting glucose, but a decreased level of high density lipoprotein (HDL)-cholesterol, compared with the healthy individuals. The treatment resulted in about a 9.4% reduction in body weight from 122.5 to 111.0 kg and a significant decrease in the concentration of CRP, but no change in TNF-α or IL-6. HOMA-IR was significantly reduced. Conclusions: The decrease in CRP level without changes in TNF-α or IL-6 concentrations after the low-calorie diet and balneological treatment, suggests that an essential amount of adipose tissue must be removed before proper adipocyte function is restored. The decrease in HOMA-IR indicates an improvement in insulin sensitivity, which is beneficial in obese patients. PMID:25990058

  10. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance

    PubMed Central

    Ringling, Rebecca E.; Gastecki, Michelle L.; Woodford, Makenzie L.; Lum-Naihe, Kelly J.; Grant, Ryan W.; Pulakat, Lakshmi; Vieira-Potter, Victoria J.; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis. PMID:27583382

  11. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.

    PubMed

    Ringling, Rebecca E; Gastecki, Michelle L; Woodford, Makenzie L; Lum-Naihe, Kelly J; Grant, Ryan W; Pulakat, Lakshmi; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis. PMID:27583382

  12. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.

    PubMed

    Ringling, Rebecca E; Gastecki, Michelle L; Woodford, Makenzie L; Lum-Naihe, Kelly J; Grant, Ryan W; Pulakat, Lakshmi; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis.

  13. Comparison of range of commercial or primary care led weight reduction programmes with minimal intervention control for weight loss in obesity: Lighten Up randomised controlled trial

    PubMed Central

    Jolly, Kate; Lewis, Amanda; Beach, Jane; Denley, John; Adab, Peymane; Deeks, Jonathan J; Aveyard, Paul

    2011-01-01

    Objective To assess the effectiveness of a range of weight management programmes in terms of weight loss. Design Eight arm randomised controlled trial. Setting Primary care trust in Birmingham, England. Participants 740 obese or overweight men and women with a comorbid disorder identified from general practice records. Interventions Weight loss programmes of 12 weeks’ duration: Weight Watchers; Slimming World; Rosemary Conley; group based, dietetics led programme; general practice one to one counselling; pharmacy led one to one counselling; choice of any of the six programmes. The comparator group was provided with 12 vouchers enabling free entrance to a local leisure (fitness) centre. Main outcome measures The primary outcome was weight loss at programme end (12 weeks). Secondary outcomes were weight loss at one year, self reported physical activity, and percentage weight loss at programme end and one year. Results Follow-up data were available for 658 (88.9%) participants at programme end and 522 (70.5%) at one year. All programmes achieved significant weight loss from baseline to programme end (range 1.37 kg (general practice) to 4.43 kg (Weight Watchers)), and all except general practice and pharmacy provision resulted in significant weight loss at one year. At one year, only the Weight Watchers group had significantly greater weight loss than did the comparator group (2.5 (95% confidence interval 0.8 to 4.2) kg greater loss,). The commercial programmes achieved significantly greater weight loss than did the primary care programmes at programme end (mean difference 2.3 (1.3 to 3.4) kg). The primary care programmes were the most costly to provide. Participants allocated to the choice arm did not have better outcomes than those randomly allocated to a programme. Conclusions Commercially provided weight management services are more effective and cheaper than primary care based services led by specially trained staff, which are ineffective. Trial registration

  14. Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

    PubMed

    Arai, Takeshi; Kim, Hyoun-ju; Hirako, Satoshi; Nakasatomi, Maki; Chiba, Hiroshige; Matsumoto, Akiyo

    2013-01-01

    We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice.

  15. Extensive impact of saturated fatty acids on metabolic and cardiovascular profile in rats with diet-induced obesity: a canonical analysis

    PubMed Central

    2013-01-01

    Background Although hypercaloric interventions are associated with nutritional, endocrine, metabolic, and cardiovascular disorders in obesity experiments, a rational distinction between the effects of excess adiposity and the individual roles of dietary macronutrients in relation to these disturbances has not previously been studied. This investigation analyzed the correlation between ingested macronutrients (including sucrose and saturated and unsaturated fatty acids) plus body adiposity and metabolic, hormonal, and cardiovascular effects in rats with diet-induced obesity. Methods Normotensive Wistar-Kyoto rats were submitted to Control (CD; 3.2 Kcal/g) and Hypercaloric (HD; 4.6 Kcal/g) diets for 20 weeks followed by nutritional evaluation involving body weight and adiposity measurement. Metabolic and hormonal parameters included glycemia, insulin, insulin resistance, and leptin. Cardiovascular analysis included systolic blood pressure profile, echocardiography, morphometric study of myocardial morphology, and myosin heavy chain (MHC) protein expression. Canonical correlation analysis was used to evaluate the relationships between dietary macronutrients plus adiposity and metabolic, hormonal, and cardiovascular parameters. Results Although final group body weights did not differ, HD presented higher adiposity than CD. Diet induced hyperglycemia while insulin and leptin levels remained unchanged. In a cardiovascular context, systolic blood pressure increased with time only in HD. Additionally, in vivo echocardiography revealed cardiac hypertrophy and improved systolic performance in HD compared to CD; and while cardiomyocyte size was unchanged by diet, nuclear volume and collagen interstitial fraction both increased in HD. Also HD exhibited higher relative β-MHC content and β/α-MHC ratio than their Control counterparts. Importantly, body adiposity was weakly associated with cardiovascular effects, as saturated fatty acid intake was directly associated with most

  16. Mathematically combined half-cell reduction potentials of low-molecular-weight thiols as markers of seed ageing.

    PubMed

    Birtić, Simona; Colville, Louise; Pritchard, Hugh W; Pearce, Stephen R; Kranner, Ilse

    2011-09-01

    The half-cell reduction potential of the glutathione disulphide (GSSG)/glutathione (GSH) redox couple appears to correlate with cell viability and has been proposed to be a marker of seed viability and ageing. This study investigated the relationship between seed viability and the individual half-cell reduction potentials (E(i)s) of four low-molecular-weight (LMW) thiols in Lathyrus pratensis seeds subjected to artificial ageing: GSH, cysteine (Cys), cysteinyl-glycine (Cys-Gly) and γ-glutamyl-cysteine (γ-Glu-Cys). The standard redox potential of γ-Glu-Cys was previously unknown and was experimentally determined. The E(i)s were mathematically combined to define a LMW thiol-disulphide based redox environment (E(thiol-disulphide)). Loss of seed viability correlated with a shift in E(thiol-disulphide) towards more positive values, with a LD(50) value of -0.90 ± 0.093 mV M (mean ± SD). The mathematical definition of E(thiol-disulphide) is envisaged as a step towards the definition of the overall cellular redox environment, which will need to include all known redox-couples.

  17. Taste acuity of obese adolescents and changes in food neophobia and food preferences during a weight reduction session.

    PubMed

    Monneuse, Marie-Odile; Rigal, Natalie; Frelut, Marie-Laure; Hladik, Claude-Marcel; Simmen, Bruno; Pasquet, Patrick

    2008-01-01

    The relationship between taste acuity and food neophobia, food familiarity and liking has been studied in the context of a residential weight reduction session (WRS; mean duration: 10 months) in 39 obese adolescents. Taste acuity was assessed using recognition thresholds for sucrose, citric acid, sodium chloride and 6-n propylthiouracil (PROP) and supra-threshold perceived intensities for sucrose, sodium chloride and PROP. Food neophobia was assessed by using the food neophobia scale at the beginning and at the end of the WRS. At these time points we used also a food familiarity and liking questionnaire to assess changes in food familiarity and likes or dislikes for different food categories. Taste acuity appeared to mediate behavioural food-related changes during the WRS. High taste acuity was associated with limited reductions in food neophobia; less sensitive subjects showed greater increases in the acceptability of healthy foods, especially fruits and vegetables. Therefore, taste perception (and particularly PROP perception) appears to be a predictor of the magnitude of food-related behavioural change achieved during a WRS.

  18. Three-week integrated body weight reduction programme markedly improves performance and work capacity in severely obese patients.

    PubMed

    Sartorio, A; Ottolini, S; Agosti, F; Massarini, M; Lafortuna, C L

    2003-06-01

    The aim of this study was to assess the effects on performance and work capacity of a short-term (3-week) integrated body weight reduction programme consisting of an energy-restricted diet, nutritional education, psychological counselling and aerobic exercise training at a constant metabolic load (5 days/week) in 71 severely obese patients (18 males and 53 females aged 29.3 +/- 0.8 years, with a mean weight of 113.8 +/- 2.2 kg and a mean BMI of 41.3 +/- 0.5 kg/m(-2)). Body mass and composition, and maximum oxygen consumption (VO2max) were determined before and after the programme. The caloric equivalent of work output and a performance index (PI) during 10 min of bicycle ergometer pedalling (50-60 rpm) and 20 min of treadmill walking (incline 0-3%) at a constant metabolic load (50% of individual VO2max during the preliminary conditioning period--1st week--and 60% during the exercise conditioning period--2nd and 3rd week) were evaluated daily throughout the study. After the programme, body mass reduced significantly (-4.5%, p<0.001), the weight loss being sustained entirely by a significant reduction in fat mass (-7.6%, p<0.001) without any significant changes in fat-free mass. Absolute and body mass-related VO2max significantly increased by respectively 14.5% and 20.2% (p<0.001). Both daily work output during constant metabolic load (ANOVA, p<0.05-0.001) and PI (ANOVA, p<0.05-0.001) increased significantly during each week of the programme, leading to a total increase in work output in response to exercise conditioning of 44.6 +/- 5.8 kcal. It is concluded that the changes in exercise capacity induced by the present programme offer significant advantages for obese patients that can be quantified in terms of an improvement in their ability to perform everyday activities, thus contributing towards improving their quality of life.

  19. Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice.

    PubMed

    Muthulakshmi, Shanmugam; Saravanan, Ramalingam

    2013-06-01

    Azelaic acid (AzA), a C9 linear α,ω-dicarboxylic acid, is found in whole grains namely wheat, rye, barley, oat seeds and sorghum. The study was performed to investigate whether AzA exerts beneficial effect on hepatic key enzymes of carbohydrate metabolism in high fat diet (HFD) induced type 2 diabetic C57BL/6J mice. C57BL/6J mice were fed high fat diet for 10 weeks and subjected to intragastric administration of various doses (20 mg, 40 mg and 80 mg/kg BW) of AzA daily for the subsequent 5 weeks. Rosiglitazone (RSG) was used as reference drug. Body weight, food intake, plasma glucose, plasma insulin, blood haemoglobin (Hb), blood glycosylated haemoglobin (HbA1c), liver glycolytic enzyme (hexokinase), hepatic shunt enzyme (glucose-6-phosphate dehydrogenase), gluconeogenic enzymes(glucose-6-phosphatase and fructose-1,6-bisphosphatase), liver glycogen, plasma and liver triglycerides were examined in mice fed with normal standard diet (NC), high fat diet (HFD), HFD with AzA (HFD + AzA) and HFD with rosiglitazone (HFD + RSG). Among the three doses, 80 mg/kg BW of AzA was able to positively regulate plasma glucose, insulin, blood HbA1c and haemoglobin levels by significantly increasing the activity of hexokinase and glucose-6-phosphate dehydrogenase and significantly decreasing the activity of glucose-6-phosphatase and fructose-1,6-bisphosphatase thereby increasing the glycogen content in the liver. From this study, we put forward that AzA could significantly restore the levels of plasma glucose, insulin, HbA1c, Hb, liver glycogen and carbohydrate metabolic key enzymes to near normal in diabetic mice and hence, AzA may be useful as a biomaterial in the development of therapeutic agents against high fat diet induced T2DM.

  20. Diet-induced obesity mediates a proinflammatory response in pancreatic β cell via toll-like receptor 4

    PubMed Central

    Li, Juan; Chen, Shufen; Qiang, Juan; Wang, Xin; Chen, Lei

    2014-01-01

    Toll-like receptor 4 has an important role in inflammation and immunity. Whether TLR4 signaling contributes to the link between insulin resistance and islet β cell dysfunction is an unanswered question. Here, we show that in the face of the same high-fat continuous stimulation for 24 weeks, in TLR4–/– HF mice, the weight, fraction of the liver, epididymal fat pad fraction, as well as blood glucose and insulin levels were lower than in the WT HF group. In TLR4–/– HF mice, the O2 consumption, CO2 production and activities were higher than in the WT HF group. Glucose tolerance test, insulin tolerance test and insulin release test suggest that the impaired insulin secretion was significantly improved in TLR4–/– HF mice, compared with the WT HF group. In TLR4–/– HF mice, islet β cell ultrastructure was not damaged in the face of the same high-fat continuous stimulation, compared to that in the WT HF group. By detecting glucose-stimulated insulin secretion in the primary islet, insulin secretion of TLR4–/– HF mice was better than that of the WT HF group, and in the TLR4–/– HF group, at the mRNA level, islet interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemotactic protein 1 (MCP-1) were significantly lower than in the WT HF group. There was the islet macrophage infiltration in the WT HF group, but no significant macrophage infiltration in the TLR4–/– HF group. These data suggest that the damaged islet functions of the high fat diet-induced obesity mice may be linked to the TLR4 expression level, and the recruitment of macrophages into the islets. PMID:26155140

  1. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

    PubMed

    Palmnäs, Marie S A; Cowan, Theresa E; Bomhof, Marc R; Su, Juliet; Reimer, Raylene A; Vogel, Hans J; Hittel, Dustin S; Shearer, Jane

    2014-01-01

    Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5-7 mg/kg/d in drinking water) treatments for 8 week (n = 10-12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation. PMID:25313461

  2. Response to diet-induced obesity produces time-dependent induction and progression of metabolic osteoarthritis in rat knees.

    PubMed

    Collins, Kelsey H; Hart, David A; Reimer, Raylene A; Seerattan, Ruth A; Herzog, Walter

    2016-06-01

    Obesity, and corresponding chronic-low grade inflammation, is associated with the onset and progression of knee OA. The origin of this inflammation is poorly understood. Here, the effect of high fat, high sucrose (HFS) diet induced obesity (DIO) on local (synovial fluid), and systemic (serum) inflammation is evaluated after a 12-week obesity induction and a further 16-week adaptation period. For 12-weeks of obesity induction, n = 40 DIO male Sprague-Dawley rats consumed a HFS diet while the control group (n = 14) remained on chow. DIO rats were allocated to prone (DIO-P, top 33% based on weight change) or resistant (DIO-R, bottom 33%) groups at 12-weeks. Animals were euthanized at 12- and after an additional 16-weeks on diet (28-weeks). At sacrifice, body composition and knee joints were collected and assessed. Synovial fluid and sera were profiled using cytokine array analysis. At 12-weeks, DIO-P animals demonstrated increased Modified Mankin scores compared to DIO-R and chow (p = 0.026), and DIO-R had higher Mankin scores compared to chow (p = 0.049). While numerous systemic and limited synovial fluid inflammatory markers were increased at 12-weeks in DIO animals compared to chow, by 28-weeks there were limited systemic differences but marked increases in local synovial fluid inflammatory marker concentrations. Metabolic OA may manifest from an initial systemic inflammatory disturbance. Twelve weeks of obesity induction leads to a unique inflammatory profile and induction of metabolic OA which is altered after a further 16-weeks of obesity and HFS diet intake, suggesting that obesity is a dynamic, progressive process. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1010-1018, 2016.

  3. Oxygen restriction as challenge test reveals early high-fat-diet-induced changes in glucose and lipid metabolism.

    PubMed

    Duivenvoorde, Loes P M; van Schothorst, Evert M; Derous, Davina; van der Stelt, Inge; Masania, Jinit; Rabbani, Naila; Thornalley, Paul J; Keijer, Jaap

    2015-06-01

    Challenge tests stress homeostasis and may reveal deviations in health that remain masked under unchallenged conditions. Ideally, challenge tests are non-invasive and applicable in an early phase of an animal experiment. Oxygen restriction (OxR; based on ambient, mild normobaric hypoxia) is a non-invasive challenge test that measures the flexibility to adapt metabolism. Metabolic inflexibility is one of the hallmarks of the metabolic syndrome. To test whether OxR can be used to reveal early diet-induced health effects, we exposed mice to a low-fat (LF) or high-fat (HF) diet for only 5 days. The response to OxR was assessed by calorimetric measurements, followed by analysis of gene expression in liver and epididymal white adipose tissue (eWAT) and serum markers for e.g. protein glycation and oxidation. Although HF feeding increased body weight, HF and LF mice did not differ in indirect calorimetric values under normoxic conditions and in a fasting state. Exposure to OxR; however, increased oxygen consumption and lipid oxidation in HF mice versus LF mice. Furthermore, OxR induced gluconeogenesis and an antioxidant response in the liver of HF mice, whereas it induced de novo lipogenesis and an antioxidant response in eWAT of LF mice, indicating that HF and LF mice differed in their adaptation to OxR. OxR also increased serum markers of protein glycation and oxidation in HF mice, whereas these changes were absent in LF mice. Cumulatively, OxR is a promising new method to test food products on potential beneficial effects for human health. PMID:24974902

  4. Properties of myenteric neurones and mucosal functions in the distal colon of diet-induced obese mice

    PubMed Central

    Reichardt, François; Baudry, Charlotte; Gruber, Lisa; Mazzuoli, Gemma; Moriez, Raphaël; Scherling, Christian; Kollmann, Patrick; Daniel, Hannelore; Kisling, Sigrid; Haller, Dirk; Neunlist, Michel; Schemann, Michael

    2013-01-01

    Colonic transit and mucosal integrity are believed to be impaired in obesity. However, a comprehensive assessment of altered colonic functions, inflammatory changes and neuronal signalling of obese animals is missing. In mice, we studied the impact of diet-induced obesity (DIO) on: (i) in vivo colonic transit; (ii) signalling in the myenteric plexus by recording responses to nicotine and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT), together with the expression of tryptophan hydroxylase (TPH) 1 and 2, serotonin reuptake transporter, choline acetyltransferase and the paired box gene 4; and (iii) expression of proinflammatory cytokines, epithelial permeability and density of macrophages, mast cells and enterochromaffin cells. Compared with controls, colon transit and neuronal sensitivity to nicotine and 2-methyl-5-HT were enhanced in DIO mice fed for 12 weeks. This was associated with increased tissue acetylcholine and 5-hydroxytryptamine (5-HT) content, and increased expression of TPH1 and TPH2. In DIO mice, upregulation of proinflammatory cytokines was found in fat tissue, but not in the gut wall. Accordingly, mucosal permeability or integrity was unaltered without signs of immune cell infiltration in the gut wall. Body weight showed positive correlations with adipocyte markers, tissue levels of 5-HT and acetylcholine, and the degree of neuronal sensitization. DIO mice fed for 4 weeks showed no neuronal sensitization, had no signs of gut wall inflammation and showed a smaller increase in leptin, interleukin-6 and monocyte chemoattractant protein 1 expression in fat tissue. DIO is associated with faster colonic transit and impacts on acetylcholine and 5-HT metabolism with enhanced responsiveness of enteric neurones to both mediators after 12 weeks of feeding. Our study demonstrates neuronal plasticity in DIO prior to the development of a pathological histology or abnormal mucosal functions. This questions the common assumption that increased mucosal inflammation and

  5. Nootkatone, a characteristic constituent of grapefruit, stimulates energy metabolism and prevents diet-induced obesity by activating AMPK.

    PubMed

    Murase, Takatoshi; Misawa, Koichi; Haramizu, Satoshi; Minegishi, Yoshihiko; Hase, Tadashi

    2010-08-01

    AMP-activated protein kinase (AMPK) is a serine/threonine kinase that is implicated in the control of energy metabolism and is considered to be a molecular target for the suppression of obesity and the treatment of metabolic syndrome. Here, we identified and characterized nootkatone, a constituent of grapefruit, as a naturally occurring AMPK activator. Nootkatone induced an increase in AMPKalpha1 and -alpha2 activity along with an increase in the AMP/ATP ratio and an increase the phosphorylation of AMPKalpha and the downstream target acetyl-CoA carboxylase (ACC), in C(2)C(12) cells. Nootkatone-induced activation of AMPK was possibly mediated both by LKB1 and Ca(2+)/calmodulin-dependent protein kinase kinase. Nootkatone also upregulated PPARgamma coactivator-1alpha in C(2)C(12) cells and C57BL/6J mouse muscle. In addition, administration of nootkatone (200 mg/kg body wt) significantly enhanced AMPK activity, accompanied by LKB1, AMPK, and ACC phosphorylation in the liver and muscle of mice. Whole body energy expenditure evaluated by indirect calorimetry was also increased by nootkatone administration. Long-term intake of diets containing 0.1% to 0.3% (wt/wt) nootkatone significantly reduced high-fat and high-sucrose diet-induced body weight gain, abdominal fat accumulation, and the development of hyperglycemia, hyperinsulinemia, and hyperleptinemia in C57BL/6J mice. Furthermore, endurance capacity, evaluated as swimming time to exhaustion in BALB/c mice, was 21% longer in mice fed 0.2% nootkatone than in control mice. These findings indicate that long-term intake of nootkatone is beneficial toward preventing obesity and improving physical performance and that these effects are due, at least in part, to enhanced energy metabolism through AMPK activation in skeletal muscle and liver. PMID:20501876

  6. Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat

    PubMed Central

    Palmnäs, Marie S. A.; Cowan, Theresa E.; Bomhof, Marc R.; Su, Juliet; Reimer, Raylene A.; Vogel, Hans J.; Hittel, Dustin S.; Shearer, Jane

    2014-01-01

    Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5–7 mg/kg/d in drinking water) treatments for 8 week (n = 10–12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation. PMID:25313461

  7. Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?

    PubMed

    Cifani, Carlo; Micioni Di Bonaventura, Maria V; Pucci, Mariangela; Giusepponi, Maria E; Romano, Adele; Di Francesco, Andrea; Maccarrone, Mauro; D'Addario, Claudio

    2015-01-01

    Several factors play a role in obesity (i.e., behavior, environment, and genetics) and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance in rats developing obesity (diet-induced obesity, DIO) or not (diet resistant, DR), when fed with a high fat diet. Rats have been followed up to 21 weeks of high fat diet exposure. After 5 weeks high fat diet exposure, the obese phenotype was developed and we observed a selective down-regulation of the orexigenic neuropeptide Y (NPY) and peroxisome proliferator-activated receptor gamma (PPAR-γ) genes. No changes were observed in the expression of the agouti-related protein (AgRP), as well as for all the anorexigenic genes under study. After long-term high fat diet exposure (21 weeks), NPY and PPAR-γ, as well as most of the genes under study, resulted not be different between DIO and DR, whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC) gene was observed in DIO rats when compared to DR rats. Moreover we observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism.

  8. Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption123

    PubMed Central

    Land, Benjamin B.; Wickham, Robert J.; Maldonado-Aviles, Jaime; de Araujo, Ivan E.; Addy, Nii A.

    2016-01-01

    Abstract The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol. PMID:27257625

  9. BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity.

    PubMed

    Kim, Do-Hwan; Do, Myoung-Sool

    2015-01-01

    Obesity is recognized as a chronic low-grade inflammatory state due to adipose tissue expansion being accompanied by an increase in the production of proinflammatory adipokines. Our group is the first to report that B-cell-activating factor (BAFF) is produced from adipocytes and functions as a proinflammatory adipokine. Here, we investigated how loss of BAFF influenced diet-induced obesity in mice by challenging BAFF(-/-) mice with a high-fat diet for 10 weeks. The results demonstrated that weight gain in BAFF(-/-) mice was >30% than in control mice, with a specific increase in the fat mass of the subcutaneous region rather than the abdominal region. Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced. A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF(-/-) mice. We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/-) mice contains antilipogenic and anti-inflammatory properties. Taken together, BAFF(-/-) improved systemic inflammation by redistributing adipose tissue into subcutaneous regions. Understanding the mechanisms by which BAFF regulates obesity in a tissue-specific manner would provide therapeutic opportunities to target obesity-related chronic diseases. PMID:25591987

  10. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

    PubMed

    Palmnäs, Marie S A; Cowan, Theresa E; Bomhof, Marc R; Su, Juliet; Reimer, Raylene A; Vogel, Hans J; Hittel, Dustin S; Shearer, Jane

    2014-01-01

    Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5-7 mg/kg/d in drinking water) treatments for 8 week (n = 10-12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation.

  11. Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice.

    PubMed

    Ii, Hiromi; Yokoyama, Naoki; Yoshida, Shintaro; Tsutsumi, Kae; Hatakeyama, Shinji; Sato, Takashi; Ishihara, Keiichi; Akiba, Satoshi

    2009-12-01

    Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A(2) (IVA-PLA(2)), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA(2)-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA(2)-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA(2)-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA(2)-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA(2)-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E(2), which has a fat storage effect, was lower in IVA-PLA(2)-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA(2) alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA(2) metabolites, such as prostaglandin E(2). IVA-PLA(2) could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease.

  12. Corepressor SMRT promotes oxidative phosphorylation in adipose tissue and protects against diet-induced obesity and insulin resistance.

    PubMed

    Fang, Sungsoon; Suh, Jae Myoung; Atkins, Annette R; Hong, Suk-Hyun; Leblanc, Mathias; Nofsinger, Russell R; Yu, Ruth T; Downes, Michael; Evans, Ronald M

    2011-02-22

    The ligand-dependent competing actions of nuclear receptor (NR)-associated transcriptional corepressor and coactivator complexes allow for the precise regulation of NR-dependent gene expression in response to both temporal and environmental cues. Here we report the mouse model termed silencing mediator of retinoid and thyroid hormone receptors (SMRT)(mRID1) in which targeted disruption of the first receptor interaction domain (RID) of the nuclear corepressor SMRT disrupts interactions with a subset of NRs and leads to diet-induced superobesity associated with a depressed respiratory exchange ratio, decreased ambulatory activity, and insulin resistance. Although apparently normal when chow fed, SMRT(mRID1) mice develop multiple metabolic dysfunctions when challenged by a high-fat diet, manifested by marked lipid accumulation in white and brown adipose tissue and the liver. The increased weight gain of SMRT(mRID1) mice on a high-fat diet occurs predominantly in fat with adipocyte hypertrophy evident in both visceral and s.c. depots. Importantly, increased inflammatory gene expression was detected only in the visceral depots. SMRT(mRID1) mice are both insulin-insensitive and refractory to the glucose-lowering effects of TZD and AICAR. Increased serum cholesterol and triglyceride levels were observed, accompanied by increased leptin and decreased adiponectin levels. Aberrant storage of lipids in the liver occurred as triglycerides and cholesterol significantly compromised hepatic function. Lipid accumulation in brown adipose tissue was associated with reduced thermogenic capacity and mitochondrial biogenesis. Collectively, these studies highlight the essential role of NR corepressors in maintaining metabolic homeostasis and describe an essential role for SMRT in regulating the progression, severity, and therapeutic outcome of metabolic diseases.

  13. Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle.

    PubMed

    Arrabal, Sergio; Lucena, Miguel Angel; Canduela, Miren Josune; Ramos-Uriarte, Almudena; Rivera, Patricia; Serrano, Antonia; Pavón, Francisco Javier; Decara, Juan; Vargas, Antonio; Baixeras, Elena; Martín-Rufián, Mercedes; Márquez, Javier; Fernández-Llébrez, Pedro; De Roos, Baukje; Grandes, Pedro; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1), 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle--regulated by both diet and CB1 receptor activity--through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD.

  14. Regulation of hypothalamic neuropeptides gene expression in diet induced obesity resistant rats: possible targets for obesity prediction?

    PubMed Central

    Cifani, Carlo; Micioni Di Bonaventura, Maria V.; Pucci, Mariangela; Giusepponi, Maria E.; Romano, Adele; Di Francesco, Andrea; Maccarrone, Mauro; D'Addario, Claudio

    2015-01-01

    Several factors play a role in obesity (i.e., behavior, environment, and genetics) and epigenetic regulation of gene expression has emerged as a potential contributor in the susceptibility and development of obesity. To investigate the individual sensitivity to weight gain/resistance, we here studied gene transcription regulation of several hypothalamic neuropeptides involved in the control of energy balance in rats developing obesity (diet-induced obesity, DIO) or not (diet resistant, DR), when fed with a high fat diet. Rats have been followed up to 21 weeks of high fat diet exposure. After 5 weeks high fat diet exposure, the obese phenotype was developed and we observed a selective down-regulation of the orexigenic neuropeptide Y (NPY) and peroxisome proliferator-activated receptor gamma (PPAR-γ) genes. No changes were observed in the expression of the agouti-related protein (AgRP), as well as for all the anorexigenic genes under study. After long-term high fat diet exposure (21 weeks), NPY and PPAR-γ, as well as most of the genes under study, resulted not be different between DIO and DR, whereas a lower expression of the anorexigenic pro-opio-melanocortin (POMC) gene was observed in DIO rats when compared to DR rats. Moreover we observed that changes in NPY and POMC mRNA were inversely correlated with gene promoters DNA methylation. Our findings suggest that selective alterations in hypothalamic peptide genes regulation could contribute to the development of overweight in rats and that environmental factor, as in this animal model, might be partially responsible of these changes via epigenetic mechanism. PMID:26106286

  15. Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle

    PubMed Central

    Arrabal, Sergio; Lucena, Miguel Angel; Canduela, Miren Josune; Ramos-Uriarte, Almudena; Rivera, Patricia; Serrano, Antonia; Pavón, Francisco Javier; Decara, Juan; Vargas, Antonio; Baixeras, Elena; Martín-Rufián, Mercedes; Márquez, Javier; Fernández-Llébrez, Pedro; De Roos, Baukje; Grandes, Pedro; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg-1, 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle—regulated by both diet and CB1 receptor activity—through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD. PMID:26671069

  16. Galectin-3 deficiency accelerates high-fat diet-induced obesity and amplifies inflammation in adipose tissue and pancreatic islets.

    PubMed

    Pejnovic, Nada N; Pantic, Jelena M; Jovanovic, Ivan P; Radosavljevic, Gordana D; Milovanovic, Marija Z; Nikolic, Ivana G; Zdravkovic, Nemanja S; Djukic, Aleksandar L; Arsenijevic, Nebojsa N; Lukic, Miodrag L

    2013-06-01

    Obesity-induced diabetes is associated with low-grade inflammation in adipose tissue and macrophage infiltration of islets. We show that ablation of galectin-3 (Gal-3), a galactoside-binding lectin, accelerates high-fat diet-induced obesity and diabetes. Obese LGALS3(-/-) mice have increased body weight, amount of total visceral adipose tissue (VAT), fasting blood glucose and insulin levels, homeostasis model assessment of insulin resistance, and markers of systemic inflammation compared with diet-matched wild-type (WT) animals. VAT of obese LGALS3(-/-) mice exhibited increased incidence of type 1 T and NKT lymphocytes and proinflammatory CD11c(+)CD11b(+) macrophages and decreased CD4(+)CD25(+)FoxP3(+) regulatory T cells and M2 macrophages. Pronounced mononuclear cell infiltrate, increased expression of NLRP3 inflammasome and interleukin-1β (IL-1β) in macrophages, and increased accumulation of advanced glycation end products (AGEs) and receptor for AGE (RAGE) expression were present in pancreatic islets of obese LGALS3(-/-) animals accompanied with elevated phosphorylated nuclear factor-κB (NF-κB) p65 and mature caspase-1 protein expression in pancreatic tissue and VAT. In vitro stimulation of LGALS3(-/-) peritoneal macrophages with lipopolysaccharide (LPS) and saturated fatty acid palmitate caused increased caspase-1-dependent IL-1β production and increased phosphorylation of NF-κB p65 compared with WT cells. Transfection of LGALS3(-/-) macrophages with NLRP3 small interfering RNA attenuated IL-1β production in response to palmitate and LPS plus palmitate. Obtained results suggest important protective roles for Gal-3 in obesity-induced inflammation and diabetes. PMID:23349493

  17. Quinoa extract enriched in 20-hydroxyecdysone protects mice from diet-induced obesity and modulates adipokines expression.

    PubMed

    Foucault, Anne-Sophie; Mathé, Véronique; Lafont, René; Even, Patrick; Dioh, Waly; Veillet, Stanislas; Tomé, Daniel; Huneau, Jean-François; Hermier, Dominique; Quignard-Boulangé, Annie

    2012-02-01

    Besides their well-known effect in the molting control in insects, ecdysteroids are steroid hormones that display potential pharmacologic and metabolic properties in mammals. The most common ecdysteroid, 20-hydroxyecdysone (20E) is found in many plants such as quinoa. The aim of the present study was to investigate the ability of quinoa extract (Q) enriched in 20E supplementation to prevent the onset of diet-induced obesity and to regulate the expression of adipocyte-specific genes in mice. Mice were fed a standard low-fat (LF) or a high-fat (HF) diet with or without supplementation by 20E-enriched Q or pure 20E for 3 weeks. Supplementation with Q reduced adipose tissue development in HF mice without modification of their body weight gain. This adipose tissue-specific effect was mainly associated with a reduced adipocyte size and a decrease in the expression of several genes involved in lipid storage, including lipoprotein lipase and phosphoenolpyruvate carboxykinase. Furthermore, Q-treated mice exhibited marked attenuation of mRNA levels of several inflammation markers (monocyte chemotactic protein-1, CD68) and insulin resistance (osteopontin, plasminogen activator inhibitor-1 (PAI-1)) as compared to HF mice. Q supplementation also reversed the effects of HF-induced downregulation of the uncoupling protein(s) (UCP(s)) mRNA levels in muscle. Similar results were obtained in mice fed a HF diet supplemented with similar amounts of pure 20E, suggesting that the latter accounted for most of the Q effects. Our study indicates that Q has an antiobesity activity in vivo and could be used as a nutritional supplement for the prevention and treatment of obesity and obesity-associated disorders.

  18. BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity.

    PubMed

    Kim, Do-Hwan; Do, Myoung-Sool

    2015-01-16

    Obesity is recognized as a chronic low-grade inflammatory state due to adipose tissue expansion being accompanied by an increase in the production of proinflammatory adipokines. Our group is the first to report that B-cell-activating factor (BAFF) is produced from adipocytes and functions as a proinflammatory adipokine. Here, we investigated how loss of BAFF influenced diet-induced obesity in mice by challenging BAFF(-/-) mice with a high-fat diet for 10 weeks. The results demonstrated that weight gain in BAFF(-/-) mice was >30% than in control mice, with a specific increase in the fat mass of the subcutaneous region rather than the abdominal region. Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced. A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF(-/-) mice. We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/-) mice contains antilipogenic and anti-inflammatory properties. Taken together, BAFF(-/-) improved systemic inflammation by redistributing adipose tissue into subcutaneous regions. Understanding the mechanisms by which BAFF regulates obesity in a tissue-specific manner would provide therapeutic opportunities to target obesity-related chronic diseases.

  19. Treadmill Intervention Attenuates the Cafeteria Diet-Induced Impairment of Stress-Coping Strategies in Young Adult Female Rats.

    PubMed

    Cigarroa, Igor; Lalanza, Jaume F; Caimari, Antoni; del Bas, Josep M; Capdevila, Lluís; Arola, Lluís; Escorihuela, Rosa M

    2016-01-01

    The current prevalence of diet-induced overweight and obesity in adolescents and adults is continuously growing. Although the detrimental biochemical and metabolic consequences of obesity are widely studied, its impact on stress-coping behavior and its interaction with specific exercise doses (in terms of intensity, duration and frequency) need further investigation. To this aim, we fed adolescent rats either an obesogenic diet (cafeteria diet, CAF) or standard chow (ST). Each group was subdivided into four subgroups according to the type of treadmill intervention as follows: a sedentary group receiving no manipulation; a control group exposed to a stationary treadmill; a low-intensity treadmill group trained at 12 m/min; and a higher intensity treadmill group trained at 17 m/min. Both the diet and treadmill interventions started at weaning and lasted for 8 weeks. Subjects were tested for anxiety-like behavior in the open field test and for coping strategies in the two-way active avoidance paradigm at week 7 and were sacrificed at week 8 for biometric and metabolic characterization. CAF feeding increased the weight gain, relative retroperitoneal white adipose tissue (RWAT %), and plasma levels of glucose, insulin, triglycerides and leptin and decreased the insulin sensitivity. Treadmill intervention partially reversed the RWAT% and triglyceride alterations; at higher intensity, it decreased the leptin levels of CAF-fed animals. CAF feeding decreased the motor activity and impaired the performance in a two-way active avoidance assessment. Treadmill intervention reduced defecation in the shuttle box, suggesting diminished anxiety. CAF feeding combined with treadmill training at 17 m/min increased the time spent in the center of the open field and more importantly, partially reversed the two-way active avoidance deficit. In conclusion, this study demonstrates that at doses that decreased anxiety-like behavior, treadmill exercise partially improved the coping strategy

  20. Anti-inflammation effect of Exercise and Korean red ginseng in aging model rats with diet-induced atherosclerosis

    PubMed Central

    Lee, Jin; Cho, Joon-Yong

    2014-01-01

    BACKGROUND/OBJECTIVES The aim of this study was to investigate the effects of exercise (EX) and Korean red ginseng (KRG) on inflammation mechanism in aging model rats with diet-induced atherosclerosis. MATERIALS/METHODS Forty-eight male Sprague-Dawley rats were divided into 6 groups: Young control (Y-C), Aging control (A-C), A-C with HFD (AHF), AHF with EX (AHF-EX), AHF-EX with KRG (AHF-EX+RG), and AHF with KRG (AHF-RG). Aging was induced by D-gal (100mg/kg) and atherosclerosis was induced by HFD (60% fat) for 9 weeks. The experimental rats were performed swimming (60 min/day, 5 days/week) and supplied KRG orally (dose of 200 mg/kg) for 8 weeks. All rat aorta samples were harvested for biochemical and immunohistochemical analyses. REULTS The EX and KRG supplementation significantly inhibited body weight and levels of TC, TG, LDL-C, and enhance of HDL-C compared with untreated AHF groups. AHF-EX, AHF-EX+RG, and AHF-RG group showed a decreased plasma CRP and increase plasma NO activities compared to AHF group. In addition, these groups revealed reduced 4-HNE, NF-kB, TNF-α, IL-6, COX-2, ICAM-1, VCAM-1 and enhanced eNOS expression in the aorta. CONCLUSION These results suggest that EX alone, KRG alone, and combined treatment of EX and KRG may be an effective anti-inflammatory therapeutic for the atherosclerosis, possibly acting via the decreased of CRP and pro-inflammation proteins and the increased NO and eNOS. PMID:24944773

  1. [Effect of MDG-1, a polysaccharide from Ophiopogon japonicas, on diversity of lactobacillus in diet-induced obese mice].

    PubMed

    Shi, Lin-lin; Wang, Yuan; Feng, Yi

    2015-02-01

    For understanding the effect of MDG-1, a water-soluble β-D-fructan polysaccharide from Ophiopogon japonicas, on intestinal microecological balance, especially on the changes of lactobacillus, sixty 8-week-old male C57BL/6J mice were given a high-fat diet for six weeks and were also gavaged with saline once a day simultaneously. Then the mice which is below 30 grams or dropped more than 10% through lavage were eliminated and the rest were randomly divided into four groups: diet-induced obese (DIO) model group (n = 12, gavaged with saline), low-dose MDG-1 group (n = 12, gavaged with MDG-1, 75 mg · kg(-1)) , medial-dose MDG- 1 group (n = 12, gavaged with 150 mg · kg(-1)), and high-dose MDG-1 group (n = 12, gavaged with 300 mg · kg(-1)) according to the weight and blood glucose; the model group and MDG-1 group were placed on a high-fat diet while the normal control group (n = 12, gavaged with saline) were kept on a low-fat diet through the experiment. After 12-weeks of treatment, feces samples were collected and cultured for intestinal microecological balance analysis. Then the intestinal probiotics were cultured through traditional methods combined with modified gradient gel electrophoresis (DGGE) method. The changes of lactobacillus in each treatment group were also detected by a statistical analysis of the total number of the intestinal flora. We have established the phylogenetic tree by 16S rDNA sequencing and use some molecular identification methods such as PCR-DGGE to analyse the changes of the dominant bacteria floras, and also get the pure culture. In conclusion, different concentrations of MDG-1 can increase the number of the intestinal probiotics, especially Taiwan lactobacillus and Lactobacillus murinus, and improve their diversity and promote proliferation in a dose-dependent way.

  2. Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity.

    PubMed

    Arnoldussen, Ilse A C; Zerbi, Valerio; Wiesmann, Maximilian; Noordman, Rikko H J; Bolijn, Simone; Mutsaers, Martina P C; Dederen, Pieter J W C; Kleemann, Robert; Kooistra, Teake; van Tol, Eric A F; Gross, Gabriele; Schoemaker, Marieke H; Heerschap, Arend; Wielinga, Peter Y; Kiliaan, Amanda J

    2016-04-01

    Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life. PMID:27012634

  3. Protein kinase Cδ contributes to phenylephrine-mediated contraction in the aortae of high fat diet-induced obese mice.

    PubMed

    Liu, Limei; Liu, Jian; Gao, Yuansheng; Yu, Xiaoxing; Dou, Dou; Huang, Yu

    2014-04-18

    The down-regulation of α-adrenoceptor-mediated signaling casacade has been implicated in obesity but the underlying mechanism remains largely unknown. The present study investigated whether inositol 1,4,5-trisphosphate (IP3) receptor and protein kinase C (PKC) were involved in the reduction of α1-adrenoceptor agonist phenylephrine-evoked contraction in aortae of high fat diet-induced obese (DIO) mice. C57BL/6 mice were fed with a rodent diet containing 45 kcal% fat for 16 weeks to induce obesity. Isolated mouse aortae were suspended in myograph for isometric force measurement. Protein phosphorylations and expressions were determined by Western blotting. In C57BL/6 mouse aortae, phenylephrine-induced contraction was partially inhibited by either IP3 receptor antagonist heparin or PKC inhibitor GFX, and the combined treatment with heparin and GFX abolished the contraction. Phenylephrine-induced contraction was significantly less in the aortae of DIO mice than those of control mice; only GFX but not heparin attenuated the contraction, indicating a diminishing role of IP3 receptor in DIO mice. Western blotting showed the reduced expression and phosphorylation of IP3 receptor and the down-regulated expression of PKC, PKCβ, PKCδ, and PKCζ in DIO mouse aortae. Importantly, PKCδ was more likely to maintain phenylephrine-mediated contraction in DIO mouse aortae because that (1) PKCδ inhibitor rottlerin but not PKCα and PKCβ inhibitor Gö6976, PKCβ inhibitor hispidin, or PKCζ pseudosubstrate inhibitor attenuated the contraction; and (2) PKCδ phosphorylation was increased but phosphorylations of PKCα, PKCβ, and PKCζ were reduced in DIO mouse aortae. The present study thus provides additional insights into the cellular mechanisms responsible for vascular dysfunction in obesity.

  4. Alterations of pancreatic islet structure, metabolism and gene expression in diet-induced obese C57BL/6J mice.

    PubMed

    Roat, Regan; Rao, Vandana; Doliba, Nicolai M; Matschinsky, Franz M; Tobias, John W; Garcia, Eden; Ahima, Rexford S; Imai, Yumi

    2014-01-01

    The reduction of functional β cell mass is a key feature of type 2 diabetes. Here, we studied metabolic functions and islet gene expression profiles of C57BL/6J mice with naturally occurring nicotinamide nucleotide transhydrogenase (NNT) deletion mutation, a widely used model of diet-induced obesity and diabetes. On high fat diet (HF), the mice developed obesity and hyperinsulinemia, while blood glucose levels were only mildly elevated indicating a substantial capacity to compensate for insulin resistance. The basal serum insulin levels were elevated in HF mice, but insulin secretion in response to glucose load was significantly blunted. Hyperinsulinemia in HF fed mice was associated with an increase in islet mass and size along with higher BrdU incorporation to β cells. The temporal profiles of glucose-stimulated insulin secretion (GSIS) of isolated islets were comparable in HF and normal chow fed mice. Islets isolated from HF fed mice had elevated basal oxygen consumption per islet but failed to increase oxygen consumption further in response to glucose or carbonyl cyanide-4-trifluoromethoxyphenylhydrazone (FCCP). To obtain an unbiased assessment of metabolic pathways in islets, we performed microarray analysis comparing gene expression in islets from HF to normal chow-fed mice. A few genes, for example, those genes involved in the protection against oxidative stress (hypoxia upregulated protein 1) and Pgc1α were up-regulated in HF islets. In contrast, several genes in extracellular matrix and other pathways were suppressed in HF islets. These results indicate that islets from C57BL/6J mice with NNT deletion mutation develop structural, metabolic and gene expression features consistent with compensation and decompensation in response to HF diet. PMID:24505268

  5. TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice

    PubMed Central

    Kentish, Stephen J.; Frisby, Claudine L.; Kritas, Stamatiki; Li, Hui; Hatzinikolas, George; O’Donnell, Tracey A.; Wittert, Gary A.; Page, Amanda J.

    2015-01-01

    Aim Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1) are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice. Methods TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined. Results Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet. Conclusion TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity. PMID:26285043

  6. Transgenic Expression of Dominant-Active IDOL in Liver Causes Diet-Induced Hypercholesterolemia and Atherosclerosis in Mice

    PubMed Central

    Calkin, Anna C.; Lee, Stephen D.; Kim, Jason; Van Stijn, Caroline; Wu, Xiao-Hui; Lusis, Aldons J.; Hong, Cynthia; Tangirala, Rajendra; Tontonoz, Peter

    2014-01-01

    Rationale The E3 ubiquitin ligase IDOL triggers lysosomal degradation of the LDL receptor. The tissue-specific effects of the IDOL pathway on plasma cholesterol and atherosclerosis have not been examined. Objective Given that the liver is the primary determinant of plasma cholesterol levels, we sought to examine the consequence of effect of chronic liver-specific expression of a dominant active form of IDOL in mice. Methods and Results We expressed a degradation-resistant, dominant-active form of IDOL (sIDOL) in C57Bl/6J mice from the liver-specific albumin promoter (L-sIDOL transgenics). L-sIDOL mice were fed a Western diet for 20 or 30 weeks and then analyzed for plasma lipid levels and atherosclerotic lesion formation. L-sIDOL mice showed dramatic reductions in hepatic LDLR protein and increased plasma LDL cholesterol levels on both chow and Western diets. Moreover, L-sIDOL mice developed marked atherosclerotic lesions when fed a Western diet. Lesion formation in L-sIDOL mice was more robust than in ApoE*3 Leiden mice and did not require the addition of cholate to the diet. Western diet-fed L-sIDOL mice had elevated expression of LXR target genes and pro-inflammatory genes in their aortas. Conclusions Liver-specific expression of dominant-active IDOL is associated with hypercholesterolemia and a marked elevation in atherosclerotic lesions. Our results show that increased activity of the IDOL pathway in the liver can override other LDLR regulatory pathways leading to cardiovascular disease. L-sIDOL mice are a robust, dominantly-inherited, diet-inducible model for the study of atherosclerosis. PMID:24935961

  7. Intestinal metaplasia with a high salt diet induces epithelial proliferation and alters cell composition in the gastric mucosa of mice.

    PubMed

    Xiao, Fang; Crissey, Mary Ann S; Lynch, John P; Kaestner, Klaus H; Silberg, Debra G; Suh, Eunran

    2005-06-01

    Intestinal metaplasia of the gastric mucosa is an important component in the pathway to adenocarcinoma. The mechanisms that induce the progression from intestinal metaplasia to cancer have not been elucidated. High dietary salt has been known as one of the risk factors for gastric cancer development in humans. Therefore, we investigated the role of high salt diet on gastric epithelial cell proliferation and differentiation, using our mouse model that ectopically expressed Cdx2 homeodomain transcription factor and induced an intestinal metaplastic phenotype in the gastric epithelia. Sixty Cdx2 transgenic and sixty age-matched wild-type littermates were studied. Fifty-percent Cdx2 transgenic and wild type mice were administered a high-salt diet and the other fifty-percent was fed a standard diet starting at 12 weeks after birth. At 10, 20 and 40 weeks after initiation of the diets, histopathological changes were determined by Hemotoxylin and Eosin, alcian blue, and periodic acid-Schiff (PAS) staining. Cell types and cell kinetics were assessed by immunohistochemistry. At 52 weeks, significant alterations in pathology were observed in the Cdx2 transgenic mice fed a high-salt diet, including elongation of gastric pits, reduction of the glandular zone in the gastric corpus, and deepening of glands in the antrum. In the Cdx2 transgenic mice fed a high salt diet, the parietal and chief cells were significantly decreased in the gastric corpus. A significant increase in cell proliferation and apoptosis in the corpus and antrum were observed in Cdx2 transgenic mice fed a high-salt diet as compared to wild-type littermates. Taken together, these data implicate that intestinal metaplasia in concert with a high-salt diet induces epithelial proliferation, apoptosis, and alters cellular types in the gastric mucosa of mice. Alteration in the composition of the gastric epithelium may play a role in influencing the microenvironment to engender susceptibility to carcinogens.

  8. MsrA Overexpression Targeted to the Mitochondria, but Not Cytosol, Preserves Insulin Sensitivity in Diet-Induced Obese Mice.

    PubMed

    Hunnicut, JennaLynn; Liu, Yuhong; Richardson, Arlan; Salmon, Adam B

    2015-01-01

    There is growing evidence that oxidative stress plays an integral role in the processes by which obesity causes type 2 diabetes. We previously identified that mice lacking the protein oxidation repair enzyme methionine sulfoxide reductase A (MsrA) are particularly prone to obesity-induced insulin resistance suggesting an unrecognized role for this protein in metabolic regulation. The goals of this study were to test whether increasing the expression of MsrA in mice can protect against obesity-induced metabolic dysfunction and to elucidate the potential underlying mechanisms. Mice with increased levels of MsrA in the mitochondria (TgMito MsrA) or in the cytosol (TgCyto MsrA) were fed a high fat/high sugar diet and parameters of glucose homeostasis were monitored. Mitochondrial content, markers of mitochondrial proteostasis and mitochondrial energy utilization were assessed. TgMito MsrA, but not TgCyto MsrA, mice remain insulin sensitive after high fat feeding, though these mice are not protected from obesity. This metabolically healthy obese phenotype of TgMito MsrA mice is not associated with changes in mitochondrial number or biogenesis or with a reduction of proteostatic stress in the mitochondria. However, our data suggest that increased mitochondrial MsrA can alter metabolic homeostasis under