Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.

PubMed

Nana, Yang; Peng, Jiao; Jianlin, Zhang; Xiangjian, Zhang; Shutong, Yao; Enxin, Zhan; Bin, Li; Chuanlong, Zong; Hua, Tian; Yanhong, Si; Yunsai, Du; Shucun, Qin; Hui, Wang

2015-01-01

Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

A new protocol for functional analysis of adipogenesis using reverse transfection technology and time-lapse video microscopy.

PubMed

Grönniger, Elke; Wessel, Sonja; Kühn, Sonja Christin; Söhle, Jörn; Wenck, Horst; Stäb, Franz; Winnefeld, Marc

2010-07-01

Since the worldwide increase in obesity represents a growing challenge for healthcare systems, research focusing on fat cell metabolism has become a focal point of interest. Here, we describe a small interfering RNA (siRNA)-technology-based screening method to study fat cell differentiation in human primary preadipocytes that could be further developed towards an automated middle-throughput screening procedure. First, we established optimal conditions for the reverse transfection of human primary preadipocytes demonstrating that an efficient reverse transfection of preadipocytes is technically feasible. Aligning the processes of reverse transfection and fat cell differentiation utilizing peroxisome proliferator-activated receptor gamma (PPAR gamma)-siRNA, we showed that preadipocyte differentiation was suppressed by knock-down of PPAR gamma, the key regulator of fat cell differentiation. The use of fluorescently labelled fatty acids in combination with fluorescence time-lapse microscopy over a longer period of time enabled us to quantify the PPAR gamma phenotype. Additionally, our data demonstrate that reverse transfection of human cultured preadipocytes with TIP60 (HIV-1 Tat-interacting protein 60)-siRNA lead to a TIP60 knock-down and subsequently inhibits fat cell differentiation, suggesting a role of this protein in human adipogenesis. In conclusion, we established a protocol that allows for an efficient functional and time-dependent analysis by quantitative time-lapse microscopy to identify novel adipogenesis-associated genes.

CDP-Diacylglycerol Synthetase Coordinates Cell Growth and Fat Storage through Phosphatidylinositol Metabolism and the Insulin Pathway

PubMed Central

Liu, Yuan; Wang, Wei; Shui, Guanghou; Huang, Xun

2014-01-01

During development, animals usually undergo a rapid growth phase followed by a homeostatic stage when growth has ceased. The increase in cell size and number during the growth phase requires a large amount of lipids; while in the static state, excess lipids are usually stored in adipose tissues in preparation for nutrient-limited conditions. How cells coordinate growth and fat storage is not fully understood. Through a genetic screen we identified Drosophila melanogaster CDP-diacylglycerol synthetase (CDS/CdsA), which diverts phosphatidic acid from triacylglycerol synthesis to phosphatidylinositol (PI) synthesis and coordinates cell growth and fat storage. Loss of CdsA function causes significant accumulation of neutral lipids in many tissues along with reduced cell/organ size. These phenotypes can be traced back to reduced PI levels and, subsequently, low insulin pathway activity. Overexpressing CdsA rescues the fat storage and cell growth phenotypes of insulin pathway mutants, suggesting that CdsA coordinates cell/tissue growth and lipid storage through the insulin pathway. We also revealed that a DAG-to-PE route mediated by the choline/ethanolamine phosphotransferase Bbc may contribute to the growth of fat cells in CdsA RNAi. PMID:24603715

Mouse fat storage-inducing transmembrane protein 2 (FIT2) promotes lipid droplet accumulation in plants

USDA-ARS?s Scientific Manuscript database

Fat Storage-Inducing Transmembrane protein 2 (FIT2) is an endoplasmic reticulum (ER)-localized protein that plays an important role in lipid droplet (LD) formation in animal cells. However, no obvious homologue of FIT2 is found in plants. Here, we tested the function of FIT2 in plant cells by ectopi...

Metabolic Effects of Chronic Cannabis Smoking

PubMed Central

Muniyappa, Ranganath; Sable, Sara; Ouwerkerk, Ronald; Mari, Andrea; Gharib, Ahmed M.; Walter, Mary; Courville, Amber; Hall, Gail; Chen, Kong Y.; Volkow, Nora D.; Kunos, George; Huestis, Marilyn A.; Skarulis, Monica C.

2013-01-01

OBJECTIVE We examined if chronic cannabis smoking is associated with hepatic steatosis, insulin resistance, reduced β-cell function, or dyslipidemia in healthy individuals. RESEARCH DESIGN AND METHODS In a cross-sectional, case-control study, we studied cannabis smokers (n = 30; women, 12; men, 18; 27 ± 8 years) and control subjects (n = 30) matched for age, sex, ethnicity, and BMI (27 ± 6). Abdominal fat depots and intrahepatic fat content were quantified by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Insulin-sensitivity indices and various aspects of β-cell function were derived from oral glucose tolerance tests (OGTT). RESULTS Self-reported cannabis use was: 9.5 (2–38) years; joints/day: 6 (3–30) [median (range)]. Carbohydrate intake and percent calories from carbohydrates, but not total energy intake, were significantly higher in cannabis smokers. There were no group differences in percent total body fat, or hepatic fat, but cannabis smokers had a higher percent abdominal visceral fat (18 ± 9 vs. 12 ± 5%; P = 0.004). Cannabis smokers had lower plasma HDL cholesterol (49 ± 14 vs. 55 ± 13 mg/dL; P = 0.02), but fasting levels of glucose, insulin, total cholesterol, LDL cholesterol, triglycerides, or free fatty acids (FFA) were not different. Adipocyte insulin resistance index and percent FFA suppression during an OGTT was lower (P < 0.05) in cannabis smokers. However, oral glucose insulin sensitivity index, measures of β-cell function, or incretin concentrations did not differ between the groups. CONCLUSIONS Chronic cannabis smoking was associated with visceral adiposity and adipose tissue insulin resistance but not with hepatic steatosis, insulin insensitivity, impaired pancreatic β-cell function, or glucose intolerance. PMID:23530011

A Regulatory Pathway, Ecdysone-Transcription Factor Relish-Cathepsin L, Is Involved in Insect Fat Body Dissociation

PubMed Central

Zhang, Yao; Lu, Yu-Xuan; Liu, Jian; Yang, Cui; Feng, Qi-Li; Xu, Wei-Hua

2013-01-01

Insect fat body is the organ for intermediary metabolism, comparable to vertebrate liver and adipose tissue. Larval fat body is disintegrated to individual fat body cells and then adult fat body is remodeled at the pupal stage. However, little is known about the dissociation mechanism. We find that the moth Helicoverpa armigera cathepsin L (Har-CL) is expressed heavily in the fat body and is released from fat body cells into the extracellular matrix. The inhibitor and RNAi experiments demonstrate that Har-CL functions in the fat body dissociation in H. armigera. Further, a nuclear protein is identified to be transcription factor Har-Relish, which was found in insect immune response and specifically binds to the promoter of Har-CL gene to regulate its activity. Har-Relish also responds to the steroid hormone ecdysone. Thus, the dissociation of the larval fat body is involved in the hormone (ecdysone)-transcription factor (Relish)-target gene (cathepsin L) regulatory pathway. PMID:23459255

Nanofat-derived stem cells with platelet-rich fibrin improve facial contour remodeling and skin rejuvenation after autologous structural fat transplantation

PubMed Central

Liang, Zhi-Jie; Chen, Hai; Zhu, Mao-Guang; Xu, Fang-Tian; He, Ning; Wei, Xiao-Juan; Li, Hong-Mian

2017-01-01

Traditional autologous fat transplantation is a common surgical procedure for treating facial soft tissue depression and skin aging. However, the transplanted fat is easily absorbed, reducing the long-term efficacy of the procedure. Here, we examined the efficacy of nanofat-assisted autologous fat structural transplantation. Nanofat-derived stem cells (NFSCs) were isolated, mechanically emulsified, cultured, and characterized. Platelet-rich fibrin (PRF) enhanced proliferation and adipogenic differentiation of NFSCs in vitro. We then compared 62 test group patients with soft tissue depression or signs of aging who underwent combined nanofat, PRF, and autologous fat structural transplantation to control patients (77 cases) who underwent traditional autologous fat transplantation. Facial soft tissue depression symptoms and skin texture were improved to a greater extent after nanofat transplants than after traditional transplants, and the nanofat group had an overall satisfaction rate above 90%. These data suggest that NFSCs function similarly to mesenchymal stem cells and share many of the biological characteristics of traditional fat stem cell cultures. Transplants that combine newly-isolated nanofat, which has a rich stromal vascular fraction (SVF), with PRF and autologous structural fat granules may therefore be a safe, highly-effective, and long-lasting method for remodeling facial contours and rejuvenating the skin. PMID:28978136

A Plant-Based Dietary Intervention Improves Beta-Cell Function and Insulin Resistance in Overweight Adults: A 16-Week Randomized Clinical Trial.

PubMed

Kahleova, Hana; Tura, Andrea; Hill, Martin; Holubkov, Richard; Barnard, Neal D

2018-02-09

The aim of this study was to test the effect of a plant-based dietary intervention on beta-cell function in overweight adults with no history of diabetes. Participants ( n = 75) were randomized to follow a low-fat plant-based diet ( n = 38) or to make no diet changes ( n = 37) for 16 weeks. At baseline and 16 weeks, beta-cell function was quantified with a mathematical model. Using a standard meal test, insulin secretory rate was calculated by C-peptide deconvolution. The Homeostasis Model Assessment (HOMA-IR) index was used to assess insulin resistance while fasting. A marked increase in meal-stimulated insulin secretion was observed in the intervention group compared with controls (interaction between group and time, Gxt, p < 0.001). HOMA-IR index fell significantly ( p < 0.001) in the intervention group (treatment effect -1.0 (95% CI, -1.2 to -0.8); Gxt, p = 0.004). Changes in HOMA-IR correlated positively with changes in body mass index (BMI) and visceral fat volume ( r = 0.34; p = 0.009 and r = 0.42; p = 0.001, respectively). The latter remained significant after adjustment for changes in BMI ( r = 0.41; p = 0.002). Changes in glucose-induced insulin secretion correlated negatively with BMI changes ( r = -0.25; p = 0.04), but not with changes in visceral fat. Beta-cell function and insulin sensitivity were significantly improved through a low-fat plant-based diet in overweight adults.

The novel SH3 domain protein Dlish/CG10933 mediates fat signaling in Drosophila by binding and regulating Dachs

PubMed Central

Zhang, Yifei; Wang, Xing; Matakatsu, Hitoshi; Fehon, Richard; Blair, Seth S

2016-01-01

Much of the Hippo and planar cell polarity (PCP) signaling mediated by the Drosophila protocadherin Fat depends on its ability to change the subcellular localization, levels and activity of the unconventional myosin Dachs. To better understand this process, we have performed a structure-function analysis of Dachs, and used this to identify a novel and important mediator of Fat and Dachs activities, a Dachs-binding SH3 protein we have named Dlish. We found that Dlish is regulated by Fat and Dachs, that Dlish also binds Fat and the Dachs regulator Approximated, and that Dlish is required for Dachs localization, levels and activity in both wild type and fat mutant tissue. Our evidence supports dual roles for Dlish. Dlish tethers Dachs to the subapical cell cortex, an effect partly mediated by the palmitoyltransferase Approximated under the control of Fat. Conversely, Dlish promotes the Fat-mediated degradation of Dachs. DOI: http://dx.doi.org/10.7554/eLife.16624.001 PMID:27692068

Regulation of PCP by the Fat signaling pathway

PubMed Central

Matis, Maja; Axelrod, Jeffrey D.

2013-01-01

Planar cell polarity (PCP) in epithelia, orthogonal to the apical–basal axis, is essential for numerous developmental events and physiological functions. Drosophila model systems have been at the forefront of studies revealing insights into mechanisms regulating PCP and have revealed distinct signaling modules. One of these, involving the atypical cadherins Fat and Dachsous and the ectokinase Four-jointed, appears to link the direction of cell polarization to the tissue axes. We discuss models for the function of this signaling module as well as several unanswered questions that may guide future investigations. PMID:24142873

Adipocyte Origins: Weighing the Possibilities

PubMed Central

Majka, Susan M.; Barak, Yaacov; Klemm, Dwight J.

2012-01-01

Adipose tissue is the primary energy reservoir in the body and an important endocrine organ that plays roles in energy homeostasis, feeding, insulin sensitivity and inflammation. While it was tacitly assumed that fat in different anatomical locations had a common origin and homogenous function, it is now clear that regional differences exist in adipose tissue characteristics and function. This is exemplified by the link between increased deep abdominal or visceral fat, but not peripheral adipose tissue, and the metabolic disturbances associated with obesity. Regional differences in fat function are due in large part to distinct adipocyte populations that comprise the different fat depots. Evidence accrued primarily in the last decade indicate that the distinct adipocyte populations are generated by a number of processes during and after development. These include the production of adipocytes from different germ cell layers, the formation of distinct preadipocyte populations from mesenchymal progenitors of mesodermal origin, and the production of adipocytes from hematopoietic stem cells from the bone marrow. This review will examine each of these process and their relevance to normal adipose tissue formation and contribution to obesity-related diseases. PMID:21544899

Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity

PubMed Central

Farb, Melissa G.; Tiwari, Stephanie; Karki, Shakun; Ngo, Doan TM; Carmine, Brian; Hess, Donald T.; Zuriaga, Maria A.; Walsh, Kenneth; Fetterman, Jessica L.; Hamburg, Naomi M.; Vita, Joseph A.; Apovian, Caroline M.; Gokce, Noyan

2013-01-01

Objective The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans. Design and Methods In 20 obese subjects (age 37±12 yrs, BMI 47±8 kg/m2) we collected subcutaneous and visceral fat during bariatric surgery and characterized adipose depot-specific gene expression, endothelial cell phenotype, and microvascular function. Vasomotor function was assessed in response to endothelium-dependent agonists using videomicroscopy of small arterioles from fat. Results Arterioles from visceral fat exhibited impaired endothelium-dependent, acetylcholine-mediated vasodilation, compared to the subcutaneous depot (p<0.001). Expression of mRNA transcripts relevant to the cyclooxygenase pathway were upregulated in visceral compared to subcutaneous fat. Pharmacological inhibition of cyclooxygenase with indomethacin improved endothelium-dependent vasodilator function of arterioles from visceral fat by 2-fold (p=0.01), whereas indomethacin had no effect in the subcutaneous depot. Indomethacin increased activation via serine-1177 phosphorylation of endothelial nitric oxide synthase in response to acetylcholine in endothelial cells from visceral fat. Inhibition of endothelial nitric oxide synthase with Nω-nitro-L-arginine methyl ester abrogated the effects of cyclooxygenase-inhibition suggesting that vascular actions of indomethacin were related to increased nitric oxide bioavailability. Conclusions Our findings suggest that cyclooxygenase-mediated vasoconstrictor prostanoids partly contribute to endothelial dysfunction of visceral adipose arterioles in human obesity. PMID:23640904

Caveolins/caveolae protect adipocytes from fatty acid-mediated lipotoxicity.

PubMed

Meshulam, Tova; Breen, Michael R; Liu, Libin; Parton, Robert G; Pilch, Paul F

2011-08-01

Mice and humans lacking functional caveolae are dyslipidemic and have reduced fat stores and smaller fat cells. To test the role of caveolins/caveolae in maintaining lipid stores and adipocyte integrity, we compared lipolysis in caveolin-1 (Cav1)-null fat cells to that in cells reconstituted for caveolae by caveolin-1 re-expression. We find that the Cav1-null cells have a modestly enhanced rate of lipolysis and reduced cellular integrity compared with reconstituted cells as determined by the release of lipid metabolites and lactic dehydrogenase, respectively, into the media. There are no apparent differences in the levels of lipolytic enzymes or hormonally stimulated phosphorylation events in the two cell lines. In addition, acute fasting, which dramatically raises circulating fatty acid levels in vivo, causes a significant upregulation of caveolar protein constituents. These results are consistent with the hypothesis that caveolae protect fat cells from the lipotoxic effects of elevated levels fatty acids, which are weak detergents at physiological pH, by virtue of the property of caveolae to form detergent-resistant membrane domains.

Caveolins/caveolae protect adipocytes from fatty acid-mediated lipotoxicity

PubMed Central

Meshulam, Tova; Breen, Michael R.; Liu, Libin; Parton, Robert G.; Pilch, Paul F.

2011-01-01

Mice and humans lacking functional caveolae are dyslipidemic and have reduced fat stores and smaller fat cells. To test the role of caveolins/caveolae in maintaining lipid stores and adipocyte integrity, we compared lipolysis in caveolin-1 (Cav1)-null fat cells to that in cells reconstituted for caveolae by caveolin-1 re-expression. We find that the Cav1-null cells have a modestly enhanced rate of lipolysis and reduced cellular integrity compared with reconstituted cells as determined by the release of lipid metabolites and lactic dehydrogenase, respectively, into the media. There are no apparent differences in the levels of lipolytic enzymes or hormonally stimulated phosphorylation events in the two cell lines. In addition, acute fasting, which dramatically raises circulating fatty acid levels in vivo, causes a significant upregulation of caveolar protein constituents. These results are consistent with the hypothesis that caveolae protect fat cells from the lipotoxic effects of elevated levels fatty acids, which are weak detergents at physiological pH, by virtue of the property of caveolae to form detergent-resistant membrane domains. PMID:21652731

IKKβ inhibition prevents fat-induced beta cell dysfunction in vitro and in vivo in rodents.

PubMed

Ivovic, Aleksandar; Oprescu, Andrei I; Koulajian, Khajag; Mori, Yusaku; Eversley, Judith A; Zhang, Liling; Nino-Fong, Rodolfo; Lewis, Gary F; Donath, Marc Y; Karin, Michael; Wheeler, Michael B; Ehses, Jan; Volchuk, Allen; Chan, Catherine B; Giacca, Adria

2017-10-01

We have previously shown that oxidative stress plays a causal role in beta cell dysfunction induced by fat. Here, we address whether the proinflammatory kinase inhibitor of (nuclear factor) κB kinase β (IKKβ), which is activated by oxidative stress, is also implicated. Fat (oleate or olive oil) was infused intravenously in Wistar rats for 48 h with or without the IKKβ inhibitor salicylate. Thereafter, beta cell function was evaluated in vivo using hyperglycaemic clamps or ex vivo in islets isolated from fat-treated rats. We also exposed rat islets to oleate in culture, with or without salicylate and 4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline; BMS-345541 (BMS, another inhibitor of IKKβ) and evaluated beta cell function in vitro. Furthermore, oleate was infused in mice treated with BMS and in beta cell-specific Ikkb-null mice. 48 h infusion of fat impaired beta-cell function in vivo, assessed using the disposition index (DI), in rats (saline: 1.41 ± 0.13; oleate: 0.95 ± 0.11; olive oil [OLO]: 0.87 ± 0.15; p < 0.01 for both fats vs saline) and in mice (saline: 2.51 ± 0.39; oleate: 1.20 ± 0.19; p < 0.01 vs saline) and ex vivo (i.e., insulin secretion, units are pmol insulin islet -1  h -1 ) in rat islets (saline: 1.51 ± 0.13; oleate: 1.03 ± 0.10; OLO: 0.91 ± 0.13; p < 0.001 for both fats vs saline) and the dysfunction was prevented by co-infusion of salicylate in rats (oleate + salicylate: 1.30 ± 0.09; OLO + salicylate: 1.33 ± 0.23) or BMS in mice (oleate + BMS: 2.25 ± 0.42) in vivo and by salicylate in rat islets ex vivo (oleate + salicylate: 1.74 ± 0.31; OLO + salicylate: 1.54 ± 0.29). In cultured islets, 48 h exposure to oleate impaired beta-cell function ([in pmol insulin islet -1  h -1 ] control: 0.66 ± 0.12; oleate: 0.23 ± 0.03; p < 0.01 vs saline), an effect prevented by both inhibitors (oleate + salicylate: 0.98 ± 0.08; oleate + BMS: 0.50 ± 0.02). Genetic inhibition of IKKβ also prevented fat-induced beta-cell dysfunction ex vivo ([in pmol insulin islet -1  h -1 ] control saline: 0.16 ± 0.02; control oleate: 0.10 ± 0.02; knockout oleate: 0.17 ± 0.04; p < 0.05 control saline vs. control oleate) and in vivo (DI: control saline: 3.86 ± 0.40; control oleate: 1.95 ± 0.29; knockout oleate: 2.96 ± 0.24; p < 0.01 control saline vs control oleate). Our results demonstrate a causal role for IKKβ in fat-induced beta cell dysfunction in vitro, ex vivo and in vivo.

Adipochemokines induced by ultraviolet irradiation contribute to impaired fat metabolism in subcutaneous fat cells.

PubMed

Kim, E J; Kim, Y K; Kim, S; Kim, J E; Tian, Y D; Doh, E J; Lee, D H; Chung, J H

2018-02-01

Adipose tissue is now appreciated as the pivotal regulator of metabolic and endocrine functions. Subcutaneous (SC) fat, in contrast to visceral fat, may protect against metabolic syndrome and systemic inflammation. We demonstrated that chronic as well as acute ultraviolet (UV) irradiation to the skin induces loss of underlying SC fat. UV-irradiated SC fat may produce chemokines or cytokines that modulate lipid homeostasis and secretion of adipokines. To elucidate UV-induced specific adipochemokines implicated in UV-induced modulation of SC fat. Primary cultured adipocytes were treated with conditioned medium from UV- or sham-irradiated skin cells. Young and older healthy participants provided SC fat from sun-exposed and sun-protected skin. Sun-protected skin from other participants was irradiated with UV. Differentially expressed adipochemokines were screened by cytokine array, and confirmed in vitro and in vivo. The functions of select adipochemokines involved in lipid metabolism were examined via short interfering RNA-mediated knockdown of cognate receptors. Specific adipochemokines, including C-X-C motif chemokine (CXCL) family members such as CXCL5/ENA-78, and C-C motif chemokine (CCL) family members such as CCL20/MIP-3α and CCL5/RANTES, were greatly induced in SC fat by UV exposure. They could impair triglyceride synthesis via downregulation of lipogenic enzymes and sterol regulatory element-binding protein-1 through their respective cognate receptors, CXC chemokine receptor type (CXC-R)2, C-C chemokine receptor type (CCR)-6, and CCR-5. In addition, UV irradiation induced infiltration of adipose tissue macrophages responsible for the secretion of several chemokines into SC fat. These UV-induced adipochemokines may be implicated in the reduction of lipogenesis in SC fat, leading to impairment of fat homeostasis and associated comorbidities such as obesity. © 2017 British Association of Dermatologists.

Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity.

PubMed

Staaf, Johan; Labmayr, Viktor; Paulmichl, Katharina; Manell, Hannes; Cen, Jing; Ciba, Iris; Dahlbom, Marie; Roomp, Kirsten; Anderwald, Christian-Heinz; Meissnitzer, Matthias; Schneider, Reinhard; Forslund, Anders; Widhalm, Kurt; Bergquist, Jonas; Ahlström, Håkan; Bergsten, Peter; Weghuber, Daniel; Kullberg, Joel

2017-03-01

Adolescents with obesity have increased risk of type 2 diabetes and metabolic syndrome (MetS). Pancreatic fat has been related to these conditions; however, little is known about associations in pediatric obesity. The present study was designed to explore these associations further. We examined 116 subjects, 90 with obesity. Anthropometry, MetS, blood samples, and oral glucose tolerance tests were assessed using standard techniques. Pancreatic fat fraction (PFF) and other fat depots were quantified using magnetic resonance imaging. The PFF was elevated in subjects with obesity. No association between PFF and body mass index-standard deviation score (BMI-SDS) was found in the obesity subcohort. Pancreatic fat fraction correlated to Insulin Secretion Sensitivity Index-2 and Homeostatic Model Assessment of Insulin Resistance in simple regression; however, when using adjusted regression and correcting for BMI-SDS and other fat compartments, PFF correlated only to visceral adipose tissue and fasting glucose. Highest levels of PFF were found in subjects with obesity and MetS. In adolescents with obesity, PFF is elevated and associated to MetS, fasting glucose, and visceral adipose tissue but not to beta-cell function, glucose tolerance, or BMI-SDS. This study demonstrates that conclusions regarding PFF and its associations depend on the body mass features of the cohort.

Dietary emulsifiers from milk and soybean differently impact adiposity and inflammation in association with modulation of colonic goblet cells in high-fat fed mice.

PubMed

Lecomte, Manon; Couëdelo, Leslie; Meugnier, Emmanuelle; Plaisancié, Pascale; Létisse, Marion; Benoit, Bérengère; Gabert, Laure; Penhoat, Armelle; Durand, Annie; Pineau, Gaëlle; Joffre, Florent; Géloën, Alain; Vaysse, Carole; Laugerette, Fabienne; Michalski, Marie-Caroline

2016-03-01

Enhanced adiposity and metabolic inflammation are major features of obesity that could be impacted by dietary emulsifiers. We investigated in high-fat fed mice the effects of using a new polar lipid (PL) emulsifier from milk (MPL) instead of soybean lecithin (soybean PL [SPL]) on adipose tissue and intestinal mucosa function. Four groups of C57BL6 mice received for 8 wks a low-fat (LF) diet or a high-fat diet devoid of PLs or an high-fat diet including MPL (high-fat-MPL) or SPL (high-fat-SPL). Compared with high-fat diet, high-fat-SPL diet increased white adipose tissue (WAT) mass (p < 0.05), with larger adipocytes (p < 0.05) and increased expression of tumor necrosis factor alpha, monochemoattractant protein-1, LPS-binding protein, and leptin (p < 0.05). This was not observed with high-fat-MPL diet despite similar dietary intakes and increased expression of fatty acid transport protein 4 and microsomal TG transfer protein, involved in lipid absorption, in upper intestine (p < 0.05). High-fat-MPL mice had a lower expression in WAT of cluster of differentiation 68, marker of macrophage infiltration, versus high-fat and high-fat-SPL mice (p < 0.05), and more goblet cells in the colon (p < 0.05). Unlike SPL, MPL in the high-fat diet did not induce WAT hypertrophy and inflammation but increased colonic goblet cells. This supports further clinical exploration of different sources of dietary emulsifiers in the frame of obesity outbreak. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effects of the type of dietary fat on acetylcholine-evoked amylase secretion and calcium mobilization in isolated rat pancreatic acinar cells.

PubMed

Yago, María D; Díaz, Ricardo J; Martínez, María A; Audi, Nama'a; Naranjo, José A; Martínez-Victoria, Emilio; Mañas, Mariano

2006-04-01

Olive oil is a major component of the Mediterranean diet, and its role in human health is being actively debated. This study aimed to clarify the mechanism of pancreatic adaptation to dietary fat. For this purpose, we examined whether dietary-induced modification of pancreatic membranes affects acinar cell function in response to the secretagogue acetylcholine (ACh). Weaning male Wistar rats were assigned to one of two experimental groups and fed for 8 weeks with a commercial chow (C) or a semisynthetic diet containing virgin olive oil as dietary fat (OO). The fatty acid composition of pancreatic plasma membranes was determined by gas-liquid chromatography. For assessment of secretory function, viable acini were incubated with ACh and amylase of supernatant was further assayed with a substrate reagent. Changes in cytosolic Ca(2+) concentration in response to ACh were measured by fura-2 AM fluorimetry. Compared to C rats, pancreatic cell membranes of OO rats had a higher level of monounsaturated fatty acids and a lower level of both saturated and polyunsaturated fatty acids, thus, reflecting the type of dietary fat given. Net amylase secretion in response to ACh was greatly enhanced after OO feeding, although this was not paralleled by enhancement of ACh-evoked Ca(2+) peak increases. In conclusion, chronic intake of diets that differ in the fat type influences not only the fatty acid composition of rat pancreatic membranes but also the responsiveness of acinar cells to ACh. This mechanism may be, at least in part, responsible for the adaptation of the exocrine pancreas to the type of fat available.

Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology.

PubMed

Nilsen, Kari-Anne; Ihle, Kate E; Frederick, Katy; Fondrk, M Kim; Smedal, Bente; Hartfelder, Klaus; Amdam, Gro V

2011-05-01

Nutrient sensitive insulin-like peptides (ILPs) have profound effects on invertebrate metabolism, nutrient storage, fertility and aging. Many insects transcribe ILPs in specialized neurosecretory cells at changing levels correlated with life history. However, the major site of insect metabolism and nutrient storage is not the brain, but rather the fat body, where functions of ILP expression are rarely studied and poorly understood. Fat body is analogous to mammalian liver and adipose tissue, with nutrient stores that often correlate with behavior. We used the honey bee (Apis mellifera), an insect with complex behavior, to test whether ILP genes in fat body respond to experimentally induced changes of behavioral physiology. Honey bee fat body influences endocrine state and behavior by secreting the yolk protein precursor vitellogenin (Vg), which suppresses lipophilic juvenile hormone and social foraging behavior. In a two-factorial experiment, we used RNA interference (RNAi)-mediated vg gene knockdown and amino acid nutrient enrichment of hemolymph (blood) to perturb this regulatory module. We document factor-specific changes in fat body ilp1 and ilp2 mRNA, the bee's ILP-encoding genes, and confirm that our protocol affects social behavior. We show that ilp1 and ilp2 are regulated independently and differently and diverge in their specific expression-localization between fat body oenocyte and trophocyte cells. Insect ilp functions may be better understood by broadening research to account for expression in fat body and not only brain.

Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology

PubMed Central

Nilsen, Kari-Anne; Ihle, Kate E.; Frederick, Katy; Fondrk, M. Kim; Smedal, Bente; Hartfelder, Klaus; Amdam, Gro V.

2011-01-01

SUMMARY Nutrient sensitive insulin-like peptides (ILPs) have profound effects on invertebrate metabolism, nutrient storage, fertility and aging. Many insects transcribe ILPs in specialized neurosecretory cells at changing levels correlated with life history. However, the major site of insect metabolism and nutrient storage is not the brain, but rather the fat body, where functions of ILP expression are rarely studied and poorly understood. Fat body is analogous to mammalian liver and adipose tissue, with nutrient stores that often correlate with behavior. We used the honey bee (Apis mellifera), an insect with complex behavior, to test whether ILP genes in fat body respond to experimentally induced changes of behavioral physiology. Honey bee fat body influences endocrine state and behavior by secreting the yolk protein precursor vitellogenin (Vg), which suppresses lipophilic juvenile hormone and social foraging behavior. In a two-factorial experiment, we used RNA interference (RNAi)-mediated vg gene knockdown and amino acid nutrient enrichment of hemolymph (blood) to perturb this regulatory module. We document factor-specific changes in fat body ilp1 and ilp2 mRNA, the bee's ILP-encoding genes, and confirm that our protocol affects social behavior. We show that ilp1 and ilp2 are regulated independently and differently and diverge in their specific expression-localization between fat body oenocyte and trophocyte cells. Insect ilp functions may be better understood by broadening research to account for expression in fat body and not only brain. PMID:21490257

Neuron-specific knockdown of the Drosophila fat induces reduction of life span, deficient locomotive ability, shortening of motoneuron terminal branches and defects in axonal targeting.

PubMed

Nakamura, Aya; Tanaka, Ryo; Morishita, Kazushige; Yoshida, Hideki; Higuchi, Yujiro; Takashima, Hiroshi; Yamaguchi, Masamitsu

2017-07-01

Mutations in FAT4 gene, one of the human FAT family genes, have been identified in Van Maldergem syndrome (VMS) and Hennekam lymphangiectasia-lymphedema syndrome (HS). The FAT4 gene encodes a large protein with extracellular cadherin repeats, EGF-like domains and Laminin G-like domains. FAT4 plays a role in tumor suppression and planar cell polarity. Drosophila contains a human FAT4 homologue, fat. Drosophila fat has been mainly studied with Drosophila eye and wing systems. Here, we specially knocked down Drosophila fat in nerve system. Neuron-specific knockdown of fat shortened the life span and induced the defect in locomotive abilities of adult flies. In consistent with these phenotypes, defects in synapse structure at neuromuscular junction were observed in neuron-specific fat-knockdown flies. In addition, aberrations in axonal targeting of photoreceptor neuron in third-instar larvae were also observed, suggesting that fat involves in axonal targeting. Taken together, the results indicate that Drosophila fat plays an essential role in formation and/or maintenance of neuron. Both VMS and HS show mental retardation and neuronal defects. We therefore consider that these two rare human diseases could possibly be caused by the defect in FAT4 function in neuronal cells. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation.

PubMed

Ahmed, Abdulrzag F; de Bock, Charles E; Lincz, Lisa F; Pundavela, Jay; Zouikr, Ihssane; Sontag, Estelle; Hondermarck, Hubert; Thorne, Rick F

2015-12-01

The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are poorly understood. High expression of Fat1 cadherin within the developing neuroepithelium and the manifestation of severe neurological phenotypes in Fat1-knockout mice suggest roles in neurogenesis. Using the SH-SY5Y model of neuronal differentiation and employing gene silencing techniques, we show that FAT1 acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation. FAT1 actions were shown to be mediated through Hippo signalling where it activated core Hippo kinase components and antagonised functions of the Hippo effector TAZ. Suppression of FAT1 promoted the nucleocytoplasmic shuttling of TAZ leading to enhanced transcription of the Hippo target gene CTGF together with accompanying increases in nuclear levels of Smad3. Silencing of TAZ reversed the effects of FAT1 depletion thus connecting inactivation of TAZ-TGFbeta signalling with Hippo signalling mediated through FAT1. These findings establish FAT1 as a new upstream Hippo element regulating early stages of differentiation in neuronal cells.

In vivo evidence for unidentified leptin-induced circulating factors that control white fat mass.

PubMed

Harris, Ruth B S

2015-12-15

Fat transplants increase body fat mass without changing the energy status of an animal and provide a tool for investigating control of total body fat. Early transplant studies found that small pieces of transplanted fat took on the morphology of the transplant recipient. Experiments described here tested whether this response was dependent upon expression of leptin receptors in either transplanted fat or the recipient mouse. Fat from leptin receptor deficient db/db mice or wild-type mice was placed subcutaneously in db/db mice. After 12 wk, cell size distribution in the transplant was the same as in endogenous fat of the recipient. Thus, wild-type fat cells, which express leptin receptors, were enlarged in a hyperleptinemic environment, indicating that leptin does not directly control adipocyte size. By contrast, db/db or wild-type fat transplanted into wild-type mice decreased in size, suggesting that a functional leptin system in the recipient is required for body fat mass to be controlled. In the final experiment, wild-type fat was transplanted into a db/db mouse parabiosed to either another db/db mouse to an ob/ob mouse or in control pairs in which both parabionts were ob/ob mice. Transplants increased in size in db/db-db/db pairs, decreased in db/db-ob/ob pairs and did not change in ob/ob-ob/ob pairs. We propose that leptin from db/db parabionts activated leptin receptors in their ob/ob partners. This, in turn, stimulated release of unidentified circulating factors, which travelled back to the db/db partner and acted on the transplant to reduce fat cell size. Copyright © 2015 the American Physiological Society.

Tangeritin inhibits adipogenesis by down-regulating C/EBPα, C/EBPβ, and PPARγ expression in 3T3-L1 fat cells.

PubMed

He, Y F; Liu, F Y; Zhang, W X

2015-10-29

The treatment of obese patients is a topic investigated by an increasing number of researchers. This study aimed to elucidate the possible inhibitory effect of tangeritin on the development and function of fat cells. 3T3-L1 fat cells were grown to confluence and subjected to different concentrations of tangeritin. The most effective tangeritin inhibition concentration was determined by the MTT assay. The treated cells were subjected to real-time reverse transcriptase PCR and western blot analysis, to detect changes in the CCAAT/enhancer binding protein (C/EBP)α, C/EBPβ, and peroxisome proliferator activated receptor (PPAR)γ expression levels. The MTT assay revealed that the fat cell growth was inhibited at a 20 ng/mL concentration of tangeritin. The results of real-time PCR revealed a significant decrease in the expression of C/EBPα, C/EBPβ, and PPARγ mRNA, following the treatment with tangeritin. Western blot analysis also presented similar results at a protein level. Therefore, we concluded that tangeritin inhibits adipogenesis via the down-regulation of C/EBPα, C/EBPβ, and PPARγ mRNA and protein expression in 3T3-L1 cells.

Growth-Blocking Peptides As Nutrition-Sensitive Signals for Insulin Secretion and Body Size Regulation

PubMed Central

Koyama, Takashi; Mirth, Christen K.

2016-01-01

In Drosophila, the fat body, functionally equivalent to the mammalian liver and adipocytes, plays a central role in regulating systemic growth in response to nutrition. The fat body senses intracellular amino acids through Target of Rapamycin (TOR) signaling, and produces an unidentified humoral factor(s) to regulate insulin-like peptide (ILP) synthesis and/or secretion in the insulin-producing cells. Here, we find that two peptides, Growth-Blocking Peptide (GBP1) and CG11395 (GBP2), are produced in the fat body in response to amino acids and TOR signaling. Reducing the expression of GBP1 and GBP2 (GBPs) specifically in the fat body results in smaller body size due to reduced growth rate. In addition, we found that GBPs stimulate ILP secretion from the insulin-producing cells, either directly or indirectly, thereby increasing insulin and insulin-like growth factor signaling activity throughout the body. Our findings fill an important gap in our understanding of how the fat body transmits nutritional information to the insulin producing cells to control body size. PMID:26928023

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

PubMed Central

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

2014-01-01

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

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

PubMed Central

2018-01-01

Muscle morphogenesis is tightly coupled with that of motor neurons (MNs). Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors. We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis and showed that it is required in the myogenic lineage to control the polarity of progenitor migration. To expand our knowledge on how Fat1 exerts its tissue-morphogenesis regulator activity, we dissected its functions by tissue-specific genetic ablation. An emblematic example of muscle under such morphogenetic control is the cutaneous maximus (CM) muscle, a flat subcutaneous muscle in which progenitor migration is physically separated from the process of myogenic differentiation but tightly associated with elongating axons of its partner MNs. Here, we show that constitutive Fat1 disruption interferes with expansion and differentiation of the CM muscle, with its motor innervation and with specification of its associated MN pool. Fat1 is expressed in muscle progenitors, in associated mesenchymal cells, and in MN subsets, including the CM-innervating pool. We identify mesenchyme-derived connective tissue (CT) as a cell type in which Fat1 activity is required for the non–cell-autonomous control of CM muscle progenitor spreading, myogenic differentiation, motor innervation, and for motor pool specification. In parallel, Fat1 is required in MNs to promote their axonal growth and specification, indirectly influencing muscle progenitor progression. These results illustrate how Fat1 coordinates the coupling of muscular and neuronal morphogenesis by playing distinct but complementary actions in several cell types. PMID:29768404

INSECT FAT BODY: ENERGY, METABOLISM, AND REGULATION

PubMed Central

Arrese, Estela L.; Soulages, Jose L.

2010-01-01

The fat body plays major roles in the life of insects. It is a dynamic tissue involved in multiple metabolic functions. One of these functions is to store and release energy in response to the energy demands of the insect. Insects store energy reserves in the form of glycogen and triglycerides in the adipocytes, the main fat body cell. Insect adipocytes can store a great amount of lipid reserves as cytoplasmic lipid droplets. Lipid metabolism is essential for growth and reproduction and provides energy needed during extended nonfeeding periods. This review focuses on energy storage and release and summarizes current understanding of the mechanisms underlying these processes in insects. PMID:19725772

Microbiota depletion promotes browning of white adipose tissue and reduces obesity

PubMed Central

Chevalier, Claire; Stojanović, Ozren; Colin, Didier J.; Stevanović, Ana; Veyrat-Durebex, Christelle; Tarallo, Valentina; Rigo, Dorothée; Germain, Stéphane; Ilievska, Miroslava; Montet, Xavier; Seimbille, Yann; Hapfelmeier, Siegfried; Trajkovski, Mirko

2015-01-01

Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity1. In response to cold or exercise brown fat cells also emerge in the white adipose tissue (named beige cells), a process known as browning2,3,4. Here, we show that the development of functional beige fat is promoted by microbiota depletion either by antibiotic treatment or in germ-free mice within the inguinal subcutaneous and perigonadal visceral adipose tissues (ingSAT and pgVAT, respectively). This leads to improved glucose tolerance, insulin sensitivity and decreased white fat and adipocyte size in lean mice and obese leptin-deficient (ob/ob) and high fat diet (HFD)-fed mice. These metabolic improvements are mediated by eosinophil infiltration and enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by suppression of the type 2 signaling and are reversed by recolonization of the antibiotic-treated, or the germ-free mice with microbes. These results provide insight into microbiota-fat signaling axis and beige fat development in health and metabolic disease. PMID:26569380

A Buoyancy-Based Screen of Drosophila Larvae for Fat-Storage Mutants Reveals a Role for Sir2 in Coupling Fat Storage to Nutrient Availability

PubMed Central

Reis, Tânia; Van Gilst, Marc R.; Hariharan, Iswar K.

2010-01-01

Obesity has a strong genetic component, but few of the genes that predispose to obesity are known. Genetic screens in invertebrates have the potential to identify genes and pathways that regulate the levels of stored fat, many of which are likely to be conserved in humans. To facilitate such screens, we have developed a simple buoyancy-based screening method for identifying mutant Drosophila larvae with increased levels of stored fat. Using this approach, we have identified 66 genes that when mutated increase organismal fat levels. Among these was a sirtuin family member, Sir2. Sirtuins regulate the storage and metabolism of carbohydrates and lipids by deacetylating key regulatory proteins. However, since mammalian sirtuins function in many tissues in different ways, it has been difficult to define their role in energy homeostasis accurately under normal feeding conditions. We show that knockdown of Sir2 in the larval fat body results in increased fat levels. Moreover, using genetic mosaics, we demonstrate that Sir2 restricts fat accumulation in individual cells of the fat body in a cell-autonomous manner. Consistent with this function, changes in the expression of metabolic enzymes in Sir2 mutants point to a shift away from catabolism. Surprisingly, although Sir2 is typically upregulated under conditions of starvation, Sir2 mutant larvae survive better than wild type under conditions of amino-acid starvation as long as sugars are provided. Our findings point to a Sir2-mediated pathway that activates a catabolic response to amino-acid starvation irrespective of the sugar content of the diet. PMID:21085633

Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations.

PubMed

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

2011-03-01

The nature of dietary fats and fasting concentrations of triglycerides affect postprandial hypertriglyceridemia and glucose homeostasis. The objectives were to examine the effects of meals enriched in monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) on postprandial lipid, glucose, and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations. Fourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals (≈10 kcal/kg body weight) containing MUFAs, SFAs, or no fat. Blood samples were collected at baseline and hourly over 8 h for analysis. The high-fat meals significantly increased postprandial concentrations of triglycerides, nonesterified fatty acids, and insulin and postprandial indexes of β cell function. However, postprandial indexes of insulin sensitivity decreased significantly. These effects were significantly attenuated with MUFAs relative to SFAs. MUFAs postprandially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations. These data suggest that, in contrast with SFAs, MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges.

Fasting, post-OGTT challenge, and nocturnal free fatty acids in prediabetic vs. normal glucose tolerant overweight and obese Latino adolescents

PubMed Central

Toledo-Corral, Claudia M.; Alderete, Tanya L.; Richey, Joyce; Sequeira, Paola; Goran, Michael I.; Weigensberg, Marc J.

2014-01-01

Background and Objective Type 2 diabetes risk and its relationship to free fatty acid (FFA) exposure and visceral fat by prediabetes status in minority adolescents has yet to be explored. Therefore, the objective of this study was to examine the association of circulating FFA under varying conditions with prediabetes in Latino adolescents and to determine the relative relationships of FFA and visceral adiposity to insulin sensitivity, secretion, and β-cell function. Subjects and Outcome Measures Overweight or obese, but otherwise healthy Latino adolescent males and females (n=164, 14.2±2.5 years) were recruited for assessment of prediabetes, abdominal fat, and FFA levels taken at a fasting state (FFAF), during an OGTT (FFAOGTT), and overnight (FFANOCTURNAL). Results Prediabetic adolescents had a higher FFAF than those with normal glucose tolerance when controlling for age, sex, pubertal status, total percent body fat, and visceral fat. FFAOGTT and FFANOCTURNAL did not differ between participants with prediabetes and those with normal glucose tolerance after adjusting for covariates. Visceral fat was independently related to insulin sensitivity and secretion in pubertal adolescents, however in post-pubertal adolescents, FFAF and visceral fat were both independent and negatively related to β-cell function. Conclusion These results support a plausible progression of the lipotoxicity theory of diabetes development during the pubertal transition. PMID:25109287

Effects of milk replacer formulation on measures of mammary growth and composition in Holstein heifers.

PubMed

Daniels, K M; Capuco, A V; McGilliard, M L; James, R E; Akers, R M

2009-12-01

Overfeeding prepubertal heifers may impair mammary parenchymal growth and reduce milk production, but evidence suggests that increased intake of a high-protein milk replacer before weaning may be beneficial. This study was designed to evaluate effects of milk replacer (MR) composition on mass and composition of mammary parenchyma and fat pad, growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis gene expression, and putative mammary epithelial stem cells. Specifically, we hypothesized that positive effects of faster rates of gain during the preweaning period alter the development, persistence, or activity of populations of putative mammary epithelial stem cells, possibly through involvement of GH/IGF-I axis molecules. Twenty-four newborn heifers were fed 1 of 4 MR diets (n = 6/diet): control [20% crude protein (CP), 21% fat MR fed at 441 g of dry matter (DM)/d], high protein, low fat (28% CP, 20% fat MR fed at 951 g of DM/d), high protein, high fat (27% CP, 28% fat MR fed at 951 g of DM/d), and high protein, high fat+ (27% CP, 28% fat MR fed at 1,431 g of DM/d). Water and starter (20% CP, 1.43% fat) were offered ad libitum. Animals were killed on d 65 and mammary tissue was subjected to biochemical, molecular, and histological examination. No differences in mammary parenchymal mass or composition, with or without adjusting for empty body weight, were detected. Mass was increased and composition of the mammary fat pad was altered by nutrient intake. No diet differences in putative mammary epithelial stem cell abundance or abundance of transcripts for genes of the GH/IGF-I axis were detected. In this study, growth of the mammary epithelium, size of the mammary epithelial stem cell population, and components of the GH/IGF-I axis did not depend on diet. However, an underlying positive correlation between telomerase, a marker of mammary stem cells, and growth of the mammary parenchyma was detected. Implications of diet-induced effects on mammary fat pad and possible effects on subsequent development and function remain to be determined.

Why does starvation make bones fat?

PubMed Central

Devlin, Maureen J.

2011-01-01

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. Here I review the possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? To evaluate these possibilities, here I review what is known about the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance. PMID:21793093

Why does starvation make bones fat?

PubMed

Devlin, Maureen J

2011-01-01

Body fat, or adipose tissue, is a crucial energetic buffer against starvation in humans and other mammals, and reserves of white adipose tissue (WAT) rise and fall in parallel with food intake. Much less is known about the function of bone marrow adipose tissue (BMAT), which are fat cells found in bone marrow. BMAT mass actually increases during starvation, even as other fat depots are being mobilized for energy. This review considers several possible reasons for this poorly understood phenomenon. Is BMAT a passive filler that occupies spaces left by dying bone cells, a pathological consequence of suppressed bone formation, or potentially an adaptation for surviving starvation? These possibilities are evaluated in terms of the effects of starvation on the body, particularly the skeleton, and the mechanisms involved in storing and metabolizing BMAT during negative energy balance. Copyright © 2011 Wiley-Liss, Inc.

Current Thoughts on Fat Grafting: Using the Evidence to Determine Fact or Fiction.

PubMed

Sinno, Sammy; Wilson, Stelios; Brownstone, Nicholas; Levine, Steven M

2016-03-01

Autologous fat grafting is an increasingly popular procedure used for facial rejuvenation and body contouring. The purpose of this article is to perform an evidence-based review to determine fact from fiction for the hot topics in autologous fat grafting. A comprehensive literature search was performed. The following key words were then searched: "fat grafting," "autologous fat grafting," "autologous fat transfer," "lipotransfer," "liposculping," and "lipofilling." The authors then assessed each modality individually for the level of evidence that exists and whether the majority of evidence supports or refutes it. A review of the literature demonstrated that there is no standard test for determining fat viability or volume augmentation after grafting. Furthermore, there is no difference in cell viability seen between syringe aspiration and liposuction pump aspiration harvest techniques (Level II). The decision to wash or centrifuge the fat plays very little role in fat graft survival (Level III). There is no difference between cell viability as a function of harvest location (Level IV). Nearly all studies show no significant effect of local anesthesia on adipocyte cells (Level IV). There are excellent data that support the fact that low-shear devices maintain fat structural integrity (Level IV). There is quality evidence that supports longevity of fat grafted to the breast (Level III). Two studies support large-volume fat grafting longevity but fail to prove their results using objective measures or with sufficiently large sample sizes (Level IV). External preexpansion devices improve total graft survival rate (Level IV). There is quality evidence to support that fat should be injected soon after harvesting, as properties of fat begin to change after processing (Level IV). Microneedling (preconditioning) before fat grafting has been demonstrated to improve fat survival (Level III). Currently, the highest levels of evidence derive from human studies of clinical trials and animal studies using human fat. The evidence presented here helps to address the need for accurate and quantitative viability assays. These assays would facilitate a systematic evaluation of each procedural step during fat graft harvest, processing, and grafting to improve the overall viability and predictability of fat grafts.

Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease.

PubMed

Burke, Shoshana; Nagajyothi, Fnu; Thi, Mia M; Hanani, Menachem; Scherer, Philipp E; Tanowitz, Herbert B; Spray, David C

2014-11-01

Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions. Copyright © 2014. Published by Elsevier Masson SAS.

Dietary ribonucleic acid suppresses inflammation of adipose tissue and improves glucose intolerance that is mediated by immune cells in C57BL/6 mice fed a high-fat diet.

PubMed

Sakai, Tohru; Taki, Tomoyo; Nakamoto, Akiko; Tazaki, Shiho; Arakawa, Mai; Nakamoto, Mariko; Tsutsumi, Rie; Shuto, Emi

2015-01-01

Recent evidence suggests that immune cells play an important role in differentiation of inflammatory macrophages in adipose tissue, which contributes to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown to modulate immune function. We hypothesized that RNA affects immune cell function in adipose tissue and then improves inflammatory response in adipose tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk. An oral glucose tolerance test was performed. Supplementation of dietary RNA in C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC) after oral glucose administration than that for control mice. The mRNA expression levels of inflammation-related cytokines in adipose tissue and serum interleukin-6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG-1 knockout mice. These results indicate that RNA improves inflammation in adipose tissue and reduces the AUC value following oral glucose administration in a T and B cell-dependent manner.

Subcutaneous adipose tissue macropage infiltration is associated with hepatic and visceral fat deposition, hyperinsulinemia, and stimulation of NF-kB stress pathway

USDA-ARS?s Scientific Manuscript database

The goal was to examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), Beta-cell function, and SAT gene expression. SAT biopsies were obtained from...

Matrix metalloproteinase (MMP)-9 in cancer-associated fibroblasts (CAFs) is suppressed by omega-3 polyunsaturated fatty acids in vitro and in vivo.

PubMed

Taguchi, Ayumi; Kawana, Kei; Tomio, Kensuke; Yamashita, Aki; Isobe, Yosuke; Nagasaka, Kazunori; Koga, Kaori; Inoue, Tomoko; Nishida, Haruka; Kojima, Satoko; Adachi, Katsuyuki; Matsumoto, Yoko; Arimoto, Takahide; Wada-Hiraike, Osamu; Oda, Katsutoshi; Kang, Jing X; Arai, Hiroyuki; Arita, Makoto; Osuga, Yutaka; Fujii, Tomoyuki

2014-01-01

Cancer associated fibroblasts (CAFs) are responsible for tumor growth, angiogenesis, invasion, and metastasis. Matrix metalloproteinase (MMP)-9 secreted from cancer stroma populated by CAFs is a prerequisite for cancer angiogenesis and metastasis. Omega-3 polyunsaturated fatty acids (omega-3 PUFA) have been reported to have anti-tumor effects on diverse types of malignancies. Fat-1 mice, which can convert omega-6 to omega-3 PUFA independent of diet, are useful to investigate the functions of endogenous omega-3 PUFA. To examine the effect of omega-3 PUFA on tumorigenesis, TC-1 cells, a murine epithelial cell line immortalized by human papillomavirus (HPV) oncogenes, were injected subcutaneously into fat-1 or wild type mice. Tumor growth and angiogenesis of the TC-1 tumor were significantly suppressed in fat-1 compared to wild type mice. cDNA microarray of the tumors derived from fat-1 and wild type mice revealed that MMP-9 is downregulated in fat-1 mice. Immunohistochemical study demonstrated immunoreactivity for MMP-9 in the tumor stromal fibroblasts was diffusely positive in wild type whereas focal in fat-1 mice. MMP-9 was expressed in primary cultured fibroblasts isolated from fat-1 and wild type mice but was not expressed in TC-1 cells. Co-culture of fibroblasts with TC-1 cells enhanced the expression and the proteinase activity of MMP-9, although the protease activity of MMP-9 in fat-1-derived fibroblasts was lower than that in wild type fibroblasts. Our data suggests that omega-3 PUFAs suppress MMP-9 induction and tumor angiogenesis. These findings may provide insight into mechanisms by which omega-3 PUFAs exert anti-tumor effects by modulating tumor microenvironment.

Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25

PubMed Central

Mullaney, Brendan; Ashrafi, Kaveh

2010-01-01

Summary Acyl-CoA synthases are important for lipid synthesis and breakdown, generation of signaling molecules and lipid modification of proteins, highlighting the challenge of understanding metabolic pathways within intact organisms. From a C. elegans mutagenesis screen, we found that loss of ACS-3, a long-chain acyl-CoA synthase, causes enhanced intestinal lipid uptake, de novo fat synthesis, and accumulation of enlarged, neutral lipid rich intestinal depots. Here, we show that ACS-3 functions in seam cells, epidermal cells anatomically distinct from sites of fat uptake and storage, and that acs-3 mutant phenotypes require the nuclear hormone receptor NHR-25, a key regulator of C. elegans molting. Our findings suggest that ACS-3 derived long chain fatty acyl-CoAs, perhaps incorporated into complex ligands such as phosphoinositides, modulate NHR-25 function, which in turn regulates an endocrine program of lipid uptake and synthesis. These results reveal a link between acyl-CoA synthase function and an NR5A family nuclear receptor in C. elegans. PMID:20889131

The value of FATS expression in predicting sensitivity to radiotherapy in breast cancer

PubMed Central

Zhang, Tiemei; Sun, Tao; Su, Yi; Zhao, Jing; Mu, Kun; Jin, Zhao; Gao, Ming; Liu, Juntian; Gu, Lin

2017-01-01

Purpose The fragile-site associated tumor suppressor (FATS) is a newly identified tumor suppressor involved in radiation-induced tumorigenesis. The purpose of this study was to characterize FATS expression in breast cancers about radiotherapy benefit, patient characteristics, and prognosis. Results The expression of FATS mRNA was silent or downregulated in 95.2% of breast cancer samples compared with paired normal controls (P < .0001). Negative status of FATS was correlated with higher nuclear grade (P = .01) and shorter disease-free survival (DFS) of breast cancer (P = .036). In a multivariate analysis, FATS expression showed favorable prognostic value for DFS (odds ratio, 0.532; 95% confidence interval, 0.299 to 0.947; (P = .032). Furthermore, improved survival time was seen in FATS-positive patients receiving radiotherapy (P = .006). The results of multivariate analysis revealed independent prognostic value of FATS expression in predicting longer DFS (odds ratio, 0.377; 95% confidence interval, 0.176 to 0.809; P = 0.012) for patients receiving adjuvant radiotherapy. In support of this, reduction of FATS expression in breast cancer cell lines, FATS positive group significantly sensitized than Knock-down of FATS group. Materials and Methods Tissue samples from 156 breast cancer patients and 42 controls in tumor bank were studied. FATS gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). FATS function was examined in breast cancer cell lines using siRNA knock-downs and colony forming assays after irradiation. Conclusions FATS status is a biomarker in breast cancer to identify individuals likely to benefit from radiotherapy. PMID:28402275

The value of FATS expression in predicting sensitivity to radiotherapy in breast cancer.

PubMed

Zhang, Jun; Wu, Nan; Zhang, Tiemei; Sun, Tao; Su, Yi; Zhao, Jing; Mu, Kun; Jin, Zhao; Gao, Ming; Liu, Juntian; Gu, Lin

2017-06-13

The fragile-site associated tumor suppressor (FATS) is a newly identified tumor suppressor involved in radiation-induced tumorigenesis. The purpose of this study was to characterize FATS expression in breast cancers about radiotherapy benefit, patient characteristics, and prognosis. The expression of FATS mRNA was silent or downregulated in 95.2% of breast cancer samples compared with paired normal controls (P < .0001). Negative status of FATS was correlated with higher nuclear grade (P = .01) and shorter disease-free survival (DFS) of breast cancer (P = .036). In a multivariate analysis, FATS expression showed favorable prognostic value for DFS (odds ratio, 0.532; 95% confidence interval, 0.299 to 0.947; (P = .032). Furthermore, improved survival time was seen in FATS-positive patients receiving radiotherapy (P = .006). The results of multivariate analysis revealed independent prognostic value of FATS expression in predicting longer DFS (odds ratio, 0.377; 95% confidence interval, 0.176 to 0.809; P = 0.012) for patients receiving adjuvant radiotherapy. In support of this, reduction of FATS expression in breast cancer cell lines, FATS positive group significantly sensitized than Knock-down of FATS group. Tissue samples from 156 breast cancer patients and 42 controls in tumor bank were studied. FATS gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). FATS function was examined in breast cancer cell lines using siRNA knock-downs and colony forming assays after irradiation. FATS status is a biomarker in breast cancer to identify individuals likely to benefit from radiotherapy.

High fat-diet and saturated fatty acid palmitate inhibits IGF-1 function in chondrocytes.

PubMed

Nazli, S A; Loeser, R F; Chubinskaya, S; Willey, J S; Yammani, R R

2017-09-01

Insulin-like growth factor-1 (IGF-1) promotes matrix synthesis and cell survival in cartilage. Chondrocytes from aged and osteoarthritic cartilage have a reduced response to IGF-1. The purpose of this study was to determine the effect of free fatty acids (FFA) present in a high-fat diet on IGF-1 function in cartilage and the role of endoplasmic reticulum (ER) stress. C57BL/6 male mice were maintained on either a high-fat (60% kcal from fat) or a low-fat (10% kcal from fat) diet for 4 months. Mice were then sacrificed; femoral head cartilage caps were collected and treated with IGF-1 to measure proteoglycan (PG) synthesis. Cultured human chondrocytes were treated with 500 μM FFA palmitate or oleate, followed by stimulation with (100 ng/ml) IGF-1 overnight to measure CHOP (a protein marker for ER stress) and PG synthesis. Human chondrocytes were pre-treated with palmitate or 1 mM 4-phenyl butyric acid (PBA) or 1 μM C-Jun N terminal Kinase (JNK) inhibitor, and IGF-1 function (PG synthesis and signaling) was measured. Cartilage explants from mice on the high fat-diet showed reduced IGF-1 mediated PG synthesis compared to a low-fat group. Treatment of human chondrocytes with palmitate induced expression of CHOP, activated JNK and inhibited IGF-1 function. PBA, a small molecule chemical chaperone that alleviates ER stress rescued IGF-1 function and a JNK inhibitor rescued IGF-1 signaling. Palmitate-induced ER stress inhibited IGF-1 function in chondrocytes/cartilage via activating the mitogen-activated protein (MAP) kinase JNK. This is the first study to demonstrate that ER stress is metabolic factor that regulates IGF-1 function in chondrocytes. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

A comparative assessment of cartilage and joint fat pad as a potential source of cells for autologous therapy development in knee osteoarthritis.

PubMed

English, A; Jones, E A; Corscadden, D; Henshaw, K; Chapman, T; Emery, P; McGonagle, D

2007-11-01

The utility of autologous chondrocytes for cartilage repair strategies in older subjects with osteoarthritis (OA) may be limited by both age-related and disease-associated decline in chondrogenesis. The aim of this work was to assess OA Hoffa's fat pad as an alternative source of autologous chondroprogenitor cells and to compare it with OA chondrocytes derived from different areas of cartilage. Cartilage and fat pad tissue digests were obtained from 26 subjects with knee OA and compared with normal bone marrow (BM) mesenchymal stem cells (MSCs) with respect to their in vitro colony-forming potential, growth kinetics, multipotentiality and clonogenicity. Flow cytometry was used to investigate their MSC marker phenotype. Expanded cultures derived from eroded areas of cartilage were slightly more chondrogenic than those derived from macroscopically normal cartilage or chondro-osteophytes; however, all cartilage-derived cultures failed to maintain their chondrogenic potency following extended expansion. In contrast, OA fat pads contained highly clonogenic and multipotential cells with stable chondrogenic potency in vitro, even after 16 population doublings. Standard colony-forming assays failed to reflect the observed functional differences between the studied tissues whereas flow cytometry revealed higher levels of a putative MSC marker low-affinity growth factor receptor (LNGFR) on culture expanded fat pad-derived, but not cartilage-derived, MSCs. In contrast to OA cartilage from three different sites, OA Hoffa's fat pad contains clonogenic cells that meet the criteria for MSCs and produce multipotential cultures that maintain their chondrogenesis long term. These findings have broad implications for future strategies aimed at cartilage repair in OA.

Tripeptidyl peptidase II promotes fat formation in a conserved fashion.

PubMed

McKay, Renée M; McKay, James P; Suh, Jae Myoung; Avery, Leon; Graff, Jonathan M

2007-12-01

Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner.

Tripeptidyl peptidase II promotes fat formation in a conserved fashion

PubMed Central

McKay, Renée M; McKay, James P; Suh, Jae Myoung; Avery, Leon; Graff, Jonathan M

2007-01-01

Tripeptidyl peptidase II (TPPII) is a multifunctional and evolutionarily conserved protease. In the mammalian hypothalamus, TPPII has a proposed anti-satiety role affected by degradation of the satiety hormone cholecystokinin 8. Here, we show that TPPII also regulates the metabolic homoeostasis of Caenorhabditis elegans; TPPII RNA interference (RNAi) decreases worm fat stores. However, this occurs independently of feeding behaviour and seems to be a function within fat-storing tissues. In mammalian cell culture, TPPII stimulates adipogenesis and TPPII RNAi blocks adipogenesis. The pro-adipogenic action of TPPII seems to be independent of protease function, as catalytically inactive TPPII also increases adipogenesis. Mice that were homozygous for an insertion in the Tpp2 locus were embryonic lethal. However, Tpp2 heterozygous mutants were lean compared with wild-type littermates, although food intake was normal. These findings indicate that TPPII has central and peripheral roles in regulating metabolism and that TPPII actions in fat-storing tissues might be an ancient function carried out in a protease-independent manner. PMID:17932511

Deregulation of the Protocadherin Gene FAT1 Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy

PubMed Central

Caruso, Nathalie; Herberth, Balàzs; Bartoli, Marc; Puppo, Francesca; Dumonceaux, Julie; Zimmermann, Angela; Denadai, Simon; Lebossé, Marie; Roche, Stephane; Geng, Linda; Magdinier, Frederique; Attarian, Shahram; Bernard, Rafaelle; Maina, Flavio; Levy, Nicolas; Helmbacher, Françoise

2013-01-01

Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts. Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains, altering the shape of selective groups of muscles in the shoulder and face. These shape abnormalities were followed by early onset regionalised muscle defects in adult Fat1-deficient mice. Tissue-specific ablation of Fat1 driven by Pax3-cre reproduced muscle shape defects in limb but not face muscles, indicating a cell-autonomous contribution of Fat1 in migrating muscle precursors. Strikingly, the topography of muscle abnormalities caused by Fat1 loss-of-function resembles that of human patients with facioscapulohumeral dystrophy (FSHD). FAT1 lies near the critical locus involved in causing FSHD, and Fat1 mutant mice also show retinal vasculopathy, mimicking another symptom of FSHD, and showed abnormal inner ear patterning, predictive of deafness, reminiscent of another burden of FSHD. Muscle-specific reduction of FAT1 expression and promoter silencing was observed in foetal FSHD1 cases. CGH array-based studies identified deletion polymorphisms within a putative regulatory enhancer of FAT1, predictive of tissue-specific depletion of FAT1 expression, which preferentially segregate with FSHD. Our study identifies FAT1 as a critical determinant of muscle form, misregulation of which associates with FSHD. PMID:23785297

Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation.

PubMed

Chu, Audrey Y; Deng, Xuan; Fisher, Virginia A; Drong, Alexander; Zhang, Yang; Feitosa, Mary F; Liu, Ching-Ti; Weeks, Olivia; Choh, Audrey C; Duan, Qing; Dyer, Thomas D; Eicher, John D; Guo, Xiuqing; Heard-Costa, Nancy L; Kacprowski, Tim; Kent, Jack W; Lange, Leslie A; Liu, Xinggang; Lohman, Kurt; Lu, Lingyi; Mahajan, Anubha; O'Connell, Jeffrey R; Parihar, Ankita; Peralta, Juan M; Smith, Albert V; Zhang, Yi; Homuth, Georg; Kissebah, Ahmed H; Kullberg, Joel; Laqua, René; Launer, Lenore J; Nauck, Matthias; Olivier, Michael; Peyser, Patricia A; Terry, James G; Wojczynski, Mary K; Yao, Jie; Bielak, Lawrence F; Blangero, John; Borecki, Ingrid B; Bowden, Donald W; Carr, John Jeffrey; Czerwinski, Stefan A; Ding, Jingzhong; Friedrich, Nele; Gudnason, Vilmunder; Harris, Tamara B; Ingelsson, Erik; Johnson, Andrew D; Kardia, Sharon L R; Langefeld, Carl D; Lind, Lars; Liu, Yongmei; Mitchell, Braxton D; Morris, Andrew P; Mosley, Thomas H; Rotter, Jerome I; Shuldiner, Alan R; Towne, Bradford; Völzke, Henry; Wallaschofski, Henri; Wilson, James G; Allison, Matthew; Lindgren, Cecilia M; Goessling, Wolfram; Cupples, L Adrienne; Steinhauser, Matthew L; Fox, Caroline S

2017-01-01

Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopic-fat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 × 10 -8 ; false discovery rate < 1%). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease.

Adipose-derived stem cell (ASC)-enriched fat grafting: experiments using White rabbits and an automated cell processing apparatus.

PubMed

Kakudo, Natsuko; Morimoto, Naoki; Ogawa, Takeshi; Hihara, Masakatsu; Lai, Fangyuan; Kusumoto, Kenji

2017-09-01

The grafting of fat mixed with adipose-derived stem cells (ASCs) is being increasingly applied to compensate for the disadvantages of previous fat grafting methods. Devices that automatically isolate fat stem cells also have recently been developed. ASCs were isolated from the inguinal region of White rabbits using Icellator ® , and the number of cells and their viability were measured. The cell count per fat graft (mL) was adjusted to the following concentrations and subcutaneously transplanted into the back: Control group, Fat + PBS; Fat + ASCs (×0.5) group, 1.6 × 10 5 cells/mL; and Fat + ASCs (×1) group, 3.2 × 10 5 cells/mL. Grafted fat weight was measured after 8 weeks, and histological, immunohistological, and specifically stained sections were prepared. Fat absorption was reduced in Fat + ASCs (×0.5) and Fat + ASCs (×1) groups. The number of blood vessels was higher in Fat + ASCs (×1) than in the control group, and blood vessel areas were higher in Fat + ASCs (×0.5) and Fat + ASCs (×1) groups than in the control group. The usefulness of the automated cell processing apparatus, Icellator ® , was confirmed, and the results obtained suggest that grafted ASCs promote the vascularization and engraftment of fat grafts.

Sequencing the transcriptome of milk production: milk trumps mammary tissue.

PubMed

Lemay, Danielle G; Hovey, Russell C; Hartono, Stella R; Hinde, Katie; Smilowitz, Jennifer T; Ventimiglia, Frank; Schmidt, Kimberli A; Lee, Joyce W S; Islas-Trejo, Alma; Silva, Pedro Ivo; Korf, Ian; Medrano, Juan F; Barry, Peter A; German, J Bruce

2013-12-12

Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation.

Premature remodeling of fat body and fat mobilization triggered by platelet-derived growth factor/VEGF receptor in Drosophila.

PubMed

Zheng, Huimei; Wang, Xuexiang; Guo, Pengfei; Ge, Wanzhong; Yan, Qinfeng; Gao, Weiqiang; Xi, Yongmei; Yang, Xiaohang

2017-05-01

In Drosophila, fat-body remodeling accompanied with fat mobilization is an ecdysone-induced dynamic process that only occurs during metamorphosis. Here, we show that the activated Drosophila platelet-derived growth factor/VEGF receptor (PVR) is sufficient to induce shape changes in the fat body, from thin layers of tightly conjugated polygonal cells to clusters of disaggregated round-shaped cells. These morphologic changes are reminiscent of those seen during early pupation upon initiation of fat-body remodeling. Activation of PVR also triggers an early onset of lipolysis and mobilization of internal storage, as revealed by the appearance of small lipid droplets and up-regulated lipolysis-related genes. We found that PVR displays a dynamic expression pattern in the fat body and peaks at the larval-prepupal transition under the control of ecdysone signaling. Removal of PVR, although it does not prevent ecdysone-induced fat-body remodeling, causes ecdysone signaling to be up-regulated. Our data reveal that PVR is active in a dual-secured mechanism that involves an ecdysone-induced fat-body remodeling pathway and a reinforced PVR pathway for effective lipid mobilization. Ectopic expression of activated c-kit-the mouse homolog of PVR in the Drosophila fat body-also results in a similar phenotype. This may suggest a novel function of c-kit as it relates to lipid metabolism in mammals.-Zheng, H., Wang, X., Guo, P., Ge, W., Yan, Q., Gao, W., Xi, Y., Yang, X. Premature remodeling of fat body and fat mobilization triggered by platelet-derived growth factor/VEGF receptor in Drosophila . © FASEB.

Effects of excess salt and fat intake on myocardial function and infarct size in rat.

PubMed

Mozaffari, Mahmood S; Patel, Champa; Ballas, Claudia; Schaffer, Stephen W

2006-03-13

Important risk factors for cardiovascular disease include excess dietary intake of saturated fat and (or) salt. This study tested the hypothesis that excess intakes of saturated fat (e.g., beef tallow) and salt cause greater myocardial cell death following ischemia-reperfusion injury than each risk factor alone. Male rats were divided into four groups: basal fat diet (4.5% as calories; control), high fat diet (40% as calories; FAT), basal fat diet and high salt (1% NaCl solution; SALT) and high fat diet and high salt (FATSALT). The gain in body weight was significantly higher for FAT and FATSALT groups than those of either the control or the SALT group. Five weeks of exposure to the dietary regimens did not significantly affect the coronary flow rate and except for the salt-fed group, had no effect on the rate-pressure-product of the isolated heart perfused in Langendorff mode. Although infarct size was not affected by the high fat diet, it was reduced by the high salt regimen relative to the high fat diet or the control groups. When rats were fed the FAT and SALT combination, the effect of salt feeding on infarct size was not observed. In addition, the FATSALT group displayed a more marked deterioration in contractile function following ischemia-reperfusion injury than the other groups. In conclusion, short-term intake of a high fat diet, which significantly increases body weight, does not worsen ischemia-reperfusion injury although the treatment prevents the reduction of infarct size associated with high salt feeding.

Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk

PubMed Central

Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

2016-01-01

Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p < 0.05). A strong association in miRNA profiles was found between HM cells and fat, whilst PBMCs and plasma were distinctly different to HM, displaying marked inter-individual variation. Considering the dominance of epithelial cells in mature milk of healthy women, these results suggest that HM miRNAs primarily originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Our findings demonstrate that unlike infant formulae, which contained very few human miRNA, HM is a rich source of lactation-specific miRNA, which could be used as biomarkers of the performance and health status of the lactating mammary gland. Given the recently identified stability, uptake and functionality of food- and milk-derived miRNA in vivo, HM miRNA are likely to contribute to infant protection and development. PMID:26854194

Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk.

PubMed

Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E; Geddes, Donna T; Kakulas, Foteini

2016-02-08

Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p < 0.05). A strong association in miRNA profiles was found between HM cells and fat, whilst PBMCs and plasma were distinctly different to HM, displaying marked inter-individual variation. Considering the dominance of epithelial cells in mature milk of healthy women, these results suggest that HM miRNAs primarily originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Our findings demonstrate that unlike infant formulae, which contained very few human miRNA, HM is a rich source of lactation-specific miRNA, which could be used as biomarkers of the performance and health status of the lactating mammary gland. Given the recently identified stability, uptake and functionality of food- and milk-derived miRNA in vivo, HM miRNA are likely to contribute to infant protection and development.

Changes in subcutaneous fat cell volume and insulin sensitivity after weight loss.

PubMed

Andersson, Daniel P; Eriksson Hogling, Daniel; Thorell, Anders; Toft, Eva; Qvisth, Veronica; Näslund, Erik; Thörne, Anders; Wirén, Mikael; Löfgren, Patrik; Hoffstedt, Johan; Dahlman, Ingrid; Mejhert, Niklas; Rydén, Mikael; Arner, Erik; Arner, Peter

2014-07-01

Large subcutaneous fat cells associate with insulin resistance and high risk of developing type 2 diabetes. We investigated if changes in fat cell volume and fat mass correlate with improvements in the metabolic risk profile after bariatric surgery in obese patients. Fat cell volume and number were measured in abdominal subcutaneous adipose tissue in 62 obese women before and 2 years after Roux-en-Y gastric bypass (RYGB). Regional body fat mass by dual-energy X-ray absorptiometry; insulin sensitivity by hyperinsulinemic-euglycemic clamp; and plasma glucose, insulin, and lipid profile were assessed. RYGB decreased body weight by 33%, which was accompanied by decreased adipocyte volume but not number. Fat mass in the measured regions decreased and all metabolic parameters were improved after RYGB (P < 0.0001). Whereas reduced subcutaneous fat cell size correlated strongly with improved insulin sensitivity (P = 0.0057), regional changes in fat mass did not, except for a weak correlation between changes in visceral fat mass and insulin sensitivity and triglycerides. The curve-linear relationship between fat cell size and fat mass was altered after weight loss (P = 0.03). After bariatric surgery in obese women, a reduction in subcutaneous fat cell volume associates more strongly with improvement of insulin sensitivity than fat mass reduction per se. An altered relationship between adipocyte size and fat mass may be important for improving insulin sensitivity after weight loss. Fat cell size reduction could constitute a target to improve insulin sensitivity. © 2014 by the American Diabetes Association.

Adipose-derived mesenchymal stem cells promote the survival of fat grafts via crosstalk between the Nrf2 and TLR4 pathways

PubMed Central

Chen, Xiaosong; Yan, Liu; Guo, Zhihui; Chen, Zhaohong; Chen, Ying; Li, Ming; Huang, Chushan; Zhang, Xiaoping; Chen, Liangwan

2016-01-01

Autologous fat grafting is an effective reconstructive surgery technique; however, its success is limited by inconsistent graft retention and an environment characterized by high oxidative stress and inflammation. Adipose-derived stem cells (ADSCs) increase the survival of fat grafts, although the underlying mechanisms remain unclear. Here, TLR4−/− and Nrf2−/− mice were used to explore the effects of oxidative stress and inflammation on the viability and function of ADSCs in vitro and in vivo. Enrichment of fat grafts with ADSCs inhibited inflammatory cytokine production, enhanced growth factor levels, increased fat graft survival, downregulated NADPH oxidase (NOX)1 and 4 expression, increased vascularization and reduced ROS production in a manner dependent on toll-like receptor (TLR)-4 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Immunohistochemical analysis showed that exposure to hypoxia enhanced ADSC growth and promoted the differentiation of ADSCs into vascular endothelial cells. Hypoxia-induced inflammatory cytokine, growth factor and NOX1/4 upregulation, as well as increased ROS production and apoptosis in ADSCs were dependent on TLR4 and Nrf2, which also modulated the effect of ADSCs on promoting endothelial progenitor cell migration and angiogenesis. Western blot analyses showed that the effects of hypoxia on ADSCs were regulated by crosstalk between Nrf2 antioxidant responses and NF-κB- and TLR4-mediated inflammatory responses. Taken together, our results indicate that ADSCs can increase the survival of fat transplants through the modulation of inflammatory and oxidative responses via Nrf2 and TLR4, suggesting potential strategies to improve the use of ADSCs for cell therapy. PMID:27607584

Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes.

PubMed

Nieuwoudt, Stephan; Fealy, Ciarán E; Foucher, Julie A; Scelsi, Amanda R; Malin, Steven K; Pagadala, Mangesh; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

2017-09-01

Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D. Copyright © 2017 the American Physiological Society.

Effects of probiotic Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS supplementation on intestinal and systemic markers of inflammation in ApoE*3Leiden mice consuming a high-fat diet.

PubMed

Oksaharju, Anna; Kooistra, Teake; Kleemann, Robert; van Duyvenvoorde, Wim; Miettinen, Minja; Lappalainen, Jani; Lindstedt, Ken A; Kovanen, Petri T; Korpela, Riitta; Kekkonen, Riina A

2013-07-14

A high-fat diet disturbs the composition and function of the gut microbiota and generates local gut-associated and also systemic responses. Intestinal mast cells, for their part, secrete mediators which play a role in the orchestration of physiological and immunological functions of the intestine. Probiotic bacteria, again, help to maintain the homeostasis of the gut microbiota by protecting the gut epithelium and regulating the local immune system. In the present study, we explored the effects of two probiotic bacteria, Lactobacillus rhamnosus GG (GG) and Propionibacterium freudenreichii spp. shermanii JS (PJS), on high fat-fed ApoE*3Leiden mice by estimating the mast cell numbers and the immunoreactivity of TNF-α and IL-10 in the intestine, as well as plasma levels of several markers of inflammation and parameters of lipid metabolism. We found that mice that received GG and PJS exhibited significantly lower numbers of intestinal mast cells compared with control mice. PJS lowered intestinal immunoreactivity of TNF-α, while GG increased intestinal IL-10. PJS was also observed to lower the plasma levels of markers of inflammation including vascular cell adhesion molecule 1, and also the amount of gonadal adipose tissue. GG lowered alanine aminotransferase, a marker of hepatocellular activation. Collectively, these data demonstrate that probiotic GG and PJS tend to down-regulate both intestinal and systemic pro-inflammatory changes induced by a high-fat diet in this humanised mouse model.

PubMed Central

MAZZOLA, R.F.; CANTARELLA, G.; TORRETTA, S.; SBARBATI, A.; LAZZARI, L.; PIGNATARO, L.

2011-01-01

SUMMARY Minimally-invasive autologous fat injection of the head and neck region can be considered a valid alternative to major invasive surgical procedures both for aesthetic and functional purposes. The favourable outcomes of autologous fat injection in otolaryngological practice are due to the filling of soft tissue and, mainly, to the potential regenerative effect of adipose-derived mesenchymal stem cells. Herewith, some important biological preliminary remarks are described underlying the potential of autologous fat injection in regenerative medicine, and personal experience in using it for both consolidated clinical applications, such as fat grafting to the face and vocal fold augmentation in the treatment of glottic incompetence, and more recent applications including the treatment of post-parotidectomy Frey syndrome and velopharyngeal insufficiency. PMID:22058586

Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice

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

Wang, Xiaoyu; Zhao, Shiqi; Su, Mengqi

Endothelial dysfunction occurs in obese patients and high-fat diet (HFD) fed experimental animals. While geraniol has been reported to ameliorate inflammation and oxidative stress, inhibit tumor cell proliferation, and improve atherosclerosis, its direct effect on endothelial function remains uncharacterized. The present study therefore investigated the effect of geraniol on endothelial function in HFD mice and its underlying mechanisms. C57 BL/6 mice were fed an HFD (n = 40) or a normal diet (n = 20) for 8 weeks. HFD fed mice then were randomized to intraperitoneal treatment with geraniol (n = 20) or vehicle (n = 20) for another 6 weeks. Acetylcholine (Ach)-induced endothelial dependent vasorelaxation was measuredmore » on wire myography; reactive oxygen species (ROS) generation was assessed by fluorescence imaging, and NADPH oxidases (NOXs) and adhesive molecules VCAM-1 and ICAM-1 protein expression by western blotting. Geraniol improved endothelial function in HFD fed mice, as evidenced by its: 1. restoring endothelial dependent vasorelaxation induced by Ach, and reversing increased VCAM-1 and ICAM-1 expression; 2. attenuating HFD induced increased serum TBARS and aortic ROS generation; and 3. downregulating aortic NOX-2 expression in both HFD fed mice and in palmitic acid treated endothelial cells. Geraniol therefore protects against endothelial dysfunction induced by HFD through reducing NOX-2 associated ROS generation. -- Highlights: •Geraniol improved endothelial dependent relaxation in high fat diet fed mice. •Geraniol alleviated vascular injury in high fat diet fed mice. •Geraniol inhibited ROS generation through downregulating NOX-2 expression.« less

Chronic intermittent fasting improves cognitive functions and brain structures in mice.

PubMed

Li, Liaoliao; Wang, Zhi; Zuo, Zhiyi

2013-01-01

Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day) fasting or high fat diet (45% caloric supplied by fat) for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice). Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals.

Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice

PubMed Central

Li, Liaoliao; Wang, Zhi; Zuo, Zhiyi

2013-01-01

Obesity is a major health issue. Obesity started from teenagers has become a major health concern in recent years. Intermittent fasting increases the life span. However, it is not known whether obesity and intermittent fasting affect brain functions and structures before brain aging. Here, we subjected 7-week old CD-1 wild type male mice to intermittent (alternate-day) fasting or high fat diet (45% caloric supplied by fat) for 11 months. Mice on intermittent fasting had better learning and memory assessed by the Barnes maze and fear conditioning, thicker CA1 pyramidal cell layer, higher expression of drebrin, a dendritic protein, and lower oxidative stress than mice that had free access to regular diet (control mice). Mice fed with high fat diet was obese and with hyperlipidemia. They also had poorer exercise tolerance. However, these obese mice did not present significant learning and memory impairment or changes in brain structures or oxidative stress compared with control mice. These results suggest that intermittent fasting improves brain functions and structures and that high fat diet feeding started early in life does not cause significant changes in brain functions and structures in obese middle-aged animals. PMID:23755298

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

PubMed Central

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

2013-01-01

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

Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study

PubMed Central

Grassi, Davide; Draijer, Richard; Schalkwijk, Casper; Desideri, Giovambattista; D’Angeli, Anatolia; Francavilla, Sandro; Mulder, Theo; Ferri, Claudio

2016-01-01

(1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001). Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001). Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest. PMID:27854314

Sequencing the transcriptome of milk production: milk trumps mammary tissue

PubMed Central

2013-01-01

Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

Application of cell co-culture system to study fat and muscle cells.

PubMed

Pandurangan, Muthuraman; Hwang, Inho

2014-09-01

Animal cell culture is a highly complex process, in which cells are grown under specific conditions. The growth and development of these cells is a highly unnatural process in vitro condition. Cells are removed from animal tissues and artificially cultured in various culture vessels. Vitamins, minerals, and serum growth factors are supplied to maintain cell viability. Obtaining result homogeneity of in vitro and in vivo experiments is rare, because their structure and function are different. Living tissues have highly ordered complex architecture and are three-dimensional (3D) in structure. The interaction between adjacent cell types is quite distinct from the in vitro cell culture, which is usually two-dimensional (2D). Co-culture systems are studied to analyze the interactions between the two different cell types. The muscle and fat co-culture system is useful in addressing several questions related to muscle modeling, muscle degeneration, apoptosis, and muscle regeneration. Co-culture of C2C12 and 3T3-L1 cells could be a useful diagnostic tool to understand the muscle and fat formation in animals. Even though, co-culture systems have certain limitations, they provide a more realistic 3D view and information than the individual cell culture system. It is suggested that co-culture systems are useful in evaluating the intercellular communication and composition of two different cell types.

Identification of a functional element in the promoter of the silkworm (Bombyx mori) fat body-specific gene Bmlp3.

PubMed

Xu, Hanfu; Deng, Dangjun; Yuan, Lin; Wang, Yuancheng; Wang, Feng; Xia, Qingyou

2014-08-01

30K proteins are a group of structurally related proteins that play important roles in the life cycle of the silkworm Bombyx mori and are largely synthesized and regulated in a time-dependent manner in the fat body. Little is known about the upstream regulatory elements associated with the genes encoding these proteins. In the present study, the promoter of Bmlp3, a fat body-specific gene encoding a 30K protein family member, was characterized by joining sequences containing the Bmlp3 promoter with various amounts of 5' upstream sequences to a luciferase reporter gene. The results indicated that the sequences from -150 to -250bp and -597 to -675bp upstream of the Bmlp3 transcription start site were necessary for high levels of luciferase activity. Further analysis showed that a 21-bp sequence located between -230 and -250 was specifically recognized by nuclear factors from silkworm fat bodies and BmE cells, and could enhance luciferase reporter-gene expression 2.8-fold in BmE cells. This study provides new insights into the Bmlp3 promoter and contributes to the further clarification of the function and developmental regulation of Bmlp3. Copyright © 2014. Published by Elsevier B.V.

Thermal Stress

DTIC Science & Technology

2011-01-01

can have a significant impact on normal physiological functioning if precipitous increases in core temperature are not adequately controlled with...anterior hypothalamusIntroduction Thermal stress can have a significant impact on normal physiological functioning if precipitous increases in core...fat and skin). The regulation of a relatively constant internal temperature is critical for normal physiological functioning of tissues and cells, as

Platelet functional and transcriptional changes induced by intralipid infusion.

PubMed

Beaulieu, Lea M; Vitseva, Olga; Tanriverdi, Kahraman; Kucukural, Alper; Mick, Eric; Hamburg, Naomi; Vita, Joseph; Freedman, Jane E

2016-06-02

Multiple studies have shown the effects of long-term exposure to high-fat or western diets on the vascular system. There is limited knowledge on the acute effects of high circulating fat levels, specifically on platelets, which have a role in many processes, including thrombosis and inflammation. This study investigated the effects of acute, high-fat exposure on platelet function and transcript profile. Twenty healthy participants were given an intravenous infusion of 20% Intralipid emulsion and heparin over 6 hours. Blood samples were taken prior to and the day after infusion to measure platelet function and transcript expression levels. Platelet aggregation was not significantly affected by Intralipid infusion, but, when mitochondria function was inhibited by carbonyl cyanide 3-chlorophenylhydrazone (CCCP) or oligomycin, platelet aggregation was higher in the post-infusion state compared to baseline. Through RNA sequencing, and verified by RT-qPCR, 902 miRNAs and 617 mRNAs were affected by Intralipid infusion. MicroRNAs increased include miR-4259 and miR-346, while miR-517b and miR-517c are both decreased. Pathway analysis identified two clusters significantly enriched, including cell motility. In conclusion, acute exposure to high fat affects mitochondrial-dependent platelet function, as well as the transcript profile.

Isolation of Endoplasmic Reticulum Fractions from Mammary Epithelial Tissue.

PubMed

Chanat, Eric; Le Parc, Annabelle; Lahouassa, Hichem; Badaoui, Bouabid

2016-06-01

In the mammary glands of lactating animals, the mammary epithelial cells that surround the lumen of the acini produce and secrete copious amounts of milk. Functional differentiation of these mammary epithelial cells depends on the development of high-efficiency secretory pathways, notably for protein and lipid secretion. Protein secretion is a fundamental process common to all animal cells that involves a subset of cellular organelles, including the endoplasmic reticulum and the Golgi apparatus. In contrast, en masse secretion of triglycerides and cholesterol esters in the form of milk fat globules is a unique feature of the mammary epithelial cell. Cytoplasmic lipid droplets, the intracellular precursors of milk fat globules, originate from the endoplasmic reticulum, as do most milk-specific proteins. This organelle is therefore pivotal in the biogenesis of milk components. Fractionation of the cell into its subcellular parts is an approach that has proven very powerful for understanding organelle function and for studying the specific role of an organelle in a given cell activity. Here we describe a method for the purification of both smooth and rough microsomes, the membrane-bound endoplasmic reticulum fragments that form from endoplasmic reticulum domains when cells are broken up, from mammary gland tissue at lactation.

Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas.

PubMed

Saisho, Yoshifumi

2016-01-01

The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better.

Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

PubMed Central

Saisho, Yoshifumi

2016-01-01

The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better. PMID:28012279

Effect of plasminogen activator inhibitor-1 on adipogenesis in vivo.

PubMed

Scroyen, Ilse; Jacobs, Frank; Cosemans, Leen; De Geest, Bart; Lijnen, H Roger

2009-02-01

To study the functional role of plasminogen activator inhibitor-1 (PAI-1) in obesity, the effect of its overexpression on de novo adipogenesis was evaluated in murine models in vivo. Therefore, 3T3-F442A preadipocytes expressing murine PAI-1 (mPAI-1) or control cells were injected in the back of male NUDE mice, which were fed a high-fat diet (HFD) for four weeks. De novo fat pads that formed from the PAI-1 expressing cells were larger (21 +/- 2.4 mg vs. 14 +/- 1.4 mg; p = 0.017) and showed a higher adipocyte density (373 +/- 28 mm(-2) vs. 301 +/- 12 mm(-2); p = 0.03) as compared to those formed from control cells. In a second model, male NUDE mice were injected in the tail vein with an adenoviral construct expressing mPAI-1 or with the empty vector, and three days later with 3T3-F442A cells. After four weeks of HFD, total body weight and de novo fat pad weight were comparable for both groups. Mild adipocyte hypotrophy was observed in the de novo fat pads of the PAI-1 overexpressing mice (1180 +/- 33 microm(2) vs. 1285 +/- 32 microm(2); p = 0.024), whereas the blood vessel size was significantly smaller than in controls (30 +/- 1.8 microm(2) vs. 63 +/- 3.6 microm(2); p < 0.0001). Thus, the effect of local or systemic PAI-1 (over)expression on adipocyte or blood vessel size and density of de novo formed fat pads appears to be different, and concentration-dependent. Whereas local expression resulted in larger fat pads, systemic overexpression had no effect on de novo adipogenesis, although angiogenesis appeared to be impaired.

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases

PubMed Central

Hardaway, Aimalie L.; Herroon, Mackenzie K.; Rajagurubandara, Erandi

2014-01-01

Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease. PMID:24398857

Wnt-signaling and planar cell polarity genes regulate axon guidance along the anteroposterior axis in C. elegans.

PubMed

Ackley, Brian D

2014-08-01

During the development of the nervous system, neurons encounter signals that inform their outgrowth and polarization. Understanding how these signals combinatorially function to pattern the nervous system is of considerable interest to developmental neurobiologists. The Wnt ligands and their receptors have been well characterized in polarizing cells during asymmetric cell division. The planar cell polarity (PCP) pathway is also critical for cell polarization in the plane of an epithelium. The core set of PCP genes include members of the conserved Wnt-signaling pathway, such as Frizzled and Disheveled, but also the cadherin-domain protein Flamingo. In Drosophila, the Fat and Dachsous cadherins also function in PCP, but in parallel to the core PCP components. C. elegans also have two Fat-like and one Dachsous-like cadherins, at least one of which, cdh-4, contributes to neural development. In C. elegans Wnt ligands and the conserved PCP genes have been shown to regulate a number of different events, including embryonic cell polarity, vulval morphogenesis, and cell migration. As is also observed in vertebrates, the Wnt and PCP genes appear to function to primarily provide information about the anterior to posterior axis of development. Here, we review the recent work describing how mutations in the Wnt and core PCP genes affect axon guidance and synaptogenesis in C. elegans. © 2013 Wiley Periodicals, Inc.

The role of environmental factors in regulating the development of cartilaginous grafts engineered using osteoarthritic human infrapatellar fat pad-derived stem cells.

PubMed

Liu, Yurong; Buckley, Conor T; Downey, Richard; Mulhall, Kevin J; Kelly, Daniel J

2012-08-01

Engineering functional cartilaginous grafts using stem cells isolated from osteoarthritic human tissue is of fundamental importance if autologous tissue engineering strategies are to be used in the treatment of diseased articular cartilage. It has previously been demonstrated that human infrapatellar fat pad (IFP)-derived stem cells undergo chondrogenesis in pellet culture; however, the ability of such cells to generate functional cartilaginous grafts has not been adequately addressed. The objective of this study was to explore how environmental conditions regulate the functional development of cartilaginous constructs engineered using diseased human IFP-derived stem cells (FPSCs). FPSCs were observed to display a diminished chondrogenic potential upon encapsulation in a three-dimensional hydrogel compared with pellet culture, synthesizing significantly lower levels of glycosaminoglycan and collagen on a per cell basis. To engineer more functional cartilaginous grafts, we next explored whether additional biochemical and biophysical stimulations would enhance chondrogenesis within the hydrogels. Serum stimulation was observed to partially recover the diminished chondrogenic potential within hydrogel culture. Over 42 days, stem cells that had first been expanded in a low-oxygen environment proliferated extensively on the outer surface of the hydrogel in response to serum stimulation, assembling a dense type II collagen-positive cartilaginous tissue resembling that formed in pellet culture. The application of hydrostatic pressure did not further enhance extracellular matrix synthesis within the hydrogels, but did appear to alter the spatial accumulation of extracellular matrix leading to the formation of a more compact tissue with superior mechanically functionality. Further work is required in order to recapitulate the environmental conditions present during pellet culture within scaffolds or hydrogels in order to engineer more functional cartilaginous grafts using human osteoarthritic FPSCs.

A Novel Porcine Model for Future Studies of Cell-enriched Fat Grafting

PubMed Central

Sørensen, Celine L.; Vester-Glowinski, Peter V.; Herly, Mikkel; Kurbegovic, Sorel; Ørholt, Mathias; Svalgaard, Jesper D.; Kølle, Stig-Frederik T.; Kristensen, Annemarie T.; Talman, Maj-Lis M.; Drzewiecki, Krzysztof T.; Fischer-Nielsen, Anne

2018-01-01

Background: Cell-enriched fat grafting has shown promising results for improving graft survival, although many questions remain unanswered. A large animal model is crucial for bridging the gap between rodent studies and human trials. We present a step-by-step approach in using the Göttingen minipig as a model for future studies of cell-enriched large volume fat grafting. Methods: Fat grafting was performed as bolus injections and structural fat grafting. Graft retention was assessed by magnetic resonance imaging after 120 days. The stromal vascular fraction (SVF) was isolated from excised fat and liposuctioned fat from different anatomical sites and analyzed. Porcine adipose-derived stem/stromal cells (ASCs) were cultured in different growth supplements, and population doubling time, maximum cell yield, expression of surface markers, and differentiation potential were investigated. Results: Structural fat grafting in the breast and subcutaneous bolus grafting in the abdomen revealed average graft retention of 53.55% and 15.28%, respectively, which are similar to human reports. Liposuction yielded fewer SVF cells than fat excision, and abdominal fat had the most SVF cells/g fat with SVF yields similar to humans. Additionally, we demonstrated that porcine ASCs can be readily isolated and expanded in culture in allogeneic porcine platelet lysate and fetal bovine serum and that the use of 10% porcine platelet lysate or 20% fetal bovine serum resulted in population doubling time, maximum cell yield, surface marker profile, and trilineage differentiation that were comparable with humans. Conclusions: The Göttingen minipig is a feasible and cost-effective, large animal model for future translational studies of cell-enriched fat grafting. PMID:29876178

Pro-Inflammatory Activated Kupffer Cells by Lipids Induce Hepatic NKT Cells Deficiency through Activation-Induced Cell Death

PubMed Central

Tang, Tongfang; Sui, Yongheng; Lian, Min; Li, Zhiping; Hua, Jing

2013-01-01

Background Dietary lipids play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) through alternation of liver innate immune response. Aims The present study was to investigate the effect of lipid on Kupffer cells phenotype and function in vivo and in vitro. And further to investigate the impact of lipid on ability of Kupffer cell lipid antigen presentation to activate NKT cells. Methods Wild type male C57BL/6 mice were fed either normal or high-fat diet. Hepatic steatosis, Kupffer cell abundance, NKT cell number and cytokine gene expression were evaluated. Antigen presentation assay was performed with Kupffer cells treated with certain fatty acids in vitro and co-cultured with NKT cells. Results High-fat diet induced hepatosteatosis, significantly increased Kupffer cells and decreased hepatic NKT cells. Lipid treatment in vivo or in vitro induced increase of pro-inflammatory cytokines gene expression and toll-like receptor 4 (TLR4) expression in Kupffer cells. Kupffer cells expressed high levels of CD1d on cell surface and only presented exogenous lipid antigen to activate NKT cells. Ability of Kupffer cells to present antigen and activate NKT cells was enhanced after lipid treatment. In addition, pro-inflammatory activated Kupffer cells by lipid treatment induced hepatic NKT cells activation-induced apoptosis and necrosis. Conclusion High-fat diet increase Kupffer cells number and induce their pro-inflammatory status. Pro-inflammatory activated Kupfffer cells by lipid promote hepatic NKT cell over-activation and cell death, which lead to further hepatic NKT cell deficiency in the development of NAFLD. PMID:24312613

Abdominal Subcutaneous Fat: A Favorable or Nonfunctional Fat Depot for Glucose Metabolism in Chinese Adults?

PubMed

Hou, Xuhong; Chen, Peizhu; Hu, Gang; Wei, Li; Jiao, Lei; Wang, Hongmei; Liang, Yebei; Bao, Yuqian; Jia, Weiping

2018-06-01

The objective of this study was to assess the associations of abdominal visceral and subcutaneous adipose tissue with blood glucose and beta-cell function. In this study, 11,223 participants without known diabetes were selected for this cross-sectional analysis. Visceral and subcutaneous fat area (VFA and SFA) were measured by magnetic resonance imaging. An oral glucose tolerance test was conducted, and beta-cell function was evaluated. Men had significantly larger VFA but smaller SFA than women. After controlling for age, linear regression showed that SFA was adversely associated with 0-minute, 30-minute, and 2-hour plasma glucose (PG) and early-, first- and second-phase disposition indices (DIs). After further adjustment for BMI and VFA, some associations of SFA with PG indices and DIs disappeared, while the other associations became significantly weaker in men (2-hour PG: 0.05 and DI 2nd : -0.05) or were reversed in women (0-minute, 30-minute, and 2-hour PG: from -0.07 to -0.04; DI 1st : 0.04, P < 0.05). After adjustment for age, BMI, and SFA, VFA was significantly and adversely associated with PG indices and DIs, with the largest standardized regression coefficients with 2-hour PG. The associations of SFA with blood glucose and beta-cell function were clinically insignificant in Chinese adults. VFA had the strongest association with 2-hour PG. © 2018 The Obesity Society.

Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad.

PubMed

Carroll, S F; Buckley, C T; Kelly, D J

2014-06-27

The objective of this study was to investigate how joint specific biomechanical loading influences the functional development and phenotypic stability of cartilage grafts engineered in vitro using stem/progenitor cells isolated from different source tissues. Porcine bone marrow derived multipotent stromal cells (BMSCs) and infrapatellar fat pad derived multipotent stromal cells (FPSCs) were seeded in agarose hydrogels and cultured in chondrogenic medium, while simultaneously subjected to 10MPa of cyclic hydrostatic pressure (HP). To mimic the endochondral phenotype observed in vivo with cartilaginous tissues engineered using BMSCs, the culture media was additionally supplemented with hypertrophic factors, while the loss of phenotype observed in vivo with FPSCs was induced by withdrawing transforming growth factor (TGF)-β3 from the media. The application of HP was found to enhance the functional development of cartilaginous tissues engineered using both BMSCs and FPSCs. In addition, HP was found to suppress calcification of tissues engineered using BMSCs cultured in chondrogenic conditions and acted to maintain a chondrogenic phenotype in cartilaginous grafts engineered using FPSCs. The results of this study point to the importance of in vivo specific mechanical cues for determining the terminal phenotype of chondrogenically primed multipotent stromal cells. Furthermore, demonstrating that stem or progenitor cells will appropriately differentiate in response to such biophysical cues might also be considered as an additional functional assay for evaluating their therapeutic potential. Copyright © 2013 Elsevier Ltd. All rights reserved.

Melipona quadrifasciata (Hymenoptera: Apidae) fat body persists through metamorphosis with a few apoptotic cells and an increased autophagy.

PubMed

Santos, Douglas Elias; Azevedo, Dihego Oliveira; Campos, Lúcio Antônio Oliveira; Zanuncio, José Cola; Serrão, José Eduardo

2015-03-01

Fat body, typically comprising trophocytes, provides energy during metamorphosis. The fat body can be renewed once the larval phase is complete or recycled and relocated to form the fat body of the adult insect. This study aims to identify the class of programmed cell death that occurs within the fat body cells during the metamorphosis of the stingless bee Melipona quadrifasciata. Using immunodetection techniques, the fat body of the post-defecating larvae and the white-, pink-, brown-, and black-eyed pupae were tested for cleaved caspase-3 and DNA integrity, followed by ultrastructural analysis and identification of autophagy using RT-PCR for the Atg1 gene. The fat body of M. quadrifasciata showed some apoptotic cells positive for cleaved caspase-3, although without DNA fragmentation. During development, the fat body cells revealed an increased number of mitochondria and free ribosomes, in addition to higher amounts of autophagy Atg1 mRNA, than that of the pupae. The fat body of M. quadrifasciata showed few cells which underwent apoptosis, but there was evidence of increased autophagy at the completion of the larval stage. All together, these data show that some fat body cells persist during metamorphosis in the stingless bee M. quadrifasciata.

The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila.

PubMed

Jacomin, Anne-Claire; Bescond, Amandine; Soleilhac, Emmanuelle; Gallet, Benoît; Schoehn, Guy; Fauvarque, Marie-Odile; Taillebourg, Emmanuel

2015-01-01

Autophagy is a catabolic process that delivers cytoplasmic components to the lysosomes. Protein modification by ubiquitination is involved in this pathway: it regulates the stability of autophagy regulators such as BECLIN-1 and it also functions as a tag targeting specific substrates to autophagosomes. In order to identify deubiquitinating enzymes (DUBs) involved in autophagy, we have performed a genetic screen in the Drosophila larval fat body. This screen identified Uch-L3, Usp45, Usp12 and Ubpy. In this paper, we show that Ubpy loss of function results in the accumulation of autophagosomes due to a blockade of the autophagy flux. Furthermore, analysis by electron and confocal microscopy of Ubpy-depleted fat body cells revealed altered lysosomal morphology, indicating that Ubpy inactivation affects lysosomal maintenance and/or biogenesis. Lastly, we have shown that shRNA mediated inactivation of UBPY in HeLa cells affects autophagy in a different way: in UBPY-depleted HeLa cells autophagy is deregulated.

The cardio-protective diet

PubMed Central

Sivasankaran, S.

2010-01-01

Globalization has made calorie rich, cheap, convenient marketed foods the main menu for the common man. Indians are particularly susceptible to the adverse outcomes of this dietary change because of ethnic, epigenetic reasons and sarcopenic adiposity (less muscle more fat for the same body weight). Children have smaller body frame making them more susceptible to adverse effects of hyperglycaemia leading to stress on beta cells and their damage. This has resulted in escalation of lifestyle diseases by three-fold, that too at our younger age group at lower body mass indices. Preventive measures are necessary in early life to protect the beta cells, to achieve a metabolically healthy society. This will help in sustaining optimal beta cell function throughout a person’s life. Modification in dietary habits by educating the society, proper food labelling and legal regulation, restricting calorie, sugar, saturated fat, trans-fat and salt intake has proved its benefits in the developed world. Changes in the quality of food is as important as restricting calorie intake. This includes facilitation of increased consumption of dietary fiber, complex carbohydrates, nuts, fruits and vegetables. Restrictions are needed to reduce trans-fats, saturated fats and cooking habits such as deep frying which oxidizes cholesterol and lipids. Foods with long shelf-life shorten the life line because of their salt, sugar or trans-fat content. Individual meals need to be targeted in the general dietary guidelines, to minimize the post-prandial metabolic insult. In general, we need healthy start to early life particularly the first twenty years of life so that the habits cultured during childhood are sustained for the rest of productive years. PMID:21150013

Comparison of purple carrot juice and β-carotene in a high-carbohydrate, high-fat diet-fed rat model of the metabolic syndrome.

PubMed

Poudyal, Hemant; Panchal, Sunil; Brown, Lindsay

2010-11-01

Anthocyanins, phenolic acids and carotenoids are the predominant phytochemicals present in purple carrots. These phytochemicals could be useful in treatment of the metabolic syndrome since anthocyanins improve dyslipidaemia, glucose tolerance, hypertension and insulin resistance; the phenolic acids may also protect against CVD and β-carotene may protect against oxidative processes. In the present study, we have compared the ability of purple carrot juice and β-carotene to reverse the structural and functional changes in rats fed a high-carbohydrate, high-fat diet as a model of the metabolic syndrome induced by diet. Cardiac structure and function were defined by histology, echocardiography and in isolated hearts and blood vessels; liver structure and function, oxidative stress and inflammation were defined by histology and plasma markers. High-carbohydrate, high-fat diet-fed rats developed hypertension, cardiac fibrosis, increased cardiac stiffness, endothelial dysfunction, impaired glucose tolerance, increased abdominal fat deposition, altered plasma lipid profile, liver fibrosis and increased plasma liver enzymes together with increased plasma markers of oxidative stress and inflammation as well as increased inflammatory cell infiltration. Purple carrot juice attenuated or reversed all changes while β-carotene did not reduce oxidative stress, cardiac stiffness or hepatic fat deposition. As the juice itself contained low concentrations of carotenoids, it is likely that the anthocyanins are responsible for the antioxidant and anti-inflammatory properties of purple carrot juice to improve glucose tolerance as well as cardiovascular and hepatic structure and function.

Tissue-specific insulin signaling mediates female sexual attractiveness

PubMed Central

Arbuthnott, Devin; Rundle, Howard D.; Promislow, Daniel E. L.; Pletcher, Scott D.

2017-01-01

Individuals choose their mates so as to maximize reproductive success, and one important component of this choice is assessment of traits reflecting mate quality. Little is known about why specific traits are used for mate quality assessment nor about how they reflect it. We have previously shown that global manipulation of insulin signaling, a nutrient-sensing pathway governing investment in survival versus reproduction, affects female sexual attractiveness in the fruit fly, Drosophila melanogaster. Here we demonstrate that these effects on attractiveness derive from insulin signaling in the fat body and ovarian follicle cells, whose signals are integrated by pheromone-producing cells called oenocytes. Functional ovaries were required for global insulin signaling effects on attractiveness, and manipulations of insulin signaling specifically in late follicle cells recapitulated effects of global manipulations. Interestingly, modulation of insulin signaling in the fat body produced opposite effects on attractiveness, suggesting a competitive relationship with the ovary. Furthermore, all investigated tissue-specific insulin signaling manipulations that changed attractiveness also changed fecundity in the corresponding direction, pointing to insulin pathway activity as a reliable link between fecundity and attractiveness cues. The cues themselves, cuticular hydrocarbons, responded distinctly to fat body and follicle cell manipulations, indicating independent readouts of the pathway activity from these two tissues. Thus, here we describe a system in which female attractiveness results from an apparent connection between attractiveness cues and an organismal state of high fecundity, both of which are created by lowered insulin signaling in the fat body and increased insulin signaling in late follicle cells. PMID:28817572

Tissue-specific insulin signaling mediates female sexual attractiveness.

PubMed

Fedina, Tatyana Y; Arbuthnott, Devin; Rundle, Howard D; Promislow, Daniel E L; Pletcher, Scott D

2017-08-01

Individuals choose their mates so as to maximize reproductive success, and one important component of this choice is assessment of traits reflecting mate quality. Little is known about why specific traits are used for mate quality assessment nor about how they reflect it. We have previously shown that global manipulation of insulin signaling, a nutrient-sensing pathway governing investment in survival versus reproduction, affects female sexual attractiveness in the fruit fly, Drosophila melanogaster. Here we demonstrate that these effects on attractiveness derive from insulin signaling in the fat body and ovarian follicle cells, whose signals are integrated by pheromone-producing cells called oenocytes. Functional ovaries were required for global insulin signaling effects on attractiveness, and manipulations of insulin signaling specifically in late follicle cells recapitulated effects of global manipulations. Interestingly, modulation of insulin signaling in the fat body produced opposite effects on attractiveness, suggesting a competitive relationship with the ovary. Furthermore, all investigated tissue-specific insulin signaling manipulations that changed attractiveness also changed fecundity in the corresponding direction, pointing to insulin pathway activity as a reliable link between fecundity and attractiveness cues. The cues themselves, cuticular hydrocarbons, responded distinctly to fat body and follicle cell manipulations, indicating independent readouts of the pathway activity from these two tissues. Thus, here we describe a system in which female attractiveness results from an apparent connection between attractiveness cues and an organismal state of high fecundity, both of which are created by lowered insulin signaling in the fat body and increased insulin signaling in late follicle cells.

Direct and Indirect Effects of Leptin on Adipocyte Metabolism

PubMed Central

Harris, Ruth B.S.

2013-01-01

Leptin is hypothesized to function as a negative feedback signal in the regulation of energy balance. It is produced primarily by adipose tissue and circulating concentrations correlate with the size of body fat stores. Administration of exogenous leptin to normal weight, leptin responsive animals inhibits food intake and reduces the size of body fat stores whereas mice that are deficient in either leptin or functional leptin receptors are hyperphagic and obese, consistent with a role for leptin in the control of body weight. This review discusses the effect of leptin on adipocyte metabolism. Because adipocytes express leptin receptors there is the potential for leptin to influence adipocyte metabolism directly. Adipocytes also are insulin responsive and receive sympathetic innervation, therefore leptin can also modify adipocyte metabolism indirectly. Studies published to date suggest that direct activation of adipocyte leptin receptors has little effect on cell metabolism in vivo, but that leptin modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. In vivo administration of leptin leads to a suppression of lipogenesis, an increase in triglyceride hydrolysis and an increase in fatty acid and glucose oxidation. Activation of central leptin receptors also contributes to the development of a catabolic state in adipocytes, but this may vary between different fat depots. Leptin reduces the size of white fat depots by inhibiting cell proliferation both through induction of inhibitory circulating factors and by contributing to sympathetic tone which suppresses adipocyte proliferation. PMID:23685313

Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications

PubMed Central

Song, Byoung-Joon; Akbar, Mohammed; Abdelmegeed, Mohamed A.; Byun, Kyunghee; Lee, Bonghee; Yoon, Seung Kew; Hardwick, James P.

2014-01-01

Mitochondria are critically important in providing cellular energy ATP as well as their involvement in anti-oxidant defense, fat oxidation, intermediary metabolism and cell death processes. It is well-established that mitochondrial functions are suppressed when living cells or organisms are exposed to potentially toxic agents including alcohol, high fat diets, smoking and certain drugs or in many pathophysiological states through increased levels of oxidative/nitrative stress. Under elevated nitroxidative stress, cellular macromolecules proteins, DNA, and lipids can undergo different oxidative modifications, leading to disruption of their normal, sometimes critical, physiological functions. Recent reports also indicated that many mitochondrial proteins are modified via various post-translation modifications (PTMs) and primarily inactivated. Because of the recently-emerging information, in this review, we specifically focus on the mechanisms and roles of five major PTMs (namely oxidation, nitration, phosphorylation, acetylation, and adduct formation with lipid-peroxides, reactive metabolites, or advanced glycation end products) in experimental models of alcoholic and nonalcoholic fatty liver disease as well as acute hepatic injury caused by toxic compounds. We also highlight the role of the ethanol-inducible cytochrome P450-2E1 (CYP2E1) in some of these PTM changes. Finally, we discuss translational research opportunities with natural and/or synthetic anti-oxidants, which can prevent or delay the onset of mitochondrial dysfunction, fat accumulation and tissue injury. PMID:25465468

Dietary fats and prevention of type 2 diabetes.

PubMed

Risérus, Ulf; Willett, Walter C; Hu, Frank B

2009-01-01

Although type 2 diabetes is determined primarily by lifestyle and genes, dietary composition may affect both its development and complications. Dietary fat is of particular interest because fatty acids influence glucose metabolism by altering cell membrane function, enzyme activity, insulin signaling, and gene expression. This paper focuses on the prevention of type 2 diabetes and summarizes the epidemiologic literature on associations between types of dietary fat and diabetes risk. It also summarizes controlled feeding studies on the effects of dietary fats on metabolic mediators, such as insulin resistance. Taken together, the evidence suggests that replacing saturated fats and trans fatty acids with unsaturated (polyunsaturated and/or monounsaturated) fats has beneficial effects on insulin sensitivity and is likely to reduce risk of type 2 diabetes. Among polyunsaturated fats, linoleic acid from the n-6 series improves insulin sensitivity. On the other hand, long-chain n-3 fatty acids do not appear to improve insulin sensitivity or glucose metabolism. In dietary practice, foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized. Additional controlled, long-term studies are needed to improve our knowledge on the optimal proportion of different types of fats to prevent diabetes.

A whole organism screen identifies novel regulators of fat storage

PubMed Central

Lemieux, George A.; Liu, Jason; Mayer, Nasima; Bainton, Roland J.; Ashrafi, Kaveh; Werb, Zena

2011-01-01

The regulation of energy homeostasis integrates diverse biological processes ranging from behavior to metabolism and is linked fundamentally to numerous disease states. To identify new molecules that can bypass homeostatic compensatory mechanisms of energy balance in intact animals, we screened for small molecule modulators of C. elegans fat content. We report on several molecules that modulate fat storage without obvious deleterious effects on feeding, growth, and reproduction. A subset of these compounds also altered fat storage in mammalian and insect cell culture. We found that one of the newly identified compounds exerts its effects in C. elegans through a pathway that requires novel functions of an AMP-activated kinase catalytic subunit and a transcription factor previously unassociated with fat regulation. Thus, our strategy identifies small molecules that are effective within the context of intact animals and reveals relationships between new pathways that operate across phyla to influence energy homeostasis. PMID:21390037

Bone and fat connection in aging bone.

PubMed

Duque, Gustavo

2008-07-01

The fat and bone connection plays an important role in the pathophysiology of age-related bone loss. This review will focus on the age-induced mechanisms regulating the predominant differentiation of mesenchymal stem cells into adipocytes. Additionally, bone marrow fat will be considered as a diagnostic and therapeutic approach to osteoporosis. There are two types of bone and fat connection. The 'systemic connection', usually seen in obese patients, is hormonally regulated and associated with high bone mass and strength. The 'local connection' happens inside the bone marrow. Increasing amounts of bone marrow fat affect bone turnover through the inhibition of osteoblast function and survival and the promotion of osteoclast differentiation and activation. This interaction is regulated by paracrine secretion of fatty acids and adipokines. Additionally, bone marrow fat could be quantified using noninvasive methods and could be used as a therapeutic approach due to its capacity to transdifferentiate into bone without affecting other types of fat in the body. The bone and fat connection within the bone marrow constitutes a typical example of lipotoxicity. Additionally, bone marrow fat could be used as a new diagnostic and therapeutic approach for osteoporosis in older persons.

Semen Quality and Sperm Function Loss by Hypercholesterolemic Diet Was Recovered by Addition of Olive Oil to Diet in Rabbit

PubMed Central

Romero, Aida A.; Funes, Abi K.; Cid-Barria, Macarena; Cabrillana, María E.; Monclus, María A.; Simón, Layla; Vicenti, Amanda E.; Fornés, Miguel W.

2013-01-01

Fat increment (0.05% cholesterol, chol) in standard diet promoted a significant increase in serum and sperm membrane chol, which ultimately altered membrane-coupled sperm specific functions: osmotic resistance, acrosomal reaction, and sperm capacitation in White New Zealand rabbits. These changes were also associated with a reduction in motility percentage and appearance of abnormal sperm morphology. The present study was carried out to evaluate the effect of dietary olive oil (OO, 7% v/w) administration to several male hypercholesterolemic rabbits (hypercholesterolemic rabbits, HCR) with altered fertility parameters. These HCR males were achieved by feeding normal rabbits with a high-fat diet (0.05% chol). HCR were associated with a modest non-significant increase in body weight (standard diet, 4.08±0.17 Kg, versus high-fat diet, 4.37±0.24 Kg). Hypercholesterolemic rabbits presented a marked decrease in semen volume, sperm cell count, and percentage of sperm motility, associated with a significant increase in sperm cell abnormalities. Moreover, sperm capacitation measured by the characteristic phosphorylated protein pattern in and induced acrosomal reaction were also altered suggesting sperm dysfunction. However, the administration of OO (for 16 weeks) to rabbits that were fed with 50% of the high-fat diet normalized serum chol. Curiously, OO supply succeeded to attenuate the seminal and sperm alterations observed in HCR group. Administration of OO alone did not cause any significant changes in above mentioned parameters. These data suggest that OO administration to HCR male rabbits recovers the loss of semen quality and sperm functionality. PMID:23326331

Axonal degeneration in Alzheimer’s disease: When signaling abnormalities meet the axonal transport system

PubMed Central

Kanaan, Nicholas M.; Pigino, Gustavo F.; Brady, Scott T.; Lazarov, Orly; Binder, Lester I.; Morfini, Gerardo A.

2012-01-01

Alzheimer’s disease (AD) is characterized by progressive, age-dependent degeneration of neurons in the central nervous system. A large body of evidence indicates that neurons affected in AD follow a dying-back pattern of degeneration, where abnormalities in synaptic function and axonal connectivity long precede somatic cell death. Mechanisms underlying dying-back degeneration of neurons in AD remain elusive but several have been proposed, including deficits in fast axonal transport (FAT). Accordingly, genetic evidence linked alterations in FAT to dying-back degeneration of neurons, and FAT defects have been widely documented in various AD models. In light of these findings, we discuss experimental evidence linking several AD-related pathogenic polypeptides to aberrant activation of signaling pathways involved in the phosphoregulation of microtubule-based motor proteins. While each pathway appears to affect FAT in a unique manner, in the context of AD, many of these pathways might work synergistically to compromise the delivery of molecular components critical for the maintenance and function of synapses and axons. Therapeutic approaches aimed at preventing FAT deficits by normalizing the activity of specific protein kinases may help prevent degeneration of vulnerable neurons in AD. PMID:22721767

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.

PubMed

Matveyenko, Aleksey V; Georgia, Senta; Bhushan, Anil; Butler, Peter C

2010-11-01

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant.

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats

PubMed Central

Matveyenko, Aleksey V.; Georgia, Senta; Bhushan, Anil

2010-01-01

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant. PMID:20587750

A diet high in fat stimulates adipocyte proliferation in older (22 month) rats.

PubMed

Ellis, J R; McDonald, R B; Stern, J S

1990-01-01

The effect of a high fat diet in stimulating adipocyte proliferation, as measured by the incorporation of [3H]-thymidine into fat cell DNA, was studied in 22-month-old female Sprague-Dawley rats. Rats were fed a low fat (n = 10) or a high fat diet (n = 9) for a total of six days. On days 4 and 5 of dietary manipulation, rats were injected with 80 microCi/100 g body weight of [3H]-thymidine. Rats were continued on their respective diets for one more day, starved for 72 h and then refed a stock diet for three weeks in order to increase turnover of stroma cells, thus diluting the specific activity of stromal DNA with minimal effect on specific activity of fat cell DNA. The diet groups did not differ significantly with respect to body masses, food intake, parametrial (PARA) and retroperitoneal (RP) depot masses, cell number or cell size. The specific activity of DNA in both PARA and RP depots was greater in the adipocyte than in the stromavascular fraction. Specific activity of fat cells was significantly greater from rats fed the high fat than the low fat diet in both PARA and RP depots. Radioautography of adipose tissue confirmed that there was a greater percentage of adipocyte nuclei labeled in the rats fed the high fat diet. Also, there were few labeled nuclei found in stroma cells. In conclusion, older female rats increased adipocyte proliferation when fed a high fat diet.

Optical visualisation of thermogenesis in stimulated single-cell brown adipocytes.

PubMed

Kriszt, Rókus; Arai, Satoshi; Itoh, Hideki; Lee, Michelle H; Goralczyk, Anna G; Ang, Xiu Min; Cypess, Aaron M; White, Andrew P; Shamsi, Farnaz; Xue, Ruidan; Lee, Jung Yeol; Lee, Sung-Chan; Hou, Yanyan; Kitaguchi, Tetsuya; Sudhaharan, Thankiah; Ishiwata, Shin'ichi; Lane, E Birgitte; Chang, Young-Tae; Tseng, Yu-Hua; Suzuki, Madoka; Raghunath, Michael

2017-05-03

The identification of brown adipose deposits in adults has led to significant interest in targeting this metabolically active tissue for treatment of obesity and diabetes. Improved methods for the direct measurement of heat production as the signature function of brown adipocytes (BAs), particularly at the single cell level, would be of substantial benefit to these ongoing efforts. Here, we report the first application of a small molecule-type thermosensitive fluorescent dye, ERthermAC, to monitor thermogenesis in BAs derived from murine brown fat precursors and in human brown fat cells differentiated from human neck brown preadipocytes. ERthermAC accumulated in the endoplasmic reticulum of BAs and displayed a marked change in fluorescence intensity in response to adrenergic stimulation of cells, which corresponded to temperature change. ERthermAC fluorescence intensity profiles were congruent with mitochondrial depolarisation events visualised by the JC-1 probe. Moreover, the averaged fluorescence intensity changes across a population of cells correlated well with dynamic changes such as thermal power, oxygen consumption, and extracellular acidification rates. These findings suggest ERthermAC as a promising new tool for studying thermogenic function in brown adipocytes of both murine and human origins.

Lipolytic signaling in response to acute exercise is altered in female mice following ovariectomy

PubMed Central

Wohlers, Lindsay M.; Jackson, Kathryn C.; Spangenburg, Espen E.

2011-01-01

Impaired ovarian function alters lipid metabolism, ultimately resulting in increased visceral fat mass. Currently, we have a poor understanding of alterations in signaling events regulating lipolysis after ovarian function declines. The purpose of this study was to determine if cellular mechanisms regulating lipolysis are altered in mice after ovariectomy (OVX) and if OVX mice exhibit impaired lipolytic signaling when stimulated by acute exercise. SHAM and OVX mice were divided into two groups: control (SHAM cont; OVX cont) or acute treadmill exercise (SHAM ex; OVX ex). The omental/mesenteric (O/M) fat mass of all OVX mice was significantly greater than the SHAM mice. Serum glycerol and blood glucose levels were significantly elevated in OVX cont compared to SHAM cont. Treadmill exercise increased serum glycerol levels only in SHAM mice, with no exercise-induced change detected in OVX mice. NEFA levels were significantly elevated by acute exercise in the SHAM and OVX groups. In O/M fat from both OVX groups there were significant increases in cytosolic ATGL and PLIN2 in the fat cake fraction with concurrent reductions in PLIN1 in the fat cake compared to SHAM. Further, exercise induced significant increases in HSL Ser660 phosphorylation in SHAM mice, but not OVX mice. This suggests that reduced ovarian function has significant effects on critical lipolytic cell signaling mechanisms in O/M adipose tissue. PMID:21815195

Acceptability and tolerance of a low tyrosine and phenylalanine diet in patients with advanced cancer -- a pilot study.

PubMed

Harvie, Michelle N; Campbell, I T; Howell, A; Thatcher, N

2002-06-01

Low phenylalanine (phe) and tyrosine (tyr) diets limit tumour growth in animal models and may offer a novel cancer therapy. We studied the efficacy and acceptability of a low phe and tyr diet in patients with advanced cancer. Patients with advanced metastatic melanoma (n=22) and metastatic breast cancer (n=15) were invited to follow a low phe and tyr diet (10 mg kg-1 phe and tyr per day) for 1 month. In those individuals who followed the diet for 1 month, we attempted to establish the effects on nutritional status (body weight, fat free mass, percentage body fat, serum albumin), immune cell function (white cell count, lymphocytes and neutrophils), plasma levels of phe-tyr and tryptophan and quality of life (Hospital Anxiety and Depression score). Only three of the 22 patients with metastatic melanoma and three of the 15 patients with metastatic breast cancer agreed to start the diet. All patients experienced problems and side-effects and increases in anxiety and depression. There were declines in weight, with loss of fat and fat free mass but slight increases in white cell counts and neutrophils. Low phe and tyr diets do not appear to be a viable treatment option for patients with advanced cancer.

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

PubMed

Narayanaswami, V; Thompson, A C; Cassis, L A; Bardo, M T; Dwoskin, L P

2013-08-01

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. 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. Striatal D2-receptor density was determined by in vitro kinetic analysis of [(3)H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [(3)H]dopamine uptake, methamphetamine-evoked [(3)H]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. 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 [(3)H]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. Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that motivation for high-fat food, but not impulsive behavior, predicts the development of obesity, whereas decreases in striatal DAT function are exhibited only after the development of obesity.

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 current animal model shows that motivation for high-fat food, but not impulsive behavior, predicts the development of obesity, whereas decreases in striatal DAT function are exhibited only after the development of obesity. PMID:23164701

Expression of an insulin-regulatable glucose carrier in muscle and fat endothelial cells

NASA Astrophysics Data System (ADS)

Vilaró, Senen; Palacín, Manuel; Pilch, Paul F.; Testar, Xavier; Zorzano, Antonio

1989-12-01

INSULIN rapidly stimulates glucose use in the major target tissues, muscle and fat, by modulating a tissue-specific glucose transporter isoform1-6. Access of glucose to the target tissue is restricted by endothelial cells which line the walls of nonfenestrated capillaries of fat and muscle7. Thus, we examined whether the capillary endothelial cells are actively involved in the modulation of glucose availability by these tissues. We report here the abundant expression of the muscle/fat glucose transporter isoform in endothelial cells, using an immunocytochemical analysis with a monoclonal antibody specific for this isoform1. This expression is restricted to endothelial cells from the major insulin target tissues, and it is not detected in brain and liver where insulin does not activate glucose transport. The expression of the muscle/fat transporter isoform in endothelial cells is significantly greater than in the neighbouring muscle and fat cells. Following administration of insulin to animals in vivo, there occurs a rapid increase in the number of muscle/fat transporters present in the lumenal plasma membrane of the capillary endothelial cells. These results document that insulin promotes the translocation of the muscle/fat glucose transporter in endothelial cells. It is therefore likely that endothelial cells play an important role in the regulation of glucose use by the major insulin target tissues in normal and diseased states.

How important are hemoparasites to migratory songbirds? Evaluating physiological measures and infection status in three neotropical migrants during stopover.

PubMed

Cornelius, E A; Davis, A K; Altizer, S A

2014-01-01

Long-distance migrations are energetically expensive for many animals, including migratory songbirds. During these demanding journeys, birds likely face limitations in allocating resources to different physiological functions, including lipid reserves needed to fuel the migration and costly immune defense against pathogens. We sampled three species of long-distance migratory songbirds during their fall migration through coastal Georgia and quantified their body condition, subcutaneous fat reserves, and infection status with blood parasites (Hemoproteus and Plasmodium). We also quantified cellular immunity, on the basis of total and differential white blood cell counts, and estimated individual stress levels, using the heterophil∶lymphocyte (H∶L) ratio. We tested whether birds infected with blood parasites had decreased fat measures, poorer body condition, or increased stress levels (as reflected by H∶L ratios). We also examined relationships between immune cell profiles and the following variables: body condition, subcutaneous fat, infection status, age, and species. Infected birds did not show greater H∶L ratios, poorer body condition, or lower fat measures, but in one species infected individuals showed significantly elevated leukocyte counts. Although we found little evidence for negative relationships between immune cell counts and body condition or fat measures, as might reflect underlying trade-offs in resource allocation, our results concerning hemoparasites are consistent with past work and suggest that chronic hemoparasite infections might have minimal effects on the outcome of long-distance migratory flight.

Membrane lipid composition of pancreatic AR42J cells: modification by exposure to different fatty acids.

PubMed

Audi, Nama'a; Mesa, María D; Martínez, María A; Martínez-Victoria, Emilio; Mañas, Mariano; Yago, María D

2007-04-01

Dietary fat type influences fatty acids in rat pancreatic membranes, in association with modulation of secretory activity and cell signalling in viable acini. We aimed to confirm whether AR42J cells are a valid model to study the interactions between lipids and pancreatic acinar cell function. For this purpose we have (i) compared the baseline fatty acid composition of AR42J cells with that of pancreatic membranes from rats fed a standard chow; (ii) investigated if fatty acids in AR42J membranes can be modified in culture; and (iii) studied if similar compositional variations that can be evoked in rats when dietary fat type is altered occur in AR42J cells. Weaning Wistar rats were fed for 8 weeks either a commercial chow (C) or semi-purified diets containing virgin olive oil (VOO) or sunflower oil (SO) as fat source. AR42J cells were incubated for 72 hrs in medium containing unmodified fetal calf serum (FCS, AR42J-C cells), FCS enriched with 18:1 n-9 (AR42J-O cells), or FCS enriched with 18:2 n-6 (AR42J-L cells). Fatty acids in crude membranes from rat pancreas and AR42J cells were determined by gas-liquid chromatography. Differences in membrane fatty acids between C rats and AR42J-C cells can be explained in part by variations in the amount of fatty acids in the extracellular environment. Supplementation of FCS with 18:1 n-9 or 18:2 n-6 changed the fatty acid spectrum of AR42J cells in a manner that resembles the pattern found, respectively, in VOO and SO rats, although AR42J-L cells were unable to accumulate 20:4 n-6. The AR42J cell line can be a useful tool to assess the effect of membrane compositional changes on acinar cell function. However, differences in baseline characteristics, and perhaps fatty acid metabolism, indicate that results obtained in AR42J cells should be confirmed with experiments in the whole animal.

10 New NIH Research Highlights | NIH MedlinePlus the Magazine

MedlinePlus

... Translational Sciences, and other NIH components. Researchers Identify Energy-Burning Fat Cells Humans have both white and brown fat cells. Brown fat burns energy and helps maintain body temperature, while white fat ...

Hematopoietic stem cells burn fat to prevent exhaustion.

PubMed

Lallemand-Breitenbach, Valerie; de Thé, Hugues

2012-10-05

Ito et al. (2012) recently report in Nature Medicine that fatty acid oxidation (FAO) regulated by PPARδ controls asymmetric division in hematopoietic stem cells (HSCs). This metabolic mechanism prevents HSC exhaustion and is downstream of the promyelocytic leukemia protein PML, suggesting therapeutic implications for HSC function and disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Fasting suppresses T cell-mediated immunity in female Mongolian gerbils (Meriones unguiculatus).

PubMed

Xu, De-Li; Wang, De-Hua

2010-01-01

Immune defense is important for organisms' survival and fitness. Small mammals in temperate zone often face seasonal food shortages. Generally fasting can suppress immune function in laboratory rodents and little information is available for wild rodents. The present study tested the hypothesis that Mongolian gerbils (Meriones unguiculatus) could inhibit T cell-mediated immunity to adapt to acute fasting. Forty-two females were divided into the fed and fasted groups, in which the latter was deprived of food for 3days. After 66h fasting, half of the gerbils in each group were injected with phosphate buffered saline or phytohaemagglutinin (PHA) solution. T cell-mediated immunity assessed by PHA response was suppressed in the fasted gerbils compared with the fed gerbils. The fasted gerbils had lower body fat mass, wet and dry thymus mass, dry spleen mass, white blood cells, serum leptin and blood glucose concentrations, but higher corticosterone concentrations than those of the controls. Moreover, PHA response was positively correlated with body fat mass and serum leptin levels in the immunochallenged groups. Taken together, acute fasting leads to immunosuppression, which might be caused by low body fat mass and low serum leptin concentrations in female Mongolian gerbils.

β-arrestin-2 is an essential regulator of pancreatic β-cell function under physiological and pathophysiological conditions.

PubMed

Zhu, Lu; Almaça, Joana; Dadi, Prasanna K; Hong, Hao; Sakamoto, Wataru; Rossi, Mario; Lee, Regina J; Vierra, Nicholas C; Lu, Huiyan; Cui, Yinghong; McMillin, Sara M; Perry, Nicole A; Gurevich, Vsevolod V; Lee, Amy; Kuo, Bryan; Leapman, Richard D; Matschinsky, Franz M; Doliba, Nicolai M; Urs, Nikhil M; Caron, Marc G; Jacobson, David A; Caicedo, Alejandro; Wess, Jürgen

2017-02-01

β-arrestins are critical signalling molecules that regulate many fundamental physiological functions including the maintenance of euglycemia and peripheral insulin sensitivity. Here we show that inactivation of the β-arrestin-2 gene, barr2, in β-cells of adult mice greatly impairs insulin release and glucose tolerance in mice fed with a calorie-rich diet. Both glucose and KCl-induced insulin secretion and calcium responses were profoundly reduced in β-arrestin-2 (barr2) deficient β-cells. In human β-cells, barr2 knockdown abolished glucose-induced insulin secretion. We also show that the presence of barr2 is essential for proper CAMKII function in β-cells. Importantly, overexpression of barr2 in β-cells greatly ameliorates the metabolic deficits displayed by mice consuming a high-fat diet. Thus, our data identify barr2 as an important regulator of β-cell function, which may serve as a new target to improve β-cell function.

Impact of CD1d deficiency on metabolism.

PubMed

Kotas, Maya E; Lee, Hui-Young; Gillum, Matthew P; Annicelli, Charles; Guigni, Blas A; Shulman, Gerald I; Medzhitov, Ruslan

2011-01-01

Invariant natural killer T cells (iNKTs) are innate-like T cells that are highly concentrated in the liver and recognize lipids presented on the MHC-like molecule CD1d. Although capable of a myriad of responses, few essential functions have been described for iNKTs. Among the many cell types of the immune system implicated in metabolic control and disease, iNKTs seem ideally poised for such a role, yet little has been done to elucidate such a possible function. We hypothesized that lipid presentation by CD1d could report on metabolic status and engage iNKTs to regulate cellular lipid content through their various effector mechanisms. To test this hypothesis, we examined CD1d deficient mice in a variety of metabolically stressed paradigms including high fat feeding, choline-deficient feeding, fasting, and acute inflammation. CD1d deficiency led to a mild exacerbation of steatosis during high fat or choline-deficient feeding, accompanied by impaired hepatic glucose tolerance. Surprisingly, however, this phenotype was not observed in Jα18⁻/⁻ mice, which are deficient in iNKTs but express CD1d. Thus, CD1d appears to modulate some metabolic functions through an iNKT-independent mechanism.

Renal cell carcinoma containing abundant non-calcified fat.

PubMed

Wasser, Elliot J; Shyn, Paul B; Riveros-Angel, Marcela; Sadow, Cheryl A; Steele, Graeme S; Silverman, Stuart G

2013-06-01

Renal masses found to contain macroscopic fatty elements on CT or MRI imaging can generally be classified as benign angiomyolipomas. Rarely, renal cell carcinomas may also contain evidence of macroscopic fat. When true adipocytic elements are present, this is generally due to a process of osseous metaplasia in which both fat cells and calcification are co-localized within the mass. We present a patient with a large papillary renal cell carcinoma containing abundant fat with sparse, punctate calcification remote from the fatty elements on imaging. This report highlights the need for radiologists to maintain caution when diagnosing renal angiomyolipomas on the basis of macroscopic fat and reviews the current literature on fat-containing renal masses.

Weight-dependent changes of immune system in adipose tissue: Importance of leptin

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

Caspar-Bauguil, S.; Groupe de Recherche et d'Etude en Nutrition; Cousin, B.

2006-07-15

Ancestral lymphoid cells reside in adipose tissues, and their numbers are highly altered in obesity. Leptin, production of which is correlated to fat mass, is strongly involved in the relationships between adipose tissues and immune system. We investigated in epididymal (EPI) and inguinal (ING) fat pads to determine whether 1) lymphocyte phenotypes were correlated to the tissue weight and 2) leptin was involved in such relationships. Immunohistological analyses revealed a tight relationship between the T and NK lymphocytes of the stromal vascular fraction and adipocytes. We identified a significant negative and positive correlation between EPI weight and the percentage ofmore » NK and total T cells respectively by cytofluorometric analyses. The NK and ancestral {gamma}{delta} T cell contents were directly dependent of leptin since they increased significantly in high-fat (HF) diet mice but not in leptin-deficient (ob/ob) mice as compared to control. By contrast, the {alpha}{beta} T cell content seemed independent of leptin because their percentages increased significantly with the EPI weight whatever the type of mice (control, HF, ob/ob). The present study suggests that adipose tissues present, according to their localization, different immunological mechanisms that might be involved in the regulation of adipose cells functions and proliferations.« less

The Influence of Macronutrients on Splanchnic and Hepatic Lymphocytes in Aging Mice.

PubMed

Le Couteur, David G; Tay, Szun S; Solon-Biet, Samantha; Bertolino, Patrick; McMahon, Aisling C; Cogger, Victoria C; Colakoglu, Feyza; Warren, Alessandra; Holmes, Andrew J; Pichaud, Nicolas; Horan, Martin; Correa, Carolina; Melvin, Richard G; Turner, Nigel; Ballard, J William O; Ruohonen, Kari; Raubenheimer, David; Simpson, Stephen J

2015-12-01

There is a strong association between aging, diet, and immunity. The effects of macronutrients and energy intake on splanchnic and hepatic lymphocytes were studied in 15 month old mice. The mice were ad-libitum fed 1 of 25 diets varying in the ratios and amounts of protein, carbohydrate, and fat over their lifetime. Lymphocytes in liver, spleen, Peyers patches, mesenteric lymph nodes, and inguinal lymph nodes were evaluated using flow cytometry. Low protein intake reversed aging changes in splenic CD4 and CD8 T cells, CD4:CD8 T cell ratio, memory/effector CD4 T cells and naïve CD4 T cells. A similar influence of total caloric intake in these ad-libitum fed mice was not apparent. Protein intake also influenced hepatic NK cells and B cells, while protein to carbohydrate ratio influenced hepatic NKT cells. Hepatosteatosis was associated with increased energy and fat intake and changes in hepatic Tregs, effector/memory T, and NK cells. Hepatic NK cells were also associated with body fat, glucose tolerance, and leptin levels while hepatic Tregs were associated with hydrogen peroxide production by hepatic mitochondria. Dietary macronutrients, particularly protein, influence splanchnic lymphocytes in old age, with downstream associations with mitochondrial function, liver pathology, and obesity-related phenotype. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

DTIC Science & Technology

2015-11-01

nitrocellulose membranes (Millipore) followed by blocking with 2% non- fat milk and incubation with primary antibodies, overnight at 4C. The b-actin...TNF-like proteins : Osteoprotegerin (OPG), RANK and RANKL, which together regulate osteoclast function (1). The dysregulation of the functional...among proteins in the same family are an indication they may have functional importance, so these residues may be important in mediating the

Elevated autophagy gene expression in adipose tissue of obese humans: A potential non-cell-cycle-dependent function of E2F1

PubMed Central

Haim, Yulia; Blüher, Matthias; Slutsky, Noa; Goldstein, Nir; Klöting, Nora; Harman-Boehm, Ilana; Kirshtein, Boris; Ginsberg, Doron; Gericke, Martin; Guiu Jurado, Esther; Kovsan, Julia; Tarnovscki, Tanya; Kachko, Leonid; Bashan, Nava; Gepner, Yiftach; Shai, Iris; Rudich, Assaf

2015-01-01

Autophagy genes' expression is upregulated in visceral fat in human obesity, associating with obesity-related cardio-metabolic risk. E2F1 (E2F transcription factor 1) was shown in cancer cells to transcriptionally regulate autophagy. We hypothesize that E2F1 regulates adipocyte autophagy in obesity, associating with endocrine/metabolic dysfunction, thereby, representing non-cell-cycle function of this transcription factor. E2F1 protein (N=69) and mRNA (N=437) were elevated in visceral fat of obese humans, correlating with increased expression of ATG5 (autophagy-related 5), MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β), but not with proliferation/cell-cycle markers. Elevated E2F1 mainly characterized the adipocyte fraction, whereas MKI67 (marker of proliferation Ki-67) was elevated in the stromal-vascular fraction of adipose tissue. In human visceral fat explants, chromatin-immunoprecipitation revealed body mass index (BMI)-correlated increase in E2F1 binding to the promoter of MAP1LC3B, but not to the classical cell cycle E2F1 target, CCND1 (cyclin D1). Clinically, omental fat E2F1 expression correlated with insulin resistance, circulating free-fatty-acids (FFA), and with decreased circulating ADIPOQ/adiponectin, associations attenuated by adjustment for autophagy genes. Overexpression of E2F1 in HEK293 cells enhanced promoter activity of several autophagy genes and autophagic flux, and sensitized to further activation of autophagy by TNF. Conversely, mouse embryonic fibroblast (MEF)-derived adipocytes from e2f1 knockout mice (e2f1−/−) exhibited lower autophagy gene expression and flux, were more insulin sensitive, and secreted more ADIPOQ. Furthermore, e2f1−/− MEF-derived adipocytes, and autophagy-deficient (by Atg7 siRNA) adipocytes were resistant to cytokines-induced decrease in ADIPOQ secretion. Jointly, upregulated E2F1 sensitizes adipose tissue autophagy to inflammatory stimuli, linking visceral obesity to adipose and systemic metabolic-endocrine dysfunction. PMID:26391754

IGF-1 Alleviates High Fat Diet-Induced Myocardial Contractile Dysfunction: Role of Insulin Signaling and Mitochondrial Function

PubMed Central

Zhang, Yingmei; Yuan, Ming; Bradley, Katherine M.; Dong, Feng; Anversa, Piero; Ren, Jun

2012-01-01

Obesity is often associated with reduced plasma IGF-1 levels, oxidative stress, mitochondrial damage and cardiac dysfunction. This study was designed to evaluate the impact of IGF-1 on high fat diet-induced oxidative, myocardial, geometric and mitochondrial responses. FVB and cardiomyocyte-specific IGF-1 overexpression transgenic mice were fed a low (10%) or high fat (45%) diet to induce obesity. High fat diet feeding led to glucose intolerance, elevated plasma levels of leptin, interleukin-6, insulin and triglyceride as well as reduced circulating IGF-1 levels. Echocardiography revealed reduced fractional shortening, increased end systolic and diastolic diameter, increased wall thickness, and cardiac hypertrophy in high fat-fed FVB mice. High fat diet promoted ROS generation, apoptosis, protein and mitochondrial damage, reduced ATP content, cardiomyocyte cross-sectional area, contractile and intracellular Ca2+ dysregulation, including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, and dampened intracellular Ca2+ rise and clearance. Western blot analysis revealed disrupted phosphorylation of insulin receptor, post-receptor signaling molecules IRS-1 (tyrosine/serine phosphorylation), Akt, GSK3β, Foxo3a, mTOR, as well as downregulated expression of mitochondrial proteins PPARγ coactivator 1α (PGC1α) and UCP-2. Intriguingly, IGF-1 mitigated high fat diet feeding-induced alterations in ROS, protein and mitochondrial damage, ATP content, apoptosis, myocardial contraction, intracellular Ca2+ handling and insulin signaling, but not whole body glucose intolerance and cardiac hypertrophy. Exogenous IGF-1 treatment also alleviated high fat diet-induced cardiac dysfunction. Our data revealed that IGF-1 alleviates high fat diet-induced cardiac dysfunction despite persistent cardiac remodeling, possibly due to preserved cell survival, mitochondrial function and insulin signaling. PMID:22275536

Histochemical and ultrastructural studies of the mosquito Aedes aegypti fat body: effects of aging and diet type

PubMed Central

Martins, Gustavo Ferreira; Serrão, José Eduardo; Ramalho-Ortigão, José Marcelo; Pimenta, Paulo Filemon Paolucci

2011-01-01

Aedes aegypti is the principal vector of dengue world wide and a major vector of urban yellow fever. Despite its epidemiological importance, not much is known regarding cellular and structural changes in the fat body in this mosquito. Here, we applied light and transmission electron microscopies in order to investigate structural changes in the fat body of three groups of A. aegypti females: newly emerged, 18-day-old sugar-fed, and 18-day-old blood-fed. The fat body consists of a layer of cells attached to the abdomen integument, formed by trophocytes and oenocytes. Trophocytes are strongly positive for carbohydrates, while oenocytes are strongly positive for proteins and lipids. Ultrastructural analyses of trophocytes from newly emerged and 18-day-old blood-fed indicate that these cells are rich in glycogen and free ribosomes. Many lipid droplets and protein granules, which are broken down after the blood meal, are also detected. In 18-day-old sugar-fed, trophocytes display a disorganized cytoplasm filled with lipid droplets, and reduced numbers of free ribosomes, glycogen, rough endoplasmic reticulum (RER) and mitochondria. Following a blood meal, the RER and mitochondria display enlarged sizes, suggestive of increased activity. In regards to oenocytes, these cells display an electron-dense cytoplasm and plasma membrane infoldings facing the hemolymph. As the A. aegypti female ages, trophocyte and oenocyte cell nuclei become larger but decrease in diameter after blood feeding. Our findings suggest that the trophocytes and oenocytes remodeling is likely involved in functional changes of fat body that take place during aging and following a blood meal in A. aegypti females. PMID:21509905

Loss of P2X7 receptor function dampens whole body energy expenditure and fatty acid oxidation.

PubMed

Giacovazzo, Giacomo; Apolloni, Savina; Coccurello, Roberto

2018-05-12

The established role of ATP-responsive P2X7 receptor in inflammatory, neurodegenerative, and immune diseases is now expanding to include several aspects of metabolic dysregulation. Indeed, P2X7 receptors are involved in β cell function, insulin secretion, and liability to diabetes, and loss of P2X7 function may increase the risk of hepatic steatosis and disrupt adipogenesis. Recently, body weight gain, abnormal lipid accumulation, adipocyte hyperplasia, increased fat mass, and ectopic fat distribution have been found in P2X7 KO mice. Here, we hypothesized that such clinical picture of dysregulated lipid metabolism might be the result of altered in vivo energy metabolism. By indirect calorimetry, we assessed 24 h of energy expenditure (EE) and respiratory exchange ratio (RER) as quotient of carbohydrate to fat oxidation in P2X7 KO mice. Moreover, we assessed the same parameters in aged-matched WT counterparts that underwent a 7-day treatment with the P2X7 antagonist A804598. We found that loss of P2X7 function elicits a severe decrease of EE that was less pronounced in A804598-treated mice. In parallel, P2X7KO mice show a drastic increase of RER, thus indicating the occurrence of a greater ratio of carbohydrate to fat oxidation. Decreased EE and fat oxidation is predictive of body weight gain, which was here confirmed. Taken together, our data provide evidence that P2X7 loss of function produces defective energy homeostasis that, together with disrupted adipogenesis, might help to explain accumulation of adipose tissue and contribute to disclose the potential role of P2X7 in metabolic diseases.

Xanthine oxidoreductase mediates membrane docking of milk-fat droplets but is not essential for apocrine lipid secretion.

PubMed

Monks, Jenifer; Dzieciatkowska, Monika; Bales, Elise S; Orlicky, David J; Wright, Richard M; McManaman, James L

2016-10-15

Xanthine oxidoreductase (XOR) modulates milk lipid secretion and lactation initiation. XOR is required for butyrophilin1a1 clustering in the membrane during milk lipid secretion. XOR mediates apical membrane reorganization during milk lipid secretion. Loss of XOR delays milk fat globule secretion. XOR loss alters the proteome of milk fat globules. Apocrine secretion is utilized by epithelial cells of exocrine glands. These cells bud off membrane-bound particles into the lumen of the gland, losing a portion of the cytoplasm in the secretion product. The lactating mammary gland secretes milk lipid by this mechanism, and xanthine oxidoreductase (XOR) has long been thought to be functionally important. We generated mammary-specific XOR knockout (MGKO) mice, expecting lactation to fail. Histology of the knockout glands showed very large lipid droplets enclosed in the mammary alveolar cells, but milk analysis showed that these large globules were secreted. Butyrophilin, a membrane protein known to bind to XOR, was clustered at the point of contact of the cytoplasmic lipid droplet with the apical plasma membrane, in the wild-type gland but not in the knockout, suggesting that XOR mediates 'docking' to this membrane. Secreted milk fat globules were isolated from mouse milk of wild-type and XOR MGKO dams, and subjected to LC-MS/MS for analysis of protein component. Proteomic results showed that loss of XOR leads to an increase in cytoplasmic, cytoskeletal, Golgi apparatus and lipid metabolism proteins associated with the secreted milk fat globule. Association of XOR with the lipid droplet results in membrane docking and more efficient retention of cytoplasmic components by the secretory cell. Loss of XOR then results in a reversion to a more rudimentary, less efficient, apocrine secretion mechanism, but does not prevent milk fat globule secretion. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Improvement of Diet-induced Obesity by Ingestion of Mushroom Chitosan Prepared from Flammulina velutipes.

PubMed

Miyazawa, Noriko; Yoshimoto, Hiroaki; Kurihara, Shoichi; Hamaya, Tadao; Eguchi, Fumio

2018-02-01

The anti-obesity effects of mushroom chitosan prepared from Flammulina velutipes were investigated using an animal model with diet-induced obesity. In this study, 5-week-old imprinting control region (ICR) mice were divided into six groups of 10 mice each and fed different diets based on the MF powdered diet (standard diet) for 6 weeks: standard diet control group, high-fat diet control group (induced dietary obesity) consisting of the standard diet and 20% lard, and mushroom chitosan groups consisting of the high-fat diet with mushroom chitosan added at 100, 500, 1,000, and 2,000 mg/kg body weight. On the final day of the experiment, mean body weight was 39.1 g in the high-fat control group and 36.3 g in the 2,000 mg/kg mushroom chitosan group, compared to 35.8 g in the standard diet control group. In the mushroom chitosan groups, a dose-dependent suppression of weight gain and marked improvements in serum triglycerides, total cholesterol, LDL-cholesterol, and HDL-cholesterol were found. The mushroom chitosan groups showed fewer and smaller fat deposits in liver cells than the high-fat diet control group, and liver weight was significantly reduced. Glutamic oxaloacetic transaminase (GOT) and glutamate pyruvic transaminase (GPT), which are indices of the hepatic function, all showed dose-dependent improvement with mushroom chitosan administration. These results suggested that mushroom chitosan acts to suppress enlargement of the liver from fat deposition resulting from a high-fat diet and to restore hepatic function. The lipid content of feces showed a marked increase correlated with the mushroom chitosan dose. These findings suggest the potential use of mushroom chitosan as a functional food ingredient that contributes to the prevention or improvement of dietary obesity by inhibiting digestion and absorption of fats in the digestive tract and simultaneously promotes lipolysis in adipocytes.

Effects of saxagliptin on glucose homeostasis and body composition of obese patients with newly diagnosed pre-diabetes.

PubMed

Wang, Zixuan; Xu, Dengcheng; Huang, Lanhui; Zhang, Tiantian; Wang, Junqiao; Chen, Qing; Kong, Lei; Zhou, Xinli

2017-08-01

To assess the effect of saxagliptin monotherapy on blood glucose and islet β-cell function in obese patients with newly diagnosed pre-diabetes and abnormal fat metabolism. A 24-week, randomized controlled trial was conducted involving 25 obese subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (mean age 45years) to receive lifestyle intervention only (control group) or combined with saxagliptin 2.5mg or 5mg daily (S2.5 or S5 group), metformin 1500mg daily (Met group). Anthropometrics, body fat and biochemical parameters were measured before and after 4, 12 and 24weeks intervention. S5 group and Met group showed a significant decrease in fasting plasma glucose (FPG) and HbA1c compared with the control group (all P<0.05) after 24-week intervention. However, the decrease in 2h postprandial plasma glucose levels (2hPPG) in S5 group were greater compared with control group (P<0.01). Insulin resistance (HOMA-IR) was reduced in S5 group, Met group and control group (P<0.05), and the β-cell function (HOMA-β) was improved in all groups (P<0.05). However, the changes in obesity-related indicators including waist circumference, hip circumference, weight, BMI, body fat, percentage of body fat and waist-to-hip fat ratio were greate in Met group (all P<0.05) compared with other groups (P>0.05). Saxagliptin monotherapy may prevent or delay the progression of IGT or IFG to type 2 diabetes mellitus in obese patients with newly diagnosed pre-diabetes. ClinicalTrials.gov: NCT01960205. Copyright © 2017 Elsevier B.V. All rights reserved.

Orexin-A/hypocretin-1 Immunoreactivity in the Lateral Hypothalamus is Reduced in Genetically Obese but not in Diet-induced Obese Mice.

PubMed

González, J Antonio; Prehn, Jochen H M

2018-01-15

The mechanisms that link diet and body weight are not fully understood. A diet high in fat often leads to obesity, and this in part is the consequence of diet-induced injury to specific hypothalamic nuclei. It has been suggested that a diet high in fat leads to cell loss in the lateral hypothalamus, which contains specific populations of neurons that are essential for regulating energy homoeostasis; however, we do not know which cell types are affected by the diet. We studied the possibility that high-fat diet leads to a reduction in orexin-A/hypocretin-1 (Hcrt1) and/or melanin-concentrating hormone (MCH) immunoreactivity in the lateral hypothalamus. We quantified immuno-labeled Hcrt1 and MCH cells in brain sections of mice fed a diet high in fat for up to 12 weeks starting at 4 weeks of age and found that this diet did not modify the number of Hcrt1- or MCH-immunoreactive neurons. By contrast, there were fewer Hcrt1- (but not MCH-) immunoreactive cells in genetically obese db/db mice compared to wild-type mice. Non-obese, heterozygous db/+ mice also had fewer Hcrt1-immunoreactive cells. Differences in the number of Hcrt1-immunoreactive cells were only a function of the db genotype but not of diet or body weight. Our findings show that the lateral hypothalamus is affected differently in the db genotype and in diet-induced obesity, and support the idea that not all hypothalamic neurons involved in energy balance regulation are sensitive to the effects of diet. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Switching from high-fat to low-fat diet normalizes glucose metabolism and improves glucose-stimulated insulin secretion and insulin sensitivity but not body weight in C57BL/6J mice.

PubMed

Agardh, Carl-David; Ahrén, Bo

2012-03-01

Environmental factors such as a high-fat diet contribute to type 2 diabetes and obesity. This study examined glycemia, insulin sensitivity, and β-cell function after switching from a high-fat diet to a low-fat diet in mice. C57BL/6J mice were fed a high-fat diet or low-fat diet for 18 months, after which mice on the high-fat diet either maintained this diet or switched to a low-fat diet for 4 weeks. Body weight and glucose and insulin responses to intraperitoneal glucose were determined. Insulin secretion (insulinogenic index: the 10-minute insulin response divided by the 10-minute glucose level) and insulin sensitivity (1 divided by basal insulin) were determined. After 18 months on a high-fat diet, mice had glucose intolerance, marked hyperinsulinemia, and increased body weight compared to mice on a low-fat diet (P < 0.001). Switching from a high-fat diet to low-fat diet normalized glucose tolerance, reduced but not normalized body weight (P < 0.001), increased insulin secretion (248 ± 39 vs 141 ± 46 pmol/mmol; P = 0.028) and improved but not normalized insulin sensitivity (3.2 ± 0.1 vs 1.0 ± 0.1 [pmol/L]; P = 0.012). Switching from a high-fat diet to low-fat diet normalizes glucose tolerance and improves but not normalizes insulin secretion and insulin sensitivity. These effects are more pronounced than the reduced body weight.

Advanced cardiac chemical exchange saturation transfer (cardioCEST) MRI for in vivo cell tracking and metabolic imaging

PubMed Central

Pumphrey, Ashley; Yang, Zhengshi; Ye, Shaojing; Powell, David K.; Thalman, Scott; Watt, David S.; Abdel-Latif, Ahmed; Unrine, Jason; Thompson, Katherine; Fornwalt, Brandon; Ferrauto, Giuseppe; Vandsburger, Moriel

2016-01-01

An improved pre-clinical cardiac chemical exchange saturation transfer (CEST) pulse sequence (cardioCEST) was used to selectively visualize paramagnetic CEST (paraCEST)-labeled cells following intramyocardial implantation. In addition, cardioCEST was used to examine the effect of diet-induced obesity upon myocardial creatine CEST contrast. CEST pulse sequences were designed from standard turbo-spin-echo and gradient-echo sequences, and a cardiorespiratory-gated steady-state cine gradient-echo sequence. In vitro validation studies performed in phantoms composed of 20mM Eu-HPDO3A, 20mM Yb-HPDO3A, or saline demonstrated similar CEST contrast by spin-echo and gradient-echo pulse sequences. Skeletal myoblast cells (C2C12) were labeled with either Eu-HPDO3A or saline using a hypotonic swelling procedure and implanted into the myocardium of C57B6/J mice. Inductively coupled plasma mass spectrometry confirmed cellular levels of Eu of 2.1 × 10−3 ng/cell in Eu-HPDO3A-labeled cells and 2.3 × 10−5 ng/cell in saline-labeled cells. In vivo cardioCEST imaging of labeled cells at ±15ppm was performed 24 h after implantation and revealed significantly elevated asymmetric magnetization transfer ratio values in regions of Eu-HPDO3A-labeled cells when compared with surrounding myocardium or saline-labeled cells. We further utilized the cardioCEST pulse sequence to examine changes in myocardial creatine in response to diet-induced obesity by acquiring pairs of cardioCEST images at ±1.8 ppm. While ventricular geometry and function were unchanged between mice fed either a high-fat diet or a corresponding control low-fat diet for 14 weeks, myocardial creatine CEST contrast was significantly reduced in mice fed the high-fat diet. The selective visualization of paraCEST-labeled cells using cardioCEST imaging can enable investigation of cell fate processes in cardioregenerative medicine, or multiplex imaging of cell survival with imaging of cardiac structure and function and additional imaging of myocardial creatine. PMID:26684053

Loss of SPARC dysregulates basal lamina assembly to disrupt larval fat body homeostasis in Drosophila melanogaster.

PubMed

Shahab, Jaffer; Baratta, Cristina; Scuric, Bianca; Godt, Dorothea; Venken, Koen J T; Ringuette, Maurice J

2015-04-01

SPARC is a collagen-binding glycoprotein whose functions during early development are unknown. We previously reported that SPARC is expressed in Drosophila by hemocytes and the fat body (FB) and enriched in basal laminae (BL) surrounding tissues, including adipocytes. We sought to explore if SPARC is required for proper BL assembly in the FB. SPARC deficiency leads to larval lethality, associated with remodeling of the FB. In the absence of SPARC, FB polygonal adipocytes assume a spherical morphology. Loss-of-function clonal analyses revealed a cell-autonomous accumulation of BL components around mutant cells that include collagen IV (Col lV), Laminin, and Perlecan. Ultrastructural analyses indicate SPARC-deficient adipocytes are surrounded by an aberrant accumulation of a fibrous extracellular matrix. Our data indicate a critical requirement for SPARC for the proper BL assembly in Drosophila FB. Since Col IV within the BL is a prime determinant of cell shape, the rounded appearance of SPARC-deficient adipocytes is due to aberrant assembly of Col IV. © 2014 Wiley Periodicals, Inc.

Oxygen tension differentially regulates the functional properties of cartilaginous tissues engineered from infrapatellar fat pad derived MSCs and articular chondrocytes.

PubMed

Buckley, C T; Vinardell, T; Kelly, D J

2010-10-01

For current tissue engineering or regenerative medicine strategies, chondrocyte (CC)- or mesenchymal stem cell (MSC)-seeded constructs are typically cultured in normoxic conditions (20% oxygen). However, within the knee joint capsule a lower oxygen tension exists. The objective of this study was to investigate how CCs and infrapatellar fad pad derived MSCs will respond to a low oxygen (5%) environment in 3D agarose culture. Our hypothesis was that culture in a low oxygen environment (5%) will enhance the functional properties of cartilaginous tissues engineered using both cell sources. Cell-encapsulated agarose hydrogel constructs (seeded with CCs or infrapatellar fat pad (IFP) derived MSCs) were prepared and cultured in a chemically defined serum-free medium in the presence (CCs and MSCs) or absence (CCs only) of transforming growth factor-beta3 (TGF-β3) in normoxic (20%) or low oxygen (5%) conditions for 42 days. Constructs were assessed at days 0, 21 and 42 in terms of mechanical properties, biochemical content and histologically. Low oxygen tension (5%) was observed to promote extracellular matrix (ECM) production by CCs cultured in the absence of TGF-β3, but was inhibitory in the presence of TGF-β3. In contrast, a low oxygen tension enhanced chondrogenesis of IFP constructs in the presence of TGF-β3, leading to superior mechanical functionality compared to CCs cultured in identical conditions. Extrapolating the results of this study to the in vivo setting, it would appear that joint fat pad derived MSCs may possess a superior potential to generate a functional repair tissue in low oxygen tensions. However, in the context of in vitro cartilage tissue engineering, CCs maintained in normoxic conditions in the presence of TGF-β3 generate the most mechanically functional tissue. Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

PubMed

Ellenbroek, Johanne H; Töns, Hendrica A; de Graaf, Natascha; Loomans, Cindy J; Engelse, Marten A; Vrolijk, Hans; Voshol, Peter J; Rabelink, Ton J; Carlotti, Françoise; de Koning, Eelco J

2013-01-01

Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice. C57BL/6J mice were fed a HFD to induce insulin resistance, or control diet for 6 weeks. The pancreas was divided in a duodenal (DR), gastric (GR) and splenic (SR) region and taken for either histology or islet isolation. The capacity of untreated islets from the three regions to adapt in an extrapancreatic location was assessed by transplantation under the kidney capsule of streptozotocin-treated mice. SR islets showed 70% increased beta cell proliferation after HFD, whereas no significant increase was found in DR and GR islets. Furthermore, isolated SR islets showed twofold enhanced glucose-induced insulin secretion after HFD, as compared with DR and GR islets. In contrast, transplantation of islets isolated from the three regions to an extrapancreatic location in diabetic mice led to a similar decrease in hyperglycemia and no difference in beta cell proliferation. HFD-induced insulin resistance leads to topologically heterogeneous beta cell adaptation and is most prominent in the splenic region of the pancreas. This topological heterogeneity in beta cell adaptation appears to result from extrinsic factors present in the islet microenvironment.

The Cell Surface Markers Expression in Postmenopausal Women and Relation to Obesity and Bone Status.

PubMed

Horváthová, Mira; Ilavská, Silvia; Štefíková, Kornélia; Szabová, Michaela; Krivošíková, Zora; Jahnová, Eva; Tulinská, Jana; Spustová, Viera; Gajdoš, Martin

2017-07-11

The age-related changes and hormonal deprivation in postmenopausal women are associated with the immune response alteration. The excessive fat accumulation, local and systemic inflammation may lead to dysregulation in immune function and relevant health problems, including obesity and osteoporosis. We analyzed the expression of cell surface markers in the venous blood specimens, stained with fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes, plasmacytoid dendritic cells (DCs) were in postmenopausal women versus fertile women. Body mass index (BMI) affected markedly the cell surface expression of CD265/RANK. Osteoporosis is linked to reduced percentage of plasmacytoid DCs, and elevated natural Treg cells ( p < 0.05). The confounding factors such as women age, BMI, bone mineral density (BMD), waist size and tissue fat affect the expression of RANK on myeloid DCs and CD40L on T-lymphocytes that might be the immunophenotypic modulators after menopause.

The Cell Surface Markers Expression in Postmenopausal Women and Relation to Obesity and Bone Status

PubMed Central

Horváthová, Mira; Ilavská, Silvia; Štefíková, Kornélia; Szabová, Michaela; Krivošíková, Zora; Jahnová, Eva; Tulinská, Jana; Spustová, Viera; Gajdoš, Martin

2017-01-01

The age-related changes and hormonal deprivation in postmenopausal women are associated with the immune response alteration. The excessive fat accumulation, local and systemic inflammation may lead to dysregulation in immune function and relevant health problems, including obesity and osteoporosis. We analyzed the expression of cell surface markers in the venous blood specimens, stained with fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes, plasmacytoid dendritic cells (DCs) were in postmenopausal women versus fertile women. Body mass index (BMI) affected markedly the cell surface expression of CD265/RANK. Osteoporosis is linked to reduced percentage of plasmacytoid DCs, and elevated natural Treg cells (p < 0.05). The confounding factors such as women age, BMI, bone mineral density (BMD), waist size and tissue fat affect the expression of RANK on myeloid DCs and CD40L on T-lymphocytes that might be the immunophenotypic modulators after menopause. PMID:28696349

[The effect of high fat feeding and rosiglitazone intervention on pancreatic alpha cell in rats].

PubMed

Wang, Xin; Yang, Wen-ying; Xiao, Jian-zhong; Zhao, Wen-hui; Wang, Na; Liu, Xue-li; Pan, Lin

2005-08-01

To observe the effect of high-fat diet and rosiglitazone intervention on the function of pancreatic alpha cell of SD rats. 36 normal male SD rats, 8-week old, were randomly divided into 3 groups i.e., a normal chow group (CC, n = 12), an isocaloric high-fat diet group (CF, n = 12), and a rosiglitazone-treated group (Ro, n = 12, rosiglitazone 3 mg.kg(-1).d(-1) and isocaloric high fat diet). Triglyceride (TG) was measured every 4 weeks after feeding for 6 weeks. After 28 weeks, the secretion of insulin and glucagon (Gg) was assessed with intravenous glucose tolerance test (IVGTT) at 0, 3, 5, and 10 minutes. (3)H-2-deoxyglucose ((3)H-2-DG) uptake by tissues was measured to evaluate the insulin sensitivity. The ratio of intra-abdominal fat mass and body weight was higher in the rats of CF and Ro group than that in the rats of CC group. At the first 10 min of IVGTT, the Gg level was higher in the CF group than that in CC group [(119.3 +/- 12.4, 82.3 +/- 6.4, 72.2 +/- 5.8, 68.2 +/- 9.1) ng/L vs (96.8 +/- 9.1, 67.6 +/- 5.9, 57.9 +/- 5.3, 55.3 +/- 6.9) ng/L, P < 0.05] and Ro group [(78.4 +/- 6.0, 59.4 +/- 4.0, 49.9 +/- 6.2, 40.9 +/- 6.0) ng/L, P < 0.01], the level was even lower in the latter group than in CC group (P < 0.01). There was no difference of insulin level among the 3 groups. By using quantitative image analysis, the integrated A (area x A) of alpha cells was significantly higher in the CF group and Ro group as compared with that in the CC group (1661 +/- 130 and 1532 +/- 132 vs 1188 +/- 104, P < 0.05). In contrast, there was no difference among the 3 groups in the integrated A of beta cells. High-fat feeding induces insulin resistance in rats, which is associated with pancreatic alpha cell proliferation and abnormal Gg secretion.

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

PubMed

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

2017-12-01

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

Isolation of Precursor Cells from Waste Solid Fat Tissue

NASA Technical Reports Server (NTRS)

Byerly, Diane; Sognier, Marguerite A.

2009-01-01

A process for isolating tissue-specific progenitor cells exploits solid fat tissue obtained as waste from such elective surgical procedures as abdominoplasties (tummy tucks) and breast reductions. Until now, a painful and risky process of aspiration of bone marrow has been used to obtain a limited number of tissue- specific progenitor cells. The present process yields more tissue-specific progenitor cells and involves much less pain and risk for the patient. This process includes separation of fat from skin, mincing of the fat into small pieces, and forcing a fat saline mixture through a sieve. The mixture is then digested with collagenase type I in an incubator. After centrifugation tissue-specific progenitor cells are recovered and placed in a tissue-culture medium in flasks or Petri dishes. The tissue-specific progenitor cells can be used for such purposes as (1) generating three-dimensional tissue equivalent models for studying bone loss and muscle atrophy (among other deficiencies) and, ultimately, (2) generating replacements for tissues lost by the fat donor because of injury or disease.

High-fat, carbohydrate-free diet markedly aggravates obesity but prevents beta-cell loss and diabetes in the obese, diabetes-susceptible db/db strain.

PubMed

Mirhashemi, Farshad; Kluth, Oliver; Scherneck, Stephan; Vogel, Heike; Kluge, Reinhart; Schurmann, Annette; Joost, Hans-Georg; Neschen, Susanne

2008-01-01

We have previously reported that a high-fat, carbohydrate-free diet prevents diabetes and beta-cell destruction in the New Zealand Obese (NZO) mouse strain. Here we investigated the effect of diets with and without carbohydrates on obesity and development of beta-cell failure in a second mouse model of type 2 diabetes, the db/db mouse. When kept on a carbohydrate-containing standard (SD; with (w/w) 5.1, 58.3, and 17.6% fat, carbohydrates and protein, respectively) or high-fat diet (HFD; 14.6, 46.7 and 17.1%), db/db mice developed severe diabetes (blood glucose >20 mmol/l, weight loss, polydipsia and polyurea) associated with a selective loss of pancreatic beta-cells, reduced GLUT2 expression in the remaining beta-cells, and reduced plasma insulin levels. In contrast, db/db mice kept on a high-fat, carbohydrate-free diet (CFD; with 30.2 and 26.4% (w/w) fat or protein) did not develop diabetes and exhibited near-normal, hyperplastic islets in spite of a morbid obesity (fat content >60%) associated with hyperinsulinaemia. These data indicate that in genetically different mouse models of obesity-associated diabetes, obesity and dietary fat are not sufficient, and dietary carbohydrates are required, for beta-cell destruction.

Rutin attenuates metabolic changes, nonalcoholic steatohepatitis, and cardiovascular remodeling in high-carbohydrate, high-fat diet-fed rats.

PubMed

Panchal, Sunil K; Poudyal, Hemant; Arumugam, Thiruma V; Brown, Lindsay

2011-06-01

Metabolic syndrome (obesity, diabetes, and hypertension) increases hepatic and cardiovascular damage. This study investigated preventive or reversal responses to rutin in high-carbohydrate, high-fat diet-fed rats as a model of metabolic syndrome. Rats were divided into 6 groups: 2 groups were fed a corn starch-rich diet for 8 or 16 wk, 2 groups were fed a high-carbohydrate, high-fat diet for 8 or 16 wk, and 2 groups received rutin (1.6 g/kg diet) in either diet for the last 8 wk only of the 16-wk protocol. Metabolic changes and hepatic and cardiovascular structure and function were then evaluated in these rats. The corn starch-rich diet contained 68% carbohydrate (mainly cornstarch) and 0.7% fat, whereas the high-carbohydrate, high-fat diet contained 50% carbohydrate (mainly fructose) and 24% fat (mainly beef tallow) along with 25% fructose in drinking water (total 68% carbohydrate using mean food and water intakes). The high-carbohydrate, high-fat diet produced obesity, dyslipidemia, hypertension, impaired glucose tolerance, hepatic steatosis, infiltration of inflammatory cells in the liver and the heart, higher cardiac stiffness, endothelial dysfunction, and higher plasma markers of oxidative stress with lower expression of markers for oxidative stress and apoptosis in the liver. Rutin reversed or prevented metabolic changes such as abdominal fat pads and glucose tolerance, reversed or prevented changes in hepatic and cardiovascular structure and function, reversed oxidative stress and inflammation in the liver and heart, and normalized expression of liver markers. These results suggest a non-nutritive role for rutin to attenuate chronic changes in metabolic syndrome.

Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice

PubMed Central

Oliveira, Ricardo B d; Carvalho, Carolina P d F; Polo, Carla C; Dorighello, Gabriel d G; Boschero, Antônio C; Oliveira, Helena C F d; Collares-Buzato, Carla B

2014-01-01

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr−/− mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr−/− mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr−/− mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr−/− mice showed no significant changes in beta-cell mass, but lower islet–duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr−/− mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion. PMID:24853046

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women.

PubMed

Dumesic, Daniel A; Akopians, Alin L; Madrigal, Vanessa K; Ramirez, Emmanuel; Margolis, Daniel J; Sarma, Manoj K; Thomas, Albert M; Grogan, Tristan R; Haykal, Rasha; Schooler, Tery A; Okeya, Bette L; Abbott, David H; Chazenbalk, Gregorio D

2016-11-01

Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction. This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia. This is a prospective cohort study. The setting was an academic medical center. Six normal weight PCOS women and 14 age- and body mass index-matched normoandrogenic ovulatory (NL) women were included. All women underwent circulating hormone and metabolic measurements; frequently sampled intravenous glucose tolerance testing; total body dual-energy x-ray absorptiometry; abdominal magnetic resonance imaging; and SC abdominal fat biopsy. Circulating hormones and metabolites, body fat and its distribution, and adipocyte size were compared between PCOS and NL women, and were correlated with each other in all women. Circulating LH and androgen levels were significantly greater in PCOS than NL women, as were fasting insulin levels, pancreatic β-cell responsiveness to glucose, and total abdominal fat mass. Intra-abdominal fat mass also was significantly increased in PCOS women and was positively correlated with circulating androgen, fasting insulin, triglyceride, and non-high-density lipoprotein cholesterol levels in all women. SC abdominal fat mass was not significantly increased in PCOS women, but contained a greater proportion of small SC abdominal adipocytes that positively correlated with serum androgen levels in all women. Hyperandrogenism in normal weight PCOS women is associated with preferential intra-abdominal fat deposition and an increased population of small SC abdominal adipocytes that could constrain SC adipose storage and promote metabolic dysfunction.

Buttock augmentation: case studies of fat injection monitored by magnetic resonance imaging.

PubMed

Murillo, William L

2004-11-01

This article examines the injection of megavolumes of autologous fat cells as a means of buttock augmentation in 162 patients over a 7-year period. The author documents the use of magnetic resonance imaging in six patients to visualize the intramuscular location, integration, and duration of the injected fat. With the patient under epidural or general anesthesia, fat cells were harvested with a 5-mm blunt cannula and then stored in an empty sterile intravenous bag or bottle trap. Decantation was the only process used to separate the fat cells from the saline and serosanguineous components. Up to 1260 cc of fat cells were been injected into each buttock, the largest amount of fat grafting ever reported. Clinical assessment estimated a 20 percent loss of augmentation effect during the first 4 months. Patients were generally pleased with the final shape and volume of the buttock contour. In follow-up evaluation, magnetic resonance imaging supported the clinical indicators that the injection of large quantities of fat cells appears to be a safe and effective method for buttock enhancement. This process has inherent advantages; nevertheless, further research is required to clarify our understanding of the predictability and longevity of this technique.

Nutrient control of gene expression in Drosophila: microarray analysis of starvation and sugar-dependent response

PubMed Central

Zinke, Ingo; Schütz, Christina S.; Katzenberger, Jörg D.; Bauer, Matthias; Pankratz, Michael J.

2002-01-01

We have identified genes regulated by starvation and sugar signals in Drosophila larvae using whole-genome microarrays. Based on expression profiles in the two nutrient conditions, they were organized into different categories that reflect distinct physiological pathways mediating sugar and fat metabolism, and cell growth. In the category of genes regulated in sugar-fed, but not in starved, animals, there is an upregulation of genes encoding key enzymes of the fat biosynthesis pathway and a downregulation of genes encoding lipases. The highest and earliest activated gene upon sugar ingestion is sugarbabe, a zinc finger protein that is induced in the gut and the fat body. Identification of potential targets using microarrays suggests that sugarbabe functions to repress genes involved in dietary fat breakdown and absorption. The current analysis provides a basis for studying the genetic mechanisms underlying nutrient signalling. PMID:12426388

Entrainment in solution of an oscillating NADH oxidase activity from the bovine milk fat globule membrane with a temperature-compensated period length suggestive of an ultradian time-keeping (clock) function

NASA Technical Reports Server (NTRS)

Morre, D. James; Lawler, Juliana; Wang, Sui; Keenan, Thomas W.; Morre, Dorothy M.

2002-01-01

Entrainment in solution of an oscillating activity with a temperature compensated period of 24 min is described for a NADH oxidase (NOX) activity of the bovine milk fat globule membrane, a derivative of the mammary epithelial cell plasma membrane. The period of 24 min remained unchanged at 17 degrees C, 27 degrees C and 37 degrees C whereas the amplitude approximately doubled with each 10 degree C rise in temperature (Q(10)congruent with 2). The periodicity was observed with both intact milk fat globule membranes and with detergent-solubilized membranes, demonstrating that the oscillations did not require an association with membranes. The periodicity was not the result of instrument variation or of chemical interactions among reactants in solution. Preparations with different periodicities entrained (autosynchronized) when mixed. Upon mixing, the preparations exhibited two oscillatory patterns but eventually a single pattern representing the mean of the farthest separated maxima of the two preparations analyzed separately emerged. The cell surface NOX protein is the first reported example of an entrainable biochemical entity with a temperature-compensated periodicity potentially capable of functioning as an ultradian or circadian clock driver.

Exercise (and Estrogen) Make Fat Cells “Fit”

PubMed Central

Vieira-Potter, Victoria J.; Zidon, Terese M.; Padilla, Jaume

2016-01-01

Adipose tissue inflammation links obesity and metabolic disease. Both exercise and estrogen improve metabolic health, enhance mitochondrial function, and have anti-inflammatory effects. We hypothesize that there is an inverse relationship between mitochondrial function and inflammation in adipose tissue and that exercise acts as an estrogen “mimetic”. Explicitly, exercise may improve adipose tissue “immunometabolism” by improving mitochondrial function and reducing inflammation. Summary Exercise improves adipose tissue metabolic health by reducing inflammation and improving mitochondrial function. PMID:25906425

Metabolic inflammation in inflammatory bowel disease: crosstalk between adipose tissue and bowel.

PubMed

Gonçalves, Pedro; Magro, Fernando; Martel, Fátima

2015-02-01

Epidemiological studies show that both the incidence of inflammatory bowel disease (IBD) and the proportion of people with obesity and/or obesity-associated metabolic syndrome increased markedly in developed countries during the past half century. Obesity is also associated with the development of more active IBD and requirement for hospitalization and with a decrease in the time span between diagnosis and surgery. Patients with IBD, especially Crohn's disease, present fat-wrapping or "creeping fat," which corresponds to ectopic adipose tissue extending from the mesenteric attachment and covering the majority of the small and large intestinal surface. Mesenteric adipose tissue in patients with IBD presents several morphological and functional alterations, e.g., it is more infiltrated with immune cells such as macrophages and T cells. All these lines of evidence clearly show an association between obesity, adipose tissue, and functional bowel disorders. In this review, we will show that the mesenteric adipose tissue and creeping fat are not innocent by standers but actively contribute to the intestinal and systemic inflammatory responses in patients with IBD. More specifically, we will review evidence showing that adipose tissue in IBD is associated with major alterations in the secretion of cytokines and adipokines involved in inflammatory process, in adipose tissue mesenchymal stem cells and adipogenesis, and in the interaction between adipose tissue and other intestinal components (immune, lymphatic, neuroendocrine, and intestinal epithelial systems). Collectively, these studies underline the importance of adipose tissue for the identification of novel therapeutic approaches for IBD.

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice.

PubMed

Calvo-Rubio, Miguel; Burón, M Isabel; López-Lluch, Guillermo; Navas, Plácido; de Cabo, Rafael; Ramsey, Jon J; Villalba, José M; González-Reyes, José A

2016-06-01

Calorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age-related diseases in a wide range of animals, including non-human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils. In this paper, we study the effect of these dietary fats on structural and physiological parameters of kidney from mice maintained on 40% CR for 6 and 18 months. Analyses were performed using quantitative electron microcopy techniques and protein expression in Western blots. CR mitigated most of the analyzed age-related parameters in kidney, such as glomerular basement membrane thickness, mitochondrial mass in convoluted proximal tubules and autophagic markers in renal homogenates. The lard group showed improved preservation of several renal structures with aging when compared to the other CR diet groups. These results indicate that dietary fat modulates renal structure and function in CR mice and plays an essential role in the determination of health span in rodents. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Quantitative monitoring of lipid accumulation over time in cultured adipocytes as function of culture conditions: toward controlled adipose tissue engineering.

PubMed

Or-Tzadikario, Shira; Sopher, Ran; Gefen, Amit

2010-10-01

Adipose tissue engineering is investigated for native fat substitutes and wound healing model systems. Research and clinical applications of bioartificial fat require a quantitative and objective method to continuously measure adipogenesis in living cultures as opposed to currently used culture-destructive techniques that stain lipid droplet (LD) accumulation. To allow standardization, automatic quantification of LD size is further needed, but currently LD size is measured mostly manually. We developed an image processing-based method that does not require staining to monitor adipose cell maturation in vitro nondestructively using optical micrographs taken consecutively during culturing. We employed our method to monitor LD accumulation in 3T3-L1 and mesenchymal stem cells over 37 days. For each cell type, percentage of lipid area, number of droplets per cell, and droplet diameter were obtained every 2-3 days. In 3T3-L1 cultures, high insulin concentration (10 microg/mL) yielded a significantly different (p < 0.01) time course of all three outcome measures. In mesenchymal stem cell cultures, high fetal bovine serum concentration (12.5%) produced significantly more lipid area (p < 0.01). Our method was able to successfully characterize time courses and extents of adipogenesis and is useful for a wide range of applications testing the effects of biochemical, mechanical, and thermal stimulations in tissue engineering of bioartificial fat constructs.

High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation that is Reversed by IL-22

PubMed Central

Gulhane, Max; Murray, Lydia; Lourie, Rohan; Tong, Hui; Sheng, Yong H.; Wang, Ran; Kang, Alicia; Schreiber, Veronika; Wong, Kuan Yau; Magor, Graham; Denman, Stuart; Begun, Jakob; Florin, Timothy H.; Perkins, Andrew; Cuív, Páraic Ó.; McGuckin, Michael A.; Hasnain, Sumaira Z.

2016-01-01

Prolonged high fat diets (HFD) induce low-grade chronic intestinal inflammation in mice, and diets high in saturated fat are a risk factor for the development of human inflammatory bowel diseases. We hypothesized that HFD-induced endoplasmic reticulum (ER)/oxidative stress occur in intestinal secretory goblet cells, triggering inflammatory signaling and reducing synthesis/secretion of proteins that form the protective mucus barrier. In cultured intestinal cells non-esterified long-chain saturated fatty acids directly increased oxidative/ER stress leading to protein misfolding. A prolonged HFD elevated the intestinal inflammatory cytokine signature, alongside compromised mucosal barrier integrity with a decrease in goblet cell differentiation and Muc2, a loss in the tight junction protein, claudin-1 and increased serum endotoxin levels. In Winnie mice, that develop spontaneous colitis, HFD-feeding increased ER stress, further compromised the mucosal barrier and increased the severity of colitis. In obese mice IL-22 reduced ER/oxidative stress and improved the integrity of the mucosal barrier, and reversed microbial changes associated with obesity with an increase in Akkermansia muciniphila. Consistent with epidemiological studies, our experiments suggest that HFDs are likely to impair intestinal barrier function, particularly in early life, which partially involves direct effects of free-fatty acids on intestinal cells, and this can be reversed by IL-22 therapy. PMID:27350069

Th17 and IL-17 Cause Acceleration of Inflammation and Fat Loss by Inducing α2-Glycoprotein 1 (AZGP1) in Rheumatoid Arthritis with High-Fat Diet.

PubMed

Na, Hyun Sik; Kwon, Jeong-Eun; Lee, Seung Hoon; Jhun, JooYeon; Kim, Sung-Min; Kim, Se-Young; Kim, Eun-Kyung; Jung, KyungAh; Park, Sung-Hwan; Cho, Mi-La

2017-05-01

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints. High-fat diet (HFD) is a risk factor for RA and is related to inflammation but responds minimally to medication. Given the association between HFD and inflammation, it is important to understand the function of inflammation-related T cells in RA with HFD. Collagen-induced arthritis (CIA), a model of RA, was induced in HFD mice by injection of collagen II, and metabolic markers and T cells were analyzed. The metabolic index and IgG assay results were higher in HFD-CIA mice than in nonfat diet-CIA mice. Numbers of inflammation-related T cells and macrophages, such as Th1 and Th17 cells and M1 macrophages, were higher in spleens of HFD-CIA mice. HFD-CIA mice had a high level of α 2 -glycoprotein 1 (Azgp1), a soluble protein that stimulates lipolysis. To examine the association between Azgp1 and Th17 cells, the reciprocal effects of Azgp1 and IL-17 on Th17 differentiation and lipid metabolism were measured. Interestingly, Azgp1 increased the Th17 population of splenocytes. Taken together, our data suggest that the acceleration of fat loss caused by Azgp1 in RA with metabolic syndrome is related to the increase of IL-17. Mice injected with the Azgp1-overexpression vector exhibited more severe CIA compared with the mock vector-injected mice. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Nervous glucose sensing regulates postnatal β cell proliferation and glucose homeostasis

PubMed Central

Tarussio, David; Metref, Salima; Seyer, Pascal; Mounien, Lourdes; Vallois, David; Magnan, Christophe; Foretz, Marc; Thorens, Bernard

2013-01-01

How glucose sensing by the nervous system impacts the regulation of β cell mass and function during postnatal development and throughout adulthood is incompletely understood. Here, we studied mice with inactivation of glucose transporter 2 (Glut2) in the nervous system (NG2KO mice). These mice displayed normal energy homeostasis but developed late-onset glucose intolerance due to reduced insulin secretion, which was precipitated by high-fat diet feeding. The β cell mass of adult NG2KO mice was reduced compared with that of WT mice due to lower β cell proliferation rates in NG2KO mice during the early postnatal period. The difference in proliferation between NG2KO and control islets was abolished by ganglionic blockade or by weaning the mice on a carbohydrate-free diet. In adult NG2KO mice, first-phase insulin secretion was lost, and these glucose-intolerant mice developed impaired glucagon secretion when fed a high-fat diet. Electrophysiological recordings showed reduced parasympathetic nerve activity in the basal state and no stimulation by glucose. Furthermore, sympathetic activity was also insensitive to glucose. Collectively, our data show that GLUT2-dependent control of parasympathetic activity defines a nervous system/endocrine pancreas axis that is critical for β cell mass establishment in the postnatal period and for long-term maintenance of β cell function. PMID:24334455

The effect of milk fat globules on adherence and internalization of Salmonella Enteritidis to HT-29 cells.

PubMed

Guri, A; Griffiths, M; Khursigara, C M; Corredig, M

2012-12-01

Milk fat globules were extracted from bovine and goat milk and incubated with HT-29 human adenocarcinoma cells to assess the attachment and internalization of Salmonella Enteritidis. Because the expression of bacterial adhesins is highly affected by the presence of antibiotic, the attachment was studied with and without antibiotic in the cell growth medium. Although no inhibitory effect of the fat globules was observed in the presence of the antibiotic, milk fat globules significantly inhibited the binding and internalization of Salmonella in medium free of antibiotic. The fat globules from both bovine and goat milk markedly reduced bacterial binding and invasion compared with controls, and the cells treated with goat milk-derived fat globules demonstrated greater protective properties than those derived from bovine milk. The effect of heat treatment on bovine fat globules was also investigated, and it was shown that the fat globules from heated milk had a higher degree of inhibition than those from unheated milk. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow-bellied marmots (Marmota flaviventris).

PubMed

Florant, Gregory L; Porst, Heather; Peiffer, Aubrey; Hudachek, Susan F; Pittman, Chris; Summers, Scott A; Rajala, Michael W; Scherer, Philipp E

2004-11-01

Leptin and adiponectin are proteins produced and secreted from white adipose tissue and are important regulators of energy balance and insulin sensitivity. Seasonal changes in leptin and adiponectin have not been investigated in mammalian hibernators in relationship to changes in fat cell and fat mass. We sought to determine the relationship between serum leptin and adiponectin levels with seasonal changes in lipid mass. We collected serum and tissue samples from marmots (Marmota flaviventris) in different seasons while measuring changes in fat mass, including fat-cell size. We found that leptin is positively associated with increasing fat mass and fat-cell size, while adiponectin is negatively associated with increasing lipid mass. These findings are consistent with the putative roles of these adipokines: leptin increases with fat mass and is involved in enhancing lipid oxidation while adiponectin appears to be higher in summer when hepatic insulin sensitivity should be maintained since the animals are eating. Our data suggest that during autumn/winter animals have switched from a lipogenic condition to a lipolytic state, which may include leptin resistance.

Modern trends in lipomodeling

PubMed Central

El-Sabbagh, Ahmed Hassan

2017-01-01

Lipomodeling is the process of relocating autologous fat to change the shape, volume, consistency, and profile of tissues, with the aim of reconstructing, rejuvenating, and regenerating body features. There have been several important advancements in lipomodeling procedures during the last thirty years. Four clinical steps are important for the success of engraftment: fat harvesting, fat processing, fat reinjection, and preconditioning of the recipient site. With the discovery of adipose derived stem cells and dedifferentiated cells, fat cells become a major tool of regenerative medicine. This article reviews recent trends in lipomodeling trying to understand most of the issues in this field. PMID:28401032

Isofraxidin, a coumarin component improves high-fat diet induced hepatic lipid homeostasis disorder and macrophage inflammation in mice.

PubMed

Li, Jian; Li, Xiaofei; Li, Zhike; Zhang, Lu; Liu, Yonggang; Ding, Hong; Yin, Shanye

2017-08-01

Isofraxidin (IF) is a coumarin compound produced in the functional foods Siberian ginseng and Apium graveolens. The first objective of this study was to investigate the protective effects and putative methods of IF in combating lipotoxicity in vitro and in vivo. Oleic acid was used to induce lipid turbulence in human hepatoma cells (HepG2). Alterations in triglyceride metabolism, inflammation and oxidative status were monitored. Results show that IF mainly reduced triglyceride accumulation, TNF-α release and ROS activation in metabolic disordered cells. Next, a high-fat diet, which induced a non-alcoholic fatty liver disease, was used to evaluate the therapeutic action of IF. Our results show that treatment with IF significantly inhibited the high-fat diet-induced elevation in body weight, liver weight, lipid metabolism (TG, TC and HDL-C) and hepatic injury in mice. In biochemical terms, treatment with IF resulted in enhanced phosphorylation of AMPKα and ACC, as well as reduced hepatic expression of FAS and HMGC, suggesting that lipogenesis was compromised. We also found robust evidence that treatment with IF significantly depleted infiltrating inflammatory cells (F4/80 + Kupffer cells and CD68 + macrophages) and inflammatory cytokine release (TNFα and IL-6). Moreover, the anti-inflammatory activity in IF-treated hepatic tissue correlated with down-regulation of TLR4 expression and NF-κB transcription. In sum, these results suggest that IF might play a protective role against lipid metabolism disorder induced by a high-fat diet via inhibition of lipid production and inflammation in the liver.

Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease.

PubMed

Pacifico, Lucia; Di Martino, Michele; Anania, Caterina; Andreoli, Gian Marco; Bezzi, Mario; Catalano, Carlo; Chiesa, Claudio

2015-04-21

To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease (NAFLD). We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction (HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue (VAT), pancreatic fat fraction (PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance (HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index (WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either: (1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/dL to < 126 mg/dL; (2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/dL and < 200 mg/dL; or (3) hemoglobin A1c value of ≥ 5.7% to < 6.5%. PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index (BMI)-SD score, and VAT. In multiple regression analysis with WBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI (standardized coefficient B, -0.398; P = 0.001) as well as HOMA-IR (0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes (OR = 3.38; 95%CI: 1.10-10.4; P = 0.034). In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.

Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease

PubMed Central

Pacifico, Lucia; Di Martino, Michele; Anania, Caterina; Andreoli, Gian Marco; Bezzi, Mario; Catalano, Carlo; Chiesa, Claudio

2015-01-01

AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease (NAFLD). METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction (HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue (VAT), pancreatic fat fraction (PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance (HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index (WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either: (1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/dL to < 126 mg/dL; (2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/dL and < 200 mg/dL; or (3) hemoglobin A1c value of ≥ 5.7% to < 6.5%. RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index (BMI)-SD score, and VAT. In multiple regression analysis with WBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI (standardized coefficient B, -0.398; P = 0.001) as well as HOMA-IR (0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes (OR = 3.38; 95%CI: 1.10-10.4; P = 0.034). CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes. PMID:25914480

A Stratified Transcriptomics Analysis of Polygenic Fat and Lean Mouse Adipose Tissues Identifies Novel Candidate Obesity Genes

PubMed Central

Morton, Nicholas M.; Nelson, Yvonne B.; Michailidou, Zoi; Di Rollo, Emma M.; Ramage, Lynne; Hadoke, Patrick W. F.; Seckl, Jonathan R.; Bunger, Lutz; Horvat, Simon; Kenyon, Christopher J.; Dunbar, Donald R.

2011-01-01

Background Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain. Results To enrich for adipose tissue obesity genes a ‘snap-shot’ pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. Conclusions A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity. PMID:21915269

A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

PubMed

Morton, Nicholas M; Nelson, Yvonne B; Michailidou, Zoi; Di Rollo, Emma M; Ramage, Lynne; Hadoke, Patrick W F; Seckl, Jonathan R; Bunger, Lutz; Horvat, Simon; Kenyon, Christopher J; Dunbar, Donald R

2011-01-01

Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain. To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.

Response to consumer demand for reduced-fat foods; multi-functional fat replacers

USDA-ARS?s Scientific Manuscript database

The excessive dietary fat intake can result in health problems such as obesity and heart-related diseases, resulting in increased consumer demand for reduced fat foods. A number of food ingredients with fat-like functions have been developed as fat alternatives in the food industry. Especially, so...

Body composition, nutritional status, and endothelial function in physically active men without metabolic syndrome--a 25 year cohort study.

PubMed

Pigłowska, Małgorzata; Kostka, Tomasz; Drygas, Wojciech; Jegier, Anna; Leszczyńska, Joanna; Bill-Bielecka, Mirosława; Kwaśniewska, Magdalena

2016-04-27

The purpose of this analysis was to investigate the relationship between body composition, metabolic parameters and endothelial function among physically active healthy middle-aged and older men. Out of 101 asymptomatic men prospectively tracked for traditional cardiovascular risk factors (mean observation period 25.1 years), 55 metabolically healthy individuals who maintained stable leisure time physical activity (LTPA) level throughout the observation and agreed to participate in the body composition assessment were recruited (mean age 60.3 ± 9.9 years). Body composition and raw bioelectrical parameters were measured with bioelectrical impedance analysis (BIA). Microvascular endothelial function was evaluated by means of the reactive hyperemia index (RHI) using Endo-PAT2000 system. Strong correlations were observed between lifetime physical activity (PA), aerobic fitness and most of analyzed body composition parameters. The strongest inverse correlation was found for fat mass (p < 0.01) while positive relationship for fat-free mass (p < 0.01), total body water (p < 0.05 for current aerobic capacity and p < 0.01 for historical PA), body cell mass (p < 0.001), muscle mass (p < 0.001), calcium and potassium (p < 0.01 and p < 0.001 for current aerobic capacity and p < 0.001 and p < 0.01 for historical PA, respectively) and glycogen mass (p < 0.001). Among metabolic parameters, HDL cholesterol (HDL-C) and uric acid were significantly associated with most body composition indicators. Regarding endothelial function, a negative correlation was found for RHI and body mass (p < 0.05) while positive relationship for RHI and body cell mass (p < 0.05), calcium (p < 0.05) and potassium mass (p < 0.05). Impaired endothelial function was observed among 8 subjects. Among bioelectrical parameters, impedance (Z) and resistance (R) normalized for subjects' height were negatively related with body mass, body mass index (BMI) and waist circumference (p < 0.001); while reactance (Xc) normalized for patients' height was negatively related with body mass (p < 0.05). The mean phase angle value was relatively high (8.83 ± 1.22) what reflects a good level of cellularity and cell function. Phase angle was positively related with body mass and BMI (p < 0.05). Both fat mass and muscle mass components are important predictors of metabolic profile. Maintaining regular high PA level and metabolically healthy status through young and middle adulthood may have beneficial influence on body composition parameters and may prevent age-related decrease of fat-free mass and endothelial dysfunction.

Direct and indirect effects of leptin on adipocyte metabolism.

PubMed

Harris, Ruth B S

2014-03-01

Leptin is hypothesized to function as a negative feedback signal in the regulation of energy balance. It is produced primarily by adipose tissue and circulating concentrations correlate with the size of body fat stores. Administration of exogenous leptin to normal weight, leptin responsive animals inhibits food intake and reduces the size of body fat stores whereas mice that are deficient in either leptin or functional leptin receptors are hyperphagic and obese, consistent with a role for leptin in the control of body weight. This review discusses the effect of leptin on adipocyte metabolism. Because adipocytes express leptin receptors there is the potential for leptin to influence adipocyte metabolism directly. Adipocytes also are insulin responsive and receive sympathetic innervation, therefore leptin can also modify adipocyte metabolism indirectly. Studies published to date suggest that direct activation of adipocyte leptin receptors has little effect on cell metabolism in vivo, but that leptin modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. In vivo administration of leptin leads to a suppression of lipogenesis, an increase in triglyceride hydrolysis and an increase in fatty acid and glucose oxidation. Activation of central leptin receptors also contributes to the development of a catabolic state in adipocytes, but this may vary between different fat depots. Leptin reduces the size of white fat depots by inhibiting cell proliferation both through induction of inhibitory circulating factors and by contributing to sympathetic tone which suppresses adipocyte proliferation. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

The effect of growth hormone treatment on metabolic and cardiovascular risk factors is similar in preterm and term short, small for gestational age children.

PubMed

de Kort, Sandra W K; Willemsen, Ruben H; van der Kaay, Danielle C M; Hokken-Koelega, Anita C S

2009-07-01

We previously reported that short, small for gestational age (SGA) children who were born preterm have a lower body fat percentage and a higher blood pressure, insulin secretion and disposition index than short SGA children born at term. Whether preterm birth also influences these parameters during GH treatment is unknown. To compare blood pressure, insulin sensitivity, beta-cell function and body composition during 4 years of GH treatment, between preterm and term short SGA children. A total of 404 prepubertal non-GH-deficient short SGA children were divided into 143 preterm (< 36 weeks) and 261 term children. Height, blood pressure (n = 404), body composition measured by dual energy X-ray absorptiometry (DXA) (n = 138) and insulin sensitivity and beta-cell function calculated from a frequent sampling intravenous glucose tolerance test (FSIGT) with tolbutamide (n = 74) or from the homeostasis model assessment of insulin resistance (HOMA-IR) (n = 204). In preterm and term children, GH treatment resulted in a similar decrease in systolic and diastolic blood pressure, body fat percentage, limb fat/total fat ratio and insulin sensitivity, and a similar increase in insulin secretion and disposition index. Lean body mass (LBM) corrected for gender and height increased in term children and did not change in preterm children. Multiple regression analysis revealed that this difference in GH effect on LBM was not associated with gestational age. The effect of GH treatment on metabolic and cardiovascular risk factors is similar in preterm and term short, SGA children.

Gravity separation of fat, somatic cells, and bacteria in raw and pasteurized milks.

PubMed

Caplan, Z; Melilli, C; Barbano, D M

2013-04-01

The objective of experiment 1 was to determine if the extent of gravity separation of milk fat, bacteria, and somatic cells is influenced by the time and temperature of gravity separation or the level of contaminating bacteria present in the raw milk. The objective of experiment 2 was to determine if different temperatures of milk heat treatment affected the gravity separation of milk fat, bacteria, and somatic cells. In raw milk, fat, bacteria, and somatic cells rose to the top of columns during gravity separation. About 50 to 80% of the fat and bacteria were present in the top 8% of the milk after gravity separation of raw milk. Gravity separation for 7h at 12°C or for 22h at 4°C produced equivalent separation of fat, bacteria, and somatic cells. The completeness of gravity separation of fat was influenced by the level of bacteria in the milk before separation. Milk with a high bacterial count had less (about 50 to 55%) gravity separation of fat than milk with low bacteria count (about 80%) in 22h at 4°C. Gravity separation caused fat, bacteria, and somatic cells to rise to the top of columns for raw whole milk and high temperature, short-time pasteurized (72.6°C, 25s) whole milk. Pasteurization at ≥76.9°C for 25s prevented all 3 components from rising, possibly due to denaturation of native bovine immunoglobulins that normally associate with fat, bacteria, and somatic cells during gravity separation. Gravity separation can be used to produce reduced-fat milk with decreased bacterial and somatic cell counts, and may be a critical factor in the history of safe and unique traditional Italian hard cheeses produced from gravity-separated raw milk. A better understanding of the mechanism of this natural process could lead to the development of new nonthermal thermal technology (that does not involve heating the milk to high temperatures) to remove bacteria and spores from milk or other liquids. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The cell size and distribution of adipocytes from subcutaneous and visceral fat is associated with type 2 diabetes mellitus in humans.

PubMed

Fang, Lingling; Guo, Fangjian; Zhou, Lihua; Stahl, Richard; Grams, Jayleen

2015-01-01

Regional deposition of adipose tissue and adipocyte morphology may contribute to increased risk for insulin resistance. The aim of this study was to compare adipocyte cell size and size distribution from multiple fat depots and to determine the association with type 2 diabetes mellitus, anthropomorphic data, and subjects' metabolic profile. Clinical data and adipose tissue from subcutaneous fat, omentum, and mesentery were collected from 30 subjects with morbid obesity. Adipocytes were isolated by collagenase digestion and sized by microscopic measurement of cell diameter. Overall, adipocytes from subcutaneous fat were larger than those from omentum or mesentery. For the subcutaneous and omental fat depots, there was a significant increase in % small cells (14.9% vs 31.4%, p = 0 .006 and 14.0% vs 30.5%, p = 0 .015, respectively) and corresponding decrease in % large cells for nondiabetic vs diabetic patients. There was a similar trend for mesentery but it did not reach statistical significance (p = 0 .090). For omentum and mesentery, there was also a significant decrease in the diameter of the small cells. Fasting glucose was positively correlated with fraction of small cells in omentum and mesentery, and HbA1C was positively correlated with fraction of small cells in the omental fat depot. There was no correlation between large cell diameter with clinical parameters in any of the fat depots. These results indicate size distribution of adipocytes, specifically an increase in the fraction of small cells, is associated with the presence of type 2 diabetes mellitus.

The cell size and distribution of adipocytes from subcutaneous and visceral fat is associated with type 2 diabetes mellitus in humans

PubMed Central

Fang, Lingling; Guo, Fangjian; Zhou, Lihua; Stahl, Richard; Grams, Jayleen

2015-01-01

Aims/hypothesis: Regional deposition of adipose tissue and adipocyte morphology may contribute to increased risk for insulin resistance. The aim of this study was to compare adipocyte cell size and size distribution from multiple fat depots and to determine the association with type 2 diabetes mellitus, anthropomorphic data, and subjects' metabolic profile. Methods: Clinical data and adipose tissue from subcutaneous fat, omentum, and mesentery were collected from 30 subjects with morbid obesity. Adipocytes were isolated by collagenase digestion and sized by microscopic measurement of cell diameter. Results: Overall, adipocytes from subcutaneous fat were larger than those from omentum or mesentery. For the subcutaneous and omental fat depots, there was a significant increase in % small cells (14.9% vs 31.4%, p = 0 .006 and 14.0% vs 30.5%, p = 0 .015, respectively) and corresponding decrease in % large cells for nondiabetic vs diabetic patients. There was a similar trend for mesentery but it did not reach statistical significance (p = 0 .090). For omentum and mesentery, there was also a significant decrease in the diameter of the small cells. Fasting glucose was positively correlated with fraction of small cells in omentum and mesentery, and HbA1C was positively correlated with fraction of small cells in the omental fat depot. There was no correlation between large cell diameter with clinical parameters in any of the fat depots. Conclusions/interpretation: These results indicate size distribution of adipocytes, specifically an increase in the fraction of small cells, is associated with the presence of type 2 diabetes mellitus. PMID:26451283

Relationship between Psychosocial Functioning and Body Fat in Preschool Children: A Longitudinal Investigation.

ERIC Educational Resources Information Center

Klesges, Robert C.; And Others

1992-01-01

Examined whether 132 preschool children who varied in levels of body fat differed on psychosocial functioning. Children did not differ in self-esteem and family functioning as function of body fat. Prospectively, physical self-esteem weakly but significantly correlated with body fat at one and two years; father's perception of family functioning…

Dietary fat without body weight gain increases in vivo MCF-7 human breast cancer cell growth and decreases natural killer cell cytotoxicity.

PubMed

Lamas, Bruno; Nachat-Kappes, Rachida; Goncalves-Mendes, Nicolas; Mishellany, Florence; Rossary, Adrien; Vasson, Marie-Paule; Farges, Marie-Chantal

2015-01-01

High-calorie (HC) diet contributes to the increased incidence of obesity, which is a risk factor for breast cancer in postmenopausal women, and in particular for estrogen receptor (ER) positive tumors. This study investigated whether an HC diet increases human ER-positive breast cancer progression and modulates natural killer (NK) cell functions. Four-week-old female BALB/c athymic nude mice were fed a HC diet (5320 kcal/kg) or standard calorie diet (SC, 2820 kcal/kg) for 6 mo. After 5 mo, the mice were randomly implanted with MCF-7 breast cancer cells (SCT and HCT) or received an isovolumic injection (SC and HC) in both inguinal fat pads. Tumor growth was greater in the HCT group than in the SC group without change in body weight. The HC diet decreased the tumor expression of genes involved in the citrate cycle and in adiponectin and lipid metabolism but increased that of genes controlling glycolysis and angiogenesis. The tumor expression level of Ki67 was increased while that of the cleaved caspase 3 and the ER-β and progesterone receptors was reduced. Tumor development in response to the HC diet was associated with smaller numbers and lower cytotoxicity of splenic NK cells. These results indicate that an HC diet without body weight gain increases ER-positive breast cancer cell proliferation and reduces tumor apoptosis. The underlying mechanisms might involve a downexpression of tumor hormonal receptor and reduced NK cell functions, and might also result in the regulation of genes involved in several cellular functions. © 2013 Wiley Periodicals, Inc.

Selenium modulates MMP2 expression through the TGFβ1/Smad signalling pathway in human umbilical vein endothelial cells and rabbits following lipid disturbance.

PubMed

Xu, Chenggui; Lu, Guihua; Li, Qinglang; Zhang, Juhong; Huang, Zhibin; Gao, Xiuren

2017-07-01

A high-fat diet is a major risk factor for coronary heart diseases. Matrix metalloprotease (MMP) expression is changed in many cardiovascular diseases. Selenium, which is an important trace element in animals, has a close relationship with cardiovascular diseases. The TGFβ1/Smad signalling pathway is ubiquitous in diverse tissues and cells, and it is also associated with the occurrence and development of cardiovascular diseases. Therefore, in this study, we aimed to determine selenium's effect on lipid metabolism, atherosclerotic plaque formation, and MMP2 expression, as well as the underlying functional mechanism. In vivo tests: 24 male New Zealand white rabbits were randomly divided into 4 groups: regular diet, high-fat diet, high-fat diet+selenium and regular diet+selenium groups. The high-fat diet induced the lipid disturbances of rabbits at week 12. Selenium supplementation lowered total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels (p<0.01). Selenium supplementation also suppressed MMP2 over-expression in thoracic aortas. In vitro tests: Human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of selenium or ox-LDL. Ox-LDL promoted MMP2 expression by increasing TGFβ1, pSmad2, pSmad3 and Smad3 expression (p<0.01). Selenium attenuated MMP2 over-expression by regulating the TGFβ1/Smad signalling pathway. Selenium suppressed high-fat diet-induced MMP2 over-expression in vivo by improving lipid metabolism. In vitro, selenium attenuated MMP2 over-expression through the TGFβ1/Smad signalling pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

A synthetic lethal screen identifies FAT1 as an antagonist of caspase-8 in extrinsic apoptosis

PubMed Central

Kranz, Dominique; Boutros, Michael

2014-01-01

The extrinsic apoptosis pathway is initiated by binding of death ligands to death receptors resulting in the formation of the death-inducing signaling complex (DISC). Activation of procaspase-8 within the DISC and its release from the signaling complex is required for processing executor caspases and commiting cell death. Here, we report that the atypical cadherin FAT1 interacts with caspase-8 preventing the association of caspase-8 with the DISC. We identified FAT1 in a genome-wide siRNA screen for synthetic lethal interactions with death receptor-mediated apoptosis. Knockdown of FAT1 sensitized established and patient-derived glioblastoma cell lines for apoptosis transduced by cell death ligands. Depletion of FAT1 resulted in enhanced procaspase-8 recruitment to the DISC and increased formation of caspase-8 containing secondary signaling complexes. In addition, FAT1 knockout cell lines generated by CRISPR/Cas9-mediated genome engineering were more susceptible for death receptor-mediated apoptosis. Our findings provide evidence for a mechanism to control caspase-8-dependent cell death by the atypical cadherin FAT1. These results contribute towards the understanding of effector caspase regulation in physiological conditions. PMID:24442637

A synthetic lethal screen identifies FAT1 as an antagonist of caspase-8 in extrinsic apoptosis.

PubMed

Kranz, Dominique; Boutros, Michael

2014-02-03

The extrinsic apoptosis pathway is initiated by binding of death ligands to death receptors resulting in the formation of the death-inducing signaling complex (DISC). Activation of procaspase-8 within the DISC and its release from the signaling complex is required for processing executor caspases and commiting cell death. Here, we report that the atypical cadherin FAT1 interacts with caspase-8 preventing the association of caspase-8 with the DISC. We identified FAT1 in a genome-wide siRNA screen for synthetic lethal interactions with death receptor-mediated apoptosis. Knockdown of FAT1 sensitized established and patient-derived glioblastoma cell lines for apoptosis transduced by cell death ligands. Depletion of FAT1 resulted in enhanced procaspase-8 recruitment to the DISC and increased formation of caspase-8 containing secondary signaling complexes. In addition, FAT1 knockout cell lines generated by CRISPR/Cas9-mediated genome engineering were more susceptible for death receptor-mediated apoptosis. Our findings provide evidence for a mechanism to control caspase-8-dependent cell death by the atypical cadherin FAT1. These results contribute towards the understanding of effector caspase regulation in physiological conditions.

Mechanical scale and load cell underwater weighing: a comparison of simultaneous measurements and the reliability of methods.

PubMed

Moon, Jordan R; Stout, Jeffrey R; Walter, Ashley A; Smith, Abbie E; Stock, Matt S; Herda, Trent J; Sherk, Vanessa D; Young, Kaelin C; Lockwood, Christopher M; Kendall, Kristina L; Fukuda, David H; Graef, Jennifer L; Cramer, Joel T; Beck, Travis W; Esposito, Enrico N

2011-03-01

Both load cell and mechanical scale-based hydrostatic weighing (HW) systems are used for the measurement of underwater weight. However, there has been no direct comparison of the 2 methods. The purpose of the current investigation was to simultaneously compare a load cell and mechanical scale for use in HW. Twenty-seven men and women (mean ± SD, age: 22 ± 2 years) participated in the 2-day investigation. Each subject completed 2 HW assessments 24 hours apart. Single-day comparisons of all trials for both days revealed no significant difference between the mechanical scale and the load cell (mean difference < 0.016 kg, p > 0.05). True underwater weight values were not significantly different between methods for either days (mean difference < 0.014 kg, p > 0.05) and accounted for a mean difference in percent fat (%FAT) of <0.108%. The 95% limits of agreement indicated a maximum difference between methods of 0.53% FAT. Both methods produced similar reliability SEM values (mechanical SEM < 0.72%FAT, load cell SEM < 0.75%FAT). In conclusion, there was no difference between mechanical scale and load cell measurements of underwater weights and the added precision of the load cell only marginally (<0.16%FAT) improved day-to-day reliability. Either a mechanical scale or load cell can be used for HW with similar accuracy and reliability in young adults with a body mass index of 18.7-34.4 (5-25%FAT).

Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice

PubMed Central

Buckman, Laura B.; Thompson, Misty M.; Lippert, Rachel N.; Blackwell, Timothy S.; Yull, Fiona E.; Ellacott, Kate L.J.

2014-01-01

Objective Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding. Methods We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus. Results Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P < 0.01) in the first 24 h after introduction of the diet. Conclusions These data reveal a novel homeostatic role for astrocytes in the acute physiologic regulation of food intake in response to high-fat feeding. PMID:25685690

Evidence for a novel functional role of astrocytes in the acute homeostatic response to high-fat diet intake in mice.

PubMed

Buckman, Laura B; Thompson, Misty M; Lippert, Rachel N; Blackwell, Timothy S; Yull, Fiona E; Ellacott, Kate L J

2015-01-01

Introduction of a high-fat diet to mice results in a period of voracious feeding, known as hyperphagia, before homeostatic mechanisms prevail to restore energy intake to an isocaloric level. Acute high-fat diet hyperphagia induces astrocyte activation in the rodent hypothalamus, suggesting a potential role of these cells in the homeostatic response to the diet. The objective of this study was to determine physiologic role of astrocytes in the acute homeostatic response to high-fat feeding. We bred a transgenic mouse model with doxycycline-inducible inhibition of NFkappaB (NFκB) signaling in astrocytes to determine the effect of loss of NFκB-mediated astrocyte activation on acute high-fat hyperphagia. ELISA was used to measure the levels of markers of astrocyte activation, glial-fibrillary acidic protein (GFAP) and S100B, in the medial basal hypothalamus. Inhibition of NFκB signaling in astrocytes prevented acute high-fat diet-induced astrocyte activation and resulted in a 15% increase in caloric intake (P < 0.01) in the first 24 h after introduction of the diet. These data reveal a novel homeostatic role for astrocytes in the acute physiologic regulation of food intake in response to high-fat feeding.

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women

PubMed Central

Akopians, Alin L.; Madrigal, Vanessa K.; Ramirez, Emmanuel; Margolis, Daniel J.; Sarma, Manoj K.; Thomas, Albert M.; Grogan, Tristan R.; Haykal, Rasha; Schooler, Tery A.; Okeya, Bette L.; Abbott, David H.; Chazenbalk, Gregorio D.

2016-01-01

Context: Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction. Objective: This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia. Design: This is a prospective cohort study. Setting: The setting was an academic medical center. Patients: Six normal weight PCOS women and 14 age- and body mass index-matched normoandrogenic ovulatory (NL) women were included. Intervention(s): All women underwent circulating hormone and metabolic measurements; frequently sampled intravenous glucose tolerance testing; total body dual-energy x-ray absorptiometry; abdominal magnetic resonance imaging; and SC abdominal fat biopsy. Main Outcome Measure(s): Circulating hormones and metabolites, body fat and its distribution, and adipocyte size were compared between PCOS and NL women, and were correlated with each other in all women. Results: Circulating LH and androgen levels were significantly greater in PCOS than NL women, as were fasting insulin levels, pancreatic β-cell responsiveness to glucose, and total abdominal fat mass. Intra-abdominal fat mass also was significantly increased in PCOS women and was positively correlated with circulating androgen, fasting insulin, triglyceride, and non-high-density lipoprotein cholesterol levels in all women. SC abdominal fat mass was not significantly increased in PCOS women, but contained a greater proportion of small SC abdominal adipocytes that positively correlated with serum androgen levels in all women. Conclusion: Hyperandrogenism in normal weight PCOS women is associated with preferential intra-abdominal fat deposition and an increased population of small SC abdominal adipocytes that could constrain SC adipose storage and promote metabolic dysfunction. PMID:27571186

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance

PubMed Central

Svensson, H; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

2016-01-01

Background/Objectives: Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Subjects/Methods: Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Results: Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R2=0.751, P<0.001). Conclusions: During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance. PMID:26563815

Body fat mass and the proportion of very large adipocytes in pregnant women are associated with gestational insulin resistance.

PubMed

Svensson, H; Wetterling, L; Bosaeus, M; Odén, B; Odén, A; Jennische, E; Edén, S; Holmäng, A; Lönn, M

2016-04-01

Pregnancy is accompanied by fat gain and insulin resistance. Changes in adipose tissue morphology and function during pregnancy and factors contributing to gestational insulin resistance are incompletely known. We sought to characterize adipose tissue in trimesters 1 and 3 (T1/T3) in normal weight (NW) and obese pregnant women, and identify adipose tissue-related factors associated with gestational insulin resistance. Twenty-two NW and 11 obese women were recruited early in pregnancy for the Pregnancy Obesity Nutrition and Child Health study. Examinations and sampling of blood and abdominal adipose tissue were performed longitudinally in T1/T3 to determine fat mass (air-displacement plethysmography); insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR); size, number and lipolytic activity of adipocytes; and adipokine release and density of immune cells and blood vessels in adipose tissue. Fat mass and HOMA-IR increased similarly between T1 and T3 in the groups; all remained normoglycemic. Adipocyte size increased in NW women. Adipocyte number was not influenced, but proportions of small and large adipocytes changed oppositely in the groups. Lipolytic activity and circulating adipocyte fatty acid-binding protein increased in both groups. Adiponectin release was reduced in NW women. Fat mass and the proportion of very large adipocytes were most strongly associated with T3 HOMA-IR by multivariable linear regression (R(2)=0.751, P<0.001). During pregnancy, adipose tissue morphology and function change comprehensively. NW women accumulated fat in existing adipocytes, accompanied by reduced adiponectin release. In comparison with the NW group, obese women had signs of adipocyte recruitment and maintained adiponectin levels. Body fat and large adipocytes may contribute significantly to gestational insulin resistance.

Propensity to high-fat diet-induced obesity in rats is associated with changes in the gut microbiota and gut inflammation.

PubMed

de La Serre, Claire Barbier; Ellis, Collin L; Lee, Jennifer; Hartman, Amber L; Rutledge, John C; Raybould, Helen E

2010-08-01

Consumption of diets high in fat and calories leads to hyperphagia and obesity, which is associated with chronic "low-grade" systemic inflammation. Ingestion of a high-fat diet alters the gut microbiota, pointing to a possible role in the development of obesity. The present study used Sprague-Dawley rats that, when fed a high-fat diet, exhibit either an obesity-prone (DIO-P) or obesity-resistant (DIO-R) phenotype, to determine whether changes in gut epithelial function and microbiota are diet or obese associated. Food intake and body weight were monitored daily in rats maintained on either low- or high-fat diets. After 8 or 12 wk, tissue was removed to determine adiposity and gut epithelial function and to analyze the gut microbiota using PCR. DIO-P but not DIO-R rats exhibit an increase in toll-like receptor (TLR4) activation associated with ileal inflammation and a decrease in intestinal alkaline phosphatase, a luminal enzyme that detoxifies lipopolysaccharide (LPS). Intestinal permeability and plasma LPS were increased together with phosphorylation of myosin light chain and localization of occludin in the cytoplasm of epithelial cells. Measurement of bacterial 16S rRNA showed a decrease in total bacterial density and an increase in the relative proportion of Bacteroidales and Clostridiales orders in high-fat-fed rats regardless of phenotype; an increase in Enterobacteriales was seen in the microbiota of DIO-P rats only. Consumption of a high-fat diet induces changes in the gut microbiota, but it is the development of inflammation that is associated with the appearance of hyperphagia and an obese phenotype.

Tissue-specific transcriptomics of the exotic invasive insect pest emerald ash borer (Agrilus planipennis).

PubMed

Mittapalli, Omprakash; Bai, Xiaodong; Mamidala, Praveen; Rajarapu, Swapna Priya; Bonello, Pierluigi; Herms, Daniel A

2010-10-28

The insect midgut and fat body represent major tissue interfaces that deal with several important physiological functions including digestion, detoxification and immune response. The emerald ash borer (Agrilus planipennis), is an exotic invasive insect pest that has killed millions of ash trees (Fraxinus spp.) primarily in the Midwestern United States and Ontario, Canada. However, despite its high impact status little knowledge exists for A. planipennis at the molecular level. Newer-generation Roche-454 pyrosequencing was used to obtain 126,185 reads for the midgut and 240,848 reads for the fat body, which were assembled into 25,173 and 37,661 high quality expressed sequence tags (ESTs) for the midgut and the fat body of A. planipennis larvae, respectively. Among these ESTs, 36% of the midgut and 38% of the fat body sequences showed similarity to proteins in the GenBank nr database. A high number of the midgut sequences contained chitin-binding peritrophin (248)and trypsin (98) domains; while the fat body sequences showed high occurrence of cytochrome P450s (85) and protein kinase (123) domains. Further, the midgut transcriptome of A. planipennis revealed putative microbial transcripts encoding for cell-wall degrading enzymes such as polygalacturonases and endoglucanases. A significant number of SNPs (137 in midgut and 347 in fat body) and microsatellite loci (317 in midgut and 571 in fat body) were predicted in the A. planipennis transcripts. An initial assessment of cytochrome P450s belonging to various CYP clades revealed distinct expression patterns at the tissue level. To our knowledge this study is one of the first to illuminate tissue-specific gene expression in an invasive insect of high ecological and economic consequence. These findings will lay the foundation for future gene expression and functional studies in A. planipennis.

Label-free imaging of Drosophila in vivo by coherent anti-Stokes Raman scattering and two-photon excitation autofluorescence microscopy

NASA Astrophysics Data System (ADS)

Chien, Cheng-Hao; Chen, Wei-Wen; Wu, June-Tai; Chang, Ta-Chau

2011-01-01

Drosophila is one of the most valuable model organisms for studying genetics and developmental biology. The fat body in Drosophila, which is analogous to the liver and adipose tissue in human, stores lipids that act as an energy source during its development. At the early stages of metamorphosis, the fat body remodeling occurs involving the dissociation of the fat body into individual fat cells. Here we introduce a combination of coherent anti-Stokes Raman scattering (CARS) and two-photon excitation autofluorescence (TPE-F) microscopy to achieve label-free imaging of Drosophila in vivo at larval and pupal stages. The strong CARS signal from lipids allows direct imaging of the larval fat body and pupal fat cells. In addition, the use of TPE-F microscopy allows the observation of other internal organs in the larva and autofluorescent globules in fat cells. During the dissociation of the fat body, the findings of the degradation of lipid droplets and an increase in autofluorescent globules indicate the consumption of lipids and the recruitment of proteins in fat cells. Through in vivo imaging and direct monitoring, CARS microscopy may help elucidate how metamorphosis is regulated and study the lipid metabolism in Drosophila.

Korean Curcuma longa L. induces lipolysis and regulates leptin in adipocyte cells and rats

PubMed Central

Song, Won-Yeong

2016-01-01

BACKGROUND/OBJECTIVES Turmeric (Curcuma longa L.) has been reported to have many biological functions including anti-obesity. Leptin, peptide hormone produced by adipocytes and its concentration is increased in proportion to the amount of the adipocytes. In the present study, we examined the effects of Korean turmeric on the regulation of adiposity and leptin levels in 3T3-L1 adipocytes and rats fed a high-fat and high-cholesterol diet. MATERIALS/METHODS Leptin secretion, free fatty acid and glycerol contents in 3T3-L1 adipocytes were measured after incubation of cells with turmeric for 24 hours. Rats were divided into four experimental groups: a normal diet group (N), a high-fat and high-cholesterol diet group (HF), a high-fat and high-cholesterol diet group supplemented with 2.5% turmeric extracts (TPA group) and a high-fat and high-cholesterol diet group supplemented with 5% turmeric extracts (TPB group). Serum samples were used for the measurement of leptin concentration. RESULTS Contents of free fatty acid and glycerol showed concentration dependent increase in response to turmeric extracts. Effects of turmeric extracts on reduction of lipid accumulation in 3T3-L1 cells were examined by Oil Red O staining. Treatment with turmeric extracts resulted in increased expression levels of adipose triglyceride lipase and hormone-sensitive lipase mRNA. The concentration of leptin from 3T3-L1 adipocytes was significantly decreased by turmeric. Proportional abdominal and epididymal fats weights of the turmeric 5% supplemented group, TPB has significantly decreased compared to the HF group. The serum levels of leptin in the TPA and TPB groups were significantly lower than those of the HF group. CONCLUSIONS Based on these results, we suggested that Korean turmeric may contribute to the decreasing of body fat and regulating leptin secretion. PMID:27698955

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.

PubMed

Tan, J; Buache, E; Alpy, F; Daguenet, E; Tomasetto, C-L; Ren, G-S; Rio, M-C

2014-07-31

MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11-/-) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11-/- epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

Effect, Feasibility, and Clinical Relevance of Cell Enrichment in Large Volume Fat Grafting: A Systematic Review.

PubMed

Rasmussen, Bo Sonnich; Lykke Sørensen, Celine; Vester-Glowinski, Peter Viktor; Herly, Mikkel; Trojahn Kølle, Stig-Frederik; Fischer-Nielsen, Anne; Drzewiecki, Krzysztof Tadeusz

2017-07-01

Large volume fat grafting is limited by unpredictable volume loss; therefore, methods of improving graft retention have been developed. Fat graft enrichment with either stromal vascular fraction (SVF) cells or adipose tissue-derived stem/stromal cells (ASCs) has been investigated in several animal and human studies, and significantly improved graft retention has been reported. Improvement of graft retention and the feasibility of these techniques are equally important in evaluating the clinical relevance of cell enrichment. We conducted a systematic search of PubMed to identify studies on fat graft enrichment that used either SVF cells or ASCs, and only studies reporting volume assessment were included. A total of 38 articles (15 human and 23 animal) were included to investigate the effects of cell enrichment on graft retention as well as the feasibility and clinical relevance of cell-enriched fat grafting. Improvements in graft retention, the SVF to fat (SVF:fat) ratio, and the ASC concentration used for enrichment were emphasized. We proposed an increased retention rate greater than 1.5-fold relative to nonenriched grafts and a maximum SVF:fat ratio of 1:1 as the thresholds for clinical relevance and feasibility, respectively. Nine studies fulfilled these criteria, whereof 6 used ASCs for enrichment. We found no convincing evidence of a clinically relevant effect of SVF enrichment in humans. ASC enrichment has shown promising results in enhancing graft retention, but additional clinical trials are needed to substantiate this claim and also determine the optimal concentration of SVF cells/ASCs for enrichment. 4. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

The sexual dimorphism of obesity

PubMed Central

Palmer, Biff F.; Clegg, Deborah J.

2015-01-01

The NIH has recently highlighted the importance of sexual dimorphisms and has mandated inclusion of both sexes in clinical trials and basic research. In this review we highlight new and novel ways sex hormones influence body adiposity and the metabolic syndrome. Understanding how and why metabolic processes differ by sex will enable clinicians to target and personalize therapies based on gender. Adipose tissue function and deposition differ by sex. Females differ with respect to distribution of adipose tissues, males tend to accrue more visceral fat, leading to the classic android body shape which has been highly correlated to increased cardiovascular risk; whereas females accrue more fat in the subcutaneous depot prior to menopause, a feature which affords protection from the negative consequences associated with obesity and the metabolic syndrome. After menopause, fat deposition and accrual shift to favor the visceral depot. This shift is accompanied by a parallel increase in metabolic risk reminiscent to that seen in men. A full understanding of the physiology behind why, and by what mechanisms, adipose tissues accumulate in specific depots and how these depots differ metabolically by sex is important in efforts of prevention of obesity and chronic disease. Estrogens, directly or through activation of their receptors on adipocytes and in adipose tissues, facilitate adipose tissue deposition and function. Evidence suggests that estrogens augment the sympathetic tone differentially to the adipose tissue depots favoring lipid accumulation in the subcutaneous depot in women and visceral fat deposition in men. At the level of adipocyte function, estrogens and their receptors influence the expandability of fat cells enhancing the expandability in the subcutaneous depot and inhibiting it in the visceral depot. Sex hormones clearly influence adipose tissue function and deposition, determining how to capture and utilize their function in a time of caloric surfeit, requires more information. The key will be harnessing the beneficial effects of sex hormones in such a way as to provide ‘healthy’ adiposity. PMID:25578600

Effect of Weight Reduction on Cardiovascular Risk Factors and CD34-positive Cells in Circulation

PubMed Central

Mikirova, Nina A; Casciari, Joseph J; Hunninghake, Ronald E; Beezley, Margaret M

2011-01-01

Being overweight or obese is associated with an increased risk for the development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease. Dyslipidemia of obesity is characterized by elevated fasting triglycerides and decreased high-density lipoprotein-cholesterol concentrations. Endothelial damage and dysfunction is considered to be a major underlying mechanism for the elevated cardiovascular risk associated with increased adiposity. Alterations in endothelial cells and stem/endothelial progenitor cell function associated with overweight and obesity predispose to atherosclerosis and thrombosis. In our study, we analyzed the effect of a low calorie diet in combination with oral supplementation by vitamins, minerals, probiotics and human chorionic gonadotropin (hCG, 125-180 IUs) on the body composition, lipid profile and CD34-positive cells in circulation. During this dieting program, the following parameters were assessed weekly for all participants: fat free mass, body fat, BMI, extracellular/intracellular water, total body water and basal metabolic rate. For part of participants blood chemistry parameters and circulating CD34-positive cells were determined before and after dieting. The data indicated that the treatments not only reduced body fat mass and total mass but also improved the lipid profile. The changes in body composition correlated with the level of lipoproteins responsible for the increased cardiovascular risk factors. These changes in body composition and lipid profile parameters coincided with the improvement of circulatory progenitor cell numbers. As the result of our study, we concluded that the improvement of body composition affects the number of stem/progenitor cells in circulation. PMID:21850193

Effect of weight reduction on cardiovascular risk factors and CD34-positive cells in circulation.

PubMed

Mikirova, Nina A; Casciari, Joseph J; Hunninghake, Ronald E; Beezley, Margaret M

2011-01-01

Being overweight or obese is associated with an increased risk for the development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease. Dyslipidemia of obesity is characterized by elevated fasting triglycerides and decreased high-density lipoprotein-cholesterol concentrations. Endothelial damage and dysfunction is considered to be a major underlying mechanism for the elevated cardiovascular risk associated with increased adiposity. Alterations in endothelial cells and stem/endothelial progenitor cell function associated with overweight and obesity predispose to atherosclerosis and thrombosis. In our study, we analyzed the effect of a low calorie diet in combination with oral supplementation by vitamins, minerals, probiotics and human chorionic gonadotropin (hCG, 125-180 IUs) on the body composition, lipid profile and CD34-positive cells in circulation. During this dieting program, the following parameters were assessed weekly for all participants: fat free mass, body fat, BMI, extracellular/intracellular water, total body water and basal metabolic rate. For part of participants blood chemistry parameters and circulating CD34-positive cells were determined before and after dieting. The data indicated that the treatments not only reduced body fat mass and total mass but also improved the lipid profile. The changes in body composition correlated with the level of lipoproteins responsible for the increased cardiovascular risk factors. These changes in body composition and lipid profile parameters coincided with the improvement of circulatory progenitor cell numbers. As the result of our study, we concluded that the improvement of body composition affects the number of stem/progenitor cells in circulation.

High fat diet impairs the function of glucagon-like peptide-1 producing L-cells.

PubMed

Richards, Paul; Pais, Ramona; Habib, Abdella M; Brighton, Cheryl A; Yeo, Giles S H; Reimann, Frank; Gribble, Fiona M

2016-03-01

Glucagon-like peptide-1 (GLP-1) acts as a satiety signal and enhances insulin release. This study examined how GLP-1 production from intestinal L-cells is modified by dietary changes. Transgenic mouse models were utilized in which L-cells could be purified by cell specific expression of a yellow fluorescent protein, Venus. Mice were fed on chow or 60% high fat diet (HFD) for 2 or 16 weeks. L-cells were purified by flow cytometry and analysed by microarray and quantitative RT-PCR. Enteroendocrine cell populations were examined by FACS analysis, and GLP-1 secretion was assessed in primary intestinal cultures. Two weeks HFD reduced the numbers of GLP-1 positive cells in the colon, and of GIP positive cells in the small intestine. Purified small intestinal L-cells showed major shifts in their gene expression profiles. In mice on HFD for 16 weeks, significant reductions were observed in the expression of L-cell specific genes, including those encoding gut hormones (Gip, Cck, Sct, Nts), prohormone processing enzymes (Pcsk1, Cpe), granins (Chgb, Scg2), nutrient sensing machinery (Slc5a1, Slc15a1, Abcc8, Gpr120) and enteroendocrine-specific transcription factors (Etv1, Isl1, Mlxipl, Nkx2.2 and Rfx6). A corresponding reduction in the GLP-1 secretory responsiveness to nutrient stimuli was observed in primary small intestinal cultures. Mice fed on HFD exhibited reduced expression in L-cells of many L-cell specific genes, suggesting an impairment of enteroendocrine cell function. Our results suggest that a western style diet may detrimentally affect the secretion of gut hormones and normal post-prandial signaling, which could impact on insulin secretion and satiety. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2012-01-01

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

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

PubMed

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

2012-09-28

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

Evidence for presence of nonesterified fatty acids as potential gustatory signaling molecules in humans.

PubMed

Kulkarni, Bhushan; Mattes, Richard

2013-02-01

Gustatory fatty acid signaling termed "fatty acid taste" is initiated when nonesterified fatty acids (NEFA) bind to putative fat receptors on taste receptor cells. However, the source and quantity of NEFA in the oral cavity of humans are unresolved. Dietary fat is comprised predominantly of triacylglycerol, and human lingual lipase is of questionable functionality. The objective of this study was to characterize the species of NEFA in saliva and quantify their individual concentrations during oral processing of high-fat foods. Participants chewed fixed amounts of almonds, coconut, walnuts, almond butter, and olive oil (stimuli that vary in physical state and fatty acid composition) for 1 min at the rate of 1 bite/s and expectorated. The salivary NEFA from the expectorant were quantitatively and qualitatively analyzed by gas chromatography-mass spectrometry. Palmitic, oleic, linoleic, and stearic acids were the 4 predominant salivary NEFA, reflecting their concentrations in the foods tested. Their significantly increased concentrations ranged from 20 to 60 µM. Previous animal electrophysiological studies suggest that these NEFA concentrations are sufficient to depolarize taste receptor cells. These data indicate NEFA concentrations likely to be sufficient to initiate gustatory signaling are present in the human oral cavity when masticating high-fat foods.

Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages.

PubMed

Tarabra, Elena; An Lee, Ting-Wen; Zammit, Victor A; Vatish, Manu; Yamada, Eijiro; Pessin, Jeffrey E; Bastie, Claire C

2017-10-17

Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency ( fynKO ) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in fynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of adipose tissue stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats.

2,4-Thiazolidinedione Treatment Improves the Innate Immune Response in Dairy Goats with Induced Subclinical Mastitis

PubMed Central

Rosa, Fernanda; Osorio, Johan S.; Trevisi, Erminio; Yanqui-Rivera, Francisco; Estill, Charles T.

2017-01-01

Mastitis is a major disease in dairy cows resulting in significant economic losses. In vitro works suggest that ruminants peroxisome proliferator-activated receptor gamma (PPARγ) can aid in improving the response to mastitis and can control milk fat synthesis. The objectives of the present experiment were to test if treatment with the putative PPARγ agonist 2,4-thiazolidinedione (TZD) improves (1) the response to subclinical mastitis and (2) milk fat production. Lactating goats received daily injections of 8 mg/kg BW of TZD or saline for 3 weeks. After one week of TZD injection, half of the goats in each group received intramammary infusion of Strep. uberis or saline in both halves for a total of 4 groups (n = 6/group). TZD treatment did not affect milk fat but had positive effect on milk somatic cells count, blood nonesterified fatty acids, inflammatory markers, and liver function. TZD significantly increased myeloperoxidase but did not affect leukocytes phagocytosis or insulin. TZD increased adipocytes size and had minor effect on expression of PPARγ target genes in mammary epithelial cells but not in adipose tissue. Overall, TZD ameliorated the response to intramammary infection but the effect on milk fat synthesis and expression of related transcripts was less than expected. PMID:28740504

PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function

PubMed Central

Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J.; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S.

2016-01-01

Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically “fatless” mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation. PMID:26589913

Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway

PubMed Central

Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O.

2017-01-01

Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans. This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12–dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans. This finding suggests the existence of a conserved CYP4V2-POR–nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage. PMID:28760992

Specific regulation of thermosensitive lipid droplet fusion by a nuclear hormone receptor pathway.

PubMed

Li, Shiwei; Li, Qi; Kong, Yuanyuan; Wu, Shuang; Cui, Qingpo; Zhang, Mingming; Zhang, Shaobing O

2017-08-15

Nuclear receptors play important roles in regulating fat metabolism and energy production in humans. The regulatory functions and endogenous ligands of many nuclear receptors are still unidentified, however. Here, we report that CYP-37A1 (ortholog of human cytochrome P450 CYP4V2), EMB-8 (ortholog of human P450 oxidoreductase POR), and DAF-12 (homolog of human nuclear receptors VDR/LXR) constitute a hormone synthesis and nuclear receptor pathway in Caenorhabditis elegans This pathway specifically regulates the thermosensitive fusion of fat-storing lipid droplets. CYP-37A1, together with EMB-8, synthesizes a lipophilic hormone not identical to Δ7-dafachronic acid, which represses the fusion-promoting function of DAF-12. CYP-37A1 also negatively regulates thermotolerance and lifespan at high temperature in a DAF-12-dependent manner. Human CYP4V2 can substitute for CYP-37A1 in C. elegans This finding suggests the existence of a conserved CYP4V2-POR-nuclear receptor pathway that functions in converting multilocular lipid droplets to unilocular ones in human cells; misregulation of this pathway may lead to pathogenic fat storage.

Intensity ratio curve analysis of small renal masses on T2-weighted magnetic resonance imaging: Differentiation of fat-poor angiomyolipoma from renal cell carcinoma.

PubMed

Moriyama, Shingo; Yoshida, Soichiro; Tanaka, Hajime; Tanaka, Hiroshi; Yokoyama, Minato; Ishioka, Junichiro; Matsuoka, Yoh; Saito, Kazutaka; Kihara, Kazunori; Fujii, Yasuhisa

2018-03-25

To assess the diagnostic ability of a pixel intensity-based analysis in evaluating the magnetic resonance imaging characteristics of small renal masses, especially in differentiating fat-poor angiomyolipoma from renal cell carcinoma. T2-weighted images from 121 solid small renal masses (<4 cm) without visible fat (14 fat-poor angiomyolipomas, 92 clear cell renal cell carcinomas, six chromophobe renal cell carcinomas and nine papillary renal cell carcinomas) were retrospectively evaluated. An intensity ratio curve was plotted using intensity ratios, which were ratios of signal intensities of tumor pixels (each pixel along a linear region of interest drawn across the renal tumor on T2-weighted image) to the signal intensity of a normal renal cortex. The diagnostic ability of the intensity ratio curve analysis was evaluated. The tumors were classified into three types: intensity ratio fat-poor angiomyolipoma (n = 19) with no pseudocapsule, iso-low intensity and no heterogeneity; intensity ratio clear cell renal cell carcinoma (n = 76) with a pseudocapsule, iso-high intensity and heterogeneity; and other type of intensity ratio (n = 26), including tumors that did not fall into the above two categories. The sensitivity/specificity/accuracy of the intensity ratio curve analysis in diagnosing fat-poor angiomyolipoma was 93%/94%/94%, respectively. When the intensity ratio curve analysis was applied only to the tumor with undetermined radiological diagnosis, the sensitivity for diagnosing fat-poor angiomyolipoma compared with subjective reading alone significantly improved (93% vs 50%; P = 0.014). Our novel semiquantitative model for combined assessment of key features of fat-poor angiomyolipoma, including low intensity, homogeneity and absence of a pseudocapsule on T2-weighted image, might make diagnosis of fat-poor angiomyolipoma more accurate. © 2018 The Japanese Urological Association.

Lipidomics: the function of vital lipids in embryogenesis preventing autism spectrum disorders, treating sterile inflammatory diatheses with a lymphopoietic central nervous system component.

PubMed

Tallberg, Thomas; Dabek, Jan; Hallamaa, Raija; Atroshi, Faik

2011-01-01

The central role performed by billions of vital central nervous system (CNS) lipids "lipidomics" in medical physiology is usually overlooked. A metabolic deficiency embracing these vital lipids can form the aetiology for a variety of diseases. CNS lipids regulate embryogenesis, cell induction, mental balance by preventing autism spectrum disorders, depression, burn-out syndromes like posttraumatic stress disease PTSD, by guarding normal immunity, treating sterile inflammatory diatheses with a titanium containing lymphopoietic CNS lipid component. The propaganda driving for unphysiological fat-free diets is dangerous and can cause serious health problems for a whole generation. This article presents a broad list of various mental and motor bodily functions of which the healthy function depends on these vital CNS lipids. A rigorous fat-free diet can provoke these metabolic lipid deficiencies but they can fortunately be compensated by dietary supplementation, but not by pharmacologic treatment.

The pituitary growth hormone cell in space

NASA Technical Reports Server (NTRS)

Hymer, Wesley C.; Grindeland, R.

1989-01-01

Growth hormone (GH), produced and secreted from specialized cells in the pituitary gland, controls the metabolism of protein, fat, and carbohydrate. It is also probably involved in the regulation of proper function of bone, muscle and immune systems. The behavior of the GH cell system was studied by flying either isolated pituitary cells or live rats. In the latter case, pituitary GH cells are prepared on return to earth and then either transplanted into hypophysectomized rats or placed into cell culture so that function of GH cells in-vivo vs. in-vitro can be compared. The results from three flights to date (STS-8, 1983; SL-3, 1985; Cosmos 1887, 1987) established that the ability of GH cells to release hormone, on return to earth, is compromised. The mechanism(s) responsible for this attenuation response is unknown. However, the data are sufficiently positive to indicate that the nature of the secretory defect resides directly within the GH cells.

Northern contaminant mixtures induced morphological and functional changes in human coronary artery endothelial cells under culture conditions typifying high fat/sugar diet and ethanol exposure.

PubMed

Florian, Maria; Yan, Jin; Ulhaq, Saad; Coughlan, Melanie; Laziyan, Mahemuti; Willmore, William; Jin, Xiaolei

2013-11-16

It has been reported that Northern populations are exposed to mixtures of various environmental contaminants unique to the Arctic (Northern contaminant mixtures - NCM) at a large range of concentrations, depending on their geological location, age, lifestyle and dietary habits. To determine if these contaminants may contribute to a cardiovascular health risk, especially when combined with a high fat and sugar diet and ethanol exposure, we treated human coronary artery endothelial cells (HCAEC) with two mixtures of 4 organic (NCM1) or 22 organic and inorganic (NCM2) chemicals detected in Northerners' blood during 2004-2005 in the presence or absence of low-density lipoprotein (1.5mg/ml), very-low-density lipoprotein (1.0mg/ml) and glucose (10mmol/L) (LVG), and in the absence or presence of 0.1% ethanol. After 24h of exposure, cell morphology and markers of cytotoxicity and endothelial function were examined. NCM1 treatment did not affect cell viability, but increased cell size, disrupted cell membrane integrity, and decreased cell density, uptake of small peptides, release of endothelin-1 (ET-1) and plasminogen activator inhibitor (PAI), while causing no changes in endothelial nitric oxide synthase (eNOS) protein expression and nitric oxide (NO) release. In contrast, NCM2 decreased cell viability, total protein yield, uptake of small peptides, eNOS protein expression, and NO release and caused membrane damage, but caused no changes in the secretion of ET-1, prostacyclin and PAI. The presence of LVG and/or alcohol did or did not influence the effects of NCM1 or NCM2 depending on the endpoint and the mixture examined. These results suggested that the effects of one or one group of contaminants may be altered by the presence of other contaminants, and that with or without the interaction of high fat and sugar diet and/or ethanol exposure, NCMs at the concentrations used caused endothelial dysfunction in vitro. It remains to be investigated if these effects of NCMs also occur in vivo. Crown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

MiR-93-5p promotes gastric cancer-cell progression via inactivation of the Hippo signaling pathway.

PubMed

Li, Li; Zhao, Jianguo; Huang, Shanshan; Wang, Yi; Zhu, Lingling; Cao, Yuan; Xiong, Jianping; Deng, Jun

2018-01-30

MiR-93-5p has been previously found to be associated with gastric cancer (GC) tumorigenesis; however, the current understanding of its function in this context remains largely incomplete. In the present study, we showed that miR-93-5p was upregulated in GC tissues. We also demonstrated that miR-93-5p overexpression promoted the proliferation, migration, invasion, and chemoresistance of SGC-7901 cells in vitro, and conversely, that endogenously silencing miR-93-5p expression induced the opposite effects in HGC-27 cells. Overexpression of miR-93-5p was found to inactivate the Hippo pathway, and furthermore, miR-93-5p knockdown activated Hippo signaling. MiR-93-5p upregulation was also shown to inhibit the expression of two well-characterized Hippo pathway regulators, protocadherin Fat 4 (FAT4), and large tumor suppressors 2 (LATS2), at both the mRNA and protein level. Additionally, the results of bioinformatics analyses and luciferase reporter assays indicated that miR-93-5p directly targets the 3'-UTR of FAT4 and LATS2. Taken together, these results demonstrate that miR-93-5p promotes GC-cell progression via the inactivation of the Hippo signaling pathway, and thus, represents a potential therapeutic target for the treatment of GC. Copyright © 2017. Published by Elsevier B.V.

Fat stores in a migratory bird: a reservoir of carotenoid pigments for times of need?

PubMed

Metzger, Benjamin J; Bairlein, Franz

2011-02-01

Carotenoids are well known for their immune-stimulant function in birds and other vertebrates. Moreover, they have potential antioxidant capacity, scavenging free radicals and protecting cell compartments from oxidation. Most essential carotenoids are fat soluble and could be stored for times of need especially in adipose tissues, built up by migratory birds as the main source of energy on long-distance flights. In an exclusive diet experiment, garden warblers (Sylvia borin) were fed ad libitum with an experimental diet, enriched with two different dose rates of carotenoids, or with control food, during the period of their first autumn migration. Plasma carotenoid content was measured via HPLC and chroma of plasma and fat examined with a spectrophotometer. Birds were infected with Isospora spp. and intensity of infection determined by oocyst counts 3 days post infection. Plasma lutein levels and chroma of subcutaneous fat stores were positively correlated and chroma values of these fat stores increased in the birds that got the higher dose rate, whereas they decreased significantly in the control group after infection with Isospora spp. Chroma of subcutaneous fat deposits in vivo and intensity of Isospora infection were negatively correlated. By measuring the chroma of fat deposits in vivo, we show that fat can be a reservoir for carotenoids. These colorful antioxidants are stored in the fat and taken from there in times of a higher demand, e.g. when mounting an immune response to parasites.

[Treatment of wrinkles of the upper lip by emulsified fat or "Nanofat": Biological and clinical study about 4 cases].

PubMed

Mesguich Batel, F; Bertrand, B; Magalon, J; François, P; Velier, M; Veran, J; Mallet, S; Jouve, E; Sabatier, F; Casanova, D

2018-02-01

Emulsified fat injection showed its interest in aesthetic facial surgery. The adipose tissue harvested is mechanically emulsified and filtered. The suspension obtained is injected into the dermis through small diameter needles (27 to 30 gauges). The objective of our study was to evaluate the biological composition of emulsified fat and its clinical effectiveness in the treatment of peri-oral wrinkles in 4 patients aged 50 to 59 years. Each patient received an intradermal injection of emulsified fat in the peri-oral wrinkles prepared from abdominal fat under local anesthesia. The cell viability, stromal vascular fraction (FVS) composition in emulsified fat and the adipocyte differentiation capacity of mesenchymal stem cells (MSC) were studied. The clinical results were evaluated by standardized photographs, 3D microphotography, confocal microscopy, and self-evaluation of patient satisfaction over a period of 4 months. The biological study of the emulsified fat found a lysis of all the adipocytes. The mean number of FVS cells was 126,330±2758 cells by cc of emulsified fat with preserved cell viability (85.1±6.84 %) and a good proportion of regeneratives cells (18.77±6.2 %). The clinical study found a tendency to decrease the volume of wrinkles on standardized photography and 3D microphotography no significative. Patients were satisfied with treatment with an average score of 7±1.15/10 to 4 months. Intradermal injection of emulsified fat seems to be an interesting treatment of face wrinkles. Our study has shown its safety, but additional studies seems necessary to confirm its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging

PubMed Central

Tuljapurkar, Sonal R; McGuire, Timothy R; Brusnahan, Susan K; Jackson, John D; Garvin, Kevin L; Kessinger, Margaret A; Lane, Judy T; O' Kane, Barbara J; Sharp, John G

2011-01-01

Hematological deficiencies increase with aging, including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age was associated with decreased numbers of side population (SP) hematopoietic stem cells, and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N = 100 subjects). In addition, BM from cadavers (N = 36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle, and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of insulin-like growth factor (IGF)-1, stromal-derived factor (SDF)-1 and interleukin (IL)-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with a decreased number of SP stem cells and IGF-1 and SDF-1 levels with aging. These data further raise a more general question as to the role of adipose cells in the regulation of tissue stem cells. PMID:21923862

Attenuated improvements in adiponectin and fat loss characterize type 2 diabetes non-remission status after bariatric surgery.

PubMed

Malin, S K; Bena, J; Abood, B; Pothier, C E; Bhatt, D L; Nissen, S; Brethauer, S A; Schauer, P R; Kirwan, J P; Kashyap, S R

2014-12-01

To identify the metabolic determinants of type 2 diabetes non-remission status after bariatric surgery at 12 and 24 months. A total of 40 adults [mean ± sd body mass index 36 ± 3 kg/m(2) , age 48 ± 9 years, glycated haemoglobin (HbA1c) 9.7 ± 2%) undergoing bariatric surgery [Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)] were enrolled in the present study, the Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial. Type 2 diabetes remission was defined as HbA1c <6.5% and fasting glucose <126 mg/dl (i.e. <7 mmol/l) without antidiabetic medication. Indices of insulin secretion and sensitivity were calculated from plasma glucose, insulin and C-peptide values during a 120-min mixed-meal tolerance test. Body fat, incretins (glucagon-like polypeptide-1, gastric inhibitory peptide, ghrelin) and adipokines [adiponectin, leptin, tumour necrosis factor-α, high-sensitivity C-reactive protein (hs-CRP)] were also assessed. At 24 months, 37 patients had available follow-up data (RYGB, n = 18; SG, n = 19). Bariatric surgery induced type 2 diabetes remission rates of 40 and 27% at 12 and 24 months, respectively. Total fat/abdominal fat loss, insulin secretion, insulin sensitivity and β-cell function (C-peptide0-120 /glucose0-120 × Matsuda index) improved more in those with remission at 12 and 24 months than in those without remission. Incretin levels were unrelated to type 2 diabetes remission, but, compared with those without remission, hs-CRP decreased and adiponectin increased more in those with remission. Only baseline adiponectin level predicted lower HbA1c levels at 12 and 24 months, and elevated adiponectin correlated with enhanced β-cell function, lower triglyceride levels and fat loss. Smaller rises in adiponectin level, a mediator of insulin action and adipose mass, characterize type 2 diabetes non-remission up to 2 years after bariatric surgery. Adjunctive strategies promoting greater fat loss and/or raising adiponectin may be key to achieving higher type 2 diabetes remission rates after bariatric surgery. © 2014 John Wiley & Sons Ltd.

Lack of angiopoietin-like-2 expression limits the metabolic stress induced by a high-fat diet and maintains endothelial function in mice.

PubMed

Yu, Carol; Luo, Xiaoyan; Farhat, Nada; Daneault, Caroline; Duquette, Natacha; Martel, Cécile; Lambert, Jean; Thorin-Trescases, Nathalie; Rosiers, Christine Des; Thorin, Eric

2014-08-15

Angiopoietin-like-2 (angptl2) is produced by several cell types including endothelial cells, adipocytes and macrophages, and contributes to the inflammatory process in cardiovascular diseases. We hypothesized that angptl2 impairs endothelial function, and that lowering angptl2 levels protects the endothelium against high-fat diet (HFD)-induced fat accumulation and hypercholesterolemia. Acute recombinant angptl2 reduced (P<0.05) acetylcholine-mediated vasodilation of isolated wild-type (WT) mouse femoral artery, an effect reversed (P<0.05) by the antioxidant N-acetylcysteine. Accordingly, in angptl2 knockdown (KD) mice, ACh-mediated endothelium-dependent vasodilation was greater (P<0.05) than in WT mice. In arteries from KD mice, prostacyclin contributed to the overall dilation unlike in WT mice. After a 3-month HFD, overall vasodilation was not altered, but dissecting out the endothelial intrinsic pathways revealed that NO production was reduced in arteries isolated from HFD-fed WT mice (P<0.05), while NO release was maintained in KD mice. Similarly, endothelium-derived hyperpolarizing factor (EDHF) was preserved in mesenteric arteries from HFD-fed KD mice but not in those from WT mice. Finally, the HFD increased (P<0.05) total cholesterol-to-high-density lipoprotein ratios, low-density lipoprotein-to-high-density lipoprotein ratios, and leptin levels in WT mice only, while glycemia remained similar in the 2 strains. KD mice displayed less triglyceride accumulation in the liver (P<0.05 versus WT), and adipocyte diameters in mesenteric and epididymal white adipose tissues were smaller (P<0.05) in KD than in WT fed an HFD, while inflammatory gene expression increased (P<0.05) in the fat of WT mice only. Lack of angptl2 expression limits the metabolic stress induced by an HFD and maintains endothelial function in mice. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Lack of Angiopoietin‐Like‐2 Expression Limits the Metabolic Stress Induced by a High‐Fat Diet and Maintains Endothelial Function in Mice

PubMed Central

Yu, Carol; Luo, Xiaoyan; Farhat, Nada; Daneault, Caroline; Duquette, Natacha; Martel, Cécile; Lambert, Jean; Thorin‐Trescases, Nathalie; Rosiers, Christine Des; Thorin, Éric

2014-01-01

Background Angiopoietin‐like‐2 (angptl2) is produced by several cell types including endothelial cells, adipocytes and macrophages, and contributes to the inflammatory process in cardiovascular diseases. We hypothesized that angptl2 impairs endothelial function, and that lowering angptl2 levels protects the endothelium against high‐fat diet (HFD)‐induced fat accumulation and hypercholesterolemia. Methods and Results Acute recombinant angptl2 reduced (P<0.05) acetylcholine‐mediated vasodilation of isolated wild‐type (WT) mouse femoral artery, an effect reversed (P<0.05) by the antioxidant N‐acetylcysteine. Accordingly, in angptl2 knockdown (KD) mice, ACh‐mediated endothelium‐dependent vasodilation was greater (P<0.05) than in WT mice. In arteries from KD mice, prostacyclin contributed to the overall dilation unlike in WT mice. After a 3‐month HFD, overall vasodilation was not altered, but dissecting out the endothelial intrinsic pathways revealed that NO production was reduced in arteries isolated from HFD‐fed WT mice (P<0.05), while NO release was maintained in KD mice. Similarly, endothelium‐derived hyperpolarizing factor (EDHF) was preserved in mesenteric arteries from HFD‐fed KD mice but not in those from WT mice. Finally, the HFD increased (P<0.05) total cholesterol–to–high‐density lipoprotein ratios, low‐density lipoprotein–to–high‐density lipoprotein ratios, and leptin levels in WT mice only, while glycemia remained similar in the 2 strains. KD mice displayed less triglyceride accumulation in the liver (P<0.05 versus WT), and adipocyte diameters in mesenteric and epididymal white adipose tissues were smaller (P<0.05) in KD than in WT fed an HFD, while inflammatory gene expression increased (P<0.05) in the fat of WT mice only. Conclusions Lack of angptl2 expression limits the metabolic stress induced by an HFD and maintains endothelial function in mice. PMID:25128474

The effects of dynamic compression on the development of cartilage grafts engineered using bone marrow and infrapatellar fat pad derived stem cells.

PubMed

Luo, Lu; Thorpe, Stephen D; Buckley, Conor T; Kelly, Daniel J

2015-09-21

Bioreactors that subject cell seeded scaffolds or hydrogels to biophysical stimulation have been used to improve the functionality of tissue engineered cartilage and to explore how such constructs might respond to the application of joint specific mechanical loading. Whether a particular cell type responds appropriately to physiological levels of biophysical stimulation could be considered a key determinant of its suitability for cartilage tissue engineering applications. The objective of this study was to determine the effects of dynamic compression on chondrogenesis of stem cells isolated from different tissue sources. Porcine bone marrow (BM) and infrapatellar fat pad (FP) derived stem cells were encapsulated in agarose hydrogels and cultured in a chondrogenic medium in free swelling (FS) conditions for 21 d, after which samples were subjected to dynamic compression (DC) of 10% strain (1 Hz, 1 h d(-1)) for a further 21 d. Both BM derived stem cells (BMSCs) and FP derived stem cells (FPSCs) were capable of generating cartilaginous tissues with near native levels of sulfated glycosaminoglycan (sGAG) content, although the spatial development of the engineered grafts strongly depended on the stem cell source. The mechanical properties of cartilage grafts generated from both stem cell sources also approached that observed in skeletally immature animals. Depending on the stem cell source and the donor, the application of DC either enhanced or had no significant effect on the functional development of cartilaginous grafts engineered using either BMSCs or FPSCs. BMSC seeded constructs subjected to DC stained less intensely for collagen type I. Furthermore, histological and micro-computed tomography analysis showed mineral deposition within BMSC seeded constructs was suppressed by the application of DC. Therefore, while the application of DC in vitro may only lead to modest improvements in the mechanical functionality of cartilaginous grafts, it may play an important role in the development of phenotypically stable constructs.

Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease.

PubMed

Granér, Marit; Nyman, Kristofer; Siren, Reijo; Pentikäinen, Markku O; Lundbom, Jesper; Hakkarainen, Antti; Lauerma, Kirsi; Lundbom, Nina; Nieminen, Markku S; Taskinen, Marja-Riitta

2015-01-01

Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study. © 2014 American Heart Association, Inc.

Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue.

PubMed

Harford, Karen A; Reynolds, Clare M; McGillicuddy, Fiona C; Roche, Helen M

2011-11-01

High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.

The influence of pericardial fat upon left ventricular function in obese females: evidence of a site-specific effect

PubMed Central

2014-01-01

Background Although increased volume of pericardial fat has been associated with decreased cardiac function, it is unclear whether this association is mediated by systemic overall obesity or direct regional fat interactions. We hypothesized that if local effects dominate, left ventricular (LV) function would be most strongly associated with pericardial fat that surrounds the left rather than the right ventricle (RV). Methods Female obese subjects (n = 60) had cardiovascular magnetic resonance (CMR) scans to obtain measures of LV function and pericardial fat volumes. LV function was obtained using the cine steady state free precession imaging in short axis orientation. The amount of pericardial fat was determined volumetrically by the cardiac gated T1 black blood imaging and normalized to body surface area. Results In this study cohort, LV fat correlated with several LV hemodynamic measurements including cardiac output (r = -0.41, p = 0.001) and stroke volume (r = -0.26, p = 0.05), as well as diastolic functional parameters including peak-early-filling rate (r = -0.38, p = 0.01), early late filling ratio (r = -0.34, p = 0.03), and time to peak-early-filling (r = 0.34, p = 0.03). These correlations remained significant even after adjusting for the body mass index and the blood pressure. However, similar correlations became weakened or even disappeared between RV fat and LV function. LV function was not correlated with systemic plasma factors, such as C-reactive protein (CRP), B-type natriuretic peptide (BNP), Interleukin-6 (IL-6), resistin and adiponectin (all p > 0.05). Conclusions LV hemodynamic and diastolic function was associated more with LV fat as compared to RV or total pericardial fat, but not with systemic inflammatory markers or adipokines. The correlations between LV function and pericardial fat remained significant even after adjusting for systemic factors. These findings suggest a site-specific influence of pericardial fat on LV function, which could imply local secretion of molecules into the underlying tissue or an anatomic effect, both mechanisms meriting future evaluation. PMID:24884541

Disruption of protein-tyrosine phosphatase 1B expression in the pancreas affects β-cell function.

PubMed

Liu, Siming; Xi, Yannan; Bettaieb, Ahmed; Matsuo, Kosuke; Matsuo, Izumi; Kulkarni, Rohit N; Haj, Fawaz G

2014-09-01

Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of glucose homeostasis and energy balance. However, the role of PTP1B in pancreatic endocrine function remains largely unknown. To investigate the metabolic role of pancreatic PTP1B, we generated mice with pancreas PTP1B deletion (panc-PTP1B KO). Mice were fed regular chow or a high-fat diet, and metabolic parameters, insulin secretion and glucose tolerance were determined. On regular chow, panc-PTP1B KO and control mice exhibited comparable glucose tolerance whereas aged panc-PTP1B KO exhibited mild glucose intolerance. Furthermore, high-fat feeding promoted earlier impairment of glucose tolerance and attenuated glucose-stimulated insulin secretion in panc-PTP1B KO mice. The secretory defect in glucose-stimulated insulin secretion was recapitulated in primary islets ex vivo, suggesting that the effects were likely cell-autonomous. At the molecular level, PTP1B deficiency in vivo enhanced basal and glucose-stimulated tyrosyl phosphorylation of EphA5 in islets. Consistently, PTP1B overexpression in the glucose-responsive MIN6 β-cell line attenuated EphA5 tyrosyl phosphorylation, and substrate trapping identified EphA5 as a PTP1B substrate. In summary, these studies identify a novel role for PTP1B in pancreatic endocrine function.

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

PubMed

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

2017-02-01

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

Evaluation of Fermented Sausages Manufactured with Reduced-fat and Functional Starter Cultures on Physicochemical, Functional and Flavor Characteristics

PubMed Central

Yoo, Seung Seok

2014-01-01

Fermented foods with probiotics having functional properties may provide beneficial effects on health. These effects are varied, depending on the type of lactic acid bacteria (LAB). Different probiotic LAB might have different functional properties. Thus, this study was performed to evaluate the quality of fermented sausages manufactured with functional starter cultures (Lactobacillus plantarum 115 and 167, and Pediococcus damnosus L12) and different fat levels, and to determine the optimum condition for the manufacture of these products. Medium-fat (~15%) fermented sausages reduced the drying time and cholesterol contents, as compared to regular-fat counterparts. In proximate analysis, the contents of moisture and protein of regular-fat products were lower than medium-fat with reduced fat content. The regular-fat products also had a lighter color and less redness, due to reduced fat content. Approximately 35 volatile compounds were identified in functional fermented sausages, and hexanal, trans-caryophyllene, and tetradecanal were the major volatile compounds. Selected mixed starter culture showed the potential possibility of replacing the commercial starter culture (LK30 plus) in flavor profiles. However, medium-fat fermented sausage containing selected mixed starter culture tended to be less acceptable than their high-fat counterparts, due to excess dry ring developed in the surface. These results indicate that the use of combinations of L. plantarum 115 and 167, and P. damnosus L12 as a starter culture, will prove useful for manufacturing the fermented sausage. PMID:26761176

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats

PubMed Central

Alam, Md. Ashraful; Kauter, Kathleen; Brown, Lindsay

2013-01-01

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats. PMID:23446977

Long-term exposure to a butter-rich diet induces mild-to-moderate steatosis in Chang liver cells and Swiss albino mice models.

PubMed

Nalloor, Thomas John Philip; Kumar, Nitesh; Narayanan, Kasinathan; Palanimuthu, Vasanth Raj

2017-05-01

Butter is one of the widely used fats present in the diet. However, there is no satisfactory study available that evaluates the effect of a high-fat diet containing butter as the principal fat on the development of non-alcoholic fatty liver disease (NAFLD). In the present study, butter was used for the development of steatosis in Chang liver cells in an in vitro study and Swiss albino mice in an in vivo study. In vitro steatosis was established, and butter was compared with oleic acid in Chang liver cells using an oil red O (ORO)-based colorimetric assay. In the in vivo study, a butter-rich special diet was fed for 15 weeks to mice, who showed no significant change in body weight. The expression pattern of phosphatase and tensin homolog (PTEN) and miR-21 was compared by reverse transcriptase-PCR. Special diet-fed animals showed downregulated PTEN compared to normal diet-fed animals, while levels of miR-21 remained the same. Elevations in biochemical parameters, viz., triglycerides and liver function tests showed symptoms of onset of NAFLD. Histophathological study of livers of test animals confirmed mild-to-moderate degree of NAFLD.

Effects of Emulsifier, Overrun and Dasher Speed on Ice Cream Microstructure and Melting Properties.

PubMed

Warren, Maya M; Hartel, Richard W

2018-03-01

Ice cream is a multiphase frozen food containing ice crystals, air cells, fat globules, and partially coalesced fat globule clusters dispersed in an unfrozen serum phase (sugars, proteins, and stabilizers). This microstructure is responsible for ice cream's melting characteristics. By varying both formulation (emulsifier content and overrun) and processing conditions (dasher speed), the effects of different microstructural elements, particularly air cells and fat globule clusters, on ice cream melt-down properties were studied. Factors that caused an increase in shear stress within the freezer, namely increasing dasher speed and overrun, caused a decrease in air cell size and an increase in extent of fat destabilization. Increasing emulsifier content, especially of polysorbate 80, caused an increase in extent of fat destabilization. Both overrun and fat destabilization influenced drip-through rates. Ice creams with a combination of low overrun and low fat destabilization had the highest drip-through rates. Further, the amount of remnant foam left on the screen increased with reduced drip-through rates. These results provide a better understanding of the effects of microstructure components and their interactions on drip-through rate. Manipulating operating and formulation parameters in ice cream manufacture influences the microstructure (air cells, ice crystals, and fat globule clusters). This work provides guidance on which parameters have most effect on air cell size and fat globule cluster formation. Further, the structural characteristics that reduce melt-down rate were determined. Ice cream manufacturers will use these results to tailor their products for the desired quality attributes. © 2018 Institute of Food Technologists®.

A 70% Ethanol Extract of Mistletoe Rich in Betulin, Betulinic Acid, and Oleanolic Acid Potentiated β-Cell Function and Mass and Enhanced Hepatic Insulin Sensitivity

PubMed Central

Ko, Byoung-Seob; Kang, Suna; Moon, Bo Reum; Ryuk, Jin Ah; Park, Sunmin

2016-01-01

We investigated that the long-term consumption of the water (KME-W) and 70% ethanol (KME-E) mistletoe extracts had antidiabetic activities in partial pancreatectomized (Px) rats. Px rats were provided with a high-fat diet containing 0.6% KME-E, 0.6% KME-W, and 0.6% dextrin (control) for 8 weeks. As normal-control, Sham-operated rats were provided with 0.6% dextrin. In cell-based studies, the effects of its main terpenoids (betulin, betulinic acid, and oleanolic acid) on glucose metabolism were measured. Both KME-W and KME-E decreased epididymal fat mass by increasing fat oxidation in diabetic rats. KME-E but not KME-W exhibited greater potentiation of first-phase insulin secretion than the Px-control in a hyperglycemic clamp. KME-E also made β-cell mass greater than the control by increasing β-cell proliferation and decreasing its apoptosis. In a euglycemic-hyperinsulinemic clamp, whole-body glucose infusion rate and hepatic glucose output increased with potentiating hepatic insulin signaling in the following order: Px-control, KME-W, KME-E, and normal-control. Betulin potentiated insulin-stimulated glucose uptake via increased PPAR-γ activity and insulin signaling in 3T3-L1 adipocytes, whereas oleanolic acid enhanced glucose-stimulated insulin secretion and cell proliferation in insulinoma cells. In conclusion, KME-E prevented the deterioration of glucose metabolism in diabetic rats more effectively than KME-W and KME-E can be a better therapeutic agent for type 2 diabetes than KME-W. PMID:26884795

Adipogenesis in thyroid eye disease.

PubMed

Crisp, M; Starkey, K J; Lane, C; Ham, J; Ludgate, M

2000-10-01

Adipogenesis contributes to the pathogenesis of thyroid eye disease (TED). Thyrotropin receptor (TSHR) transcripts are present in orbital fat. This study was conducted to determine whether they are expressed as functional protein, and if so, whether this is restricted to TED orbits or to a particular stage in adipocyte differentiation. Samples of fat were obtained from 18 TED-affected orbits and 4 normal orbits, and 9 were obtained from nonorbital locations. Frozen sections were examined by immunocytochemistry using monoclonal antibodies specific for the human TSHR. Samples were disaggregated and the preadipocytes separated from the mature by differential centrifugation and cultured in serum-free or DM and examined for morphologic changes, oil red O and TSHR staining, and TSH-induced cyclic adenosine monophosphate (cAMP) production. Marked immunoreactivity was observed in frozen sections from all three TED samples and faint staining in both normal orbital fat samples. In vitro, 1% to 5% of preadipocytes displayed TSHR immunoreactivity in five of six TED and two of three normal orbital samples and in three of five nonorbital samples. Differentiation, was induced in all 14 orbital samples. Three of four nonorbital samples contained occasional differentiated cells. Fifty percent to 70% of differentiating cells demonstrated receptor immunoreactivity. Two of three TED and four of four nonorbital preadipocytes in DM and/or mature adipocytes displayed a TSH-mediated increase in cAMP. The results indicate that orbital fat TSHR transcripts are expressed as protein, which can be functional. This is not aberrant in TED orbits, although expression may be upregulated. The majority of preadipocytes undergoing differentiation express the receptor, indicating a key role for this population in one mechanism for increasing orbital volume.

TRIENNIAL GROWTH AND DEVELOPMENT SYMPOSIUM: Dedifferentiated fat cells: Potential and perspectives for their use in clinical and animal science purpose.

PubMed

Duarte, M S; Bueno, R; Silva, W; Campos, C F; Gionbelli, M P; Guimarães, S E F; Silva, F F; Lopes, P S; Hausman, G J; Dodson, M V

2017-05-01

An increasing body of evidences has demonstrated the ability of the mature adipocyte to dedifferentiate into a population of proliferative-competent cells known as dedifferentiated fat (DFAT) cells. As early as the 1970s, in vitro studies showed that DFAT cells may be obtained by ceiling culture, which takes advantage of the buoyancy property of lipid-filled cells. It was documented that DFAT cells may acquire a phenotype similar to mesenchymal stem cells and yet may differentiate into multiple cell lineages, such as skeletal and smooth muscle cells, cardiomyocytes, osteoblasts, and adipocytes. Additionally, recent studies showed the ability of isolated mature adipocytes to dedifferentiate in vivo and the capacity of the progeny cells to redifferentiate into mature adipocytes, contributing to the increase of body fatness. These findings shed light on the potential for use of DFAT cells, not only for clinical purposes but also within the animal science field, because increasing intramuscular fat without excessive increase in other fat depots is a challenge in livestock production. Knowledge of the mechanisms underlying the dedifferentiation and redifferentiation of DFAT cells will allow the development of strategies for their use for clinical and animal science purposes. In this review, we highlight several aspects of DFAT cells, their potential for clinical purposes, and their contribution to adipose tissue mass in livestock.

Physicochemical, rheological and functional properties of fats and oils in relation to cookie quality: a review.

PubMed

Devi, Amita; Khatkar, B S

2016-10-01

Sincere efforts of researchers are underway to understand the functionality of different fats and oils in relation to cookie quality. The quality of cookie primarily relies upon the functionality of fats and oils in cookie system which ultimately is combined result of their physical, chemical, and rheological properties. Effects of some major fats and oils such as butter, bakery fat, hydrogenated fat, lard, margarine, palm oil, sunflower oil, coconut oil, and soybean oil on the physical and sensory characteristics of cookie have been studied. Previous studies reported that fats and oils had radical contribution in cookie quality and most authors agree on the fact that different fats and oils affect the cookie quality to different extent. Furthermore, it was observed by many researchers that with oils, dough was softer and cookie spread was higher as compared with that of fats. It is important to understand the molecular basis of the difference in technological changes in cookies properties with different fats and oils. This review focuses on the current knowledge of quality determining physical, chemical, thermal, microstructural, and functional properties of fats and oils in relation to cookie dough rheology and cookie quality.

Amyloid Precursor Protein and Proinflammatory Changes Are Regulated in Brain and Adipose Tissue in a Murine Model of High Fat Diet-Induced Obesity

PubMed Central

Puig, Kendra L.; Floden, Angela M.; Adhikari, Ramchandra; Golovko, Mikhail Y.; Combs, Colin K.

2012-01-01

Background Middle age obesity is recognized as a risk factor for Alzheimer's disease (AD) although a mechanistic linkage remains unclear. Based upon the fact that obese adipose tissue and AD brains are both areas of proinflammatory change, a possible common event is chronic inflammation. Since an autosomal dominant form of AD is associated with mutations in the gene coding for the ubiquitously expressed transmembrane protein, amyloid precursor protein (APP) and recent evidence demonstrates increased APP levels in adipose tissue during obesity it is feasible that APP serves some function in both disease conditions. Methodology/Principal Findings To determine whether diet-induced obesity produced proinflammatory changes and altered APP expression in brain versus adipose tissue, 6 week old C57BL6/J mice were maintained on a control or high fat diet for 22 weeks. Protein levels and cell-specific APP expression along with markers of inflammation and immune cell activation were compared between hippocampus, abdominal subcutaneous fat and visceral pericardial fat. APP stimulation-dependent changes in macrophage and adipocyte culture phenotype were examined for comparison to the in vivo changes. Conclusions/Significance Adipose tissue and brain from high fat diet fed animals demonstrated increased TNF-α and microglial and macrophage activation. Both brains and adipose tissue also had elevated APP levels localizing to neurons and macrophage/adipocytes, respectively. APP agonist antibody stimulation of macrophage cultures increased specific cytokine secretion with no obvious effects on adipocyte culture phenotype. These data support the hypothesis that high fat diet-dependent obesity results in concomitant pro-inflammatory changes in brain and adipose tissue that is characterized, in part, by increased levels of APP that may be contributing specifically to inflammatory changes that occur. PMID:22276186

High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress.

PubMed

Balakumar, M; Raji, L; Prabhu, D; Sathishkumar, C; Prabu, P; Mohan, V; Balasubramanyam, M

2016-12-01

In the context of high human consumption of fructose diets, there is an imperative need to understand how dietary fructose intake influence cellular and molecular mechanisms and thereby affect β-cell dysfunction and insulin resistance. While evidence exists for a relationship between high-fat-induced insulin resistance and metabolic disorders, there is lack of studies in relation to high-fructose diet. Therefore, we attempted to study the effect of different diets viz., high-fat diet (HFD), high-fructose diet (HFS), and a combination (HFS + HFD) diet on glucose homeostasis and insulin sensitivity in male Wistar rats compared to control animals fed with normal pellet diet. Investigations include oral glucose tolerance test, insulin tolerance test, histopathology by H&E and Masson's trichrome staining, mRNA expression by real-time PCR, protein expression by Western blot, and caspase-3 activity by colorimetry. Rats subjected to high-fat/fructose diets became glucose intolerant, insulin-resistant, and dyslipidemic. Compared to control animals, rats subjected to different combination of fat/fructose diets showed increased mRNA and protein expression of a battery of ER stress markers both in pancreas and liver. Transcription factors of β-cell function (INSIG1, SREBP1c and PDX1) as well as hepatic gluconeogenesis (FOXO1 and PEPCK) were adversely affected in diet-induced insulin-resistant rats. The convergence of chronic ER stress towards apoptosis in pancreas/liver was also indicated by increased levels of CHOP mRNA & increased activity of both JNK and Caspase-3 in rats subjected to high-fat/fructose diets. Our study exposes the experimental support in that high-fructose diet is equally detrimental in causing metabolic disorders.

Conference on Biological Actions and Medical Applications of Dimethyl Sulfoxide (DMSO), 15-17 September 1982.

DTIC Science & Technology

1983-06-01

Effects on Isolated Fat Cells. By PAUL B. WIESER ......... 135 Induction of Glohin Gene Expression During Erythroid Cell Differentiation. By RICHARD A...lipolysis and decreases insulin-stimulated glucose oxidation in free while fat cells of rat." It V also enhances heme synthesis in quail embryo yolk sac...metabolism of fat cells. Biochem. Pharma- col. 26: 775-778. 18. TERASAWA. T., Y. MIt RA & R. MASJDA. 1981. The mechanism of the action of DMSO on the

Deficient of a clock gene, brain and muscle Arnt-like protein-1 (BMAL1), induces dyslipidemia and ectopic fat formation.

PubMed

Shimba, Shigeki; Ogawa, Tomohiro; Hitosugi, Shunsuke; Ichihashi, Yuya; Nakadaira, Yuki; Kobayashi, Munehiro; Tezuka, Masakatsu; Kosuge, Yasuhiro; Ishige, Kumiko; Ito, Yoshihisa; Komiyama, Kazuo; Okamatsu-Ogura, Yuko; Kimura, Kazuhiro; Saito, Masayuki

2011-01-01

A link between circadian rhythm and metabolism has long been discussed. Circadian rhythm is controlled by positive and negative transcriptional and translational feedback loops composed of several clock genes. Among clock genes, the brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) play important roles in the regulation of the positive rhythmic transcription. In addition to control of circadian rhythm, we have previously shown that BMAL1 regulates adipogenesis. In metabolic syndrome patients, the function of BMAL1 is dysregulated in visceral adipose tissue. In addition, analysis of SNPs has revealed that BMAL1 is associated with susceptibility to hypertension and type II diabetes. Furthermore, the significant roles of BMAL1 in pancreatic β cells proliferation and maturation were recently reported. These results suggest that BMAL1 regulates energy homeostasis. Therefore, in this study, we examined whether loss of BMAL1 function is capable of inducing metabolic syndrome. Deficient of the Bmal1 gene in mice resulted in elevation of the respiratory quotient value, indicating that BMAL1 is involved in the utilization of fat as an energy source. Indeed, lack of Bmal1 reduced the capacity of fat storage in adipose tissue, resulting in an increase in the levels of circulating fatty acids, including triglycerides, free fatty acids, and cholesterol. Elevation of the circulating fatty acids level induced the formation of ectopic fat in the liver and skeletal muscle in Bmal1 -/- mice. Interestingly, ectopic fat formation was not observed in tissue-specific (liver or skeletal muscle) Bmal1 -/- mice even under high fat diet feeding condition. Therefore, we were led to conclude that BMAL1 is a crucial factor in the regulation of energy homeostasis, and disorders of the functions of BMAL1 lead to the development of metabolic syndrome.

FAT/CD36 expression alone is insufficient to enhance cellular uptake of oleate

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

Eyre, Nicholas S.; Cleland, Leslie G.; Mayrhofer, Graham

2008-06-06

Fatty acid translocase (FAT/CD36) is one of several proteins implicated in receptor-mediated uptake of long-chain fatty acids (LCFAs). We have tested whether levels of FAT/CD36 correlate with cellular oleic acid import, using a Tet-Off inducible transfected CHO cell line. Consistent with our previous findings, FAT/CD36 was enriched in lipid raft-derived detergent-resistant membranes (DRMs) that also contained caveolin-1, the marker protein of caveolae. Furthermore in transfected cells, plasma membrane FAT/CD36 co-localized extensively with the lipid raft-enriched ganglioside GM1, and partially with a caveolin-1-EGFP fusion protein. Nevertheless, even at high levels of expression, FAT/CD36 did not affect uptake of oleic acid. Wemore » propose that the ability of FAT/CD36 to mediate enhanced uptake of LCFAs is dependent on co-expression of other proteins or factors that are lacking in CHO cells.« less

Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men

PubMed Central

Lin, Ping; Seenivasan, Thanalakshmi; Livingston, Edward H.; Snell, Peter G.; Grundy, Scott M.

2007-01-01

Objective South Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians. Research Design and Methods Twenty-nine South Asian and 18 Caucasian non-diabetic men (age 27±3 and 27±3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size. Results Compared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22±6 and 15±4% of body weight; p-value<0.0001), higher SA fat (3.5±1.9 and 2.2±1.3 kg, respectively; p-value = 0.004), but no differences in IP fat (1.0±0.5 and 1.0±0.7 kg, respectively; p-value = 0.4). SA adipocyte cell size was significantly higher in South Asians (3491±1393 and 1648±864 µm2; p-value = 0.0001) and was inversely correlated with both glucose disposal rate (r-value = −0.57; p-value = 0.0008) and plasma adiponectin concentrations (r-value = −0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians. Conclusions Insulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat. PMID:17726542

New Advanced Technologies in Stem Cell Therapy

DTIC Science & Technology

2013-09-01

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

Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

PubMed

Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

2014-08-01

Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells. © 2014 International Federation for Cell Biology.

Investigating the mincing method for isolation of adipose-derived stem cells from pregnant women fat.

PubMed

Li, Yuan-Sheng; Chen, Pao-Jen; Wu, Li-Wei; Chou, Pei-Wen; Sun, Li-Yi; Chiou, Tzyy-Wen

2018-02-01

The success of stem cell application in regenerative medicine, usually require a stable source of stem or progenitor cells. Fat tissue represents a good source of stem cells because it is rich in stem cells and there are fewer ethical issues related to the use of such stem cells, unlike embryonic stem cells. Therefore, there has been increased interest in adipose-derived stem cells (ADSCs) for tissue engineering applications. Here, we aim to provide an easy processing method for isolating adult stem cells from human adipose tissue harvested from the subcutaneous fat of the abdominal wall during gynecologic surgery. We used a homogenizer to mince fat and compared the results with those obtained from the traditional cut method involving a sterile scalpel and forceps. Our results showed that our method provides another stable and quality source of stem cells that could be used in cases with a large quantity of fat. Furthermore, we found that pregnancy adipose-derived stem cells (P-ADSCs) could be maintained in vitro for extended periods with a stable population doubling and low senescence levels. P-ADSCs could also differentiate in vitro into adipogenic, osteogenic, chondrogenic, and insulin-producing cells in the presence of lineage-specific induction factors. In conclusion, like human lipoaspirates, adipose tissues obtained from pregnant women contain multipotent cells with better proliferation and showed great promise for use in both stem cell banking studies as well as in stem cell therapy.

Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

PubMed Central

Mato, M; Ookawara, S; Sakamoto, A; Aikawa, E; Ogawa, T; Mitsuhashi, U; Masuzawa, T; Suzuki, H; Honda, M; Yazaki, Y; Watanabe, E; Luoma, J; Yla-Herttuala, S; Fraser, I; Gordon, S; Kodama, T

1996-01-01

The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system. Images Fig. 1 Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:8622926

Changes in human bone marrow fat content associated with changes in hematopoietic stem cell numbers and cytokine levels with aging.

PubMed

Tuljapurkar, Sonal R; McGuire, Timothy R; Brusnahan, Susan K; Jackson, John D; Garvin, Kevin L; Kessinger, Margaret A; Lane, Judy T; O' Kane, Barbara J; Sharp, John G

2011-11-01

Hematological deficiencies increase with aging, including anemias, reduced responses to hematopoietic stress and myelodysplasias. This investigation tested the hypothesis that increased bone marrow (BM) fat content in humans with age was associated with decreased numbers of side population (SP) hematopoietic stem cells, and this decrease correlated with changes in cytokine levels. BM was obtained from the femoral head and trochanteric region of the femur removed at surgery for total hip replacement (N = 100 subjects). In addition, BM from cadavers (N = 36), with no evidence of hip disease, was evaluated for fat content. Whole trabecular marrow samples were ground in a sterile mortar and pestle, and cellularity and lipid content determined. Marrow cells were stained with Hoechst dye and SP profiles were acquired. Plasma levels of insulin-like growth factor (IGF)-1, stromal-derived factor (SDF)-1 and interleukin (IL)-6 were measured using ELISA. Fat content in the BM of human subjects and cadavers increased with age. The numbers of SP stem cells in BM as well as plasma IGF-1 and SDF-1 levels decreased in correlation with increased BM fat. IL-6 had no relationship to changes in marrow fat. These data suggest that increased BM fat may be associated with a decreased number of SP stem cells and IGF-1 and SDF-1 levels with aging. These data further raise a more general question as to the role of adipose cells in the regulation of tissue stem cells. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

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

PubMed Central

Rapiejko, P J; Malbon, C C

1987-01-01

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

Ca2+ signaling in taste bud cells and spontaneous preference for fat: unresolved roles of CD36 and GPR120.

PubMed

Abdoul-Azize, Souleymane; Selvakumar, Subramaniam; Sadou, Hassimi; Besnard, Philippe; Khan, Naim Akhtar

2014-01-01

Recent compelling evidences from rodent and human studies raise the possibility for an additional sixth taste modality devoted to oro-gustatory perception of dietary lipids. Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. A number of studies have suggested that lingual CD36, a glycoprotein, highly expressed by circumvallate papillae of the tongue, is implicated in the perception of dietary fat taste. G protein-coupled receptors (GPCRs) are important signaling molecules for many aspects of cellular functions. It has been shown that these receptors, particularly GPR120, are also involved in lipid taste perception. We have shown that dietary long-chain fatty acids (LCFAs), in CD36-positive taste bud cells (TBC), induce increases in free intracellular Ca(2+) concentrations, [Ca(2+)]i, by recruiting Ca(2+) from endoplasmic reticulum (ER) pool via inositol 1,4,5-triphosphate production, followed by Ca(2+) influx via opening of store-operated Ca(2+) (SOC) channels. GPR120 is also coupled to increases in [Ca(2+)]i by dietary fatty acids. We observed that stromal interaction molecule 1 (STIM1), a sensor of Ca(2+) depletion in the ER, mediated fatty acid-induced Ca(2+) signaling and spontaneous preference for fat in the mouse. In this review article, we discuss the recent advances and unresolved roles of CD36 and GPR120 in lipid taste signaling in taste bud cells. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Dietary saturated and unsaturated fats as determinants of blood pressure and vascular function.

PubMed

Hall, Wendy L

2009-06-01

The amount and type of dietary fat have long been associated with the risk of CVD. Arterial stiffness and endothelial dysfunction are important risk factors in the aetiology of CHD. A range of methods exists to assess vascular function that may be used in nutritional science, including clinic and ambulatory blood pressure monitoring, pulse wave analysis, pulse wave velocity, flow-mediated dilatation and venous occlusion plethysmography. The present review focuses on the quantity and type of dietary fat and effects on blood pressure, arterial compliance and endothelial function. Concerning fat quantity, the amount of dietary fat consumed habitually appears to have little influence on vascular function independent of fatty acid composition, although single high-fat meals postprandially impair endothelial function compared with low-fat meals. The mechanism is related to increased circulating lipoproteins and NEFA which may induce pro-inflammatory pathways and increase oxidative stress. Regarding the type of fat, cross-sectional data suggest that saturated fat adversely affects vascular function whereas polyunsaturated fat (mainly linoleic acid (18 : 2n-6) and n-3 PUFA) are beneficial. EPA (20 : 5n-3) and DHA (22 : 6n-3) can reduce blood pressure, improve arterial compliance in type 2 diabetics and dyslipidaemics, and augment endothelium-dependent vasodilation. The mechanisms for this vascular protection, and the nature of the separate physiological effects induced by EPA and DHA, are priorities for future research. Since good-quality observational or interventional data on dietary fatty acid composition and vascular function are scarce, no further recommendations can be suggested in addition to current guidelines at the present time.

An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

PubMed Central

Seco, J.

2017-01-01

For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes. PMID:28883835

Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome.

PubMed

Ezeh, Uche; Pall, Marita; Mathur, Ruchi; Azziz, Ricardo

2014-07-01

Are differences in metabolic dysfunction between polycystic ovary syndrome (PCOS) and control women related to differences in their fat to lean mass (F/L) ratio? Compared with controls of similar body mass index (BMI), women with PCOS demonstrate adverse body composition characterized by increased whole body fat relative to lean mass (i.e. a higher F/L ratio), which is associated with differences in metabolic dysfunction between the two groups. Previous studies examining body composition and insulin resistance (IR) in PCOS have yielded conflicting results. Excess total fat mass (i.e. fat mass index [fat BMI]) correlates with IR, whereas increased total lean mass (i.e. lean BMI) has been associated with higher insulin sensitivity. However, the role of the F/L ratio, which integrates the antagonistic effects of both fat and lean mass depots, on IR in PCOS, has not been investigated. We conducted a prospective cross-sectional study of 120 women between the ages of 22-44 years to study the relation of the F/L ratio with measures of insulin action and secretion in both steady and dynamic states. Sixty PCOS (by NIH, 1990 criteria) and 60 control (age, race and BMI-matched) women were prospectively studied for body composition (by bioelectrical impedance analysis [BIA]) and basal IR and insulin secretion by the homeostasis model assessment (HOMA-IR and HOMA-%β-cell function, respectively) in a tertiary care academic referral center. A subset of 12 PCOS and 12 matched control women also underwent a modified frequently sampled intravenous glucose tolerance test (FSIVGTT) to determine glucose uptake and insulin secretion in dynamic state. Our results indicate that women with PCOS demonstrated greater degrees of hyperandrogenism, and higher waist-to-hip ratio (WHR), %body fat, fat BMI, F/L, fasting insulin levels, and HOMA-IR and HOMA-%β-cell values, than controls. In models adjusted for WHR and free testosterone and diagnostic groups, fasting insulin levels, HOMA-IR, and HOMA-%beta cell function were positively related to the F/L ratio. A positive relationship was also found in both study groups between F/L and the FSIVGTT measures insulin sensitivity (Si) and acute insulin response to glucose (AIRg). The F/L tended to negatively correlate with glucose effectiveness or non-insulin-mediated glucose transport (Sg) only in PCOS women. Regional tissue sub-compartments, which have been shown to have potential independent associations with metabolic variables, cannot be determined by bioelectrical impedance analysis (BIA). The current results suggest that BIA could be used to assess F/L in place of dual energy X-ray absorptiometry (DXA) in research protocols, and that F/L could possibly be used as an alternative to WHR as a surrogate marker of metabolic dysfunction in clinical practice. This work was supported by grants R01-DK073632 and R01-HD29364 from the NIH and an endowment of the Helping Hand of Los Angeles, Inc. (to R.A.). The authors have no competing interests to declare. Not applicable.

High fat diet triggers cell cycle arrest and excessive apoptosis of granulosa cells during the follicular development

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

Wu, Yanqing; Zhang, Zhenghong; Liao, Xinghui

The regulatory mechanism of granulosa cells (GCs) proliferation during the follicular development is complicated and multifactorial, which is essential for the oocyte growth and normal ovarian functions. To investigate the role of high fat diet (HFD) on the proliferation of GCs, 4-week old female mice were fed with HFD or normal control diet (NC) for 15 weeks or 20 weeks and then detected the expression level of some regulatory molecules of cell cycle and apoptosis. The abnormal ovarian morphology was observed at 20 weeks. Further mechanistic studies indicated that HFD induced-obesity caused elevated apoptotic levels in GCs of the ovariesmore » in a time-dependent manner. Moreover, cell cycle progress was also impacted after HFD fed. The cell cycle inhibitors, p27{sup Kip1} and p21{sup Cip1}, were significantly induced in the ovaries from the mice in HFD group when compared with that in the ovaries from the mice in NC group. Subsequently, the expression levels of Cyclin D1, D3 and CDK4 were also significantly influenced in the ovaries from the mice fed with HFD in a time-dependent manner. The present results suggested that HFD induced-obesity may trigger cell cycle arrest and excessive apoptosis of GCs, causing the abnormal follicular development and ovarian function failure. - Highlights: • HFD induced-obesity leads to abnormal ovarian morphology. • HFD induced-obesity triggers excessive apoptosis in the ovary. • HFD induced-obesity up-regulates cell cycle inhibitors p21{sup Cip1} and p27{sup Kip1} in the ovary. • HFD induced-obesity causes cell cycle arrest in the ovary.« less

Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism.

PubMed

Wang, Rong; Yu, Zhen; Sunchu, Bharath; Shoaf, James; Dang, Ivana; Zhao, Stephanie; Caples, Kelsey; Bradley, Lynda; Beaver, Laura M; Ho, Emily; Löhr, Christiane V; Perez, Viviana I

2017-06-01

Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Rapamycin, an inhibitor of mTOR, inhibits cell senescence in vitro and increases longevity in several species. Nrf2 levels have been shown to decrease with aging and silencing Nrf2 gene induces premature senescence. Therefore, we explored whether Nrf2 is involved in the mechanism by which rapamycin delays cell senescence. In wild-type (WT) mouse fibroblasts, rapamycin increased the levels of Nrf2, and this correlates with the activation of autophagy and a reduction in the induction of cell senescence, as measured by SA-β-galactosidase (β-gal) staining, senescence-associated secretory phenotype (SASP), and p16 and p21 molecular markers. In Nrf2KO fibroblasts, however, rapamycin still decreased β-gal staining and the SASP, but rapamycin did not activate the autophagy pathway or decrease p16 and p21 levels. These observations were further confirmed in vivo using Nrf2KO mice, where rapamycin treatment led to a decrease in β-gal staining and pro-inflammatory cytokines in serum and fat tissue; however, p16 levels were not significantly decreased in fat tissue. Consistent with literature demonstrating that the Stat3 pathway is linked to the production of SASP, we found that rapamycin decreased activation of the Stat3 pathway in cells or tissue samples from both WT and Nrf2KO mice. Our data thus suggest that cell senescence is a complex process that involves at least two arms, and rapamycin uses Nrf2 to regulate cell cycle arrest, but not the production of SASP. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Stromal Gene Expression and Function in Primary Breast Tumors that Metastasize to Bone Cancer

DTIC Science & Technology

2006-07-01

surrounding bone microenvironment were investigated by purifying endothelial cells from tumor-burdened and non-tumor burdened spines . 4T1...of Balb/c mice. Fresh resected tissue (normal fat pad, primary tumor tissue or the metastatic sites spine , femur and lung) was obtained and cell... Hedgehog signalling pathway: Lasp1, CREBBP/EP300 inhibitory protein 1 and FoxP1. Of interest as well are a number of differentially regulated ESTs

Corn silk maysin ameliorates obesity in vitro and in vivo via suppression of lipogenesis, differentiation, and function of adipocytes.

PubMed

Lee, Chang Won; Seo, Jeong Yeon; Kim, Sun-Lim; Lee, Jisun; Choi, Ji Won; Park, Yong Il

2017-09-01

Present study was aimed to investigate the potential anti-obesity effects of maysin, a major flavonoid of corn silk, in vitro and in vivo using 3T3-L1 preadipocyte cells and C57BL/6 mice. Maysin decreased the levels of intracellular lipid droplets and triglycerides (TG), and down-regulated the protein expression levels of C/EBP-β, C/EBP-α, PPAR-γ, and aP2 in 3T3-L1 preadipocyte cells, suggesting that maysin inhibits lipid accumulation and adipocyte differentiation. In addition, maysin was shown to induce the apoptotic cell death in 3T3-L1 preadipocyte cells via activation of caspase cascades and mitochondrial dysfunction, which may ultimately lead to reduction of adipose tissue mass. Furthermore, oral administration of maysin (25mg/kg body weight) decreased weight gain and epididymal fat weight in high-fat diet (HFD)-fed C57BL/6 mice. Administration of maysin also reduced serum levels of TG, total-cholesterol, LDL-cholesterol, and glucose. Taken collectively, these results suggest for the first time that the purified maysin exerts an anti-obesity effect in vitro and in vivo. These observations may support the applicability of maysin as a potent functional ingredient in health-beneficial foods or as a therapeutic agent to prevent or treat obesity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Variation in PPARG is associated with longitudinal change in insulin resistance in Mexican Americans at risk for type 2 diabetes.

PubMed

Black, Mary Helen; Wu, Jun; Takayanagi, Miwa; Wang, Nan; Taylor, Kent D; Haritunians, Talin; Trigo, Enrique; Lawrence, Jean M; Watanabe, Richard M; Buchanan, Thomas A; Xiang, Anny H

2015-03-01

Peroxisome proliferator-activated receptor gamma (PPARG) is a susceptibility locus for type 2 diabetes mellitus (T2DM). Although cross-sectional associations have been reported, primarily for Pro12Ala, few longitudinal studies in nondiabetic populations have been conducted. This study aimed to examine whether and to what extent variation in PPARG is associated with longitudinal changes in anthropometric and metabolic traits in Mexican Americans at risk for T2DM. Subjects were participants of BetaGene, a family-based study of obesity, insulin resistance, and β-cell function, who completed a baseline and follow-up study visit (n = 378; mean followup, 4.6 ± 1.5 y). Phenotypes included body fat assessed by dual-energy x-ray absorptiometry; insulin sensitivity (SI), acute insulin response, and β-cell function (disposition index; DI) were estimated from iv glucose tolerance tests with Minimal Model analysis. Eighteen tag single nucleotide polymorphisms (SNPs) capturing variation in a 156-kb region surrounding PPARG were tested for association with changes in longitudinal traits. P-values were Bonferroni-corrected for multiple testing. Six SNPs (rs2972164, rs11128598, rs17793951, rs1151996, rs1175541, rs3856806) were significantly associated with rate of change in SI after adjustment for age, sex, and body fat percentage, but not with changes in adiposity. rs17793951 also had a significant effect on change in DI over time. Association between rs1175541 and change in SI varied by changes in adiposity such that only carriers of the minor allele who reduced body fat over followup improved SI. rs1306470 (captured Pro12Ala, r(2) = 0.9) was not associated with rates of change in any traits and its effects were not modified by changes in adiposity. Variation in PPARG, but not Pro12Ala, contributes to declining SI and concomitant deterioration in β-cell function in Mexican Americans at risk for T2DM.

The engulfment receptor Draper is required for autophagy during cell death.

PubMed

McPhee, Christina K; Baehrecke, Eric H

2010-11-01

Autophagy is a process to degrade and recycle cytoplasmic contents. Autophagy is required for survival in response to starvation, but has also been associated with cell death. How autophagy functions during cell survival in some contexts and cell death in others is unknown. Drosophila larval salivary glands undergo programmed cell death requiring autophagy genes, and are cleared in the absence of known phagocytosis. Recently, we demonstrated that Draper (Drpr), the Drosophila homolog of C. elegans engulfment receptor CED-1, is required for autophagy induction: during cell death, but not during cell survival. drpr mutants fail to clear salivary glands. drpr knockdown in salivary glands prevents the induction of autophagy, and Atg1 misexpression in drpr null mutants suppresses salivary gland persistence. Surprisingly, drpr knockdown cell-autonomously prevents autophagy induction in dying salivary gland cells, but not in larval fat body cells following starvation. This is the first engulfment factor shown to function in cellular self-clearance, and the first report of a cell-death-specific autophagy regulator.

Regulation of peroxisome proliferator-activated receptor gamma on milk fat synthesis in dairy cow mammary epithelial cells.

PubMed

Liu, Lili; Lin, Ye; Liu, Lixin; Wang, Lina; Bian, Yanjie; Gao, Xuejun; Li, Qingzhang

2016-12-01

Peroxisome proliferator-activated receptor gamma (PPARγ) participates in lipogenesis in rats, goats, and humans. However, the exact mechanism of PPARγ regulation on milk fat synthesis in dairy cow mammary epithelial cells (DCMECs) remains largely unexplored. The aim of this study was to investigate the role of PPARγ regarding milk fat synthesis in DCMECs and to ascertain whether milk fat precursor acetic acid and palmitic acid could interact with PPARγ signaling to regulate milk fat synthesis. For this study, we examined the effects of PPARγ overexpression and gene silencing on cell growth, triacylglycerol synthesis, and the messenger RNA (mRNA) and protein expression levels of genes involved in milk fat synthesis in DCMECs. In addition, we investigated the influences of acetic acid and palmitic acid on the mRNA and protein levels of milk lipogenic genes and triacylglycerol synthesis in DCMECs transfected with PPARγ small interfering RNA (siRNA) and PPARγ expression vector. The results showed that when PPARγ was silenced, cell viability, proliferation, and triacylglycerol secretion were obviously reduced. Gene silencing of PPARγ significantly downregulated the expression levels of milk fat synthesis-related genes in DCMECs. PPARγ overexpression improved cell viability, proliferation, and triacylglycerol secretion. The expression levels of milk lipogenic genes were significantly increased when PPARγ was overexpressed. Acetic acid and palmitic acid could markedly improve triacylglycerol synthesis and upregulate the expression levels of PPARγ and other lipogenic genes in DCMECs. These results suggest that PPARγ is a positive regulator of milk fat synthesis in DCMECs and that acetic acid and palmitic acid could partly regulate milk fat synthesis in DCMECs via PPARγ signaling.

Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

PubMed

Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

2012-06-01

A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

New data on harmful effects of trans-fatty acids.

PubMed

Ginter, E; Simko, V

2016-01-01

Various margarines containing trans-fatty acids were marketed as being healthier because of the absence of cholesterol, suggesting to use margarine instead of butter. Fifteen years ago, research documented the grave health risk of trans-fats (T-fat). US FDA in 2015 finalized its decision that T-fat is not safe and set a three-year time limit for complete removal of T-fat from all foods. The greatest danger from T-fat lies in its capacity to distort the cell membranes. The primary health risk identified for T-fat consumption is an elevated risk of coronary heart disease. T-fats have an adverse effect on the brain and nervous system. T-fat from the diet is incorporated into brain cell membranes and alter the ability of neurons to communicate. This can diminish mental performance. Relationship between T-fat intake and depression risk was observed. There is growing evidence for a possible role of T-fat in the development of Alzheimer´s disease and cognitive decline with age.

Differential activation of Fyn kinase distinguishes saturated and unsaturated fats in mouse macrophages

PubMed Central

Tarabra, Elena; An Lee, Ting-Wen; Zammit, Victor A.; Vatish, Manu; Yamada, Eijiro; Pessin, Jeffrey E.; Bastie, Claire C.

2017-01-01

Diet-induced obesity is associated with increased adipose tissue activated macrophages. Yet, how macrophages integrate fatty acid (FA) signals remains unclear. We previously demonstrated that Fyn deficiency (fynKO) protects against high fat diet-induced adipose tissue macrophage accumulation. Herein, we show that inflammatory markers and reactive oxygen species are not induced in fynKO bone marrow-derived macrophages exposed to the saturated FA palmitate, suggesting that Fyn regulates macrophage function in response to FA signals. Palmitate activates Fyn and re-localizes Fyn into the nucleus of RAW264.7, J774 and wild-type bone marrow-derived macrophages. Similarly, Fyn activity is increased in cells of adipose tissue stromal vascular fraction of high fat-fed control mice, with Fyn protein being located in the nucleus of these cells. We demonstrate that Fyn modulates palmitate-dependent oxidative stress in macrophages. Moreover, Fyn catalytic activity is necessary for its nuclear re-localization and downstream effects, as Fyn pharmacological inhibition abolishes palmitate-induced Fyn nuclear redistribution and palmitate-dependent increase of oxidative stress markers. Importantly, mono-or polyunsaturated FAs do not activate Fyn, and fail to re-localize Fyn to the nucleus. Together these data demonstrate that macrophages integrate nutritional FA signals via a differential activation of Fyn that distinguishes, at least partly, the effects of saturated versus unsaturated fats. PMID:29156823

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

PubMed Central

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

2013-01-01

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

Proteome profile and biological activity of caprine, bovine and human milk fat globules.

PubMed

Spertino, Stefano; Cipriani, Valentina; De Angelis, Chiara; Giuffrida, Maria Gabriella; Marsano, Francesco; Cavaletto, Maria

2012-04-01

Upon combining bidimensional electrophoresis with monodimensional separation, a more comprehensive analysis of the milk fat globule membrane has been obtained. The proteomic profile of caprine milk fat globules revealed the presence of butyrophilin, lactadherin and perilipin as the major proteins, they were also associated to bovine and human milk fat globule membranes. Xanthine dehydrogenase/oxidase has been detected only in monodimensional gels. Biological activity of milk fat globules has been evaluated in Caco2-cells, as a representative model of the intestinal barrier. The increase of cell viability was indicative of a potential nutraceutical role for the whole milk fat globule, suggesting a possible employment in milk formula preparation.

The Functional SNPs in the 5’ Regulatory Region of the Porcine PPARD Gene Have Significant Association with Fat Deposition Traits

PubMed Central

Hu, Shanyao; Lin, Bin; Yan, Dechao; Xu, Zaiyan; Zhang, Zijun; Mao, Yuanliang; Mao, Huimin; Wang, Litong; Wang, Guoshui; Xiong, Yuanzhu; Zuo, Bo

2015-01-01

Peroxisome proliferator-activated receptor delta (PPARD) is a key regulator of lipid metabolism, insulin sensitivity, cell proliferation and differentiation. In this study, we identified two Single Nucleotide Polymorphisms (SNPs, g.1015 A>G and g.1018 T>C) constituting four haplotypes (GT, GC, AC and AT) in the 5’ regulatory region of porcine PPARD gene. Functional analysis of the four haplotypes showed that the transcriptional activity of the PPARD promoter fragment carrying haplotype AC was significantly lower than that of the other haplotypes in 3T3-L1, C2C12 and PK-15 cells, and haplotype AC had the lowest binding capacities to the nuclear extracts. Transcription factor 7-like 2 (TCF7L2) enhanced the transcription activities of promoter fragments of PPARD gene carrying haplotypes GT, GC and AT in C2C12 and 3T3-L1 cells, and increased the protein expression of PPARD gene in C2C12 myoblasts. TCF7L2 differentially bound to the four haplotypes, and the binding capacity of TCF7L2 to haplotype AC was the lowest. There were significant associations between -655A/G and fat deposition traits in three pig populations including the Large White × Meishan F2 pigs, France and American Large White pigs. Pigs with genotype GG had significantly higher expression of PPARD at both mRNA and protein level than those with genotype AG. These results strongly suggested that the SNPs in 5’ regulatory region of PPARD genes had significant impact on pig fat deposition traits. PMID:26599230

The fake fat phenomenon in organizing pleuritis: a source of confusion with desmoplastic malignant mesotheliomas.

PubMed

Churg, Andrew; Cagle, Philip; Colby, Thomas V; Corson, Joseph M; Gibbs, Allen R; Hammar, Samuel; Ordonez, Nelson; Roggli, Victor L; Tazelaar, Henry D; Travis, William D; Wick, Mark

2011-12-01

We report 9 patients with pleural biopsies referred because of concern about infiltration of what appeared to be chest wall fat by pan-keratin-positive spindled cells, a finding that led to a consideration of desmoplastic mesothelioma. All patients showed pleural effusions/pleural thickening on computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic paucicellular pleura with circular fat-like spaces and, sometimes, adjacent oblate spaces mostly deep in the fibrotic area. Indistinct, keratin-positive, spindle cells arranged parallel to the pleural surface coursed between these fat-like spaces. S-100 stains were negative around the fat-like spaces. Vimentin stains showed that the spaces did not have a cellular lining of any kind. Sometimes the spaces contained faintly hematoxyphilic material that was Alcian blue positive, and similar material was seen in the fibrotic stroma. Follow-up with periods ranging from 6 to 30 months revealed that 8 cases had stable disease on chest imaging or by clinical findings. One case had slowly progressive pleural thickening. These observations suggest that spaces resembling fat may be encountered in fibrotic pleurae and that horizontally oriented keratin-positive spindled cells between the fat-like spaces deep in the fibrotic portion of a thickened pleura represent a benign finding seen in some cases of organizing pleuritis/fibrothorax. The spaces themselves are probably artifacts derived from the biopsy procedure and/or cutting artifacts. In contrast, in true desmoplastic mesotheliomas there is downward, rather than horizontal, growth of keratin-positive spindled cells running between clearly definable fat cells.

Gene-activated fat grafts for the repair of spinal cord injury: a pilot study.

PubMed

Betz, Volker M; Sitoci-Ficici, K Hakan; Uckermann, Ortrud; Leipnitz, Elke; Iltzsche, Anne; Thirion, Christian; Salomon, Michael; Zwipp, Hans; Schackert, Gabriele; Betz, Oliver B; Kirsch, Matthias

2016-02-01

Spinal cord injury (SCI) is a complex disease requiring a concerted multi-target approach. The most appropriate combination of therapeutic gene, cellular vehicle, and space filling scaffold still has to be determined. We present an approach that employs syngeneic adipose tissue serving as a three-dimensional biological implant, source of progenitor cells, and delivery system for therapeutic genes. In this pilot experiment, we evaluated the feasibility and short-term effects using gene-activated autologous fat grafts after SCI. An experimental SCI model was established in syngeneic Fischer 344 rats by a T9-T10 hemimyelonectomy. Fat tissue was harvested from two donor rats. Animals were divided into four groups and treated with either (i) fat grafts activated by an adenoviral vector carrying the human NT-3 cDNA, (ii) or BDNF, (iii) or with untreated fat grafts or (iv) remained untreated. Animals were euthanized either 7 or 21 days after surgery, and spinal cord tissue was investigated by histological and immunohistochemical methods. NT-3 and BDNF were produced by gene-activated fat grafts for at least 21 days in vitro and in vivo. Fat tissue grafts remained stable at the site of implantation at 7 days and at 21 days. Neither BDNF-activated nor NT-3-activated fat graft had a detectable limiting effect on the neuronal degeneration. BDNF recruited microglia to perilesional site and attenuated their inflammatory response. Gene-activated syngeneic fat tissue serves as a three-dimensional biological material delivering therapeutic molecules to the site of SCI over an extended period of time. The BDNF-fat graft attenuated the inflammatory response. Whether these findings translate into functional recovery will require extended observation times.

Microfiltration of raw whole milk to select fractions with different fat globule size distributions: process optimization and analysis.

PubMed

Michalski, M C; Leconte, N; Briard-Bion, V; Fauquant, J; Maubois, J L; Goudédranche, H

2006-10-01

We present an extensive description and analysis of a microfiltration process patented in our laboratory to separate different fractions of the initial milk fat globule population according to the size of the native milk fat globules (MFG). We used nominal membrane pore sizes of 2 to 12 microm and a specially designed pilot rig. Using this process with whole milk [whose MFG have a volume mean diameter (d43) = 4.2 +/- 0.2 microm] and appropriate membrane pore size and hydrodynamic conditions, we collected 2 extremes of the initial milk fat globule distribution consisting of 1) a retentate containing large MFG of d43 = 5 to 7.5 microm (with up to 250 g/kg of fat, up to 35% of initial milk fat, and up to 10% of initial milk volume), and 2) a permeate containing small MFG of d43 = 0.9 to 3.3 microm (with up to 16 g/kg of fat, up to 30% of initial milk fat, and up to 83% of initial milk volume and devoid of somatic cells). We checked that the process did not mechanically damage the MFG by measuring their zeta-potential. This new microfiltration process, avoiding milk aging, appears to be more efficient than gravity separation in selecting native MFG of different sizes. As we summarize from previous and new results showing that the physico-chemical and technological properties of native milk fat globules vary according to their size, the use of different fat globule fractions appears to be advantageous regarding the quality of cheeses and can lead to new dairy products with adapted properties (sensory, functional, and perhaps nutritional).

High-Fat-Diet-Induced Deficits in Dopamine Terminal Function Are Reversed by Restoring Insulin Signaling.

PubMed

Fordahl, Steve C; Jones, Sara R

2017-02-15

Systemically released insulin crosses the blood-brain barrier and binds to insulin receptors on several neural cell types, including dopaminergic neurons. Insulin has been shown to decrease dopamine neuron firing in the ventral tegmental area (VTA), but potentiate release and reuptake at dopamine terminals in the nucleus accumbens (NAc). Here we show that prolonged consumption of a high fat diet blocks insulin's effects in the NAc, but insulin's effects are restored by inhibiting protein tyrosine phosphatase 1B, which supports insulin receptor signaling. Mice fed a high fat diet (60% kcals from fat) displayed significantly higher fasting blood glucose 160 mg/dL, compared to 101 mg/dL for control-diet-fed mice, and high-fat-diet-fed mice showed reduced blood glucose clearance after an intraperitoneal glucose tolerance test. Using fast scan cyclic voltammetry to measure electrically evoked dopamine in brain slices containing the NAc core, high-fat-diet-fed mice exhibited slower dopamine reuptake compared to control-diet-fed mice (2.2 ± 0.1 and 2.67 ± 0.15 μM/s, respectively). Moreover, glucose clearance rate was negatively correlated with V max . Insulin (10 nM to 1 μM) dose dependently increased reuptake rates in control-diet-fed mice compared with in the high-fat-diet group; however, the small molecule insulin receptor sensitizing agent, TCS 401 (300 nM), restored reuptake in high-fat-diet-fed mice to control-diet levels, and a small molecule inhibitor of the insulin receptor, BMS 536924 (300 nM), attenuated reuptake, similar to high-fat-diet-fed mice. These data show that a high-fat diet impairs dopamine reuptake by attenuating insulin signaling at dopamine terminals.

[Effect of early high fat diet on pancreatic β cellularity and insulin sensibility in young rats].

PubMed

Xie, Kun-Xia; Xiao, Yan-Feng; Xu, Er-Di; Yin, Chun-Yan; Yi, Xiao-Qing; Chang, Ming

2010-09-01

To study the effects of early high fat diet on sugar metaboliam, insulin sensibility and pancreatic β cellularity in young rats. Sixty male weaned young rats were randomly fed with high fat diet (high fat group) and normal diet (control group). The body weight, viscus fattiness and fasting plasma glucose (FPG) were measured after 3, 6 and 9 weeks. Serum insulin level was measured with radioimmunoassay. The ultrastructure of pancreas was observed under an electricmicroscope. The high fat group had significantly higher body weight and visceral fat weight than the control group after 3 weeks. There were no significant differences in the FPG level between the two groups at all time points. The levels of fasting insulin and HOMAIR in the high fat group were significantly higher than those in the control group after 3, 6 and 9 weeks (P<0.01). Dilation of rough endoplasmic reticulum and mild swelling of mitochondria of islet β-cells were observed in the high fat group after 6 weeks. Early high fat diet may induce a reduction in insulin sensitivity and produce insulin resistance in young rats. Endoplasmic reticulum expansion in β-cells may be an early sign of β-cell damage due to obesity.

Expanded Stem Cells, Stromal-Vascular Fraction, and Platelet-Rich Plasma Enriched Fat: Comparing Results of Different Facial Rejuvenation Approaches in a Clinical Trial

PubMed Central

Rigotti, Gino; Charles-de-Sá, Luiz; Gontijo-de-Amorim, Natale Ferreira; Takiya, Christina Maeda; Amable, Paola Romina; Borojevic, Radovan; Benati, Donatella; Bernardi, Paolo; Sbarbati, Andrea

2016-01-01

Background In a previous study, the authors demonstrated that treatment with expanded adipose-derived stem cells or stromal vascular fraction (SVF)-enriched fat modify the pattern of the dermis in human beings, representing a skin rejuvenation effect. Considering that expanded stem cells require a cell factor, the authors wanted to assess similar results by replacing them with platelet-rich plasma (PRP), which is easier to obtain and for which an empirical regenerative effect has been already described. Objectives To determine if PRP injection could replace the cutaneous regenerative effect of adipose-derived stem cells. Methods This study was performed in 13 patients who were candidates for facelift. The patients underwent sampling of fat by liposuction from the abdomen and submitted to one of three protocols: injection of SVF-enriched fat or expanded adipose-derived stem cells or fat plus PRP in the preauricular areas. Fragments of skin were removed before and 3 months after treatment and analyzed by optical and electron microscopy. Results The use of fat plus PRP led to the presence of more pronounced inflammatory infiltrates and a greater vascular reactivity, increasing in vascular permeability and a certain reactivity of the nervous component. The addition of PRP did not improve the regenerative effect. Conclusion The use of PRP did not have significant advantages in skin rejuvenation over the use of expanded adipose-derived stem cells or SVF-enriched fat. The effect of increased vascular reactivity may be useful in pathological situations in which an intense angiogenesis is desirable, such as tissular ischemia. Level of Evidence: 4 Therapeutic PMID:26879294

Low osmolality and shear stress during liposuction impair cell viability in autologous fat grafting.

PubMed

Ismail, T; Bürgin, J; Todorov, A; Osinga, R; Menzi, N; Largo, R D; Haug, M; Martin, I; Scherberich, A; Schaefer, D J

2017-05-01

Liposuction and subsequent autologous fat grafting have become essential techniques for fat augmentation in plastic surgery. However, standard harvesting techniques that ensure the survival of adipocytes and stromal vascular fraction (SVF) cells and thus preserve the transplanted fat volume are lacking. In particular, the effect of different parameters of the tumescent solution has not been studied in this context. We hypothesized that the osmolality of the tumescent solution could have a significant effect on the survival of adipocytes and SVF cells. We developed two distinct in vitro models based on freshly harvested excision fat from patients undergoing surgical treatment. First, we investigated the effect of osmolality by incubating excision fat in different tumescent solutions and analyzed the total cell survival and the differentiation potential of SVF cells. Vital whole-mount staining, isolation yield of SVF cells, clonogenicity, and osteogenic and adipogenic differentiation capacities were analyzed. Second, we addressed the additional effect of mechanical stress by simulating a liposuction on pieces of excision fat after incubation with the tumescent solutions. Osmolality of the tumescent solution by itself did not have a significant effect on adipocyte and SVF viability or SVF differentiation. However, when osmolality was combined with liposuction, a significant trend toward lower viability and more lipid droplets with lower osmolality was observed. Especially, SVF viability was significantly lower after liposuction with a hypotonic (150 mOsm/kg) solution. This study demonstrates the considerable effect of osmolality during liposuction and may lead to the development of "cell-protective" tumescent solutions. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

A bilaminated decellularized scaffold for islet transplantation: Structure, properties and functions in diabetic mice.

PubMed

Wang, Xi; Wang, Kai; Zhang, Wei; Qiang, Ming; Luo, Ying

2017-09-01

Ectopic transplantation of islets provides a beta cell-replacement approach that may allow the recovery of physiological regulation of the blood sugar level in patients with Type I diabetes (T1D). In development of new extrahepatic islet transplantation protocols in support of the islet engraftment, it is pivotal to develop scaffold materials with multifaceted functions to provide beneficial microenvironment, mediate host response in favor of vascularization/islet integration and maintain long-term islet function at the transplantation site. In this study, a new composite bilaminar decellularized scaffold (CDS) was fabricated with differential structural, degradation and mechanical properties by the combination of a fast-degrading porous collagen matrix and a mechanically supportive porcine pericardium. When investigated in the epididymal fat pad in syngeneic mouse models, it was shown that CDS could serve as superior scaffolds to promote islet adhesion and viability, and islet-CDS constructs also allowed rapid reversal of the hyperglycemic condition in the host. The engraftment and effects of islets were achieved at low islet numbers, accompanied by minimal adverse tissue reactions and optimal islet integration with the surrounding fat tissue. The bioactive surface, mechanical/chemical durability and biocompatibility of the CDS may all have played important roles in facilitating the engraftment of islets. Our study provided new insights into scaffold's function in the interplay of cells, materials and host tissue and the extracellular matrix-based scaffolds have potential for clinical translation in the beta cell-replacement therapy to treat T1D. Copyright © 2017 Elsevier Ltd. All rights reserved.

β-Cell lipotoxicity after an overnight intravenous lipid challenge and free fatty acid elevation in African American versus American white overweight/obese adolescents.

PubMed

Hughan, Kara S; Bonadonna, Riccardo C; Lee, SoJung; Michaliszyn, Sara F; Arslanian, Silva A

2013-05-01

Overweight/obese (OW/OB) African American (AA) adolescents have a more diabetogenic insulin secretion/sensitivity pattern compared with their American white (AW) peers. The present study investigated β-cell lipotoxicity to test whether increased free fatty acid (FFA) levels result in greater β-cell dysfunction in AA vs AW OW/OB adolescents. Glucose-stimulated insulin secretion was modeled, from glucose and C-peptide concentrations during a 2-hour hyperglycemic (225 mg/dL) clamp in 22 AA and 24 AW OW/OB adolescents, on 2 occasions after a 12-hour overnight infusion of either normal saline or intralipid (IL) in a random sequence. β-Cell function relative to insulin sensitivity, the disposition index (DI), was examined during normal saline and IL conditions. Substrate oxidation was evaluated with indirect calorimetry and body composition and abdominal adiposity with dual-energy X-ray absorptiometry and magnetic resonance imaging at L4-L5, respectively. Age, sex, body mass index, total and sc adiposity were similar between racial groups, but visceral adiposity was significantly lower in AAs. During IL infusion, FFAs and fat oxidation increased and insulin sensitivity decreased similarly in AAs and AWs. β-Cell glucose sensitivity of first- and second-phase insulin secretion did not change significantly during IL infusion in either group, but DI in each phase decreased significantly and similarly in AAs and AWs. Overweight/obese AA and AW adolescents respond to an overnight fat infusion with significant declines in insulin sensitivity, DI, and β-cell function relative to insulin sensitivity, suggestive of β-cell lipotoxicity. However, contrary to our hypothesis, there does not seem to be a race differential in β-cell lipotoxicity. Longer durations of FFA elevation may unravel such race-related contrasts.

JNK Activation of BIM Promotes Hepatic Oxidative Stress, Steatosis, and Insulin Resistance in Obesity.

PubMed

Litwak, Sara A; Pang, Lokman; Galic, Sandra; Igoillo-Esteve, Mariana; Stanley, William J; Turatsinze, Jean-Valery; Loh, Kim; Thomas, Helen E; Sharma, Arpeeta; Trepo, Eric; Moreno, Christophe; Gough, Daniel J; Eizirik, Decio L; de Haan, Judy B; Gurzov, Esteban N

2017-12-01

The members of the BCL-2 family are crucial regulators of the mitochondrial pathway of apoptosis in normal physiology and disease. Besides their role in cell death, BCL-2 proteins have been implicated in the regulation of mitochondrial oxidative phosphorylation and cellular metabolism. It remains unclear, however, whether these proteins have a physiological role in glucose homeostasis and metabolism in vivo. In this study, we report that fat accumulation in the liver increases c-Jun N-terminal kinase-dependent BCL-2 interacting mediator of cell death (BIM) expression in hepatocytes. To determine the consequences of hepatic BIM deficiency in diet-induced obesity, we generated liver-specific BIM-knockout (BLKO) mice. BLKO mice had lower hepatic lipid content, increased insulin signaling, and improved global glucose metabolism. Consistent with these findings, lipogenic and lipid uptake genes were downregulated and lipid oxidation enhanced in obese BLKO mice. Mechanistically, BIM deficiency improved mitochondrial function and decreased oxidative stress and oxidation of protein tyrosine phosphatases, and ameliorated activation of peroxisome proliferator-activated receptor γ/sterol regulatory element-binding protein 1/CD36 in hepatocytes from high fat-fed mice. Importantly, short-term knockdown of BIM rescued obese mice from insulin resistance, evidenced by reduced fat accumulation and improved insulin sensitivity. Our data indicate that BIM is an important regulator of liver dysfunction in obesity and a novel therapeutic target for restoring hepatocyte function. © 2017 by the American Diabetes Association.

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

PubMed Central

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

2014-01-01

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

Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

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

Kanno, Ayumi, E-mail: akanno@med.kobe-u.ac.jp; Asahara, Shun-ichiro, E-mail: asahara@med.kobe-u.ac.jp; Masuda, Katsuhisa, E-mail: katsuhisa.m.0707@gmail.com

A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage ofmore » insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.« less

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

USDA-ARS?s Scientific Manuscript database

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...

Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice.

PubMed

Wang, Xiaoyu; Zhao, Shiqi; Su, Mengqi; Sun, Li; Zhang, Song; Wang, Dingyu; Liu, Zhaorui; Yuan, Yue; Liu, Yang; Li, Yue

2016-05-20

Endothelial dysfunction occurs in obese patients and high-fat diet (HFD) fed experimental animals. While geraniol has been reported to ameliorate inflammation and oxidative stress, inhibit tumor cell proliferation, and improve atherosclerosis, its direct effect on endothelial function remains uncharacterized. The present study therefore investigated the effect of geraniol on endothelial function in HFD mice and its underlying mechanisms. C57 BL/6 mice were fed an HFD (n = 40) or a normal diet (n = 20) for 8 weeks. HFD fed mice then were randomized to intraperitoneal treatment with geraniol (n = 20) or vehicle (n = 20) for another 6 weeks. Acetylcholine (Ach)-induced endothelial dependent vasorelaxation was measured on wire myography; reactive oxygen species (ROS) generation was assessed by fluorescence imaging, and NADPH oxidases (NOXs) and adhesive molecules VCAM-1 and ICAM-1 protein expression by western blotting. Geraniol improved endothelial function in HFD fed mice, as evidenced by its: 1. restoring endothelial dependent vasorelaxation induced by Ach, and reversing increased VCAM-1 and ICAM-1 expression; 2. attenuating HFD induced increased serum TBARS and aortic ROS generation; and 3. downregulating aortic NOX-2 expression in both HFD fed mice and in palmitic acid treated endothelial cells. Geraniol therefore protects against endothelial dysfunction induced by HFD through reducing NOX-2 associated ROS generation. Copyright © 2016 Elsevier Inc. All rights reserved.

Obesity suppresses circulating level and function of endothelial progenitor cells and heart function

PubMed Central

2012-01-01

Background and aim This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs) and left ventricular ejection fraction (LVEF). Methods High fat diet (45 Kcal% fat) was given to 8-week-old C57BL/6 J mice (n = 8) for 20 weeks to induce obesity (group 1). Another age-matched group (n = 8) were fed with control diet for 20 weeks as controls (group 2). The animals were sacrificed at the end of 20 weeks after obesity induction. Results By the end of study period, the heart weight, body weight, abdominal fat weight, serum levels of total cholesterol and fasting blood sugar were remarkably higher in group 1 than in group 2 (all p<0.01). The circulating level of EPCs (C-kit/CD31, Sca-1/KDR, CXCR4/CD34) was significantly lower in group 1 than in group 2 (p<0.03) at 18 h after critical limb ischemia induction. The angiogenesis and migratory ability of bone marrow-derived EPCs was remarkably impaired in group 1 compared to that in group 2 (all p<0.01). The repair ability of aortic endothelium damage by lipopolysaccharide was notably attenuated in group 1 compared with that in group 2 (p<0.01). Collagen deposition (Sirius red staining) and fibrotic area (Masson's Trichrome staining) in LV myocardium were notably increased in group 1 compared with group 2 (p<0.001). LVEF was notably lower, whereas LV end-diastolic and end-systolic dimensions were remarkably higher in group 1 than in group 2 (all p<0.001). Conclusions Obesity diminished circulating EPC level, impaired the recovery of damaged endothelium, suppressed EPC angiogenesis ability and LVEF, and increased LV remodeling. PMID:22747715

Commercialization opportunities of oleogels for functional foods

USDA-ARS?s Scientific Manuscript database

Oleogels (or organogels) have been recognized as very promising candidates as trans fat and saturated fat replacements. Not only can the oleogel technology remove harmful fats in foods, but it also can produce a variety of functional foods when functional ingredients such as omega-3 oil, phytosterol...

The effect of polarity of extractives on the durability of wood

Treesearch

Roderquita K. Moore; Jonathan Smaglick; Erick Arellano-ruiz; Michael Leitch; Doreen Mann

2015-01-01

Extractives are low molecular weight compounds and regarded as nonstructural wood constituents. These compounds are present in trees and can be extracted by organic solvents. Extractives consist of several classes of compounds that diversify the biological function of the tree. Fats are an energy source for the wood cells whereas terpenoids, resin acids, and phenolic...

High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice.

PubMed

Chang, Seo-Na; Han, Juhee; Abdelkader, Tamer Said; Kim, Tae-Hyoun; Lee, Ji Min; Song, Juha; Kim, Kyung-Sul; Park, Jong-Hwan; Park, Jae-Hak

2014-09-01

Prostate cancer is the most frequently diagnosed cancer in Western men, and more men have been diagnosed at younger ages in recent years. A high-fat Western-style diet is a known risk factor for prostate cancer and increases oxidative stress. We evaluated the association between dietary animal fat and expression of antioxidant enzymes, particularly glutathione peroxidase 3 (GPx3), in the early stages of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Six-week-old male nontransgenic and TRAMP mice were placed on high animal fat (45% Kcal fat) or control (10% Kcal fat) diets and sacrificed after 5 or 10 weeks. The histopathological score increased with age and high-fat diet consumption. The histopathological scores in dorsal and lateral lobes increased in the 10-week high-fat diet group (6.2±0.2 and 6.2±0.4, respectively) versus the 10-week control diet group (5.3±0.3 and 5.2±0.2, respectively). GPx3 decreased both at the mRNA and protein levels in mouse prostate. GPx3 mRNA expression decreased (∼36.27% and ∼23.91%, respectively) in the anterior and dorsolateral prostate of TRAMP mice fed a high-fat diet compared to TRAMP mice fed a control diet. Cholesterol treatment increased PC-3 human prostate cancer cell proliferation, decreased GPx3 mRNA and protein levels, and increased H2 O2 levels in culture medium. Moreover, increasing GPx3 mRNA expression by troglitazone in PC-3 cells decreased cell proliferation and lowered H2 O2 levels. Dietary fat enhances prostate cancer progression, possibly by suppressing GPx3 expression and increasing proliferation of prostate intraepithelial neoplasia (PIN) epithelial cells. © 2014 Wiley Periodicals, Inc.

Retromer Ensures the Degradation of Autophagic Cargo by Maintaining Lysosome Function in Drosophila.

PubMed

Maruzs, Tamás; Lőrincz, Péter; Szatmári, Zsuzsanna; Széplaki, Szilvia; Sándor, Zoltán; Lakatos, Zsolt; Puska, Gina; Juhász, Gábor; Sass, Miklós

2015-10-01

The retromer is an evolutionarily conserved coat complex that consists of Vps26, Vps29, Vps35 and a heterodimer of sorting nexin (Snx) proteins in yeast. Retromer mediates the recycling of transmembrane proteins from endosomes to the trans-Golgi network, including receptors that are essential for the delivery of hydrolytic enzymes to lysosomes. Besides its function in lysosomal enzyme receptor recycling, involvement of retromer has also been proposed in a variety of vesicular trafficking events, including early steps of autophagy and endocytosis. Here we show that the late stages of autophagy and endocytosis are impaired in Vps26 and Vps35 deficient Drosophila larval fat body cells, but formation of autophagosomes and endosomes is not compromised. Accumulation of aberrant autolysosomes and amphisomes in the absence of retromer function appears to be the consequence of decreased degradative capacity, as they contain undigested cytoplasmic material. Accordingly, we show that retromer is required for proper cathepsin L trafficking mainly independent of LERP, the Drosophila homolog of the cation-independent mannose 6-phosphate receptor. Finally, we find that Snx3 and Snx6 are also required for proper autolysosomal degradation in Drosophila larval fat body cells. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Prostaglandin E2 signals white-to-brown adipogenic differentiation

PubMed Central

García-Alonso, Verónica; Clària, Joan

2014-01-01

The formation of new adipocytes from precursor cells is a crucial aspect of normal adipose tissue function. During the adipogenic process, adipocytes differentiated from mesenchymal stem cells give rise to two main types of fat: white adipose tissue (WAT) characterized by the presence of adipocytes containing large unilocular lipid droplets, and brown adipose tissue (BAT) composed by multilocular brown adipocytes packed with mitochondria. WAT is not only important for energy storage but also as an endocrine organ regulating whole body homeostasis by secreting adipokines and other mediators, which directly impact metabolic functions in obesity. By contrast, BAT is specialized in dissipating energy in form of heat and has salutary effects in combating obesity and associated disorders. Unfortunately, WAT is the predominant fat type, whereas BAT is scarce and located in discrete pockets in adult humans. Luckily, another type of brown adipocytes, called beige or brite (brown-in-white) adipocytes, with similar functions to those of “classical” brown adipocytes has recently been identified in WAT. In this review, a close look is given into the role of bioactive lipid mediators in the regulation of adipogenesis, with a special emphasis on the role of the microsomal prostaglandin E (PGE) synthase-1, a terminal enzyme in PGE2 biosynthesis, as a key regulator of white-to-brown adipogenesis in WAT. PMID:26317053

Tissue-Specific Transcriptomics of the Exotic Invasive Insect Pest Emerald Ash Borer (Agrilus planipennis)

PubMed Central

Mittapalli, Omprakash; Bai, Xiaodong; Bonello, Pierluigi; Herms, Daniel A.

2010-01-01

Background The insect midgut and fat body represent major tissue interfaces that deal with several important physiological functions including digestion, detoxification and immune response. The emerald ash borer (Agrilus planipennis), is an exotic invasive insect pest that has killed millions of ash trees (Fraxinus spp.) primarily in the Midwestern United States and Ontario, Canada. However, despite its high impact status little knowledge exists for A. planipennis at the molecular level. Methodology and Principal Findings Newer-generation Roche-454 pyrosequencing was used to obtain 126,185 reads for the midgut and 240,848 reads for the fat body, which were assembled into 25,173 and 37,661 high quality expressed sequence tags (ESTs) for the midgut and the fat body of A. planipennis larvae, respectively. Among these ESTs, 36% of the midgut and 38% of the fat body sequences showed similarity to proteins in the GenBank nr database. A high number of the midgut sequences contained chitin-binding peritrophin (248)and trypsin (98) domains; while the fat body sequences showed high occurrence of cytochrome P450s (85) and protein kinase (123) domains. Further, the midgut transcriptome of A. planipennis revealed putative microbial transcripts encoding for cell-wall degrading enzymes such as polygalacturonases and endoglucanases. A significant number of SNPs (137 in midgut and 347 in fat body) and microsatellite loci (317 in midgut and 571 in fat body) were predicted in the A. planipennis transcripts. An initial assessment of cytochrome P450s belonging to various CYP clades revealed distinct expression patterns at the tissue level. Conclusions and Significance To our knowledge this study is one of the first to illuminate tissue-specific gene expression in an invasive insect of high ecological and economic consequence. These findings will lay the foundation for future gene expression and functional studies in A. planipennis. PMID:21060843

The "starfield" pattern of cerebral fat embolism from bone marrow necrosis in sickle cell crisis.

PubMed

Dhakal, Laxmi P; Bourgeois, Kirk; Barrett, Kevin M; Freeman, William D

2015-04-01

Sickle cell disease may manifest with cerebrovascular and systemic complications. Sickle crisis that results in avascular necrosis of long bones with resultant cerebral fat embolism syndrome is rare and has a characteristic "starfield" pattern on MRI. This "starfield" MRI pattern should raise suspicion for sickle cell crisis in patients without a known history of the disease, which can lead to earlier sickle cell red blood cell exchange transfusion and treatment. We present a case of a male who presented emergently with acute seizure, coma with a characteristic MRI pattern, which lead to the diagnosis of avascular bone marrow necrosis and cerebral fat embolism syndrome from sickle cell crisis.

(-)-Epicatechin-induced recovery of mitochondria from simulated diabetes: Potential role of endothelial nitric oxide synthase.

PubMed

Ramírez-Sánchez, Israel; Rodríguez, Alonso; Moreno-Ulloa, Aldo; Ceballos, Guillermo; Villarreal, Francisco

2016-05-01

(-)-Epicatechin increases indicators associated with mitochondrial biogenesis in endothelial cells and myocardium. We investigated endothelial nitric oxide synthase involvement on (-)-epicatechin-induced increases in indicators associated with mitochondrial biogenesis in human coronary artery endothelial cells cultured in normal-glucose and high-glucose media, as well as to restore indicators of cardiac mitochondria from the effects of simulated diabetes. Here, we demonstrate the role of endothelial nitric oxide synthase on (-)-epicatechin-induced increases in mitochondrial proteins, transcription factors and sirtuin 1 under normal-glucose conditions. In simulated diabetes endothelial nitric oxide synthase function, mitochondrial function-associated and biogenesis-associated indicators were adversely impacted by high glucose, effects that were reverted by (-)-epicatechin. As an animal model of type 2 diabetes, 2-month old C57BL/6 mice were fed a high-fat diet for 16 weeks. Fasting and fed blood glucose levels were increased and NO plasma levels decreased. High-fat-diet-fed mice myocardium revealed endothelial nitric oxide synthase dysfunction, reduced mitochondrial activity and markers of mitochondrial biogenesis. The administration of 1 mg/kg (-)-epicatechin for 15 days by oral gavage shifted these endpoints towards control mice values. Results suggest that endothelial nitric oxide synthase mediates (-)-epicatechin-induced increases of indicators associated with mitochondrial biogenesis in endothelial cells. (-)-Epicatechin also counteracts the negative effects that high glucose or simulated type 2 diabetes has on endothelial nitric oxide synthase function. © The Author(s) 2016.

Maternal fat-soluble vitamins, brain development, and regulation of feeding behavior: an overview of research.

PubMed

Sánchez-Hernández, Diana; Anderson, G Harvey; Poon, Abraham N; Pannia, Emanuela; Cho, Clara E; Huot, Pedro S P; Kubant, Ruslan

2016-10-01

Recent research shows a link between vitamin intake during pregnancy and offspring health. Inadequate intakes of water-soluble vitamins during pregnancy lead to obesity and characteristics of the metabolic syndrome, concurrent with altered developments in food intake regulatory pathways. Few studies, however, have reported on the effects of fat-soluble vitamins (A, D, E, and K) on the development of food intake regulatory pathways. The majority of studies to date have focused on associations between inadequate and high intakes of folic acid and vitamin D and neurocognitive development of the offspring. Hence, the objective of this review is to present an evaluation of the role of maternal vitamins A, D, E, and K in brain development and function of neural pathways that regulate feeding behaviors. PubMed and Google Scholar were searched from 1975 through September, 2016. Most studies supporting a role for fat-soluble vitamins in regulating brain development and associated behaviors have been conducted in animal and cell models, leaving uncertain their relevance to neurocognitive development and function in humans. Nevertheless, although current research on defining the role of maternal fat-soluble vitamins in offspring's brain development is limited, it is sufficient to warrant further investigations on their impact when intake amounts during pregnancy are not only inadequate but also exceed requirements. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of abhydrolase domain containing 5 gene (ABHD5) expression and variations on chicken fat metabolism.

PubMed

Ouyang, Hongjia; Liu, Qing; Xu, Jiguo; Zeng, Fang; Pang, Xiaolin; Jebessa, Endashaw; Liang, Shaodong; Nie, Qinghua; Zhang, Xiquan

2016-01-01

Abhydrolase domain containing 5 gene (ABHD5), also known as comparative gene identification 58 (CGI-58), is a member of the α/β-hydrolase family as a protein cofactor of ATGL stimulating its triacylglycerol hydrolase activity. In this study, we aim to characterize the expression and variations of ABHD5 and to study their functions in chicken fat metabolism. We compared the ABHD5 expression level in various tissues and under different nutrition conditions, identified the variations of ABHD5, and associated them with production traits in an F2 resource population of chickens. Overexpression analysis with two different genotypes and siRNA interfering analysis of ABHD5 were performed in chicken preadipocytes. Chicken ABDH5 was expressed widely and most predominantly in adipose tissue. Five SNPs of the ABHD5 gene were identified and genotyped in the F2 resource population. The c.490C > T SNP was associated with subcutaneous fat thickness (P < 0.01), carcass weight (P < 0.05), body weight (P < 0.05), shank diameter (P < 0.05), and shank length (P < 0.05). The c.423T > C SNP was also associated with chicken body weight (P < 0.05) and shank diameter (P < 0.05). In chicken preadipocytes, overexpression of wild type ABDH5 did not affect the mRNA level of ATGL (adipose triglyceride lipase) but markedly decreased (P < 0.05) the TG (triglyceride) content of the cell, whereas overexpression of mutation type ABHD5 did not affect either ATGL expression or TG content of the cell. The expression of ATGL and TG content of the cell were decreased (P < 0.05) after ABHD5 knockdown in preadipocytes. The mRNA level of ABHD5 was regulated by both feeding and fasting, and by consumption of a high fat diet. It was increased greatly by fasting (P < 0.05) and was returned to control levels after re-feeding in the adipose tissues, and down-regulated in abdominal fat (P < 0.05) and the liver (P < 0.01) of chickens with a high fat diet. These results suggest that expression and variations of ABHD5 may affect fat metabolism through regulating the activity of ATGL in chickens. © 2015 Poultry Science Association Inc.

Study of oleanolic acid on the estrodiol production and the fat production of mouse preadipocyte 3T3-L1 in vitro.

PubMed

Wan, Qian; Lu, Hua; Liu, Xia; Yie, Shangmian; Xiang, Junbei; Yao, Zouying

2015-01-01

The women during the menopause period have an increased tendency for the obesity, which represents the more fat production than during the premenopausal period. Although this is not beneficial overall, it could provide a compensatory source for the estrogen production for the menopausal women. So it would be meaningful to find an agent that could inhibit the fat production while does not disturb the total estrogen production by fat tissues. In the present study, the effect of oleanolic acid (OA) on the fat production and the total estrogen production of the differentiating mouse preadipocyte 3T3-L1 as well as the mechanisms behind those effects were preliminarily investigated. The cell line 3T3-L1 was chosen as the model cell because it is usually used for the research about the obesity. During the induced differentiation of 3T3-L1 cells, cells were intervened continuously with OA. The fat production was determined with the oil red staining assay and the total estrogen production was measured with the ELISA assay. Finally, the expression patterns for important genes of the fat production and the estrogen production were studied, respectively with the real-time fluorescence quantitative PCR (qPCR). The results showed that for the differentiating 3T3-L1 cells, OA could significantly inhibit the fat production and did not disturb the total estrogen production significantly. In the mechanism studies, OA was found to significantly down-regulate ACC, the key gene for fat synthesis, which could explain the inhibitory effect of OA on the fat production; OA was also found to significantly up-regulate CYP11A1, CYP17, CYP19, the key genes for the estrogen synthesis and significantly down-regulate CYP1A1, the key gene for the estrogen decomposition, which preliminarily explained the lack of the effect of OA on the total estrogen production. In conclusion, OA was found able to inhibit the fat production while maintaining the total estrogen level and the mechanisms for the above findings were preliminarily clarified, which suggests that OA may be useful to treat the menopausal obesity.

Overexpression of SREBP1 (sterol regulatory element binding protein 1) promotes de novo fatty acid synthesis and triacylglycerol accumulation in goat mammary epithelial cells.

PubMed

Xu, H F; Luo, J; Zhao, W S; Yang, Y C; Tian, H B; Shi, H B; Bionaz, M

2016-01-01

Sterol regulatory element binding protein 1 (SREBP1; gene name SREBF1) is known to be the master regulator of lipid homeostasis in mammals, including milk fat synthesis. The major role of SREBP1 in controlling milk fat synthesis has been demonstrated in bovine mammary epithelial cells. Except for a demonstrated role in controlling the expression of FASN, a regulatory role of SREBP1 on milk fat synthesis is very likely, but has not yet been demonstrated in goat mammary epithelial cells (GMEC). To explore the regulatory function of SREBP1 on de novo fatty acids and triacylglycerol synthesis in GMEC, we overexpressed the mature form of SREBP1 (active NH2-terminal fragment) in GMEC using a recombinant adenovirus vector (Ad-nSREBP1), with Ad-GFP (recombinant adenovirus of green fluorescent protein) as control, and infected the GMEC for 48 h. In infected cells, we assessed the expression of 20 genes related to milk fat synthesis using real time-quantitative PCR, the protein abundance of SREBP1 and FASN by Western blot, the production of triacylglycerol, and the fatty acid profile. Expression of SREBF1 was modest in mammary compared with the other tissues in dairy goats but its expression increased approximately 30-fold from pregnancy to lactation. The overexpression of the mature form of SREBP1 was confirmed by >200-fold higher expression of SREBF1 in Ad-nSREBP1 compared with Ad-GFP. We observed no changes in amount of the precursor form of SREBP1 protein but a >10-fold increase of the mature form of SREBP1 protein with Ad-nSREBP1. Compared with Ad-GFP cells (control), Ad-nSREBP1 cells had a significant increase in expression of genes related to long-chain fatty acid activation (ACSL1), transport (FABP3), desaturation (SCD1), de novo synthesis of fatty acids (ACSS2, ACLY, IDH1, ACACA, FASN, and ELOVL6), and transcriptional factors (NR1H3 and PPARG). We observed a >10-fold increase in expression of INSIG1 but SCAP was downregulated by Ad-nSREBP1. Among genes related to milk fat synthesis and lipid droplet formation, only LPIN1 and DGAT1 were upregulated by Ad-nSREBP1. Compared with the Ad-GFP, the cellular triacylglycerol content was higher and the percentage of C16:0 and C18:1 increased, whereas that of C16:1, C18:0, and C18:2 decreased in Ad-nSREBP1 cells. Overall, the data provide strong support for a central role of SREBP1 in the regulation of milk fat synthesis in goat mammary cells. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Dietary fat overcomes the protective activity of thrombospondin-1 signaling in the Apc(Min/+) model of colon cancer.

PubMed

Soto-Pantoja, D R; Sipes, J M; Martin-Manso, G; Westwood, B; Morris, N L; Ghosh, A; Emenaker, N J; Roberts, D D

2016-05-30

Thrombospondin 1 is a glycoprotein that regulates cellular phenotype through interactions with its cellular receptors and extracellular matrix-binding partners. Thrombospondin 1 locally regulates angiogenesis and inflammatory responses that contribute to colorectal carcinogenesis in Apc(Min/+) mice. The ability of thrombospondin 1 to regulate responses of cells and tissues to a variety of stresses suggested that loss of thrombospondin 1 may also have broader systemic effects on metabolism to modulate carcinogenesis. Apc(Min/+):Thbs1(-/-) mice exhibited decreased survival and higher tumor multiplicities in the small and large intestine relative to Apc(Min/+) mice when fed a low (5%) fat western diet. However, the protective effect of endogenous thrombospondin 1 was lost when the mice were fed a western diet containing 21% fat. Biochemical profiles of liver tissue identified systemic metabolic changes accompanying the effects of thrombospondin 1 and dietary lipid intake on tumorigenesis. A high-fat western diet differentially regulated elements of amino acid, energy and lipid metabolism in Apc(Min/+):Thbs1(-/-) mice relative to Apc(Min/+):Thbs1(+/+)mice. Metabolic changes in ketone body and tricarboxylic acid cycle intermediates indicate functional interactions between Apc and thrombospondin 1 signaling that control mitochondrial function. The cumulative diet-dependent differential changes observed in Apc(Min/+):Thbs1(-/-) versus Apc(Min/+) mice include altered amino acid and lipid metabolism, mitochondrial dysfunction, eicosanoids and ketone body formation. This metabolic profile suggests that the protective role of thrombospondin 1 to decrease adenoma formation in Apc(Min/+) mice results in part from improved mitochondrial function.

Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner.

PubMed

Munir, Hafsa; Ward, Lewis S C; Sheriff, Lozan; Kemble, Samuel; Nayar, Saba; Barone, Francesca; Nash, Gerard B; McGettrick, Helen M

2017-06-01

Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage-induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα-treated endothelial cells (EC), but MSC-derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL-6 and TGFβ1 signalling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them, and mature adipocytes from adipose tissue were all immunoprotective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive "abnormal" adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immunoprotective phenotype. Stem Cells 2017;35:1636-1646. © 2017 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation

PubMed Central

Cox, R F; Hernandez-Santana, A; Ramdass, S; McMahon, G; Harmey, J H; Morgan, M P

2012-01-01

Background: Mammographic microcalcifications represent one of the most reliable features of nonpalpable breast cancer yet remain largely unexplored and poorly understood. Methods: We report a novel model to investigate the in vitro mineralisation potential of a panel of mammary cell lines. Primary mammary tumours were produced by implanting tumourigenic cells into the mammary fat pads of female BALB/c mice. Results: Hydroxyapatite (HA) was deposited only by the tumourigenic cell lines, indicating mineralisation potential may be associated with cell phenotype in this in vitro model. We propose a mechanism for mammary mineralisation, which suggests that the balance between enhancers and inhibitors of physiological mineralisation are disrupted. Inhibition of alkaline phosphatase and phosphate transport prevented mineralisation, demonstrating that mineralisation is an active cell-mediated process. Hydroxyapatite was found to enhance in vitro tumour cell migration, while calcium oxalate had no effect, highlighting potential consequences of calcium deposition. In addition, HA was also deposited in primary mammary tumours produced by implanting the tumourigenic cells into the mammary fat pads of female BALB/c mice. Conclusion: This work indicates that formation of mammary HA is a cell-specific regulated process, which creates an osteomimetic niche potentially enhancing breast tumour progression. Our findings point to the cells mineralisation potential and the microenvironment regulating it, as a significant feature of breast tumour development. PMID:22233923

Effects of Erythropoietin on Adipose Tissue: A Possible Strategy in Refilling

PubMed Central

Sabbatini, Maurizio; Bosetti, Michela; Borrone, Alessia; Boldorini, Renzo; Taveggia, Antonio; Verna, Giovanni; Cannas, Mario

2015-01-01

Background: The increased resorption and the difficulty of the fat graft take following autologous fat transplantation procedure are associated with reduced fat tissue revascularization and increased apoptosis of adipose cells. We suppose that the lipofilling procedure induces an inflammatory environment within the fat graft mass, whose evolution influences the efficacy of autologous fat graft survival. Erythropoietin (EPO) is a glycoprotein hormone known to exert angiogenetic and anti-inflammatory effects; therefore, our purpose was to investigate its reaction with adipose tissue used in lipofilling. Methods: Fat masses were harvested using manual suction lipectomy and then seeded on dishes in appropriate culture and treated for 3 weeks with 3 doses of EPO. CD31 and CD68 immunohistochemistry was used to identify microvessels and several infiltrating leukocyte cells. Results: Following EPO administration, we have detected an increase in the number of CD31-positive microvessel endothelium cells and CD31-positive small leukocytes and a reduction of CD68-positive cells. These effects were more conspicuous following higher EPO dose. Conclusions: Our findings evidence EPO treatment as a useful strategy to sustain the revascularization of grafted tissue and to reduce its inflammatory state. PMID:26034645

High hydrostatic pressure inactivation of Lactobacillus plantarum cells in (O/W)-emulsions is independent from cell surface hydrophobicity and lipid phase parameters

NASA Astrophysics Data System (ADS)

Kafka, T. A.; Reitermayer, D.; Lenz, C. A.; Vogel, R. F.

2017-07-01

Inactivation efficiency of high hydrostatic pressure (HHP) processing of food is strongly affected by food matrix composition. We investigated effects of fat on HHP inactivation of spoilage-associated Lactobacillus (L.) plantarum strains using defined oil-in-water (O/W)-emulsion model systems. Since fat-mediated effects on HHP inactivation could be dependent on interactions between lipid phase and microbial cells, three major factors possibly influencing such interactions were considered, that is, cell surface hydrophobicity, presence and type of surfactants, and oil droplet size. Pressure tolerance varied noticeably among L. plantarum strains and was independent of cell surface hydrophobicity. We showed that HHP inactivation of all strains tended to be more effective in presence of fat. The observation in both, surfactant-stabilized and surfactant-free (O/W)-emulsion, indicates that cell surface hydrophobicity is no intrinsic pressure resistance factor. In contrast to the presence of fat per se, surfactant type and oil droplet size did not affect inactivation efficiency.

[Clear cell acanthoma with dendritica cells charged with melanine and fat].

PubMed

Sánchez Yus, E; Iglesias Díez, L

1975-01-01

A Clear Cell Acanthoma is presented, located in the abdominal region, in a 60-year old man, who had had it all his life. The lesion was warty in appearance and brown in colour. Histologically, among the clear cells, numerous dendrytical cells were found which simultaneously contained melanine grains and small drops of neutral fat. These findings are discussed.

Phosphorylation at tyrosine 114 of Proliferating Cell Nuclear Antigen (PCNA) is required for adipogenesis in response to high fat diet

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

Lo, Yuan-Hung; Ho, Po-Chun; Chen, Min-Shan

Highlights: Black-Right-Pointing-Pointer Proliferating Cell Nuclear Antigen (PCNA) is phosphorylated at Y114. Black-Right-Pointing-Pointer Phospho-Y114 of PCNA is not required for cell proliferation for normal growth. Black-Right-Pointing-Pointer MCE during adipogenesis is abolished in the lack of the phosphorylation. Black-Right-Pointing-Pointer Homozygous Y114F mice are resistant to high fat diet induced obesity. Black-Right-Pointing-Pointer Our results shed light on the interface between proliferation and differentiation. -- Abstract: Clonal proliferation is an obligatory component of adipogenesis. Although several cell cycle regulators are known to participate in the transition between pre-adipocyte proliferation and terminal adipocyte differentiation, how the core DNA synthesis machinery is coordinately regulated in adipogenesismore » remains elusive. PCNA (Proliferating Cell Nuclear Antigen) is an indispensable component for DNA synthesis during proliferation. Here we show that PCNA is subject to phosphorylation at the highly conserved tyrosine residue 114 (Y114). Replacing the Y114 residue with phenylalanine (Y114F), which is structurally similar to tyrosine but cannot be phosphorylated, does not affect normal animal development. However, when challenged with high fat diet, mice carrying homozygous Y114F alleles (PCNA{sup F/F}) are resistant to adipose tissue enlargement in comparison to wild-type (WT) mice. Mouse embryonic fibroblasts (MEFs) harboring WT or Y114F mutant PCNA proliferate at similar rates. However, when subjected to adipogenesis induction in culture, PCNA{sup F/F} MEFs are not able to re-enter the cell cycle and fail to form mature adipocytes, while WT MEFs undergo mitotic clonal expansion in response to the adipogenic stimulation, accompanied by enhanced Y114 phosphorylation of PCNA, and differentiate to mature adipocytes. Consistent with the function of Y114 phosphorylation in clonal proliferation in adipogenesis, fat tissues isolated from WT mice contain significantly more adipocytes than those isolated from PCNA{sup F/F} mice. This study identifies a critical role for PCNA in adipose tissue development, and for the first time identifies a role of the core DNA replication machinery at the interface between proliferation and differentiation.« less

Insect transferrin functions as an antioxidant protein in a beetle larva.

PubMed

Kim, Bo Yeon; Lee, Kwang Sik; Choo, Young Moo; Kim, Iksoo; Je, Yeon Ho; Woo, Soo Dong; Lee, Sang Mong; Park, Hyun Cheol; Sohn, Hung Dae; Jin, Byung Rae

2008-06-01

In insects transferrin is known as an iron transporter, an antibiotic agent, a vitellogenin, and a juvenile hormone regulated protein. Here, a novel functional role for insect transferrin as an antioxidant protein is demonstrated. Stressors, such as heat shock, fungal challenge, and H(2)O(2) exposure, cause upregulation of the white-spotted flower chafer Protaetia brevitarsis (Coleoptera: Scarabaeidae) transferrin (PbTf) mRNA in the fat body and increases PbTf protein levels in the hemolymph. RNA interference (RNAi) treated PbTf reduction causes increased iron and H(2)O(2) levels in the hemolymph and results in induction of apoptotic cell death in the fat body during exposure to stress. The observed effects of PbTf RNAi suggest that PbTf inhibits stress-induced apoptosis by diminishing the Fenton reaction via the binding of iron, thus supporting an antioxidant role for PbTf in stress responses.

Site-Specific Fat-1 Knock-In Enables Significant Decrease of n-6PUFAs/n-3PUFAs Ratio in Pigs

PubMed Central

Li, Mengjing; Ouyang, Hongsheng; Yuan, Hongming; Li, Jianing; Xie, Zicong; Wang, Kankan; Yu, Tingting; Liu, Minghao; Chen, Xue; Tang, Xiaochun; Jiao, Huping; Pang, Daxin

2018-01-01

The fat-1 gene from Caenorhabditis elegans encodes a fatty acid desaturase which was widely studied due to its beneficial function of converting n-6 polyunsaturated fatty acids (n-6PUFAs) to n-3 polyunsaturated fatty acids (n-3PUFAs). To date, many fat-1 transgenic animals have been generated to study disease pathogenesis or improve meat quality. However, all of them were generated using a random integration method with variable transgene expression levels and the introduction of selectable marker genes often raise biosafety concern. To this end, we aimed to generate marker-free fat-1 transgenic pigs in a site-specific manner. The Rosa26 locus, first found in mouse embryonic stem cells, has become one of the most common sites for inserting transgenes due to its safe and ubiquitous expression. In our study, the fat-1 gene was inserted into porcine Rosa 26 (pRosa26) locus via Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. The Southern blot analysis of our knock-in pigs indicated a single copy of the fat-1 gene at the pRosa26 locus. Furthermore, this single-copy fat-1 gene supported satisfactory expression in a variety of tissues in F1 generation pigs. Importantly, the gas chromatography analysis indicated that these fat-1 knock-in pigs exhibited a significant increase in the level of n-3PUFAs, leading to an obvious decrease in the n-6PUFAs/n-3PUFAs ratio from 9.36 to 2.12 (***P < 0.0001). Altogether, our fat-1 knock-in pigs hold great promise for improving the nutritional value of pork and serving as an animal model to investigate therapeutic effects of n-3PUFAs on various diseases. PMID:29563188

High Intensity Interval Training Improves Glycaemic Control and Pancreatic β Cell Function of Type 2 Diabetes Patients.

PubMed

Madsen, Søren Møller; Thorup, Anne Cathrine; Overgaard, Kristian; Jeppesen, Per Bendix

2015-01-01

Physical activity improves the regulation of glucose homeostasis in both type 2 diabetes (T2D) patients and healthy individuals, but the effect on pancreatic β cell function is unknown. We investigated glycaemic control, pancreatic function and total fat mass before and after 8 weeks of low volume high intensity interval training (HIIT) on cycle ergometer in T2D patients and matched healthy control individuals. Study design/method: Elderly (56 yrs±2), non-active T2D patients (n = 10) and matched (52 yrs±2) healthy controls (CON) (n = 13) exercised 3 times (10×60 sec. HIIT) a week over an 8 week period on a cycle ergometer. Participants underwent a 2-hour oral glucose tolerance test (OGTT). On a separate day, resting blood pressure measurement was conducted followed by an incremental maximal oxygen uptake (VO2max) cycle ergometer test. Finally, a whole body dual X-ray absorptiometry (DXA) was performed. After 8 weeks of training, the same measurements were performed. Results: in the T2D-group, glycaemic control as determined by average fasting venous glucose concentration (p = 0.01), end point 2-hour OGTT (p = 0.04) and glycosylated haemoglobin (p = 0.04) were significantly reduced. Pancreatic homeostasis as determined by homeostatic model assessment of insulin resistance (HOMA-IR) and HOMA β cell function (HOMA-%β) were both significantly ameliorated (p = 0.03 and p = 0.03, respectively). Whole body insulin sensitivity as determined by the disposition index (DI) was significantly increased (p = 0.03). During OGTT, the glucose continuum was significantly reduced at -15 (p = 0.03), 30 (p = 0.03) and 120 min (p = 0.03) and at -10 (p = 0.003) and 0 min (p = 0.003) with an additional improvement (p = 0.03) of its 1st phase (30 min) area under curve (AUC). Significant abdominal fat mass losses were seen in both groups (T2D: p = 0.004 and CON: p = 0.02) corresponding to a percentage change of -17.84%±5.02 and -9.66%±3.07, respectively. Conclusion: these results demonstrate that HIIT improves overall glycaemic control and pancreatic β cell function in T2D patients. Additionally, both groups experienced abdominal fat mass losses. These findings demonstrate that HIIT is a health beneficial exercise strategy in T2D patients. ClinicalTrials.gov NCT02333734 http://clinicaltrials.gov/ct2/show/NCT02333734.

High Intensity Interval Training Improves Glycaemic Control and Pancreatic β Cell Function of Type 2 Diabetes Patients

PubMed Central

Madsen, Søren Møller; Thorup, Anne Cathrine; Overgaard, Kristian; Jeppesen, Per Bendix

2015-01-01

Physical activity improves the regulation of glucose homeostasis in both type 2 diabetes (T2D) patients and healthy individuals, but the effect on pancreatic β cell function is unknown. We investigated glycaemic control, pancreatic function and total fat mass before and after 8 weeks of low volume high intensity interval training (HIIT) on cycle ergometer in T2D patients and matched healthy control individuals. Study design/method: Elderly (56 yrs±2), non-active T2D patients (n = 10) and matched (52 yrs±2) healthy controls (CON) (n = 13) exercised 3 times (10×60 sec. HIIT) a week over an 8 week period on a cycle ergometer. Participants underwent a 2-hour oral glucose tolerance test (OGTT). On a separate day, resting blood pressure measurement was conducted followed by an incremental maximal oxygen uptake (V˙O2max) cycle ergometer test. Finally, a whole body dual X-ray absorptiometry (DXA) was performed. After 8 weeks of training, the same measurements were performed. Results: in the T2D-group, glycaemic control as determined by average fasting venous glucose concentration (p = 0.01), end point 2-hour OGTT (p = 0.04) and glycosylated haemoglobin (p = 0.04) were significantly reduced. Pancreatic homeostasis as determined by homeostatic model assessment of insulin resistance (HOMA-IR) and HOMA β cell function (HOMA-%β) were both significantly ameliorated (p = 0.03 and p = 0.03, respectively). Whole body insulin sensitivity as determined by the disposition index (DI) was significantly increased (p = 0.03). During OGTT, the glucose continuum was significantly reduced at -15 (p = 0.03), 30 (p = 0.03) and 120 min (p = 0.03) and at -10 (p = 0.003) and 0 min (p = 0.003) with an additional improvement (p = 0.03) of its 1st phase (30 min) area under curve (AUC). Significant abdominal fat mass losses were seen in both groups (T2D: p = 0.004 and CON: p = 0.02) corresponding to a percentage change of -17.84%±5.02 and -9.66%±3.07, respectively. Conclusion: these results demonstrate that HIIT improves overall glycaemic control and pancreatic β cell function in T2D patients. Additionally, both groups experienced abdominal fat mass losses. These findings demonstrate that HIIT is a health beneficial exercise strategy in T2D patients. Trial Registration ClinicalTrials.gov NCT02333734 http://clinicaltrials.gov/ct2/show/NCT02333734 PMID:26258597

Effect of varying the salt and fat content in Cheddar cheese on aspects of the performance of a commercial starter culture preparation during ripening.

PubMed

Yanachkina, Palina; McCarthy, Catherine; Guinee, Tim; Wilkinson, Martin

2016-05-02

Production of healthier reduced-fat and reduced-salt cheeses requires careful selection of starter bacteria, as any substantial alterations to cheese composition may prompt changes in the overall performance of starters during cheese ripening. Therefore, it is important to assess the effect of compositional alterations on the individual strain response during cheese ripening for each optimised cheese matrix. In the current study, the effect of varying fat and salt levels in Cheddar cheese on the performance of a commercial Lactococcus lactis culture preparation, containing one L. lactis subsp. lactis strain and one L. lactis subsp. cremoris strain was investigated. Compositional variations in fat or salt levels did not affect overall starter viability, yet reduction of fat by 50% significantly delayed non-starter lactic acid bacteria (NSLAB) populations at the initial ripening period. In comparison to starter viability, starter autolysis, as measured by release of intracellular lactate dehydrogenase (LDH) or post-proline dipeptidyl aminopeptidase (Pep X) into cheese juices, decreased significantly with lower salt addition levels in full-fat Cheddar. Conversely, reducing fat content of cheese resulted in a significantly higher release of intracellular Pep X, and to a lesser extent intracellular LDH, into juices over ripening. Flow cytometry (FCM) indicated that the permeabilised and dead cell sub-populations were generally lower in juices from cheeses with reduced salt content, however no significant differences were observed between different salt and fat treatments. Interestingly, fat reductions by 30 and 50% in cheeses with reduced or half added salt contents appeared to balance out the effect of salt, and enhanced cell permeabilisation, cell death, and also cell autolysis in these variants. Overall, this study has highlighted that alterations in both salt and fat levels in cheese influence certain aspects of starter performance during ripening, including autolysis, permeabilisation, and intracellular enzyme release. However, it may be possible to reduce the fat and salt content of Cheddar cheese by 30 or 50%, respectively, without largely altering permeabilised and dead cell sub-populations and, in turn, the amount of released intracellular Pep X activity, such that these performance parameters are similar to those observed for control full-fat, full-salt Cheddar cheese. Copyright © 2016 Elsevier B.V. All rights reserved.

Oxidative stress and anti-oxidant enzyme activities in the trophocytes and fat cells of queen honeybees (Apis mellifera).

PubMed

Hsieh, Yu-Shan; Hsu, Chin-Yuan

2013-08-01

Trophocytes and fat cells of queen honeybees have been used for delayed cellular senescence studies, but their oxidative stress and anti-oxidant enzyme activities with advancing age are unknown. In this study, we assayed reactive oxygen species (ROS) and anti-oxidant enzymes in the trophocytes and fat cells of young and old queens. Young queens had lower ROS levels, lower superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, and higher thioredoxin reductase (TR) activity compared to old queens. These results show that oxidative stress and anti-oxidant enzyme activities in trophocytes and fat cells increase with advancing age in queens and suggest that an increase in oxidative stress and a consequent increase in stress defense mechanisms are associated with the longevity of queen honeybees.

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

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

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

1985-11-01

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

Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas.

PubMed

Furukawa, Toru; Sakamoto, Hitomi; Takeuchi, Shoko; Ameri, Mitra; Kuboki, Yuko; Yamamoto, Toshiyuki; Hatori, Takashi; Yamamoto, Masakazu; Sugiyama, Masanori; Ohike, Nobuyuki; Yamaguchi, Hiroshi; Shimizu, Michio; Shibata, Noriyuki; Shimizu, Kyoko; Shiratori, Keiko

2015-03-06

Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we identified recurrent mutations of BRCA2 and FAT genes. BRCA2 showed somatic or germline premature termination mutations, with loss of the wild-type allele in 3 of 7 tumors. FAT1, FAT3, and FAT4 showed somatic or germline missense mutations in 4 of 7 tumors. The germline FAT mutations were with loss of the wild-type allele. Loss of BRCA2 expression was observed in 5 of 11 tumors. One patient with a BRCA2-mutated tumor experienced complete remission of liver metastasis following cisplatinum chemotherapy. In conclusion, acinar cell carcinomas show a distinct mutation pattern and often harbor somatic or germline mutations of BRCA2 and FAT genes. This result may warrant assessment of BRCA2 abrogation in patients with the carcinoma to determine their sensitivity to chemotherapy.

The “Starfield” Pattern of Cerebral Fat Embolism From Bone Marrow Necrosis in Sickle Cell Crisis

PubMed Central

Dhakal, Laxmi P.; Bourgeois, Kirk; Barrett, Kevin M.

2015-01-01

Sickle cell disease may manifest with cerebrovascular and systemic complications. Sickle crisis that results in avascular necrosis of long bones with resultant cerebral fat embolism syndrome is rare and has a characteristic “starfield” pattern on MRI. This “starfield” MRI pattern should raise suspicion for sickle cell crisis in patients without a known history of the disease, which can lead to earlier sickle cell red blood cell exchange transfusion and treatment. We present a case of a male who presented emergently with acute seizure, coma with a characteristic MRI pattern, which lead to the diagnosis of avascular bone marrow necrosis and cerebral fat embolism syndrome from sickle cell crisis PMID:25829988

Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: Correlation with cytokines

PubMed Central

Brusnahan, S.K.; McGuire, T.R.; Jackson, J.D.; Lane, J.T.; Garvin, K.L.; O’Kane, B.J.; Berger, A.M.; Tuljapurkar, S.R.; Kessinger, M.A.; Sharp, J.G.

2010-01-01

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N = 100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean = 30.7, SEM = 2) decreased and IL-6 levels (mean = 4.4, SEM = 1) increased with age as did marrow fat (mean = 1.2 mm fat/g, SEM = 0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive. PMID:21035480

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

PubMed

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

2012-02-01

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

Comparison of Cellular Alterations in Fat Cells Harvested With Laser-Assisted Liposuction and Suction-Assisted Liposuction.

PubMed

Yildiz, Kemalettin; Taşli, Pakize Neslihan; Şahin, Fikrettin; Güneren, Ethem

2016-05-01

The aim of the present study was to evaluate the viability and proliferative capacity of adipose-derived stem cells obtained by laser-assisted liposuction (LAL). Fat tissue was obtained from 7 male patients treated surgically for gynecomastia. On one side, harvesting was made before LAL, while it was implemented after LAL on the contralateral side. Viability, cell surface antigens, pluripotency, and apoptosis were assessed and compared in these samples. Cells harvested before and after LAL did not exhibit any significant difference in terms of surface cell markers. Number of viable stem cells was lower initially after exposure to laser, while this difference was reversed at the end of 72 hours. Genetic indicators of cellular differentiation were similar in both groups. Apoptosis indicators were increased remarkably after laser exposure in the first 24 hours, but this increase was absent 72 hours after LAL procedure. The authors' results have promising clinical relevance since mesenchymal stem cells harvested during LAL have maintained appropriate cellular features to be used for autologous fat transfer and fat grafting.

Effect of the interaction between diet composition and the PPM1K genetic variant on insulin resistance and β cell function markers during weight loss: results from the Nutrient Gene Interactions in Human Obesity: implications for dietary guidelines (NUGENOB) randomized trial.

PubMed

Goni, Leticia; Qi, Lu; Cuervo, Marta; Milagro, Fermín I; Saris, Wim H; MacDonald, Ian A; Langin, Dominique; Astrup, Arne; Arner, Peter; Oppert, Jean-Michel; Svendstrup, Mathilde; Blaak, Ellen E; Sørensen, Thorkild Ia; Hansen, Torben; Martínez, J Alfredo

2017-09-01

Background: Circulating branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) have been shown to be associated with insulin resistance and diabetes risk. The common rs1440581 T allele in the protein phosphatase Mg2+/Mn2+ dependent 1K ( PPM1K ) gene has been related to elevated BCAA concentrations and risk of type 2 diabetes. Objective: In the present study, we tested whether dietary fat and carbohydrate intakes influenced the association between the rs1440581 PPM1K genetic variant and glucose-metabolism traits during weight loss. Design: The rs1440581 PPM1K genetic variant was genotyped in a total of 757 nondiabetic individuals who were randomly assigned to 1 of 2 energy-restricted diets that differed in macronutrient composition (low-fat diet: 20-25% fat, 15% protein, and 60-65% carbohydrate; high-fat diet: 40-45% fat, 15% protein, and 40-45% carbohydrate). The changes in fasting glucose, fasting insulin, insulin resistance (homeostasis model assessment of insulin resistance) and homeostasis model assessment of β cell function (HOMA-B) were measured after a mean ± SD weight loss of 6.8 ± 3.4 kg over 10 wk and analyzed according to the presence of the T allele of rs1440581. Results: The rs1440581 T allele was associated with a smaller improvement in glucose concentrations after the 10-wk dietary intervention (β ± SE: 0.05 ± 0.02 mg/dL; P = 0.03). In addition, significant gene-diet interactions were shown for the rs1440581 PPM1K genetic variant in relation to changes in insulin and HOMA-B ( P -interaction = 0.006 and 0.002, respectively). In response to the high-fat diet, the T allele was associated with a higher reduction of insulin (β ± SE: -0.77 ± 0.40 μU/mL; P = 0.04) and HOMA-B (β ± SE: -13.2 ± 3.81; P = 0.003). An opposite effect was observed in the low-fat diet group, although in this group the T allele was marginally ( P = 0.10) and not significantly ( P = 0.24) associated with insulin and HOMA-B, respectively. Conclusion: PPM1K rs1440581 may affect changes in glucose metabolism during weight loss, and this effect is dependent on dietary fat and carbohydrate intakes. This trial was registered at controlled-trials.com as ISRCTN25867281. © 2017 American Society for Nutrition.

Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome

PubMed Central

Ezeh, Uche; Pall, Marita; Mathur, Ruchi; Azziz, Ricardo

2014-01-01

STUDY QUESTION Are differences in metabolic dysfunction between polycystic ovary syndrome (PCOS) and control women related to differences in their fat to lean mass (F/L) ratio? SUMMARY ANSWER Compared with controls of similar body mass index (BMI), women with PCOS demonstrate adverse body composition characterized by increased whole body fat relative to lean mass (i.e. a higher F/L ratio), which is associated with differences in metabolic dysfunction between the two groups. WHAT IS KNOWN ALREADY Previous studies examining body composition and insulin resistance (IR) in PCOS have yielded conflicting results. Excess total fat mass (i.e. fat mass index [fat BMI]) correlates with IR, whereas increased total lean mass (i.e. lean BMI) has been associated with higher insulin sensitivity. However, the role of the F/L ratio, which integrates the antagonistic effects of both fat and lean mass depots, on IR in PCOS, has not been investigated. STUDY DESIGN, SIZE, DURATION We conducted a prospective cross-sectional study of 120 women between the ages of 22–44 years to study the relation of the F/L ratio with measures of insulin action and secretion in both steady and dynamic states. PARTICIPANTS/MATERIALS, SETTING, METHODS Sixty PCOS (by NIH, 1990 criteria) and 60 control (age, race and BMI-matched) women were prospectively studied for body composition (by bioelectrical impedance analysis [BIA]) and basal IR and insulin secretion by the homeostasis model assessment (HOMA-IR and HOMA-%β-cell function, respectively) in a tertiary care academic referral center. A subset of 12 PCOS and 12 matched control women also underwent a modified frequently sampled intravenous glucose tolerance test (FSIVGTT) to determine glucose uptake and insulin secretion in dynamic state. MAIN RESULTS AND THE ROLE OF CHANCE Our results indicate that women with PCOS demonstrated greater degrees of hyperandrogenism, and higher waist-to-hip ratio (WHR), %body fat, fat BMI, F/L, fasting insulin levels, and HOMA-IR and HOMA-%β-cell values, than controls. In models adjusted for WHR and free testosterone and diagnostic groups, fasting insulin levels, HOMA-IR, and HOMA-%beta cell function were positively related to the F/L ratio. A positive relationship was also found in both study groups between F/L and the FSIVGTT measures insulin sensitivity (Si) and acute insulin response to glucose (AIRg). The F/L tended to negatively correlate with glucose effectiveness or non-insulin-mediated glucose transport (Sg) only in PCOS women. LIMITATIONS, REASONS FOR CAUTION Regional tissue sub-compartments, which have been shown to have potential independent associations with metabolic variables, cannot be determined by bioelectrical impedance analysis (BIA). WIDER IMPLICATIONS OF THE FINDINGS The current results suggest that BIA could be used to assess F/L in place of dual energy X-ray absorptiometry (DXA) in research protocols, and that F/L could possibly be used as an alternative to WHR as a surrogate marker of metabolic dysfunction in clinical practice. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants R01-DK073632 and R01-HD29364 from the NIH and an endowment of the Helping Hand of Los Angeles, Inc. (to R.A.). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER Not applicable. PMID:24813197

The brown adipocyte differentiation pathway in birds: An evolutionary road not taken

PubMed Central

Mezentseva, Nadejda V; Kumaratilake, Jaliya S; Newman, Stuart A

2008-01-01

Background Thermogenic brown adipose tissue has never been described in birds or other non-mammalian vertebrates. Brown adipocytes in mammals are distinguished from the more common white fat adipocytes by having numerous small lipid droplets rather than a single large one, elevated numbers of mitochondria, and mitochondrial expression of the nuclear gene UCP1, the uncoupler of oxidative phosphorylation responsible for non-shivering thermogenesis. Results We have identified in vitro inductive conditions in which mesenchymal cells isolated from the embryonic chicken limb bud differentiate into avian brown adipocyte-like cells (ABALCs) with the morphological and many of the biochemical properties of terminally differentiated brown adipocytes. Avian, and as we show here, lizard species lack the gene for UCP1, although it is present in amphibian and fish species. While ABALCs are therefore not functional brown adipocytes, they are generated by a developmental pathway virtually identical to brown fat differentiation in mammals: both the common adipogenic transcription factor peroxisome proliferator-activated receptor-γ (PPARγ), and a coactivator of that factor specific to brown fat differentiation in mammals, PGC1α, are elevated in expression, as are mitochondrial volume and DNA. Furthermore, ABALCs induction resulted in strong transcription from a transfected mouse UCP1 promoter. Conclusion These findings strongly suggest that the brown fat differentiation pathway evolved in a common ancestor of birds and mammals and its thermogenicity was lost in the avian lineage, with the degradation of UCP1, after it separated from the mammalian lineage. Since this event occurred no later than the saurian ancestor of birds and lizards, an implication of this is that dinosaurs had neither UCP1 nor canonically thermogenic brown fat. PMID:18426587

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

PubMed

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

2014-06-01

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

Fas cell surface death receptor controls hepatic lipid metabolism by regulating mitochondrial function.

PubMed

Item, Flurin; Wueest, Stephan; Lemos, Vera; Stein, Sokrates; Lucchini, Fabrizio C; Denzler, Rémy; Fisser, Muriel C; Challa, Tenagne D; Pirinen, Eija; Kim, Youngsoo; Hemmi, Silvio; Gulbins, Erich; Gross, Atan; O'Reilly, Lorraine A; Stoffel, Markus; Auwerx, Johan; Konrad, Daniel

2017-09-07

Nonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, and cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic fatty acid accumulation. Here, we show that the Fas cell surface death receptor (Fas/CD95/Apo-1) regulates hepatic mitochondrial metabolism. Hepatic Fas overexpression in chow-fed mice compromises fatty acid oxidation, mitochondrial respiration, and the abundance of mitochondrial respiratory complexes promoting hepatic lipid accumulation and insulin resistance. In line, hepatocyte-specific ablation of Fas improves mitochondrial function and ameliorates high-fat-diet-induced hepatic steatosis, glucose tolerance, and insulin resistance. Mechanistically, Fas impairs fatty acid oxidation via the BH3 interacting-domain death agonist (BID). Mice with genetic or pharmacological inhibition of BID are protected from Fas-mediated impairment of mitochondrial oxidation and hepatic steatosis. We suggest Fas as a potential novel therapeutic target to treat obesity-associated fatty liver and insulin resistance.Hepatic steatosis is a common disease closely associated with metabolic syndrome and insulin resistance. Here Item et al. show that Fas, a member of the TNF receptor superfamily, contributes to mitochondrial dysfunction, steatosis development, and insulin resistance under high fat diet.

Fatty Liver

MedlinePlus

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

Mangiferin protects mitochondrial function by preserving mitochondrial hexokinase-II in vessel endothelial cells.

PubMed

Song, Junna; Li, Yi; Song, Junmei; Hou, Fangjie; Liu, Baolin; Li, Aiying

2017-07-01

Hexokinase-II (HK-II) confers protection against cell death and this study was designed to investigate the effect of mangiferin on the regulation of mitochondrial HK-II. In vessel endothelial cells, saturated fatty acid palmitate (PA) stimulation induced HK-II detachment from mitochondria due to cellular acidification. Mangiferin reduced lactate accumulation by improving pyruvate dehydrogenase activity, promoted Akt translocation to HK-II and prevented HK-II detachment from mitochondria. Knockdown of Akt2 diminished the protective effect of mangiferin on mitochondrial HK-II, confirming the role of Akt in the regulation of HK-II. Mangiferin prevented mitochondrial permeability transition pore opening, restored mitochondrial membrane potential and thereby protected cell from apoptosis. In high-fat diet fed mice, oral administration of mangiferin induced Akt phosphorylation, increased HK-II binding to mitochondria and resultantly protected vessel endothelial function, demonstrating its protective effect on endothelial integrity in vivo. This finding provided a novel strategy for the protection of mitochondrial function in the endothelium. Copyright © 2017 Elsevier B.V. All rights reserved.

Fractalkine (CX3CL1) is involved in the early activation of hypothalamic inflammation in experimental obesity.

PubMed

Morari, Joseane; Anhe, Gabriel F; Nascimento, Lucas F; de Moura, Rodrigo F; Razolli, Daniela; Solon, Carina; Guadagnini, Dioze; Souza, Gabriela; Mattos, Alexandre H; Tobar, Natalia; Ramos, Celso D; Pascoal, Vinicius D; Saad, Mario J; Lopes-Cendes, Iscia; Moraes, Juliana C; Velloso, Licio A

2014-11-01

Hypothalamic inflammation is a common feature of experimental obesity. Dietary fats are important triggers of this process, inducing the activation of toll-like receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells, which are the cellular components of the innate immune system in the brain, are expected to play a role in the early activation of diet-induced hypothalamic inflammation. Here, we use bone marrow transplants to generate mice chimeras that express a functional TLR4 in the entire body except in bone marrow-derived cells or only in bone marrow-derived cells. We show that a functional TLR4 in bone marrow-derived cells is required for the complete expression of the diet-induced obese phenotype and for the perpetuation of inflammation in the hypothalamus. In an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly induced in the neurons of the hypothalamus after the introduction of a high-fat diet. The inhibition of hypothalamic fractalkine reduces diet-induced hypothalamic inflammation and the recruitment of bone marrow-derived monocytic cells to the hypothalamus; in addition, this inhibition reduces obesity and protects against diet-induced glucose intolerance. Thus, fractalkine is an important player in the early induction of diet-induced hypothalamic inflammation, and its inhibition impairs the induction of the obese and glucose intolerance phenotypes. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Non-Invasive Detection of Lactate as a Biomarker of Response using Spectral Selective Multiple Quantum Editing Sequence (SS-SelMQC)

DTIC Science & Technology

2013-11-01

breast tumor cell lines injected into mammary fat pad (m.f.p) in nude mice. Tumor cells (5x106 cells) were injected into the m.f.p and tumor...the inguinal mammary fat pad (MFP) of anaesthetized mice. 4-6-week-old female athymic nu/nu mice (Animal Production Area of the NCI- Frederick...6 the subcutaneous fat in the hips of animals that were about to receive these tumors. Mice were monitored twice weekly for tumor growth. Tumor

First evidence for the anti-inflammatory activity of fucoxanthin in high-fat-diet-induced obesity in mice and the antioxidant functions in PC12 cells.

PubMed

Tan, Cong-ping; Hou, Yun-hua

2014-04-01

Obesity, characterized as a state of low-level inflammation, is a powerful determinant influencing the development of insulin resistance and progression to type 2 diabetes. The purpose of the present study was to investigate the anti-inflammatory activity of fucoxanthin in experimental high-fat-diet-induced obesity in mice and antioxidant activity in PC12 cells under oxidative stress situation. The anti-inflammatory potential of fucoxanthin in the regulation of maleic dialdehyde (MDA), polymorphonuclear cells (PMNs), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), and cyclooxygenase-2 (COX-2) was determined by ELISA. Fucoxanthin significantly inhibited obesity-induced upregulation of the production of IL-1β, TNF-α, iNOS, and COX-2. Moreover, fucoxanthin suppressed MDA and infiltration of PMNs. The protective effects were associated with lack of hypertrophy and crown-like structures in mammary gland. At the same time, fucoxanthin showed an advantage of antioxidant activity in PC12 cells under oxidative stress situation. These results suggest that supplementation of fucoxanthin is a promising strategy for blocking macrophage-mediated inflammation and inflammation-induced obesity and its associated complications.

Adhesive interactions between milk fat globule membrane and Lactobacillus rhamnosus GG inhibit bacterial attachment to Caco-2 TC7 intestinal cell.

PubMed

Guerin, Justine; Soligot, Claire; Burgain, Jennifer; Huguet, Marion; Francius, Gregory; El-Kirat-Chatel, Sofiane; Gomand, Faustine; Lebeer, Sarah; Le Roux, Yves; Borges, Frederic; Scher, Joël; Gaiani, Claire

2018-07-01

Milk is the most popular matrix for the delivery of lactic acid bacteria, but little is known about how milk impacts bacterial functionality. Here, the adhesion mechanisms of Lactobacillus rhamnosus GG (LGG) surface mutants to a milk component, the milk fat globule membrane (MFGM), were compared using atomic force microscopy (AFM). AFM results revealed the key adhesive role of the LGG SpaCBA pilus in relation to MFGM. A LGG mutant without exopolysaccharides but with highly exposed pili improved the number of adhesive events between LGG and MFGM compared to LGG wild type (WT). In contrast, the number of adhesive events decreased significantly for a LGG mutant without SpaCBA pili. Moreover, the presence of MFGM in the dairy matrix was found to decrease significantly the bacterial attachment ability to Caco-2 TC7 cells. This work thus demonstrated a possible competition between LGG adhesion to MFGM and to epithelial intestinal cells. This competition could negatively impact the adhesion capacity of LGG to intestinal cells in vivo, but requires further substantiation. Copyright © 2018 Elsevier B.V. All rights reserved.

The interrelationship between bone and fat: from cellular see-saw to endocrine reciprocity.

PubMed

Sadie-Van Gijsen, H; Crowther, N J; Hough, F S; Ferris, W F

2013-07-01

The number of mature osteoblasts and marrow adipocytes in bone is influenced by the differentiation of the common mesenchymal progenitor cell towards one phenotype and away from the other. Consequently, factors which promote adipogenesis not only lead to fatty marrow but also inhibit osteoblastogenesis, resulting in decreased osteoblast numbers, diminished bone formation and, potentially, inadequate bone mass and osteoporosis. In addition to osteoblast and bone adipocyte numbers being influenced by this skewing of progenitor cell differentiation towards one phenotype, mature osteoblasts and adipocytes secrete factors which may evoke changes in the cell fate and function of each other. This review examines the endogenous factors, such as PPAR-γ2, Wnt, IGF-1, GH, FGF-2, oestrogen, the GP130 signalling cytokines, vitamin D and glucocorticoids, which regulate the selection between osteoblastogenesis and adipogenesis and the interrelationship between fat and bone. The role of adipokines on bone, such as adiponectin and leptin, as well as adipose-derived oestrogen, is reviewed and the role of bone as an energy regulating endocrine organ is discussed.

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

PubMed

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

2006-07-01

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

RAGE regulates the metabolic and inflammatory response to high-fat feeding in mice.

PubMed

Song, Fei; Hurtado del Pozo, Carmen; Rosario, Rosa; Zou, Yu Shan; Ananthakrishnan, Radha; Xu, Xiaoyuan; Patel, Payal R; Benoit, Vivian M; Yan, Shi Fang; Li, Huilin; Friedman, Richard A; Kim, Jason K; Ramasamy, Ravichandran; Ferrante, Anthony W; Schmidt, Ann Marie

2014-06-01

In mammals, changes in the metabolic state, including obesity, fasting, cold challenge, and high-fat diets (HFDs), activate complex immune responses. In many strains of rodents, HFDs induce a rapid systemic inflammatory response and lead to obesity. Little is known about the molecular signals required for HFD-induced phenotypes. We studied the function of the receptor for advanced glycation end products (RAGE) in the development of phenotypes associated with high-fat feeding in mice. RAGE is highly expressed on immune cells, including macrophages. We found that high-fat feeding induced expression of RAGE ligand HMGB1 and carboxymethyllysine-advanced glycation end product epitopes in liver and adipose tissue. Genetic deficiency of RAGE prevented the effects of HFD on energy expenditure, weight gain, adipose tissue inflammation, and insulin resistance. RAGE deficiency had no effect on genetic forms of obesity caused by impaired melanocortin signaling. Hematopoietic deficiency of RAGE or treatment with soluble RAGE partially protected against peripheral HFD-induced inflammation and weight gain. These findings demonstrate that high-fat feeding induces peripheral inflammation and weight gain in a RAGE-dependent manner, providing a foothold in the pathways that regulate diet-induced obesity and offering the potential for therapeutic intervention. © 2014 by the American Diabetes Association.

Adiposopathy and epigenetics: an introduction to obesity as a transgenerational disease.

PubMed

Bays, Harold; Scinta, Wendy

2015-11-01

To examine the contribution of generational epigenetic dysregulation to the inception of obesity and its adiposopathic consequences. Sources for this review included searches of PubMed, Google Scholar, and international government/major association websites using terms including adiposity, adiposopathy, epigenetics, genetics, and obesity. Excessive energy storage in adipose tissue often results in fat cell and fat organ dysfunction, which may cause metabolic and fat mass disorders. The adverse clinical manifestations of obesity are not solely due to the amount of body fat (adiposity), but are also dependent on anatomical and functional perturbations (adiposopathy or 'sick fat'). This review describes extragenetic factors and genetic conditions that promote obesity. It also serves as an introduction to epigenetic dysregulation (i.e., abnormalities in gene expression that occur without alteration in the genetic code itself), which may contribute to obesity and adiposopathic metabolic health outcomes in offspring. Within the epigenetic paradigm, obesity is a transgenerational disease, with weight lost or gained by either parent potentially impacting generational risk for obesity and its complications. Epigenetics may be an important contributor to the emergence of obesity and its complications as global epidemics. Although transgenerational epigenetic influences present challenges, they may also present interventional opportunities, via justifying weight management for individuals before, during, and after pregnancy and for future generations.

Enterobacter cloacae administration induces hepatic damage and subcutaneous fat accumulation in high-fat diet fed mice.

PubMed

Keskitalo, Anniina; Munukka, Eveliina; Toivonen, Raine; Hollmén, Maija; Kainulainen, Heikki; Huovinen, Pentti; Jalkanen, Sirpa; Pekkala, Satu

2018-01-01

Accumulating evidence indicates that gut microbiota plays a significant role in obesity, insulin resistance and associated liver disorders. Family Enterobacteriaceae and especially Enterobacter cloacae strain B29 have been previously linked to obesity and hepatic damage. The underlying mechanisms, however, remain unclear. Therefore, we comprehensively examined the effects of E. cloacae subsp. cloacae (ATCC® 13047™) administration on host metabolism of mice fed with high-fat diet (HFD). C57BL/6N mice were randomly divided into HFD control, chow control, and E. cloacae treatment groups. The E. cloacae treatment group received live bacterial cells in PBS intragastrically twice a week, every other week for 13 weeks. Both control groups received PBS intragastrically. After the 13-week treatment period, the mice were sacrificed for gene and protein expression and functional analyses. Our results show that E. cloacae administration increased subcutaneous fat mass and the relative proportion of hypertrophic adipocytes. Both subcutaneous and visceral fat had signs of decreased insulin signaling and elevated lipolysis that was reflected in higher serum glycerol levels. In addition, E. cloacae -treated mice had significantly higher hepatic AST and AST/ALT ratio, and their liver histology indicated fibrosis, demonstrating that E. cloacae subsp. cloacae administration promotes hepatic damage in HFD fed mice.

An in vitro and in vivo study of a 4-herb formula on the management of diet-induced metabolic syndrome.

PubMed

Wat, Elaine; Wang, Yanping; Chan, Ken; Law, Hon Wai; Koon, Chi Man; Lau, Kit Man; Leung, Ping Chung; Yan, Choly; Lau, Clara Bik San

2018-03-15

Metabolic syndrome is the cluster of risk factors that leads to increased episodes of cardiovascular disease (CVD). These risk factors include but are not limited to obesity, non-alcoholic fatty liver (NAFLD), dyslipidemia, and type 2 diabetes. Since the pathogenesis of metabolic syndrome has multiple metabolic origins, there is no single treatment for it. Pharmacological approaches consist of separate drugs which target at individual risk factors which pose various side effects. Functional foods or nutraceuticals which have potentially important anti-obesity properties have thus attracted great attention. Schisandrae Fructus is a Chinese herb traditionally used as a liver tonic. Silymarin, an extract of the milk thistle (Silybum marianum), is a dietary supplement that is widely used in western society for the prevention and treatment of liver problems. Crataegus Fructus (hawthorn) is traditionally used to promote digestion and dissipate food stagnation. Momordica charantia (bitter melon) is traditionally used for treatment of diabetes in Ayurvedic Medicine. We aimed to develop a multi-targeted herbal formula to target on the multiple risk factors of metabolic syndrome using individual herbs. This proposed herbal formula include sylimarin and Schisandrae Fructus, for NAFLD; Crataegus Fructus for obesity and hyperlipidemia; and Momordica charantia for hyperglycemia. For in vitro study, we carried out insulin-induced 3T3-L1 adipocytes differentiation and fluorescent tagged cholesterol-treated Caco-2 cell assay to study for adipogenesis and cholesterol uptake into Caco-2 cells, respectively. Oleic acid-induced HepG2 cell assay was used to study for oleic acid-induced fatty liver, and brush border membrane vesicles (BBMV) assay was used to study for glucose uptake from the gut. For in vivo study, we performed an 8-week and a 12-week treatment studies, with each study comprising of 4 groups of C57Bl/6 male mice given: (i) Normal-chow diet; (ii)-(iv) High-fat diet (contains 21% fat and 0.15% cholesterol). After the initial 8 weeks of normal chow or high-fat diet feeding to induce obesity, animals were given: (i) Normal-chow diet; (ii) High-fat diet; (iii) High-fat diet + 2% herbal formula; or (iv) High-fat diet + 4% herbal formula as treatment for another 8 weeks or 12 weeks. Our in vitro results suggested Crataegus Fructus aqueous extract exerted potent inhibitory effects on 3T3-L1 preadipocytes differentiation and cholesterol uptake into Caco-2 cells. Schisandrae Fructus aqueous extract and milk thistle exerted inhibitory effects on oleic acid-induced fatty liver in HepG2 cells. Momordica charantia extract on the other hand, exerted significant inhibitory effect on glucose uptake into BBMV. Our in vivo results showed that our herbal formula exhibited a trend to reduce diet-induced increase in body weight and fat pad mass (epididymal, perirenal and inguinal fat); and significantly reduced diet-induced increase in liver weight, liver lipid, and plasma lipid dose-dependently. Besides, high-fat diet induced a significant reduction in adiponectin level which was significantly improved by herbal formula supplementation at 4%. There was however no significant effect of the herbal formula on diet-induced increase in plasma glucose or insulin levels at either dose. Herbal formula also significantly reduced diet-induced inflammation in the liver at both doses. Taken together, these data suggested the potential of our novel multi-targeted herbal formula to be used as a therapeutic agent for diet-induced metabolic syndrome, with special emphasis on NAFLD. Copyright © 2018. Published by Elsevier GmbH.

Tradeoffs between immune function and childhood growth among Amazonian forager-horticulturalists.

PubMed

Urlacher, Samuel S; Ellison, Peter T; Sugiyama, Lawrence S; Pontzer, Herman; Eick, Geeta; Liebert, Melissa A; Cepon-Robins, Tara J; Gildner, Theresa E; Snodgrass, J Josh

2018-04-24

Immune function is an energetically costly physiological activity that potentially diverts calories away from less immediately essential life tasks. Among developing organisms, the allocation of energy toward immune function may lead to tradeoffs with physical growth, particularly in high-pathogen, low-resource environments. The present study tests this hypothesis across diverse timeframes, branches of immunity, and conditions of energy availability among humans. Using a prospective mixed-longitudinal design, we collected anthropometric and blood immune biomarker data from 261 Amazonian forager-horticulturalist Shuar children (age 4-11 y old). This strategy provided baseline measures of participant stature, s.c. body fat, and humoral and cell-mediated immune activity as well as subsample longitudinal measures of linear growth (1 wk, 3 mo, 20 mo) and acute inflammation. Multilevel analyses demonstrate consistent negative effects of immune function on growth, with children experiencing up to 49% growth reduction during periods of mildly elevated immune activity. The direct energetic nature of these relationships is indicated by ( i ) the manifestation of biomarker-specific negative immune effects only when examining growth over timeframes capturing active competition for energetic resources, ( ii ) the exaggerated impact of particularly costly inflammation on growth, and ( iii ) the ability of children with greater levels of body fat (i.e., energy reserves) to completely avoid the growth-inhibiting effects of acute inflammation. These findings provide evidence for immunologically and temporally diverse body fat-dependent tradeoffs between immune function and growth during childhood. We discuss the implications of this work for understanding human developmental energetics and the biological mechanisms regulating variation in human ontogeny, life history, and health.

HealthLines: Facts About Fat

MedlinePlus

... Current Issue Past Issues Health Lines Facts About Fat Past Issues / Fall 2008 Table of Contents For ... Writer, NLM Scientists are learning more about our fat cells, and their findings could explain why some ...

Structural and functional changes in acute liver injury.

PubMed

Smuckler, E A

1976-06-01

Carbon tetrachloride produces liver cell injury in a variety of animal species. The first structurally recognizable changes occur in the endoplasmic reticulum, with alteration in ribosome-membrane interactions. Later there is an increase in intracellular fat, and the formation of tangled nets of the ergastoplasm. At no time are there changes in mitochondria or single membrane limited bodies in cells with intact plasmalemma, although a relative increase in cell sap may appear. In dead cells (those with plasmalemma discontinuties) crystalline deposits of calcium phosphatase may be noted. Functional changes are related to the endoplasmic reticulum and the plasma membrane. An early decrease in protein synthesis takes place; an accumulation of neutral lipid is related to this change. Later alterations in the ergastoplasmic functions (e.g., mixed function oxidation) occurs. Carbon tetrachloride is not the active agent; rather, a product of its metabolism, probably the CC1, free radical, is. The mechanisms of injury include macromolecular adduction and peroxide propagation. A third possibility includes a cascade effect with the production of secondary and tertiary products, also toxic in nature, with the ability to produce more widespread damage to intracellular structures.

Maternal high-fat diet impairs glucose metabolism, β-cell function and proliferation in the second generation of offspring rats.

PubMed

Huang, Yan-Hong; Ye, Ting-Ting; Liu, Chong-Xiao; Wang, Lei; Chen, Yuan-Wen; Dong, Yan

2017-01-01

This study aimed to assess the impact of perinatal high-fat (HF) diet in female Sprague-Dawley rats (F0) on glucose metabolism and islet function in their early life of second-generation of offspring (F2). F0 rats were fed with a standard chow (SC) or HF diet for 8 weeks before mating, up to termination of lactation for their first-generation of offspring (F1-SC and F1-HF). F1 females were mated with normal males at the age of week 11, and producing F2 offspring (F2-SC, F2-HF). All the offspring were fed SC diet after weaning for 3 weeks. The glucose level and islet function of F2 offspring were assessed at the age of week 3 and 12. The F2-HF offspring had a high birth weight and maintained a higher body mass at the age of week 3 and 12, along with an impaired glucose tolerance and lower serum insulin levels compared with the F2-SC. β-cell proliferation was also impaired in the islets of F2-HF rats at the age of week 3 and 12. The pancreatic and duodenal homeobox factor-1 (Pdx1) and Neurogenic differentiation 1 (NeuroD1) expressions were decreased in the islet of F2-HF rats at the age of week 12. Maternal HF diet during pre-gestation, gestation, and lactation in rats could result in the increased body weight and glucose intolerance in their early life of F2 offspring due to impaired β-cell function and proliferation.

TM6SF2 is a regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content

PubMed Central

Mahdessian, Hovsep; Taxiarchis, Apostolos; Popov, Sergej; Silveira, Angela; Franco-Cereceda, Anders; Hamsten, Anders; Eriksson, Per; van't Hooft, Ferdinand

2014-01-01

Genome-wide association studies have identified a locus on chromosome 19 associated with plasma triglyceride (TG) concentration and nonalcoholic fatty liver disease. However, the identity and functional role of the gene(s) responsible for these associations remain unknown. Of 19 expressed genes contained in this locus, none has previously been implicated in lipid metabolism. We performed gene expression studies and expression quantitative trait locus analysis in 206 human liver samples to identify the putative causal gene. Transmembrane 6 superfamily member 2 (TM6SF2), a gene with hitherto unknown function, expressed predominantly in liver and intestine, was identified as the putative causal gene. TM6SF2 encodes a protein of 351 amino acids with 7–10 predicted transmembrane domains. Otherwise, no other protein features were identified which could help to elucidate the function of TM6SF2. Protein subcellular localization studies with confocal microscopy demonstrated that TM6SF2 is localized in the endoplasmic reticulum and the ER-Golgi intermediate compartment of human liver cells. Functional studies for secretion of TG-rich lipoproteins (TRLs) and lipid droplet content were performed in human hepatoma Huh7 and HepG2 cells using confocal microscopy and siRNA inhibition and overexpression techniques. In agreement with the genome-wide association data, it was found that TM6SF2 siRNA inhibition was associated with reduced secretion of TRLs and increased cellular TG concentration and lipid droplet content, whereas TM6SF2 overexpression reduced liver cell steatosis. We conclude that TM6SF2 is a regulator of liver fat metabolism with opposing effects on the secretion of TRLs and hepatic lipid droplet content. PMID:24927523

Fat tissue after lipolysis of lipomas: a histopathological and immunohistochemical study.

PubMed

Bechara, Falk G; Sand, Michael; Hoffmann, Klaus; Sand, Daniel; Altmeyer, Peter; Stücker, Markus

2007-07-01

Injections with Lipostabil, a phosphatidylcholine (PDC) containing substance, have become a popular technique to treat localized fat accumulation and lipomas for aesthetic reasons. Despite its frequent use, the mechanism of action of PDC and histological changes of treated fat tissue still remain unclear. To investigate the histological changes of lipomas after treatment with PDC. In all, fourteen lipomas (n = 14) in five patients presenting with multiple lipomas were treated with intralesional injections of PDC (Lipostabil, Nettermann, Germany). Histological changes with immunohistochemical analysis of the inflammatory process were evaluated 4, 10, 24, 48 h, 10 days, 30 days and 60 days after lipolysis. Between 4 and 48 h after injection, histology shows a lobular neutrophilic infiltrate with partially destroyed fat cells. At day 10 the inflammatory process is accompanied by an infiltration of T-lymphocytes. After 60 days formation of macrophages with foam cells are visible, accompanied by thickened septa and capsula. Lipolysis with PDC results in a distinct inflammatory reaction of affected fat tissue, similar to factitial panniculitis. Early destruction of fat cells may suggest the involvement of detergent or osmotic mechanisms in the process.

The relationship of body fatness and body fat distribution with microvascular recruitment: The Amsterdam Growth and Health Longitudinal Study.

PubMed

Wijnstok, Nienke; Hoekstra, Trynke; Eringa, Etto; Smulders, Yvo; Twisk, Jos; Serne, Erik

2012-04-01

Microvascular function has been proposed to link body fatness to CVD and DM2. Current knowledge of these relationships is mainly based on studies in selected populations of extreme phenotypes. Whether these findings can be translated to the general population remains to be investigated. To assess the relationship of body fatness and body fat distribution with microvascular function in a healthy population-based cohort. Body fatness parameters were obtained by anthropometry and whole-body dual-X-ray absorptiometry (DEXA) in 2000 and 2006. Microvascular recruitment (i.e., absolute increase in perfused capillaries after arterial occlusion, using nailfold capillaroscopy) was measured in 2006. Linear regression analysis was used to examine the relationship of (changes in) body fatness and body fat distribution with microvascular recruitment. RESULTS Data were available for 259 participants (116 men). Capillary density was higher in women than in men (difference 7.3/ mm(2); p < 0.05). In the total population, the relationship between total body fatness and microvascular recruitment was positive (β = 0.43; p = 0.002), whereas a central pattern of fat distribution (trunk-over-total fatness) showed a negative relationship (β = -26.2; p = 0.032) with microvascular recruitment. However, no association remained apparent after adjustment for gender. In addition, there was no relationship between 6-year changes in body fatness or fat distribution and microvascular recruitment. Women show higher capillary recruitment values than men. This study does not support a linear relationship between microvascular function and body fatness or body fat distribution within a population-based normal range. © 2012 John Wiley & Sons Ltd.

Experimental and theoretical investigation of deformation and fracture of subcutaneous fat under compression

NASA Astrophysics Data System (ADS)

Sapozhnikov, S. B.; Ignatova, A. V.

2013-01-01

The subcutaneous fat is considered as a structural material undergoing large inelastic deformations and failure under uniform compression. In calculation, the fat is replaced with a set of cells operating in parallel and suffering failure independently of one another. An elementary cell is considered as a closed thin-wall cylindrical shell filled with an incompressible liquid. All cells in the model are of the same size, and their material is hyperelastic, whose stiffness grows in tension. By comparing experimental data with the mathematical shell model, three parameters are determined to describe the hyperelastic behavior of the cells in transverse compression. A mathematical model with seven constants is presented for describing the deformation of subcutaneous fat under compression. The results obtained are used in a model of human thorax subjected to a local pulse action corresponding to the loading of human body under the impact of a bullet on an armor vest.

New Advanced Technologies in Stem Cell Therapy

DTIC Science & Technology

2014-11-01

6-8 wks old utrophin/dystrophin double knockout (dKO) mice, a severe animal model of DMD, have an excess of ectopic fat , calcium deposits and...tissues in skeletal muscle alter the tissue environment and induce deregulation of muscle homeostasis; however, the cellular origin of muscle fat ...as a major contributor to ectopic fat cell, calcium deposits and fibrotic tissue formation within dystrophic muscle. In the current study, we propose

Therapeutic assessment of cytochrome C for the prevention of obesity through endothelial cell-targeted nanoparticulate system.

PubMed

Hossen, Md Nazir; Kajimoto, Kazuaki; Akita, Hidetaka; Hyodo, Mamoru; Ishitsuka, Taichi; Harashima, Hideyoshi

2013-03-01

Because the functional apoptosis-initiating protein, cytochrome C (CytC) is rapidly cleared from the circulation (t1/2 (half-life): 4 minutes), it cannot be used for in vivo therapy. We report herein on a hitherto unreported strategy for delivering exogenous CytC as a potential and safe antiobesity drug for preventing diet-induced obesity, the most common type of obesity in humans. The functional activity of CytC encapsulated in prohibitin (a white fat vessel-specific receptor)-targeted nanoparticles (PTNP) was evaluated quantitatively, as evidenced by the observations that CytC-loaded PTNP causes apoptosis in primary adipose endothelial cells in a dose-dependent manner, whereas CytC alone did not. The delivery of a single dose of CytC through PTNP into the circulation disrupted the vascular structure by the targeted apoptosis of adipose endothelial cells in vivo. Intravenous treatment of CytC-loaded PTNP resulted in a substantial reduction in obesity in high-fat diet (HFD) fed wild-type (wt) mice, as evidenced by the dose-dependent prevention of the percentage of increase in body weight and decrease in serum leptin levels. In addition, no detectable hepatotoxicity was found to be associated with this prevention. Thus, the finding highlights the promising potential of CytC for use as an antiobesity drug, when delivered through a nanosystem.

The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation.

PubMed

Chen, Weiqin; Yechoor, Vijay K; Chang, Benny Hung-Junn; Li, Ming V; March, Keith L; Chan, Lawrence

2009-10-01

Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. BSCL2 encodes a protein called seipin, whose function is largely unknown. In this study, we investigated the role of Bscl2 in the regulation of adipocyte differentiation. Bscl2 mRNA is highly up-regulated during standard hormone-induced adipogenesis in 3T3-L1 cells in vitro. However, this up-regulation does not occur during mesenchymal stem cell (C3H10T1/2 cells) commitment to the preadipocyte lineage. Knockdown of Bscl2 by short hairpin RNA in C3H10T1/2 cells has no effect on bone morphogenetic protein-4-induced preadipocyte commitment. However, knockdown in 3T3-L1 cells prevents adipogenesis induced by a standard hormone cocktail, but adipogenesis can be rescued by the addition of peroxisome proliferator-activated receptor-gamma agonist pioglitazone at an early stage of differentiation. Interestingly, pioglitazone-induced differentiation in the absence of standard hormone is not associated with up-regulated Bscl2 expression. On the other hand, short hairpin RNA-knockdown of Bscl2 largely blocks pioglitazone-induced adipose differentiation. These experiments suggest that Bscl2 may be essential for normal adipogenesis; it works upstream or at the level of peroxisome proliferator-activated receptor-gamma, enabling the latter to exert its full activity during adipogenesis. Loss of Bscl2 function thus interferes with the normal transcriptional cascade of adipogenesis during fat cell differentiation, resulting in near total loss of fat or lipodystrophy.

Lack of a direct role for macrosialin in oxidized LDL metabolism.

PubMed

de Beer, Maria C; Zhao, Zhenze; Webb, Nancy R; van der Westhuyzen, Deneys R; de Villiers, Willem J S

2003-04-01

Murine macrosialin (MS), a scavenger receptor family member, is a heavily glycosylated transmembrane protein expressed predominantly in macrophage late endosomes. MS is also found on the cell surface where it is suggested, on the basis of ligand blotting, to bind oxidized LDL (oxLDL). Here we report on the regulation of MS by an atherogenic high-fat diet and oxLDL, and on the inability of MS in transfected cells to bind oxLDL. MS expression was markedly increased in the livers of atherosclerosis-susceptible C57BL/6 and atherosclerosis-resistant C3H/HeJ mice fed an atherogenic high-fat diet. In resident-mouse peritoneal macrophages, treatment with oxLDL upregulated MS mRNA and protein expression 1.5- to 3-fold. MS, overexpressed in COS-7 cells through adenovirus mediated gene transfer, bound oxLDL by ligand blotting. However, no binding of oxLDL to MS was observed in intact transfected COS-7 and Chinese hamster ovary cells, despite significant cell surface expression of MS. Furthermore, inhibition of MS through gene silencing did not affect the binding of oxLDL to macrophages. We conclude that although MS expression in macrophages and Kupffer cells is responsive to a proatherogenic inflammatory diet and to oxLDL, MS does not function as an oxLDL receptor on the cell surface.

Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be Protective Adaptions in Ischemic CAD.

PubMed

Hannukainen, J C; Lautamäki, R; Mari, A; Pärkkä, J P; Bucci, M; Guzzardi, M A; Kajander, S; Tuokkola, T; Knuuti, J; Iozzo, P

2016-07-01

Insulin resistance, β-cell dysfunction, and ectopic fat deposition have been implicated in the pathogenesis of coronary artery disease (CAD) and type 2 diabetes, which is common in CAD patients. We investigated whether CAD is an independent predictor of these metabolic abnormalities and whether this interaction is influenced by superimposed myocardial ischemia. We studied CAD patients with (n = 8) and without (n = 14) myocardial ischemia and eight non-CAD controls. Insulin sensitivity and secretion and substrate oxidation were measured during fasting and oral glucose tolerance testing. We used magnetic resonance imaging/spectroscopy, positron emission and computerized tomography to characterize CAD, cardiac function, pericardial and abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism and a proportional decline in β-cell insulin secretion and reduction in lipid oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and pancreatic fat contents were similar in all groups and related with surrounding adipose masses or systemic insulin sensitivity. In ischemic CAD patients, glucose oxidation is enhanced and correlates inversely with insulin secretion. This can be seen as a mechanism to prevent glucose lowering because glucose is required in oxygen-deprived tissues. On the other hand, the accumulation of cardiac triglycerides may be a physiological adaptation to the limited fatty acid oxidative capacity. Our results underscore the urgent need of clinical trials that define the optimal/safest glycemic range in situations of myocardial ischemia.

Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be Protective Adaptions in Ischemic CAD

PubMed Central

Hannukainen, J. C.; Lautamäki, R.; Mari, A.; Pärkkä, J. P.; Bucci, M.; Guzzardi, M. A.; Kajander, S.; Tuokkola, T.; Knuuti, J.

2016-01-01

Background: Insulin resistance, β-cell dysfunction, and ectopic fat deposition have been implicated in the pathogenesis of coronary artery disease (CAD) and type 2 diabetes, which is common in CAD patients. We investigated whether CAD is an independent predictor of these metabolic abnormalities and whether this interaction is influenced by superimposed myocardial ischemia. Methods and Results: We studied CAD patients with (n = 8) and without (n = 14) myocardial ischemia and eight non-CAD controls. Insulin sensitivity and secretion and substrate oxidation were measured during fasting and oral glucose tolerance testing. We used magnetic resonance imaging/spectroscopy, positron emission and computerized tomography to characterize CAD, cardiac function, pericardial and abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism and a proportional decline in β-cell insulin secretion and reduction in lipid oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and pancreatic fat contents were similar in all groups and related with surrounding adipose masses or systemic insulin sensitivity. Conclusions: In ischemic CAD patients, glucose oxidation is enhanced and correlates inversely with insulin secretion. This can be seen as a mechanism to prevent glucose lowering because glucose is required in oxygen-deprived tissues. On the other hand, the accumulation of cardiac triglycerides may be a physiological adaptation to the limited fatty acid oxidative capacity. Our results underscore the urgent need of clinical trials that define the optimal/safest glycemic range in situations of myocardial ischemia. PMID:27045985

Inflammation-induced formation of fat-associated lymphoid clusters

PubMed Central

Bénézech, Cécile; Kruglov, Andrei A.; Loo, Yunhua; Nakamura, Kyoko; Zhang, Yang; Nayar, Saba; Jones, Lucy H.; Flores-Langarica, Adriana; McIntosh, Alistair; Marshall, Jennifer; Barone, Francesca; Besra, Gurdyal; Miles, Katherine; Allen, Judith E.; Gray, Mohini; Kollias, George; Cunningham, Adam F.; Withers, David R.; Toellner, Kai Michael; Jones, Nick D.; Veldhoen, Marc; Nedospasov, Sergei A.; McKenzie, Andrew N.J.; Caamaño, Jorge H.

2015-01-01

Fat-associated lymphoid clusters (FALCs) are a recently discovered type of lymphoid tissue associated with visceral fat. Here we show that distribution of FALCs was heterogeneous with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 B cells in the peritoneal cavity through high expression of the chemokine CXCL13 and supported B cell proliferation and germinal center differentiation during peritoneal immune challenges. FALC formation was induced by inflammation, which triggered recruitment of myeloid cells that express tumor necrosis factor (TNF) necessary for TNF receptor-signaling in stromal cells. CD1d-restricted Natural killer T (NKT) cells were likewise required for inducible formation of FALCs. Thus, FALCs support and coordinate innate B and T cell activation during serosal immune responses. PMID:26147686

Prenatal Androgen Excess Negatively Impacts Body Fat Distribution in a Nonhuman Primate Model of Polycystic Ovary Syndrome (PCOS)

PubMed Central

Bruns, Cristin M; Baum, Scott T; Colman, Ricki J; Dumesic, Daniel A; Eisner, Joel R; Jensen, Michael D; Whigham, Leah D; Abbott, David H

2008-01-01

Introduction Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with PCOS women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic beta-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI). Objective To determine whether PA females have altered body fat distribution. Design Five EPA, 5 LPA, and 5 control adult female monkeys underwent somatometrics, dual x-ray absorptiometry (DXA) and abdominal computed tomography (CT). Five control and 5 EPA females underwent an intravenous glucose tolerance test to assess the relationship between body composition and glucoregulation. Results There were no differences in age, weight, BMI, or somatometrics. LPA females had ∼20% greater DXA-determined total fat and percent body fat, as well as total and percent abdominal fat than EPA or control females (p≤0.05). LPA females also had ∼40% more CT-determined non-visceral abdominal fat than EPA or control females (p≤0.05). The volume of visceral fat was similar among the 3 groups. EPA (R2=0.94, p≤0.01) and LPA (R2=0.53, p=0.16) females had a positive relationship between visceral fat and BMI, although not significant for LPA females. Conversely, control females had a positive relationship between non-visceral fat and BMI (R2=0.98, p≤0.001). There was a positive relationship between basal insulin and total body (R2=0.95, p≤0.007), total abdominal (R2=0.81, p≤0.04), and visceral (R2=0.82, p≤0.03) fat quantities in EPA, but not control females. Conclusions Prenatal androgenization in female rhesus monkeys induces adiposity-dependent visceral fat accumulation, and late gestation androgenization causes increased total body and non-visceral fat mass. Early gestation androgenization induces visceral fat-dependent hyperinsulinemia. The relationship between the timing of prenatal androgen exposure and body composition phenotypes in this nonhuman primate model for PCOS may provide insight into the heterogeneity of metabolic defects found in PCOS women. PMID:17471299

Prenatal androgen excess negatively impacts body fat distribution in a nonhuman primate model of polycystic ovary syndrome.

PubMed

Bruns, C M; Baum, S T; Colman, R J; Dumesic, D A; Eisner, J R; Jensen, M D; Whigham, L D; Abbott, D H

2007-10-01

Prenatally androgenized (PA) female rhesus monkeys share metabolic abnormalities in common with polycystic ovary syndrome (PCOS) women. Early gestation exposure (E) results in insulin resistance, impaired pancreatic beta-cell function and type 2 diabetes, while late gestation exposure (L) results in supranormal insulin sensitivity that declines with increasing body mass index (BMI). To determine whether PA females have altered body fat distribution. Five early-treated PA (EPA), five late-treated PA (LPA) and five control adult female monkeys underwent somatometrics, dual-X-ray absorptiometry (DXA) and abdominal computed tomography (CT). Five control and five EPA females underwent an intravenous glucose tolerance test to assess the relationship between body composition and glucoregulation. There were no differences in age, weight, BMI or somatometrics. LPA females had approximately 20% greater DXA-determined total fat and percent body fat, as well as total and percent abdominal fat than EPA or control females (P< or =0.05). LPA females also had approximately 40% more CT-determined non-visceral abdominal fat than EPA or control females (P< or =0.05). The volume of visceral fat was similar among the three groups. EPA (R (2)=0.94, P< or =0.01) and LPA (R (2)=0.53, P=0.16) females had a positive relationship between visceral fat and BMI, although not significant for LPA females. Conversely, control females had a positive relationship between non-visceral fat and BMI (R (2)=0.98, P< or =0.001). There was a positive relationship between basal insulin and total body (R (2)=0.95, P< or =0.007), total abdominal (R (2)=0.81, P< or =0.04) and visceral (R (2)=0.82, P< or =0.03) fat quantities in EPA, but not control females. Prenatal androgenization in female rhesus monkeys induces adiposity-dependent visceral fat accumulation, and late gestation androgenization causes increased total body and non-visceral fat mass. Early gestation androgenization induces visceral fat-dependent hyperinsulinemia. The relationship between the timing of prenatal androgen exposure and body composition phenotypes in this nonhuman primate model for PCOS may provide insight into the heterogeneity of metabolic defects found in PCOS women.

Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function.

PubMed

Cortés, Berenice; Núñez, Isabel; Cofán, Montserrat; Gilabert, Rosa; Pérez-Heras, Ana; Casals, Elena; Deulofeu, Ramón; Ros, Emilio

2006-10-17

We sought to investigate whether the addition of walnuts or olive oil to a fatty meal have differential effects on postprandial vasoactivity, lipoproteins, markers of oxidation and endothelial activation, and plasma asymmetric dimethylarginine (ADMA). Compared with a Mediterranean diet, a walnut diet has been shown to improve endothelial function in hypercholesterolemic patients. We hypothesized that walnuts would reverse postprandial endothelial dysfunction associated with consumption of a fatty meal. We randomized in a crossover design 12 healthy subjects and 12 patients with hypercholesterolemia to 2 high-fat meal sequences to which 25 g olive oil or 40 g walnuts had been added. Both test meals contained 80 g fat and 35% saturated fatty acids, and consumption of each meal was separated by 1 week. Venipunctures and ultrasound measurements of brachial artery endothelial function were performed after fasting and 4 h after test meals. In both study groups, flow-mediated dilation (FMD) was worse after the olive oil meal than after the walnut meal (p = 0.006, time-period interaction). Fasting, but not postprandial, triglyceride concentrations correlated inversely with FMD (r = -0.324; p = 0.024). Flow-independent dilation and plasma ADMA concentrations were unchanged, and the concentration of oxidized low-density lipoproteins decreased (p = 0.051) after either meal. The plasma concentrations of soluble inflammatory cytokines and adhesion molecules decreased (p < 0.01) independently of meal type, except for E-selectin, which decreased more (p = 0.033) after the walnut meal. Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or ADMA. Both walnuts and olive oil preserve the protective phenotype of endothelial cells.

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

PubMed Central

Michailidou, Z.; Carter, R. N.; Marshall, E.; Sutherland, H. G.; Brownstein, D. G.; Owen, E.; Cockett, K.; Kelly, V.; Ramage, L.; Al-Dujaili, E. A. S.; Ross, M.; Maraki, I.; Newton, K.; Holmes, M. C.; Seckl, J. R.; Morton, N. M.; Kenyon, C. J.; Chapman, K. E.

2008-01-01

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GRβgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin-aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.—Michailidou, Z., Carter, R. N., Marshall, E., Sutherland, H. G., Brownstein, D. G., Owen, E., Cockett, K., Kelly, V., Ramage, L., Al-Dujaili, E. A. S., Ross, M., Maraki, I., Newton, K., Holmes, M. C., Seckl, J. R., Morton, N. M., Kenyon, C. J., Chapman, K. E. Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet. PMID:18697839

Peroxisomal membrane channel Pxmp2 in the mammary fat pad is essential for stromal lipid homeostasis and for development of mammary gland epithelium in mice.

PubMed

Vapola, Miia H; Rokka, Aare; Sormunen, Raija T; Alhonen, Leena; Schmitz, Werner; Conzelmann, Ernst; Wärri, Anni; Grunau, Silke; Antonenkov, Vasily D; Hiltunen, J Kalervo

2014-07-01

To understand the functional role of the peroxisomal membrane channel Pxmp2, mice with a targeted disruption of the Pxmp2 gene were generated. These mice were viable, grew and bred normally. However, Pxmp2(-/-) female mice were unable to nurse their pups. Lactating mammary gland epithelium displayed secretory lipid droplets and milk proteins, but the size of the ductal system was greatly reduced. Examination of mammary gland development revealed that retarded mammary ductal outgrowth was due to reduced proliferation of epithelial cells during puberty. Transplantation experiments established the Pxmp2(-/-) mammary stroma as a tissue responsible for suppression of epithelial growth. Morphological and biochemical examination confirmed the presence of peroxisomes in the mammary fat pad adipocytes, and functional Pxmp2 was detected in the stroma of wild-type mammary glands. Deletion of Pxmp2 led to an elevation in the expression of peroxisomal proteins in the mammary fat pad but not in liver or kidney of transgenic mice. Lipidomics of Pxmp2(-/-)mammary fat pad showed a decrease in the content of myristic acid (C14), a principal substrate for protein myristoylation and a potential peroxisomal β-oxidation product. Analysis of complex lipids revealed a reduced concentration of a variety of diacylglycerols and phospholipids containing mostly polyunsaturated fatty acids that may be caused by activation of lipid peroxidation. However, an antioxidant-containing diet did not stimulate mammary epithelial proliferation in Pxmp2(-/-) mice. The results point to disturbances of lipid metabolism in the mammary fat pad that in turn may result in abnormal epithelial growth. The work reveals impaired mammary gland development as a new category of peroxisomal disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

High Endogenous Accumulation of ω-3 Polyunsaturated Fatty Acids Protect against Ischemia-Reperfusion Renal Injury through AMPK-Mediated Autophagy in Fat-1 Mice.

PubMed

Gwon, Do Hyeong; Hwang, Tae Woong; Ro, Ju-Ye; Kang, Yoon-Joong; Jeong, Jin Young; Kim, Do-Kyung; Lim, Kyu; Kim, Dong Woon; Choi, Dae Eun; Kim, Jwa-Jin

2017-09-30

Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce ω3-Polyunsaturated fatty acids (ω3-PUFAs) from ω6-Polyunsaturated fatty acids (ω6-PUFAs) without a dietary ω3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. ω3-PUFAs show protective effects against various renal injuries and it has recently been reported that ω3-PUFAs regulate autophagy. We assessed whether ω3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham ( n = 10), fat-1 sham ( n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI ( n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, ω3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.

Comparison of mesenchymal stem cells derived from fat, bone marrow, Wharton's jelly, and umbilical cord blood for treating spinal cord injuries in dogs.

PubMed

Ryu, Hak-Hyun; Kang, Byung-Jae; Park, Sung-Su; Kim, Yongsun; Sung, Gyu-Jin; Woo, Heung-Myong; Kim, Wan Hee; Kweon, Oh-Kyeong

2012-12-01

Previous animal studies have shown that transplantation of mesenchymal stem cells (MSCs) into spinal cord lesions enhances axonal regeneration and promotes functional recovery. We isolated the MSCs derived from fat, bone marrow, Wharton's jelly and umbilical cord blood (UCB) positive for MSC markers and negative for hematopoietic cell markers. Their effects on the regeneration of injured canine spinal cords were compared. Spinal cord injury was induced by balloon catheter compression. Dogs with injured spinal cords were treated with only matrigel or matrigel mixed with each type of MSCs. Olby and modified Tarlov scores, immunohistochemistry, ELISA and Western blot analysis were used to evaluate the therapeutic effects. The different MSC groups showed significant improvements in locomotion at 8 weeks after transplantation (P<0.05). This recovery was accompanied by increased numbers of surviving neuron and neurofilament-positive fibers in the lesion site. Compared to the control, the lesion sizes were smaller, and fewer microglia and reactive astrocytes were found in the spinal cord epicenter of all MSC groups. Although there were no significant differences in functional recovery among the MSCs groups, UCB-derived MSCs (UCSCs) induced more nerve regeneration and anti-inflammation activity (P<0.05). Transplanted MSCs survived for 8 weeks and reduced IL-6 and COX-2 levels, which may have promoted neuronal regeneration in the spinal cord. Our data suggest that transplantation of MSCs promotes functional recovery after SCI. Furthermore, application of UCSCs led to more nerve regeneration, neuroprotection and less inflammation compared to other MSCs.

Mathematical modeling of planar cell polarity signaling in the Drosophila melanogaster wing

NASA Astrophysics Data System (ADS)

Amonlirdviman, Keith

Planar cell polarity (PCP) signaling refers to the coordinated polarization of cells within the plane of various epithelial tissues to generate sub-cellular asymmetry along an axis orthogonal to their apical-basal axes. For example, in the Drosophila wing, PCP is seen in the parallel orientation of hairs that protrude from each of the approximately 30,000 epithelial cells to robustly point toward the wing tip. Through a poorly understood mechanism, cell clones mutant for some PCP signaling components, including some, but not all alleles of the receptor frizzled, cause polarity disruptions of neighboring, wild-type cells, a phenomenon referred to as domineering nonautonomy. Previous models have proposed diffusible factors to explain nonautonomy, but no such factors have yet been found. This dissertation describes the mathematical modeling of PCP in the Drosophila wing, based on a contact dependent signaling hypothesis derived from experimental results. Intuition alone is insufficient to deduce that this hypothesis, which relies on a local feedback loop acting at the cell membrane, underlies the complex patterns observed in large fields of cells containing mutant clones, and others have argued that it cannot account for observed phenotypes. Through reaction-diffusion, partial differential equation modeling and simulation, the feedback loop is shown to fully reproduce PCP phenotypes, including domineering nonautonomy. The sufficiency of this model and the experimental validation of model predictions argue that previously proposed diffusible factors need not be invoked to explain PCP signaling and reveal how specific protein-protein interactions lead to autonomy or domineering nonautonomy. Based on these results, an ordinary differential equation model is derived to study the relationship of the feedback loop with upstream signaling components. The cadherin Fat transduces a cue to the local feedback loop, biasing the polarity direction of each cell toward the wing tip. The feedback loop then amplifies and propagates PCP across the pupal wing, but polarity information does not always propagate correctly across cells lacking Fat function. Using the simplified model, the presence and severity of polarity defects in fat clones is shown to be an inherent consequence of the feedback loop when confronted with irregular variations in cell geometry.

16S rRNA gene-based association study identified microbial taxa associated with pork intramuscular fat content in feces and cecum lumen.

PubMed

Fang, Shaoming; Xiong, Xingwei; Su, Ying; Huang, Lusheng; Chen, Congying

2017-07-19

Intramuscular fat (IMF) that deposits among muscle fibers or within muscle cells is an important meat quality trait in pigs. Previous studies observed the effects of dietary nutrients and additives on improving the pork IMF. Gut microbiome plays an important role in host metabolism and energy harvest. Whether gut microbiota exerts effect on IMF remains unknown. In this study, we investigated the microbial community structure of 500 samples from porcine cecum and feces using high-throughput 16S rRNA gene sequencing. We found that phylogenetic composition and potential function capacity of microbiome varied between two types of samples. Bacteria wide association study identified 119 OTUs significantly associated with IMF in the two types of samples (FDR < 0.1). Most of the IMF-associated OTUs belong to the bacteria related to polysaccharide degradation and amino acid metabolism (such as Prevotella, Treponema, Bacteroides and Clostridium). Potential function capacities related to metabolisms of carbohydrate, energy and amino acids, cell motility, and membrane transport were significantly associated with IMF content. FishTaco analysis suggested that the shifts of potential function capacities of microbiome associated with IMF might be caused by the IMF-associated microbial taxa. This study firstly evaluated the contribution of gut microbiome to porcine IMF content. The results presented a potential capacity for improving IMF through modulating gut microbiota.

Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

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

Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya

2009-12-18

Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4more » daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.« less

Arterial stiffness, body fat compartments, central hemodynamics, renal function and left atrial size.

PubMed

Katulska, Katarzyna; Milewska, Agata; Wykretowicz, Mateusz; Krauze, Tomasz; Przymuszala, Dagmara; Piskorski, Jaroslaw; Stajgis, Marek; Guzik, Przemyslaw; Wysocki, Henryk; Wykrętowicz, Andrzej

2013-10-01

Left atrial (LA) size is an important predictor of stroke, death, and atrial fibrillation. It was demonstrated recently that body fat, arterial stiffness and renal functions are associated with LA diameter. However, data are lacking for comprehensive assessments of all these risk factors in a single population. Therefore, the aim of the present study was to investigate the association between LA size and different fat descriptors, central hemodynamics, arterial stiffness, and renal function in healthy subjects. To this end, body fat percentage, abdominal, subcutaneous fat, and general descriptors of body fat were estimated in 162 healthy subjects (mean age 51 years). Echocardiography was performed to assess LA diameter. Arterial stiffness and peripheral and central hemodynamics were estimated by digital volume pulse analysis and pulse wave analysis. Glomerular filtration rate was estimated by MDRD formula. There were significant (p < 0.05) bivariate correlations between LA diameter and all descriptors of body fat (except subcutaneous fat). Arterial stiffness and estimated glomerular filtration rate (eGFR) were also significantly correlated with LA size. Multiple regression analysis including all significant confounders, such as sex, mean arterial pressure, arterial stiffness, eGFR and body fat descriptors, explained 35% of variance in LA diameter. In conclusion, the present study reveals significant, independent relationships between body fat, arterial stiffness, and LA size.

Detection of non-milk fat in milk fat by gas chromatography and linear discriminant analysis.

PubMed

Gutiérrez, R; Vega, S; Díaz, G; Sánchez, J; Coronado, M; Ramírez, A; Pérez, J; González, M; Schettino, B

2009-05-01

Gas chromatography was utilized to determine triacylglycerol profiles in milk and non-milk fat. The values of triacylglycerol were subjected to linear discriminant analysis to detect and quantify non-milk fat in milk fat. Two groups of milk fat were analyzed: A) raw milk fat from the central region of Mexico (n = 216) and B) ultrapasteurized milk fat from 3 industries (n = 36), as well as pork lard (n = 2), bovine tallow (n = 2), fish oil (n = 2), peanut (n = 2), corn (n = 2), olive (n = 2), and soy (n = 2). The samples of raw milk fat were adulterated with non-milk fats in proportions of 0, 5, 10, 15, and 20% to form 5 groups. The first function obtained from the linear discriminant analysis allowed the correct classification of 94.4% of the samples with levels <10% of adulteration. The triacylglycerol values of the ultrapasteurized milk fats were evaluated with the discriminant function, demonstrating that one industry added non-milk fat to its product in 80% of the samples analyzed.

LAM-1 and FAT Genes Control Development of the Leaf Blade in Nicotiana sylvestris.

PubMed Central

McHale, NA

1993-01-01

Leaf primordia of the lam-1 mutant of Nicotiana sylvestris grow normally in length but remain bladeless throughout development. The blade initiation site is established at the normal time and position in lam-1 primordia. Anticlinal divisions proceed normally in the outer L1 and L2 layers, but the inner L3 cells fail to establish the periclinal divisions that normally generate the middle mesophyll core. The lam-1 mutation also blocks formation of blade mesophyll from distal L2 cells. This suggests that LAM-1 controls a common step in initiation of blade tissue from the L2 and L3 lineage of the primordium. Another recessive mutation (fat) was isolated in N. sylvestris that induces abnormal periclinal divisions in the mesophyll during blade initiation and expansion. This generates a blade approximately twice its normal thickness by doubling the number of mesophyll cell layers from four to approximately eight. Presumably, the fat mutation defines a negative regulator involved in repression of periclinal divisions in the blade. The lam-1 fat double mutant shows radial proliferation of mesophyll cells at the blade initiation site. This produces a highly disorganized, club-shaped blade that appears to represent an additive effect of the lam-1 and fat mutations on blade founder cells. PMID:12271096

Reciprocal Relation between Marrow Adiposity and the Amount of Bone in the Axial and Appendicular Skeleton of Young Adults

PubMed Central

Di Iorgi, Natascia; Rosol, Michael; Mittelman, Steven D.; Gilsanz, Vicente

2008-01-01

Background: Studies in the elderly suggest a reciprocal relation between increased marrow adiposity and bone loss, supporting basic research data indicating that osteoblasts and adipocytes share a common progenitor cell. However, whether this relation represents a preferential differentiation of stromal cells from osteoblasts to adipocytes or whether a passive accumulation of fat as bone is lost and marrow space increases with aging is unknown. To address this question and avoid the confounding effect of bone loss, we examined teenagers and young adults. Methods: Using computed tomography, we obtained measurements of bone density and cross-sectional area of the lumbar vertebral bodies and cortical bone area, cross-sectional area, marrow canal area, and fat density in the marrow of the femurs in 255 sexually mature subjects (126 females, 129 males; 15–24.9 yr of age). Additionally, values for total body fat were obtained with dual-energy x-ray absorptiometry. Results: Regardless of gender, reciprocal relations were found between fat density and measures of vertebral bone density and femoral cortical bone area (r = 0.19–0.39; all P values ≤ .03). In contrast, there was no relation between marrow canal area and cortical bone area in the femurs, neither between fat density and the cross-sectional dimensions of the bones. We also found no relation between anthropometric or dual-energy x-ray absorptiometry fat values and measures for marrow fat density. Conclusions: Our results indicate an inverse relation between bone marrow adiposity and the amount of bone in the axial and appendicular skeleton and support the notion of a common progenitor cell capable of mutually exclusive differentiation into the cell lineages responsible for bone and fat formation. PMID:18381577

Potential drawbacks in cell-assisted lipotransfer: A systematic review of existing reports (Review)

PubMed Central

HUANG, SHENG; ZHAO, WEILIANG; WANG, ZIHUA; TAO, KAI; LIU, XIAOYAN; CHANG, PENG

2016-01-01

Cell-assisted lipotransfer (CAL) has been widely used in various clinical applications, including breast augmentation following mammectomy, soft-tissue reconstruction and wound healing. However, the clinical application of CAL has been restricted due to the transplanted fat tissues being readily liquefied and absorbed. The present review examines 57 previously published studies involving CAL, including fat grafting or fat transfer with human adipose-stem cells in all known databases. Of these 57 articles, seven reported the clinical application of CAL. In the 57 studies, the majority of the fat tissues were obtained from the abdomen via liposuction of the seven clinical studies, four were performed in patients requiring breast augmentation, one in a patient requiring facial augmentation, one in a patient requiring soft tissue augmentation/reconstruction and one in a patient requiring fat in their upper arms. Despite the potential risks, there has been an increased demand for CAL in in cosmetic or aesthetic applications. Thus, criteria and guidelines are necessary for the clinical application of CAL technology. PMID:26677061

ApoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells.

PubMed

Hirasawa, Hideyuki; Tanaka, Shinya; Sakai, Akinori; Tsutsui, Masato; Shimokawa, Hiroaki; Miyata, Hironori; Moriwaki, Sawako; Niida, Shumpei; Ito, Masako; Nakamura, Toshitaka

2007-07-01

Osteoblast apoptosis increased in the tibias of apoE(-/-) mice fed with a high-fat diet, decreasing bone formation. The expression of p53 mRNA in marrow adherent cells increased. LDL or oxidized LDL increased apoptosis in the calvarial cells of apoE(-/-) mice. The increase in p53-mediated apoptosis is apparently related to a high-fat diet-induced osteopenia in apoE(-/-) mice. The effects of high-fat loading and the apolipoprotein E (apoE) gene on bones have not been elucidated. We hypothesized that apoE gene deficiency (apoE(-/-)) modulates the effects of high-fat loading on bones. We assessed this hypothesis using wildtype (WT) and apoE(-/-) mice fed a standard (WTS and ApoES groups) or a high-fat diet (WTHf and ApoEHf groups). The concentration of serum lipid levels and bone chemical markers were measured. Histomorphometry of the femurs was performed using microCT and a microscope. Bone marrow adherent cells from the femurs were used for colony-forming unit (CFU)-fibroblastic (CFU-f) assay and mRNA expressions analysis. The apoptotic cells in the tibias were counted. TUNEL fluorescein assay and Western analysis were performed in cultures of calvarial cells by the addition of low-density lipoprotein (LDL) or oxidized LDL. In the ApoEHf group, the values of cortical bone volume and trabecular and endocortical bone formation of the femurs decreased, and urinary deoxypyridinoline increased. Subsequent analysis revealed that the number of apoptotic cells in the tibias of the ApoES group increased, and more so in the ApoEHf group. The ratio of alkaline phosphatase-positive CFU-f to total CFU-f was decreased in the ApoEHf group. p53 mRNA expression in adherent cells of the apoE(-/-) mice increased and had a significantly strong positive correlation with serum LDL. TUNEL fluorescein assay of osteoblastic cells revealed an increase of apoptotic cells in the apoE(-/-) mice. The number of apoptotic cells in the apoE(-/-) mice increased with the addition of 100 microg/ml LDL or oxidized LDL. The p53 protein expression in apoE(-/-) cells exposed to 100 microg/ml LDL or oxidized LDL increased. We concluded that apoE gene deficiency enhances the reduction of bone formation induced by a high-fat diet through the stimulation of p53-mediated apoptosis in osteoblastic cells.

The Body Fat-Cognition Relationship in Healthy Older Individuals: Does Gynoid vs Android Distribution Matter?

PubMed

Forte, R; Pesce, C; De Vito, G; Boreham, C A G

2017-01-01

To examine the relationship between regional and whole body fat accumulation and core cognitive executive functions. Cross-sectional study. 78 healthy men and women aged between 65 and 75 years recruited through consumer's database. DXA measured percentage total body fat, android, gynoid distribution and android/gynoid ratio; inhibition and working memory updating through Random Number Generation test and cognitive flexibility by Trail Making test. First-order partial correlations between regional body fat and cognitive executive function were computed partialling out the effects of whole body fat. Moderation analysis was performed to verify the effect of gender on the body fat-cognition relationship. Results showed a differentiated pattern of fat-cognition relationship depending on fat localization and type of cognitive function. Statistically significant relationships were observed between working memory updating and: android fat (r = -0.232; p = 0.042), gynoid fat (r = 0.333; p = 0.003) and android/gynoid ratio (r = -0.272; p = 0.017). Separating genders, the only significant relationship was observed in females between working memory updating and gynoid fat (r = 0.280; p = 0.045). In spite of gender differences in both working memory updating and gynoid body fat levels, moderation analysis did not show an effect of gender on the relationship between gynoid fat and working memory updating. Results suggest a protective effect of gynoid body fat and a deleterious effect of android body fat. Although excessive body fat increases the risk of developing CDV, metabolic and cognitive problems, maintaining a certain proportion of gynoid fat may help prevent cognitive decline, particularly in older women. Guidelines for optimal body composition maintenance for the elderly should not target indiscriminate weight loss, but weight maintenance through body fat/lean mass control based on non-pharmacological tools such as physical exercise, known to have protective effects against CVD risk factors and age-related cognitive deterioration.

Adipose tissue: cell heterogeneity and functional diversity.

PubMed

Esteve Ràfols, Montserrat

2014-02-01

There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

PubMed Central

González-Alonso, Adrián; Ramírez-Tortosa, César L.; Varela-López, Alfonso; Roche, Enrique; Arribas, María I.; Ramírez-Tortosa, M. Carmen; Giampieri, Francesca; Ochoa, Julio J.; Quiles, José L.

2015-01-01

An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources. PMID:26426013

Lipid-binding analysis using a fat blot assay.

PubMed

Munnik, Teun; Wierzchowiecka, Magdalena

2013-01-01

Protein-lipid interactions play an important role in lipid metabolism, membrane trafficking and cell -signaling by regulating protein localization, activation, and function. The Fat Blot assay is a relatively simple and inexpensive method to examine these interactions using nitrocellulose membrane-immobilized lipids. The assay is adapted from the method by Dowler et al. (Sci STKE 129:pl6, 2002) and provides qualitative and quantitative information on the relative affinity with which a protein binds to a particular lipid. To perform a Fat Blot assay, serial dilutions of different phospholipids are spotted onto a nitrocellulose membrane. These membranes are then incubated with a lipid-binding protein possessing a GST (or other epitope) tag. The membranes are washed and the protein, which is bound to the membrane by virtue of its interaction with the lipid's head group, is detected by immunoblotting with an antibody against GST (or other epitope). The procedure only requires a few micrograms of protein and is quick, simple and cheap to perform.

High fat programming of beta cell compensation, exhaustion, death and dysfunction.

PubMed

Cerf, Marlon E

2015-03-01

Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cell-assisted lipotransfer: Friend or foe in fat grafting? Systematic review and meta-analysis.

PubMed

Laloze, J; Varin, A; Gilhodes, J; Bertheuil, N; Grolleau, J L; Brie, J; Usseglio, J; Sensebe, L; Filleron, T; Chaput, B

2018-02-01

Autologous fat grafting is a common procedure for soft-tissue reconstruction but is associated with a graft resorption rate ranging from 20% to 80%. To improve the fat graft survival rate, a new technique, called cell-assisted lipotransfer (CAL), was developed. With CAL, fat is injected along with adipose-derived stromal cells that are assumed to improve fat survival rate. We conducted an evidence-based meta-analysis to evaluate the efficacy and safety of CAL as compared with conventional autologous fat grafting (non-CAL). The databases MEDLINE (via PubMed), Cochrane Library, EBSCO, Web of Science, and EMBASE were searched for reports of clinical trials, case series, and cohorts available from 2008 to 2016. We conducted a meta-analysis of the efficacy of CAL with data analysis concerning fat survival rate. The incidence of complications and the need for multiple procedures were evaluated to determine the safety of CAL. We identified 25 studies (696 patients) that were included in the systematic review; 16 studies were included in the meta-analysis to evaluate the efficacy of CAL. The fat survival rate was significantly higher with CAL than non-CAL (64% vs. 44%, p < .0001) independent of injection site (breast and face). This benefit of CAL was significant for only injection volumes <100 ml (p = .03). The two groups did not differ in frequency of multiple procedures after fat grafting, but the incidence of complications was greater with CAL than non-CAL (8.4% vs. 1.5%, p = .0019). The CAL method is associated with better fat survival rate than with conventional fat grafting but only for small volumes of fat grafting (<100 ml). Nonetheless, the new technique is associated with more complications and did not reduce the number of surgical procedures needed after the first fat grafting. More prospective studies are required to draw clinical conclusions and to demonstrate the real benefit of CAL as compared with common autologous fat grafting. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of diet-induced obesity on intestinal stem cells: hyperproliferation but impaired intrinsic function that requires insulin/IGF1.

PubMed

Mah, Amanda T; Van Landeghem, Laurianne; Gavin, Hannah E; Magness, Scott T; Lund, P Kay

2014-09-01

Nutrient intake regulates intestinal epithelial mass and crypt proliferation. Recent findings in model organisms and rodents indicate nutrient restriction impacts intestinal stem cells (ISC). Little is known about the impact of diet-induced obesity (DIO), a model of excess nutrient intake on ISC. We used a Sox9-EGFP reporter mouse to test the hypothesis that an adaptive response to DIO or associated hyperinsulinemia involves expansion and hyperproliferation of ISC. The Sox9-EGFP reporter mouse allows study and isolation of ISC, progenitors, and differentiated lineages based on different Sox9-EGFP expression levels. Sox9-EGFP mice were fed a high-fat diet for 20 weeks to induce DIO and compared with littermates fed low-fat rodent chow. Histology, fluorescence activated cell sorting, and mRNA analyses measured impact of DIO on jejunal crypt-villus morphometry, numbers, and proliferation of different Sox9-EGFP cell populations and gene expression. An in vitro culture assay directly assessed functional capacity of isolated ISC. DIO mice exhibited significant increases in body weight, plasma glucose, insulin, and insulin-like growth factor 1 (IGF1) levels and intestinal Igf1 mRNA. DIO mice had increased villus height and crypt density but decreased intestinal length and decreased numbers of Paneth and goblet cells. In vivo, DIO resulted in a selective expansion of Sox9-EGFP(Low) ISC and percentage of ISC in S-phase. ISC expansion significantly correlated with plasma insulin levels. In vitro, isolated ISC from DIO mice formed fewer enteroids in standard 3D Matrigel culture compared to controls, indicating impaired ISC function. This decreased enteroid formation in isolated ISC from DIO mice was rescued by exogenous insulin, IGF1, or both. We conclude that DIO induces specific increases in ISC and ISC hyperproliferation in vivo. However, isolated ISC from DIO mice have impaired intrinsic survival and growth in vitro that can be rescued by exogenous insulin or IGF1.

Ubiquitin‑like protein FAT10 regulates DNA damage repair via modification of proliferating cell nuclear antigen.

PubMed

Chen, Zhenchuan; Zhang, Wei; Yun, Zhimin; Zhang, Xue; Gong, Feng; Wang, Yunfang; Ji, Shouping; Leng, Ling

2018-06-01

In response to DNA damage, proliferating cell nuclear antigen (PCNA) has an important role as a positive regulator and as a scaffold protein associated with DNA damage bypass and repair pathways by serving as a platform for the recruitment of associated components. As demonstrated in the present study, the ubiquitin‑like modifier human leukocyte antigen F locus adjacent transcript 10 (FAT10), which binds to PCNA but has not previously been demonstrated to be associated with the DNA damage response (DDR), is induced by ultraviolet/ionizing radiation and VP‑16 treatment in HeLa cells. Furthermore, DNA damage enhances FAT10 expression. Immunoprecipitation analysis suggested PCNA is modified by FAT10, and the degradation of FATylated PCNA located in the cytoplasm is regulated by the 26S proteasome, which is also responsible for the upregulation of nuclear foci formation. Furthermore, immunofluorescence experiment suggested FAT10 co‑localizes with PCNA in nuclear foci, thus suggesting that FATylation of PCNA may affect DDR via the induction of PCNA degradation in the cytoplasm or nucleus. In addition, immunohistochemistry experiment suggested the expression levels of FAT10 and PCNA are enhanced in HCC tissues compared with healthy liver tissues; however, the expression of FAT10 is suppressed in regenerated liver tissues, which express high levels of PCNA, thus suggesting that the association between FAT10 and PCNA expression is only exhibited in tumor tissues. In conclusion, the results of the present study suggest that FAT10 may be involved in DDR and therefore the progression of tumorigenesis.

Temperature sensing of adipose tissue heating with the luminescent upconversion nanoparticles as nanothermometer: in vitro study

NASA Astrophysics Data System (ADS)

Yanina, I. Yu.; Volkova, E. K.; Zaharevich, A. M.; Konyukhova, J. G.; Kochubey, V. I.; Tuchin, V. V.

2017-03-01

The luminescence spectra of upconversion nanoparticles (UCNPs) imbedded in fat tissue were measured in a wide temperature range, from room to human body and further to hyperthermic temperatures. The two types of synthesized UCNP [NaYF4:Yb3+, Er3+] specimens, namely, powdered as-is and embedded into polymer film, were used. The results show that the luminescence of UCNPs placed under the adipose tissue layer is reasonably good sensitive to temperature change and reflects phase transitions of lipids in tissue cells. The most likely, multiple phase transitions are associated with the different components of fat cells such as phospholipids of cell membrane and lipids of fat droplets. In the course of fat cell heating, lipids of fat droplet first transit from a crystalline form to a liquid crystal form and then to a liquid form, which is characterized by much less scattering. The phase transitions of lipids were observed as the changes of the slope of the temperature dependence of UCNP luminescence intensity. The obtained results confirm a high sensitivity of the luminescent UCNPs to the temperature variations within tissues and show a strong potential for providing a controllable tissue thermolysis.

A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induce Apoptosis

DTIC Science & Technology

2007-09-01

mm3 tumor sections were bilaterally transplanted using a trochar into the axillary mammary fat pads. For studies using tumor models which were... fat pads at 107 cells per site. Tumor growth was tracked by weekly measurements of tumor length (l) and width (w) using Vernier calipers, from which...breast cancer, was originally developed by bilateral injection of 107 MCF-7 cells, grown in tissue culture, into the axillary mammary fat pads of female

Perinatal Maternal Mortality in Sickle Cell Anemia: Two Case Reports and Review of the Literature.

PubMed

Rizk, Sanaa; Pulte, Elizabeth D; Axelrod, David; Ballas, Samir K

As outcomes of patients with sickle cell anemia improve and survival into adulthood with good quality of life and expectation of long-term survival becomes more common, challenges have developed, including issues related to reproduction. Pregnancy is frequently complicated in patients with sickle cell anemia with mortality up to 4.0%. Here we report maternal perinatal mortality in two women with sickle cell anemia who died post-partum due to acute chest syndrome (ACS), caused by bone marrow fat embolism and review the literature pertinent to this subject. Patient A was a 28-year-old woman with sickle cell anemia with multiple complications. At 30 weeks' gestation she developed hemolysis associated with poor placental function necessitating delivery by C-section. The fetus was delivered successfully but she died due to multi organ failure after delivery. Autopsy showed pulmonary and amniotic fluid embolization. Patient B was a 37-year-old woman with uncomplicated sickle cell anemia who presented with pre term labor and crisis, then ACS and fetal distress. The infant was delivered successfully but the patient died after cardiovascular collapse. Autopsy results showed fat and bone marrow embolization as the cause of death. Pregnancy continues to be high risk for patients with sickle cell anemia including those with mild disease. Maternal perinatal mortality could be unpredictable due to serious complications of sickle cell disease. More studies to assess maternal perinatal mortality are needed.

Controlling Cell Function with Geometry

NASA Astrophysics Data System (ADS)

Mrksich, Milan

2012-02-01

This presentation will describe the use of patterned substrates to control cell shape with examples that illustrate the ways in which cell shape can regulate cell function. Most cells are adherent and must attach to and spread on a surface in order to survive, proliferate and function. In tissue, this surface is the extracellular matrix (ECM), an insoluble scaffold formed by the assembly of several large proteins---including fibronectin, the laminins and collagens and others---but in the laboratory, the surface is prepared by adsorbing protein to glass slides. To pattern cells, gold-coated slides are patterned with microcontact printing to create geometric features that promote cell attachment and that are surrounded by inert regions. Cells attach to these substrates and spread to adopt the shape defined by the underlying pattern and remain stable in culture for several days. Examples will be described that used a series of shapes to reveal the relationship between the shape of the cell and the structure of its cytoskeleton. These geometric cues were used to control cell polarity and the tension, or contractility, present in the cytoskeleton. These rules were further used to control the shapes of mesenchymal stem cells and in turn to control the differentiation of these cells into specialized cell types. For example, stem cells that were patterned into a ``star'' shape preferentially differentiated into bone cells whereas those that were patterned into a ``flower'' shape preferred a fat cell fate. These influences of shape on differentiation depend on the mechanical properties of the cytoskeleton. These examples, and others, reveal that shape is an important cue that informs cell function and that can be combined with the more common soluble cues to direct and study cell function.

Concentrated Growth Factor Enhanced Fat Graft Survival: A Comparative Study.

PubMed

Hu, Yun; Jiang, Yichen; Wang, Muyao; Tian, Weidong; Wang, Hang

2018-06-08

Concentrated growth factors (CGFs) belong to a new generation biomaterials that concentrate large number of growth factors and CD34 stem cells in small volume of plasma. The purpose of this study was to evaluate the impact of the new technique, CGF, on fat graft survival, which compared with platelet-rich plasma (PRP) and platelet-rich fibrin (PRF). Nude mice received fat graft were divided into PRP group, PRF group, CGF group, and saline. The grafts were volumetrically and histologically evaluated at 4, 8, and 12 weeks after fat grafting. In vitro growth factor levels in PRP, PRF, and CGF were compared using enzyme-linked immunoassay method. Cell count and real-time polymerase chain reaction were used to evaluate the impact of CGF in medium on human adipose-derived stem cell (hADSC) proliferation and vascular differentiation, respectively. Fat graft weight was significantly higher in the CGF group than those in the other groups, and histologic evaluation revealed greater vascularity, fewer cysts, and less fibrosis. Adding CGF to the medium maximally promoted hADSC proliferation and expressing vascular endothelial growth factor and PECAM-1. In this preliminary study, CGF treatment improved the survival and quality of fat grafts.

Nutritional deficiency, immunologic function, and disease.

PubMed Central

Good, R. A.; Fernandes, G.; Yunis, E. J.; Cooper, W. C.; Jose, D. C.; Kramer, T. R.; Hansen, M. A.

1976-01-01

Several experiments conducted by our group over a period of 6 years have shown that nutritional stress, especially protein and/or calorie deprivation, leads to many, often dramatic, changes in the immune responses of mice, rats, and guinea pigs. Chronic protein deprivation (CPD) has been shown to create an enhancing effect on the cell-mediated immune responses of these animals. Humoral responses under CPD conditions were most often found to be depressed, but sometimes were unaffected, depending on the nature of the antigen employed. Chronic protein deprivation, consistent with the pattern just mentioned, improved tumor immunity by depressing production of B-cell blocking factors, and, in at least one instance, resistance to development of mammary adenocarcinoma in C3H mice was associated with evidence of increased numbers of T suppressor cells. Profound nutritional deficits (less than 5% protein per total daily food intake) depressed both cellular and humoral immunity. Early, though temporary, protein deprivation caused a long-term depression of both cellular and humoral immunity also, with the humoral component being the first to recover. Manipulation of protein and calories was found to have a profound effect on certain autoimmune conditions. Diets high in fat and low in protein favored reproduction but shortened the life of NZB mice, whereas diets high in protein and low in fat inhibited development of autoimmunity and prolonged life. Chronic moderate protein restriction permitted NZB mice to maintain their normally waning immunologic functions much longer than mice fed a normal protein intake. Further, the low-protein diet was associated with a delay in development of manifestations of autoimmunity. Decreasing dietary calories by a reduction of fats, carbohydrates, and proteins more than doubled the average life span of (NZB X NZW)F1 mice, a strain prone to early death from autoimmune disease. Histopathologic studies using immunofluorescent microscopy revealed that the development of the renal lesions caused by the deposition of antigen-antibody complexes, which is so characteristic of these mice, was markedly delayed. PMID:8988

Rust preventive oil additives based on microbial fats

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

Salenko, V.I.; Fedorov, V.V.; Kazantsev, Yu.E.

1983-03-01

This article investigates the composition and lubricating properties of microbial fats obtained from microorganisms grown on various hydrocarbon substrates (n-paraffins, alcohols, natural gas, petroleum distillates, etc.). Focuses on the protective functions of the 4 main fractions (unsaponifiables, free fatty acids, glycerides, and phospholipids) which comprise the microbial fat from a yeast grown on purified liquid n-paraffins. Concludes that neutralized microbial fats can be used as preservative additives; that the principal components of the microbial fats have the properties necessary for oil-soluble corrosion inhibitors; that the phospholipids of the microbial fat can fulfill the functions of not only preservative additives, butmore » also highly effective operational/ preservative additives; and that fats of microbial origin can be used in the development of multipurpose polyfunctional additives.« less

Histochemistry and ultrastructure of urocytes in the pupae of the stingless bee Melipona quadrifasciata (Hymenoptera: Meliponini).

PubMed

Furtado, Waléria C A; Azevedo, Dihego O; Martins, Gustavo F; Zanuncio, José C; Serrão, José Eduardo

2013-12-01

The main cell types of the adult bee fat body are trophocytes and oenocytes; however, in pupae of some newly emerged bees, trophocytes are modified into cells called urocytes, which possibly function as a substitute for Malpighian tubules during metamorphosis when larval tubules are not functional and/or storage of urate salts is required. This study evaluated the morphology of urocytes in the stingless bee Melipona quadrifasciata and the possibility of maintaining these cells in primary culture. The urocytes M. quadrifasciata are white spherical cells with an irregular surface as observed by stereomicroscopy. They may be found individually or in groups associated with tracheae. Urocytes have a single, small, and spherical nucleus and cytoplasm rich in neutral polysaccharides, lipid droplets, protein, and granules containing calcium and urate salts. Our findings suggest that urocytes play a role in storage of neutral polysaccharides and calcium in M. quadrifasciata pupae and that these cells can be cultured for 72 h.

Contrasting apoptotic responses of conjugated linoleic acid in the liver of obese Zucker rats fed palm oil or ovine fat.

PubMed

Lopes, Paula A; Martins, Susana V; Viana, Ricardo S J; Ramalho, Rita M; Alfaia, Cristina M; Pinho, Mário S; Jerónimo, Eliana; Bessa, Rui J B; Castro, Matilde F; Rodrigues, Cecília M P; Prates, José A M

2011-08-01

We hypothesized that reducing weight properties of conjugated linoleic acid (CLA) are due to adipocyte apoptosis and that CLA differentially modulates the apoptotic responses in hepatic lipotoxicity from rats fed saturated fat diets. Obese Zucker rats were fed atherogenic diets (2%w/w of cholesterol) formulated with high (15%w/w) saturated fat, from vegetable or animal origin, supplemented or not with 1% of a mixture (1:1) of cis-9, trans-11 and trans-10, cis-12 CLA isomers for 14 weeks. CLA induced no changes on retroperitoneal fat depot weight, which was in line with similar levels of apoptosis. Interestingly, CLA had a contrasting effect on cell death in the liver according to the dietary fat. CLA increased hepatocyte apoptosis, associated with upregulation of Fas protein in rats fed palm oil, compared to rats receiving palm oil alone. However, rats fed ovine fat alone displayed the highest levels of hepatic cell death, which were decreased in rats fed ovine fat plus CLA. This reducing effect of CLA was related to positively restoring endoplasmic reticulum (ER) ATF-6α, BiP and CHOP protein levels and increasing phosphorylated c-Jun NH(2)-terminal kinase (JNK) and c-Jun, thus suggesting an adaptive response of cell survival. These findings reinforce the role of CLA as regulator of apoptosis in the liver. Moreover, the dietary fat composition is a key factor in activation of apoptosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bone marrow mesenchymal stem cell-derived extracellular vesicles improve the survival of transplanted fat grafts

PubMed Central

Huang, He; Feng, Shaoqing; Zhang, Wenjie; Li, Wei; Xu, Peng; Wang, Xiangsheng; Ai, Ai

2017-01-01

Autologous fat grafting is a promising surgical technique for soft tissue augmentation, reconstruction and rejuvenation. However, it is limited by the low survival rate of the transplanted fat, due to the slow revascularization of such grafts. Previous studies have demonstrated that bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) are proangiogenic. The present study aimed to investigate whether BMSC-EVs could improve the survival of transplanted fat grafts. Extracellular vesicles were isolated from the supernatant of cultured rat bone marrow mesenchymal stem cells, and characterized by flow cytometry and scanning electron microscopy. Their proangiogenic potential was measured in vitro using tube formation and cell migration assays. Subsequently, human fat tissue grafts, alongside various concentrations of BMSC-EVs, were subcutaneously injected into nude mice. A total of 12 weeks following transplantation, the mice were sacrificed and the grafts were harvested. The grafts from the experimental group had a higher survival rate and an increased number of vessels compared with grafts from the control group, as demonstrated by tissue volume, weight and histological analyses. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the expression levels of proangiogenic factors were increased in the experimental group compared with in the control group, thus suggesting that BMSC-EVs may promote neovascularization by stimulating the secretion of proangiogenic factors. The present study is the first, to the best of our knowledge, to demonstrate that supplementation of fat grafts with BMSC-EVs improves the long-term retention and quality of transplanted fat. PMID:28713978

β-Cell Lipotoxicity After an Overnight Intravenous Lipid Challenge and Free Fatty Acid Elevation in African American Versus American White Overweight/Obese Adolescents

PubMed Central

Hughan, Kara S.; Bonadonna, Riccardo C.; Lee, SoJung; Michaliszyn, Sara F.

2013-01-01

Objective: Overweight/obese (OW/OB) African American (AA) adolescents have a more diabetogenic insulin secretion/sensitivity pattern compared with their American white (AW) peers. The present study investigated β-cell lipotoxicity to test whether increased free fatty acid (FFA) levels result in greater β-cell dysfunction in AA vs AW OW/OB adolescents. Research Design and Methods: Glucose-stimulated insulin secretion was modeled, from glucose and C-peptide concentrations during a 2-hour hyperglycemic (225 mg/dL) clamp in 22 AA and 24 AW OW/OB adolescents, on 2 occasions after a 12-hour overnight infusion of either normal saline or intralipid (IL) in a random sequence. β-Cell function relative to insulin sensitivity, the disposition index (DI), was examined during normal saline and IL conditions. Substrate oxidation was evaluated with indirect calorimetry and body composition and abdominal adiposity with dual-energy X-ray absorptiometry and magnetic resonance imaging at L4-L5, respectively. Results: Age, sex, body mass index, total and sc adiposity were similar between racial groups, but visceral adiposity was significantly lower in AAs. During IL infusion, FFAs and fat oxidation increased and insulin sensitivity decreased similarly in AAs and AWs. β-Cell glucose sensitivity of first- and second-phase insulin secretion did not change significantly during IL infusion in either group, but DI in each phase decreased significantly and similarly in AAs and AWs. Conclusions: Overweight/obese AA and AW adolescents respond to an overnight fat infusion with significant declines in insulin sensitivity, DI, and β-cell function relative to insulin sensitivity, suggestive of β-cell lipotoxicity. However, contrary to our hypothesis, there does not seem to be a race differential in β-cell lipotoxicity. Longer durations of FFA elevation may unravel such race-related contrasts. PMID:23526462

Mouse fat storage-inducing transmembrane protein 2 (FIT2) promotes lipid droplet accumulation in plants.

PubMed

Cai, Yingqi; McClinchie, Elizabeth; Price, Ann; Nguyen, Thuy N; Gidda, Satinder K; Watt, Samantha C; Yurchenko, Olga; Park, Sunjung; Sturtevant, Drew; Mullen, Robert T; Dyer, John M; Chapman, Kent D

2017-07-01

Fat storage-inducing transmembrane protein 2 (FIT2) is an endoplasmic reticulum (ER)-localized protein that plays an important role in lipid droplet (LD) formation in animal cells. However, no obvious homologue of FIT2 is found in plants. Here, we tested the function of FIT2 in plant cells by ectopically expressing mouse (Mus musculus) FIT2 in Nicotiana tabacum suspension-cultured cells, Nicotiana benthamiana leaves and Arabidopsis thaliana plants. Confocal microscopy indicated that the expression of FIT2 dramatically increased the number and size of LDs in leaves of N. benthamiana and Arabidopsis, and lipidomics analysis and mass spectrometry imaging confirmed the accumulation of neutral lipids in leaves. FIT2 also increased seed oil content by ~13% in some stable, overexpressing lines of Arabidopsis. When expressed transiently in leaves of N. benthamiana or suspension cells of N. tabacum, FIT2 localized specifically to the ER and was often concentrated at certain regions of the ER that resembled ER-LD junction sites. FIT2 also colocalized at the ER with other proteins known to be involved in triacylglycerol biosynthesis or LD formation in plants, but not with ER resident proteins involved in electron transfer or ER-vesicle exit sites. Collectively, these results demonstrate that mouse FIT2 promotes LD accumulation in plants, a surprising functional conservation in the context of a plant cell given the apparent lack of FIT2 homologues in higher plants. These results suggest also that FIT2 expression represents an effective synthetic biology strategy for elaborating neutral lipid compartments in plant tissues for potential biofuel or bioproduct purposes. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Mouse fat storage-inducing transmembrane protein 2 (FIT2) promotes lipid droplet accumulation in plants

DOE PAGES

Cai, Yingqi; McClinchie, Elizabeth; Price, Ann; ...

2017-01-18

Fat storage-inducing transmembrane protein 2 (FIT2) is an endoplasmic reticulum (ER)-localized protein that plays an important role in lipid droplet (LD) formation in animal cells. However, no obvious homologue of FIT2 is found in plants. We tested the function of FIT2 in plant cells by ectopically expressing mouse (Mus musculus) FIT2 in Nicotiana tabacum suspension-cultured cells, Nicotiana benthamiana leaves and Arabidopsis thaliana plants. Confocal microscopy indicated that the expression of FIT2 dramatically increased the number and size of LDs in leaves of N. benthamiana and Arabidopsis, and lipidomics analysis and mass spectrometry imaging confirmed the accumulation of neutral lipids inmore » leaves. FIT2 also increased seed oil content by ~13% in some stable, overexpressing lines of Arabidopsis. Furthermore, when expressed transiently in leaves of N. benthamiana or suspension cells of N. tabacum, FIT2 localized specifically to the ER and was often concentrated at certain regions of the ER that resembled ER-LD junction sites. FIT2 also colocalized at the ER with other proteins known to be involved in triacylglycerol biosynthesis or LD formation in plants, but not with ER resident proteins involved in electron transfer or ERvesicle exit sites. Collectively, these results demonstrate that mouse FIT2 promotes LD accumulation in plants, a surprising functional conservation in the context of a plant cell given the apparent lack of FIT2 homologues in higher plants. Our results suggest also that FIT2 expression represents an effective synthetic biology strategy for elaborating neutral lipid compartments in plant tissues for potential biofuel or bioproduct purposes.« less

Mouse fat storage-inducing transmembrane protein 2 (FIT2) promotes lipid droplet accumulation in plants

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

Cai, Yingqi; McClinchie, Elizabeth; Price, Ann

Fat storage-inducing transmembrane protein 2 (FIT2) is an endoplasmic reticulum (ER)-localized protein that plays an important role in lipid droplet (LD) formation in animal cells. However, no obvious homologue of FIT2 is found in plants. We tested the function of FIT2 in plant cells by ectopically expressing mouse (Mus musculus) FIT2 in Nicotiana tabacum suspension-cultured cells, Nicotiana benthamiana leaves and Arabidopsis thaliana plants. Confocal microscopy indicated that the expression of FIT2 dramatically increased the number and size of LDs in leaves of N. benthamiana and Arabidopsis, and lipidomics analysis and mass spectrometry imaging confirmed the accumulation of neutral lipids inmore » leaves. FIT2 also increased seed oil content by ~13% in some stable, overexpressing lines of Arabidopsis. Furthermore, when expressed transiently in leaves of N. benthamiana or suspension cells of N. tabacum, FIT2 localized specifically to the ER and was often concentrated at certain regions of the ER that resembled ER-LD junction sites. FIT2 also colocalized at the ER with other proteins known to be involved in triacylglycerol biosynthesis or LD formation in plants, but not with ER resident proteins involved in electron transfer or ERvesicle exit sites. Collectively, these results demonstrate that mouse FIT2 promotes LD accumulation in plants, a surprising functional conservation in the context of a plant cell given the apparent lack of FIT2 homologues in higher plants. Our results suggest also that FIT2 expression represents an effective synthetic biology strategy for elaborating neutral lipid compartments in plant tissues for potential biofuel or bioproduct purposes.« less

Endurance exercise in a rat model of metabolic syndrome.

PubMed

Cameron, Isabelle; Alam, Mohammad Ashraful; Wang, Jianxiong; Brown, Lindsay

2012-11-01

We have measured the responses to endurance exercise training on body composition and glucose regulation, as well as cardiovascular and liver structure and function in rats fed a high carbohydrate and high fat (HCHF) diet as a model of human metabolic syndrome. Male Wistar rats (9-10 weeks old) were randomly allocated into corn starch (CS) or HCHF diet groups for 16 weeks; half of each group were exercised on a treadmill for 20, 25, and then 30 min/day, 5 days/week, during the last 8 weeks of the protocol. Metabolic, cardiovascular, and liver parameters were monitored. The HCHF diet induced symptoms of metabolic syndrome, including obesity, dyslipidemia, impaired glucose tolerance, and increased systolic blood pressure associated with the development of cardiovascular remodeling and nonalcoholic steatohepatitis. Exercise in HCHF rats decreased body mass, abdominal fat pads and circumference, blood glucose concentrations, plasma lipid profiles, systolic blood pressure, left ventricular diastolic stiffness, collagen deposition and inflammatory cell infiltration in the left ventricle, improved aortic contractile and relaxation responses, and decreased liver mass and hepatic fat accumulation. This study demonstrates that endurance exercise is effective in this rat model of diet-induced metabolic syndrome in improving body composition and glucose regulation, as well as cardiovascular and liver structure and function.

A potential bioactive hard-stock fat replacer comprised of a molecular gel.

PubMed

Rogers, Michael A; Spagnuolo, Paul A; Wang, Tzu-Min; Angka, Leonard

2017-05-01

Short-chain ceramides, such as N -acetoyl-d-erythro-sphingosine (C2), have a remarkable ability to structure edible oils, such as canola oil, into self-standing organogels without any added saturated or trans fats. These short-chain ceramides are ubiquitously found in foods ranging from eggs to soybeans. As the ceramide fatty acid chain length increases, there is an increase in the melting temperature of the organogel and a decrease in the elastic modulus. Gelation ability is lost at 2 wt% when the fatty acid chain length increases to six carbons; however, organogels form at 5 wt% up to 18 carbons. Short-chain ceramides, C2, decrease cell viability of colon, prostate, ovarian, and leukemia cell lines, while ceramides with long-chain fatty acids, C18, do not affect the viability of these cancer cell lines. This suggests that a bioactive spreadable fat, with no trans or added saturated fat, with the potential to alter the viability of cancer cell growth, is possible.

Historical Overview of Stem Cell Biology and Fat Grafting.

PubMed

Varghese, Jajini; Mosahebi, Afshin

2017-07-01

The last two decades have seen significant advances within the field of adipose stromal cell transfers, with novel clinical applications being published every few months. This article gives a brief historical overview of the development of stem cell biology and fat grafting. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Protection of brain and pancreas from high-fat diet: effects of catechin and caffeine.

PubMed

Unno, Keiko; Yamamoto, Hiroyuki; Maeda, Ken-Ichi; Takabayashi, Fumiyo; Yoshida, Hirotoshi; Kikunaga, Naomi; Takamori, Nina; Asahina, Shunsuke; Iguchi, Kazuaki; Sayama, Kazutoshi; Hoshino, Minoru

2009-02-16

To investigate the effect of a high-fat diet on brain and pancreas functions, we used SAMP10 mice that have characteristics of brain atrophy and cognitive dysfunction with aging. Simultaneously, we investigated the effect of green tea catechin consumption on high-fat diet feeding, because green tea catechin has been reported to improve brain atrophy, brain dysfunction and obesity. The body weight of mice fed a high-fat diet from 2 to 12 months was higher than that of the control, although the calorie intake was not. The high-fat diet also increased insulin secretion; however, the hypersecretion of insulin and obesity were suppressed when mice were fed a high-fat diet with green tea catechin and caffeine. Furthermore, brain atrophy was suppressed and the working memory, tested using Y-maze, improved in mice fed a high-fat diet containing green tea catechin and caffeine. The secretion of insulin might affect both obesity and brain function. A strong correlation was found between working memory and insulin release in mice fed a high-fat diet with green tea catechin and/or caffeine. The results indicate the protective effect of green tea catechin and caffeine on the functions of brain and pancreas in mice fed a high-fat diet.

The Relative Associations of β-Cell Function and Insulin Sensitivity with Glycemic Status and Incident Glycemic Progression in Migrant Asian Indians in the United States: the MASALA study

PubMed Central

Gujral, UP; Narayan, KMV; Kahn, SE; Kanaya, AM

2013-01-01

AIMS We assessed the relative associations of β-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States. METHODS A 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISIM) estimated insulin sensitivity, and the Disposition Index (DIo) estimated β-cell function. Visceral fat was measured by abdominal CT. After 2.5 years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia. RESULTS Mean age was 57±8 years and BMI 26.1±4.6 kg/m2. Log ISIM and log DIo were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DIo remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-year) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-β(OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression. CONCLUSIONS The association of DIo with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-β with incident glycemic progression implies innate β-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia. PMID:24211090

Body composition of children with cancer during treatment and in survivorship.

PubMed

Murphy, Alexia J; White, Melinda; Elliott, Sarah A; Lockwood, Liane; Hallahan, Andrew; Davies, Peter Sw

2015-10-01

Malnutrition as assessed with the use of body-composition measurements is a poorly understood short- and long-term complication of childhood cancer. We aimed to evaluate the body composition of 2 childhood cancer cohorts as follows: 1) children currently undergoing cancer treatment and 2) childhood cancer survivors. We also aimed to compare the prevalence of obesity and undernutrition between the cancer groups and investigate the impact of cancer type on body composition. Eighty-two children during the treatment of cancer and 53 childhood cancer survivors were involved in the study. Height, weight, body cell mass, percentage of fat, fat mass index, and fat-free mass index were assessed. Subjects were compared with age- and sex-matched healthy controls. The on-treatment group had a higher percentage of fat (P = 0.0001) and fat mass index (P = 0.0001) and a significantly lower body cell mass index (P = 0.0001) and fat-free mass index (P = 0.003) than did matched controls. The survivor group had a significantly higher percentage of fat (P = 0.03) and fat mass index (P = 0.04) and significantly lower body cell mass index (P = 0.0001) than did matched controls. The prevalence of undernutrition was high in both groups with 48% (95% CI: 36%, 60%) of the on-treatment group and 53% (95% CI: 40%, 66%) of the survivors considered undernourished. According to the percentage of fat cutoffs, significantly more on-treatment patients were obese (55%; 95% CI: 40%, 60%) than were survivors (26%; 95% CI: 14%, 38%) (P = 0.005). There were no statistically significant differences in body composition between cancer types in either the on-treatment or the survivor group. Overnutrition and undernutrition are major concerns in the short and long term for children with cancer. Children treated for cancer have increased fat mass and decreased body cell mass, which are evident during treatment and in survivorship. This trial was registered at http://www.ANZCTR.org.au as ACTRN12614001279617 and ACTRN12614001269628. © 2015 American Society for Nutrition.

Mesenchymal Stem Cells in the Bone Marrow Provide a Supportive Niche for Early Disseminated Breast Tumor Initiating Cells

DTIC Science & Technology

2013-06-01

transplanted into the mammary fat pad of NUDE mice to establish tumorigenicity in vivo. At 3 months post- injection , micrometastases to the lung, liver...E-cadherin, nuclear β catenin and fibronectin but were negative for ERα and vimentin. The injection of bone marrow isolated from mice previously... injected with tumorspheres into the mammary fat pad, resulted in large tumor formation in the mammary fat pad 2 months post- injection . The tumors

Understanding Collagen Organization in Breast Tumors to Predict and Prevent Metastasis

DTIC Science & Technology

2015-11-01

and their mechanism of action. We have explored stromal effects of macrophages in the E0771 murine mammary adenocarcinoma grown in the mammary fat ...and impacted tumor progression in breast tumor cell lines grown in the mammary fat pad (Figure 2 in Madden K, et al. 2013, Figure 9 here). We then...expression of TNF-α. To test this hypothesis, we grew mammary fat pad (MFP) tumors using a breast tumor cell line (E0771, a mammary adenocarcinoma derived from

Site-Specific Fat-1 Knock-In Enables Significant Decrease of n-6PUFAs/n-3PUFAs Ratio in Pigs.

PubMed

Li, Mengjing; Ouyang, Hongsheng; Yuan, Hongming; Li, Jianing; Xie, Zicong; Wang, Kankan; Yu, Tingting; Liu, Minghao; Chen, Xue; Tang, Xiaochun; Jiao, Huping; Pang, Daxin

2018-05-04

The fat-1 gene from Caenorhabditis elegans encodes a fatty acid desaturase which was widely studied due to its beneficial function of converting n-6 polyunsaturated fatty acids (n-6PUFAs) to n-3 polyunsaturated fatty acids (n-3PUFAs). To date, many fat-1 transgenic animals have been generated to study disease pathogenesis or improve meat quality. However, all of them were generated using a random integration method with variable transgene expression levels and the introduction of selectable marker genes often raise biosafety concern. To this end, we aimed to generate marker-free fat-1 transgenic pigs in a site-specific manner. The Rosa26 locus, first found in mouse embryonic stem cells, has become one of the most common sites for inserting transgenes due to its safe and ubiquitous expression. In our study, the fat-1 gene was inserted into porcine Rosa 26 (pRosa26) locus via Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) system. The Southern blot analysis of our knock-in pigs indicated a single copy of the fat-1 gene at the pRosa26 locus. Furthermore, this single-copy fat-1 gene supported satisfactory expression in a variety of tissues in F1 generation pigs. Importantly, the gas chromatography analysis indicated that these fat-1 knock-in pigs exhibited a significant increase in the level of n-3PUFAs, leading to an obvious decrease in the n-6PUFAs/n-3PUFAs ratio from 9.36 to 2.12 (*** P < 0.0001). Altogether, our fat-1 knock-in pigs hold great promise for improving the nutritional value of pork and serving as an animal model to investigate therapeutic effects of n-3PUFAs on various diseases. Copyright © 2018 Li et al.

Identification of a potential functional single nucleotide polymorphism for fatness and growth traits in the 3'-untranslated region of the PCSK1 gene in chickens.

PubMed

Zhang, K; Cheng, B H; Yang, L L; Wang, Z P; Zhang, H L; Xu, S S; Wang, S Z; Wang, Y X; Zhang, H; Li, H

2017-11-01

Prohormone convertase 1/3 is a serine endoprotease belonging to the subtilisin-like proprotein convertase family that is encoded by the () gene, and its major function is the processing and bioactivation of the proproteins of many kinds of neuroendocrine hormones, including insulin, cholecystokinin, and adrenocorticotropic hormone. The results of our previous genomewide association study indicated that the gene might be an important candidate gene for fatness traits in chickens. The objectives of this study were to investigate the tissue expression profiles of gene and to identify functional variants associated with fatness and growth traits in the chicken. The results indicated that mRNA was widely expressed in various tissues, especially neuroendocrine and intestinal tissues. Of these 2 tissue types, mRNA expression in lean males was significantly higher than in fat males. A SNP in the 3' untranslated region of (c.*900G > A) was identified. Association analysis in the Arbor Acres commercial broiler population and Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) population showed that the SNP c.*900G > A was associated with abdominal fat weight, abdominal fat percentage, BW, metatarsus length, and metatarsal circumference. In the 5th to 19th generation (G to G) of NEAUHLF, the allele frequency of c.*900G > A changed along with selection for abdominal fat content. At G, allele G of c.*900G > A was predominate in the lean line, whereas allele A was predominate in the fat line. Functional analysis demonstrated that allele A of c.*900G > A reduced mRNA stability and consequently downregulated gene expression. These results suggested that c.*900G > A was a functional SNP for fatness and growth traits in the chicken. The results of this study provide basic molecular information for the role of gene in avian growth and development, especially obesity.

The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity

PubMed Central

Cantó, Carles; Houtkooper, Riekelt H.; Pirinen, Eija; Youn, Dou Y.; Oosterveer, Maaike H.; Cen, Yana; Fernandez-Marcos, Pablo J.; Yamamoto, Hiroyasu; Andreux, Pénélope A.; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A.; Auwerx, Johan

2013-01-01

SUMMARY As NAD+ is a rate-limiting co-substrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38 —both NAD+ consumers— increases NAD+ bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD+ precursor with the ability to increase NAD+ levels, Sir2-dependent gene silencing and replicative lifespan in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD+ levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin, NR, could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function. PMID:22682224

A Fat-Facets-Dscam1-JNK Pathway Enhances Axonal Growth in Development and after Injury

PubMed Central

Koch, Marta; Nicolas, Maya; Zschaetzsch, Marlen; de Geest, Natalie; Claeys, Annelies; Yan, Jiekun; Morgan, Matthew J.; Erfurth, Maria-Luise; Holt, Matthew; Schmucker, Dietmar; Hassan, Bassem A.

2018-01-01

Injury to the adult central nervous systems (CNS) can result in severe long-term disability because damaged CNS connections fail to regenerate after trauma. Identification of regulators that enhance the intrinsic growth capacity of severed axons is a first step to restore function. Here, we conducted a gain-of-function genetic screen in Drosophila to identify strong inducers of axonal growth after injury. We focus on a novel axis the Down Syndrome Cell Adhesion Molecule (Dscam1), the de-ubiquitinating enzyme Fat Facets (Faf)/Usp9x and the Jun N-Terminal Kinase (JNK) pathway transcription factor Kayak (Kay)/Fos. Genetic and biochemical analyses link these genes in a common signaling pathway whereby Faf stabilizes Dscam1 protein levels, by acting on the 3′-UTR of its mRNA, and Dscam1 acts upstream of the growth-promoting JNK signal. The mammalian homolog of Faf, Usp9x/FAM, shares both the regenerative and Dscam1 stabilizing activities, suggesting a conserved mechanism. PMID:29472843

Modulation of Rhamm (CD168) for selective adipose tissue development

DOEpatents

Turley, Eva A; Bissell, Mina J

2014-05-06

Herein is described the methods and compositions for modulation of Rhamm, also known as CD 186, and its effects on wound repair, muscle differentiation, bone density and adipogeneisis through its ability to regulate mesenchymal stem cell differentiation. Compositions and methods are provided for blocking Rhamm function for selectively increasing subcutaneous, but not, visceral fat. Compositions and methods for modulating Rhamm in wound repair are also described.

Naringenin Inhibits Adipogenesis and Reduces Insulin Sensitivity and Adiponectin Expression in Adipocytes

PubMed Central

Richard, Allison J.; Ribnicky, David M.; Stephens, Jacqueline M.

2013-01-01

Adipose tissue development and function are widely studied to examine the relationship between obesity and the metabolic syndrome. It is well documented that the inability of adipose tissue to properly increase its lipid storage capacity during the obese state can lead to metabolic dysfunction. In a blind screen of 425 botanicals, we identified naringenin as an inhibitor of adipocyte differentiation. Naringenin is one of the most abundant citrus flavonoids, and recent studies have demonstrated antihyperlipidemic capabilities. These studies have largely focused on the effects of naringenin on the liver. Our biochemical studies clearly demonstrate that naringenin inhibits adipogenesis and impairs mature fat cell function. Naringenin specifically inhibited adipogenesis in a dose-dependent fashion as judged by examining lipid accumulation and induction of adipocyte marker protein expression. In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Exposure to naringenin also inhibited adiponectin protein expression in mature murine and human adipocytes. Our studies have revealed that naringenin may have a negative impact on adipocyte-related diseases by limiting differentiation of preadipocytes, by significantly inducing insulin resistance, and by decreasing adiponectin expression in mature fat cells. PMID:23983791

St. John’s Wort inhibits insulin signaling in murine and human adipocytes

PubMed Central

Richard, Allison J.; Amini, Zhaleh J.; Ribnicky, David M.; Stephens, Jacqueline M.

2012-01-01

Adipocytes are insulin-sensitive cells that play a major role in energy homeostasis. Obesity is the primary disease of fat cells and a major risk factor for the development of Type 2 diabetes, cardiovascular disease, and metabolic syndrome. The use of botanicals in the treatment of metabolic diseases is an emerging area of research. In previous studies, we screened over 425 botanical extracts for their ability to modulate adipogenesis and insulin sensitivity. We identified St. John’s Wort (SJW) extracts as inhibitors of adipogenesis of 3T3-L1 cells and demonstrated that these extracts also inhibited insulin-sensitive glucose uptake in mature fat cells. In these follow-up studies we have further characterized the effects of SJW on insulin action in both murine and human fat cells. We have shown that SJW also attenuates insulin-sensitive glucose uptake in human adipocytes. Moreover, SJW inhibits IRS-1 tyrosine phosphorylation in both murine and human fat cells. Botanical extracts are complex mixtures. Many bioactive compounds have been identified in SJW, including hypericin (HI) and hyperforin (HF). We have examined the ability of HI and HF, purified from SJW, to modulate adipocyte development and insulin action in mature adipocytes. Our novel studies indicate that the profound effects of SJW on adipogenesis, IRS-1 activation, and insulin-stimulated glucose uptake are not mediated by HI and/or HF. Nonetheless, we propose that extracts of SJW may contribute to adipocyte related diseases by limiting differentiation of preadipocytes and significantly inducing insulin resistance in mature fat cells. PMID:22198320

Angiomyolipoma with Minimal Fat: Can It Be Differentiated from Clear Cell Renal Cell Carcinoma by Using Standard MR Techniques?

PubMed Central

Hindman, Nicole; Ngo, Long; Genega, Elizabeth M.; Melamed, Jonathan; Wei, Jesse; Braza, Julia M.; Rofsky, Neil M.

2012-01-01

Purpose: To retrospectively assess whether magnetic resonance (MR) imaging with opposed-phase and in-phase gradient-echo (GRE) sequences and MR feature analysis can differentiate angiomyolipomas (AMLs) that contain minimal fat from clear cell renal cell carcinomas (RCCs), with particular emphasis on small (<3-cm) masses. Materials and Methods: Institutional review board approval and a waiver of informed consent were obtained for this HIPAA-compliant study. MR images from 108 pathologically proved renal masses (88 clear cell RCCs and 20 minimal fat AMLs from 64 men and 44 women) at two academic institutions were evaluated. The signal intensity (SI) of each renal mass and spleen on opposed-phase and in-phase GRE images was used to calculate an SI index and tumor-to-spleen SI ratio. Two radiologists who were blinded to the pathologic results independently assessed the subjective presence of intravoxel fat (ie, decreased SI on opposed-phase images compared with that on in-phase images), SI on T1-weighted and T2-weighted images, cystic degeneration, necrosis, hemorrhage, retroperitoneal collaterals, and renal vein thrombosis. Results were analyzed by using the Wilcoxon rank sum test, two-tailed Fisher exact test, and multivariate logistic regression analysis for all renal masses and for small masses. A P value of less than .05 was considered to indicate a statistically significant difference. Results: There were no differences between minimal fat AMLs and clear cell RCCs for the SI index (8.05% ± 14.46 vs 14.99% ± 19.9; P = .146) or tumor-to-spleen ratio (−8.96% ± 16.6 and −15.8% ± 22.4; P = .227) when all masses or small masses were analyzed. Diagnostic accuracy (area under receiver operating characteristic curve) for the SI index and tumor-to-spleen ratio was 0.59. Intratumoral necrosis and larger size were predictive of clear cell RCC (P < .001) for all lesions, whereas low SI (relative to renal parenchyma SI) on T2-weighted images, smaller size, and female sex correlated with minimal fat AML (P < .001) for all lesions. Conclusion: The diagnostic accuracy of opposed-phase and in-phase GRE MR imaging for the differentiation of minimal fat AML and clear cell RCC is poor. In this cohort, low SI on T2-weighted images relative to renal parenchyma and small size suggested minimal fat AML, whereas intratumoral necrosis and large size argued against this diagnosis. © RSNA, 2012 PMID:23012463

Effect of Diet and Exercise on the Peripheral Immune System in Young Balb/c Mice

PubMed Central

Martínez-Carrillo, B. E.; Jarillo-Luna, R. A.; Campos-Rodríguez, R.; Valdés-Ramos, R.; Rivera-Aguilar, V.

2015-01-01

Although diet and exercise clearly have an influence on immune function, studies are scarce on the effect caused by exercise and the consumption of a carbohydrate-rich or fat-rich diet on the peripheral immune system. The aim of the present study was to evaluate the effect of exercise and the two aforementioned unbalanced diets on young Balb/c mice, especially in relation to BMI, the level of glucose, and the percentage of lymphocyte subpopulations in peripheral blood. The changes found were then related to the synthesis of leptin and adiponectin as well as the production of oxidative stress. The increase in BMI found with the carbohydrate-rich and fat-rich diets showed correlation with the levels of leptin and adiponectin. An increase in leptin and a decrease in adiponectin directly correlated with an increase in total lymphocytes and CD4+ cells and with a decrease in B cells. The increase in leptin also correlated with an increase in CD8+ cells. Glycemia and oxidative stress increased with the two unbalanced diets, negatively affecting the proliferation of total lymphocytes and the percentage of B cells, apparently by causing alterations in proteins through carbonylation. These alterations caused by an unbalanced diet were not modified by moderate exercise. PMID:26634209

ω-3 polyunsaturated fatty acids direct differentiation of the membrane phenotype in mesenchymal stem cells to potentiate osteogenesis

PubMed Central

Levental, Kandice R.; Surma, Michal A.; Skinkle, Allison D.; Lorent, Joseph H.; Zhou, Yong; Klose, Christian; Chang, Jeffrey T.; Hancock, John F.; Levental, Ilya

2017-01-01

Mammalian cells produce hundreds of dynamically regulated lipid species that are actively turned over and trafficked to produce functional membranes. These lipid repertoires are susceptible to perturbations from dietary sources, with potentially profound physiological consequences. However, neither the lipid repertoires of various cellular membranes, their modulation by dietary fats, nor their effects on cellular phenotypes have been widely explored. We report that differentiation of human mesenchymal stem cells (MSCs) into osteoblasts or adipocytes results in extensive remodeling of the plasma membrane (PM), producing cell-specific membrane compositions and biophysical properties. The distinct features of osteoblast PMs enabled rational engineering of membrane phenotypes to modulate differentiation in MSCs. Specifically, supplementation with docosahexaenoic acid (DHA), a lipid component characteristic of osteoblast membranes, induced broad lipidomic remodeling in MSCs that reproduced compositional and structural aspects of the osteoblastic PM phenotype. The PM changes induced by DHA supplementation potentiated osteogenic differentiation of MSCs concurrent with enhanced Akt activation at the PM. These observations prompt a model wherein the DHA-induced lipidome leads to more stable membrane microdomains, which serve to increase Akt activity and thereby enhance osteogenic differentiation. More broadly, our investigations suggest a general mechanism by which dietary fats affect cellular physiology through remodeling of membrane lipidomes, biophysical properties, and signaling. PMID:29134198

Evaluation of Bone Marrow Processing Protocol for Therapeutic Applications via Culture and Characterization of Mesenchymal Stem Cells.

PubMed

Verma, Poonam; Bansal, Himanshu; Agrawal, Anupama; Leon, Jerry; Sundell, I Birgitta; Koka, Prasad S

Human mesenchymal stem cells from bone marrow (hMSCs) have broad therapeutic potential. These cells can be are readily isolated from bone marrow by their property to adhere to tissue culture treated culture wares. However, the proliferation rates and other properties of the cells gradually change during expansion. This study aims to validate the protocol of isolation and differentiation of hMSCs from bone marrow for therapeutic applications. Sixty ml of bone marrow was extracted from 5 patients and MSCs were isolated. These were characterized by Flow Cytometry, CFU assay and were differentiated into bone, fat cells and neurocytes. The cells were having healthy morphology. These were positive for the markers CD105, CD90 and CD73 and negative for CD45, CD34 and HLA-DR. The cells could differentiate into fat, bone and neural cells. MSCs from the bone marrow were isolated and differentiated. These cells were morphologically healthy and passed CFU assay. The cells exhibited differentiation potential into bone, fat and neural tissue. These cells can be used in therapeutic applications.

Adiponectin and Its Receptors in the Ovary: Further Evidence for a Link between Obesity and Hyperandrogenism in Polycystic Ovary Syndrome

PubMed Central

Comim, Fabio V.; Hardy, Kate; Franks, Stephen

2013-01-01

Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS. PMID:24260388

Drosophila Spidey/Kar Regulates Oenocyte Growth via PI3-Kinase Signaling

PubMed Central

Cinnamon, Einat; Sawala, Annick; Tittiger, Claus; Paroush, Ze'ev

2016-01-01

Cell growth and proliferation depend upon many different aspects of lipid metabolism. One key signaling pathway that is utilized in many different anabolic contexts involves Phosphatidylinositide 3-kinase (PI3K) and its membrane lipid products, the Phosphatidylinositol (3,4,5)-trisphosphates. It remains unclear, however, which other branches of lipid metabolism interact with the PI3K signaling pathway. Here, we focus on specialized fat metabolizing cells in Drosophila called larval oenocytes. In the presence of dietary nutrients, oenocytes undergo PI3K-dependent cell growth and contain very few lipid droplets. In contrast, during starvation, oenocytes decrease PI3K signaling, shut down cell growth and accumulate abundant lipid droplets. We now show that PI3K in larval oenocytes, but not in fat body cells, functions to suppress lipid droplet accumulation. Several enzymes of fatty acid, triglyceride and hydrocarbon metabolism are required in oenocytes primarily for lipid droplet induction rather than for cell growth. In contrast, a very long chain fatty-acyl-CoA reductase (FarO) and a putative lipid dehydrogenase/reductase (Spidey, also known as Kar) not only promote lipid droplet induction but also inhibit oenocyte growth. In the case of Spidey/Kar, we show that the growth suppression mechanism involves inhibition of the PI3K signaling pathway upstream of Akt activity. Together, the findings in this study show how Spidey/Kar and FarO regulate the balance between the cell growth and lipid storage of larval oenocytes. PMID:27500738

γ-Oryzanol protects pancreatic β-cells against endoplasmic reticulum stress in male mice.

PubMed

Kozuka, Chisayo; Sunagawa, Sumito; Ueda, Rei; Higa, Moritake; Tanaka, Hideaki; Shimizu-Okabe, Chigusa; Ishiuchi, Shogo; Takayama, Chitoshi; Matsushita, Masayuki; Tsutsui, Masato; Miyazaki, Jun-ichi; Oyadomari, Seiichi; Shimabukuro, Michio; Masuzaki, Hiroaki

2015-04-01

Endoplasmic reticulum (ER) stress is profoundly involved in dysfunction of β-cells under high-fat diet and hyperglycemia. Our recent study in mice showed that γ-oryzanol, a unique component of brown rice, acts as a chemical chaperone in the hypothalamus and improves feeding behavior and diet-induced dysmetabolism. However, the entire mechanism whereby γ-oryzanol improves glucose metabolism throughout the body still remains unclear. In this context, we tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells using murine β-cell line MIN6. In MIN6 cells with augmented ER stress by tunicamycin, γ-oryzanol decreased exaggerated expression of ER stress-related genes and phosphorylation of eukaryotic initiation factor-2α, resulting in restoration of glucose-stimulated insulin secretion and prevention of apoptosis. In islets from high-fat diet-fed diabetic mice, oral administration of γ-oryzanol improved glucose-stimulated insulin secretion on following reduction of exaggerated ER stress and apoptosis. Furthermore, we examined the impact of γ-oryzanol on low-dose streptozotocin-induced diabetic mice, where exaggerated ER stress and resultant apoptosis in β-cells were observed. Also in this model, γ-oryzanol attenuated mRNA level of genes involved in ER stress and apoptotic signaling in islets, leading to amelioration of glucose dysmetabolism. Taken together, our findings demonstrate that γ-oryzanol directly ameliorates ER stress-induced β-cell dysfunction and subsequent apoptosis, highlighting usefulness of γ-oryzanol for the treatment of diabetes mellitus.

Insulin resistance impairs nigrostriatal dopamine function.

PubMed

Morris, J K; Bomhoff, G L; Gorres, B K; Davis, V A; Kim, J; Lee, P-P; Brooks, W M; Gerhardt, G A; Geiger, P C; Stanford, J A

2011-09-01

Clinical studies have indicated a link between Parkinson's disease (PD) and Type 2 Diabetes. Although preclinical studies have examined the effect of high-fat feeding on dopamine function in brain reward pathways, the effect of diet on neurotransmission in the nigrostriatal pathway, which is affected in PD and parkinsonism, is less clear. We hypothesized that a high-fat diet, which models early-stage Type 2 Diabetes, would disrupt nigrostriatal dopamine function in young adult Fischer 344 rats. Rats were fed a high fat diet (60% calories from fat) or a normal chow diet for 12 weeks. High fat-fed animals were insulin resistant compared to chow-fed controls. Potassium-evoked dopamine release and dopamine clearance were measured in the striatum using in vivo electrochemistry. Dopamine release was attenuated and dopamine clearance was diminished in the high-fat diet group compared to chow-fed rats. Magnetic resonance imaging indicated increased iron deposition in the substantia nigra of the high fat group. This finding was supported by alterations in the expression of several proteins involved in iron metabolism in the substantia nigra in this group compared to chow-fed animals. The diet-induced systemic and basal ganglia-specific changes may play a role in the observed impairment of nigrostriatal dopamine function. Copyright © 2011 Elsevier Inc. All rights reserved.

Postprandial lymphatic pump function after a high-fat meal: a characterization of contractility, flow, and viscosity

PubMed Central

Kassis, Timothy; Yarlagadda, Sri Charan; Kohan, Alison B.; Tso, Patrick; Breedveld, Victor

2016-01-01

Dietary lipids are transported from the intestine through contractile lymphatics. Chronic lipid loads can adversely affect lymphatic function. However, the acute lymphatic pump response in the mesentery to a postprandial lipid meal has gone unexplored. In this study, we used the rat mesenteric collecting vessel as an in vivo model to quantify the effect of lipoproteins on vessel function. Lipid load was continuously monitored by using the intensity of a fluorescent fatty-acid analog, which we infused along with a fat emulsion through a duodenal cannula. The vessel contractility was simultaneously quantified. We demonstrated for the first time that collecting lymphatic vessels respond to an acute lipid load by reducing pump function. High lipid levels decreased contraction frequency and amplitude. We also showed a strong tonic response through a reduction in the end-diastolic and systolic diameters. We further characterized the changes in flow rate and viscosity and showed that both increase postprandially. In addition, shear-mediated Ca2+ signaling in lymphatic endothelial cells differed when cultured with lipoproteins. Together these results show that the in vivo response could be both shear and lipid mediated and provide the first evidence that high postprandial lipid has an immediate negative effect on lymphatic function even in the acute setting. PMID:26968208

Sedentary lifestyle related exosomal release of Hotair from gluteal-femoral fat promotes intestinal cell proliferation

PubMed Central

Lu, Xiaozhao; Bai, Danna; Liu, Xiangwei; Zhou, Chen; Yang, Guodong

2017-01-01

Pioneering epidemiological work has established strong association of sedentary lifestyle and obesity with the risk of colorectal cancer, while the detailed underlying mechanism remains unknown. Here we show that Hotair (HOX transcript antisense RNA) is a pro-adipogenic long non-coding RNA highly expressed in gluteal-femoral fat over other fat depots. Hotair knockout in adipose tissue results in gluteal-femoral fat defect. Squeeze of the gluteal-femoral fat induces intestinal proliferation in wildtype mice, while not in Hotair knockout mice. Mechanistically, squeeze of the gluteal-femoral fat induces exosomal Hotair secretion mainly by transcriptional upregulation of Hotair via NFκB. And increased exosomal Hotair in turn circulates in the blood and is partially endocytosed by the intestine, finally promoting the stemness and proliferation of intestinal stem/progenitor cells via Wnt activation. Clinically, obese subjects with sedentary lifestyle have much higher exosomal HOTAIR expression in the serum. These findings establish that sedentary lifestyle promotes exosomal Hotair release from the gluteal-femoral fat, which in turn facilitates intestinal stem and/or progenitor proliferation, raising a possible link between sedentary lifestyle with colorectal tumorigenesis. PMID:28361920

Sedentary lifestyle related exosomal release of Hotair from gluteal-femoral fat promotes intestinal cell proliferation.

PubMed

Lu, Xiaozhao; Bai, Danna; Liu, Xiangwei; Zhou, Chen; Yang, Guodong

2017-03-31

Pioneering epidemiological work has established strong association of sedentary lifestyle and obesity with the risk of colorectal cancer, while the detailed underlying mechanism remains unknown. Here we show that Hotair (HOX transcript antisense RNA) is a pro-adipogenic long non-coding RNA highly expressed in gluteal-femoral fat over other fat depots. Hotair knockout in adipose tissue results in gluteal-femoral fat defect. Squeeze of the gluteal-femoral fat induces intestinal proliferation in wildtype mice, while not in Hotair knockout mice. Mechanistically, squeeze of the gluteal-femoral fat induces exosomal Hotair secretion mainly by transcriptional upregulation of Hotair via NFκB. And increased exosomal Hotair in turn circulates in the blood and is partially endocytosed by the intestine, finally promoting the stemness and proliferation of intestinal stem/progenitor cells via Wnt activation. Clinically, obese subjects with sedentary lifestyle have much higher exosomal HOTAIR expression in the serum. These findings establish that sedentary lifestyle promotes exosomal Hotair release from the gluteal-femoral fat, which in turn facilitates intestinal stem and/or progenitor proliferation, raising a possible link between sedentary lifestyle with colorectal tumorigenesis.

Insights into the Melipona scutellaris (Hymenoptera, Apidae, Meliponini) fat body transcriptome.

PubMed

de Sousa, Cristina Soares; Serrão, José Eduardo; Bonetti, Ana Maria; Amaral, Isabel Marques Rodrigues; Kerr, Warwick Estevam; Maranhão, Andréa Queiroz; Ueira-Vieira, Carlos

2013-07-01

The insect fat body is a multifunctional organ analogous to the vertebrate liver. The fat body is involved in the metabolism of juvenile hormone, regulation of environmental stress, production of immunity regulator-like proteins in cells and protein storage. However, very little is known about the molecular mechanisms involved in fat body physiology in stingless bees. In this study, we analyzed the transcriptome of the fat body from the stingless bee Melipona scutellaris. In silico analysis of a set of cDNA library sequences yielded 1728 expressed sequence tags (ESTs) and 997 high-quality sequences that were assembled into 29 contigs and 117 singlets. The BLAST X tool showed that 86% of the ESTs shared similarity with Apis mellifera (honeybee) genes. The M. scutellaris fat body ESTs encoded proteins with roles in numerous physiological processes, including anti-oxidation, phosphorylation, metabolism, detoxification, transmembrane transport, intracellular transport, cell proliferation, protein hydrolysis and protein synthesis. This is the first report to describe a transcriptomic analysis of specific organs of M. scutellaris. Our findings provide new insights into the physiological role of the fat body in stingless bees.

Insights into the Melipona scutellaris (Hymenoptera, Apidae, Meliponini) fat body transcriptome

PubMed Central

de Sousa, Cristina Soares; Serrão, José Eduardo; Bonetti, Ana Maria; Amaral, Isabel Marques Rodrigues; Kerr, Warwick Estevam; Maranhão, Andréa Queiroz; Ueira-Vieira, Carlos

2013-01-01

The insect fat body is a multifunctional organ analogous to the vertebrate liver. The fat body is involved in the metabolism of juvenile hormone, regulation of environmental stress, production of immunity regulator-like proteins in cells and protein storage. However, very little is known about the molecular mechanisms involved in fat body physiology in stingless bees. In this study, we analyzed the transcriptome of the fat body from the stingless bee Melipona scutellaris. In silico analysis of a set of cDNA library sequences yielded 1728 expressed sequence tags (ESTs) and 997 high-quality sequences that were assembled into 29 contigs and 117 singlets. The BLAST X tool showed that 86% of the ESTs shared similarity with Apis mellifera (honeybee) genes. The M. scutellaris fat body ESTs encoded proteins with roles in numerous physiological processes, including anti-oxidation, phosphorylation, metabolism, detoxification, transmembrane transport, intracellular transport, cell proliferation, protein hydrolysis and protein synthesis. This is the first report to describe a transcriptomic analysis of specific organs of M. scutellaris. Our findings provide new insights into the physiological role of the fat body in stingless bees. PMID:23885214

Reducing Compounds Equivocally Influence Oxidation during Digestion of a High-Fat Beef Product, which Promotes Cytotoxicity in Colorectal Carcinoma Cell Lines.

PubMed

Van Hecke, Thomas; Wouters, An; Rombouts, Caroline; Izzati, Tazkiyah; Berardo, Alberto; Vossen, Els; Claeys, Erik; Van Camp, John; Raes, Katleen; Vanhaecke, Lynn; Peeters, Marc; De Vos, Winnok H; De Smet, Stefaan

2016-02-24

We studied the formation of malondialdehyde, 4-hydroxy-nonenal, and hexanal (lipid oxidation products, LOP) during in vitro digestion of a cooked low-fat and high-fat beef product in response to the addition of reducing compounds. We also investigated whether higher LOP in the digests resulted in a higher cyto- and genotoxicity in Caco-2, HT-29 and HCT-116 cell lines. High-fat compared to low-fat beef digests contained approximately 10-fold higher LOP concentrations (all P < 0.001), and induced higher cytotoxicity (P < 0.001). During digestion of the high-fat product, phenolic acids (gallic, ferulic, chlorogenic, and caffeic acid) displayed either pro-oxidant or antioxidant behavior at lower and higher doses respectively, whereas ascorbic acid was pro-oxidant at all doses, and the lipophilic reducing compounds (α-tocopherol, quercetin, and silibinin) all exerted a clear antioxidant effect. During digestion of the low-fat product, the hydrophilic compounds and quercetin were antioxidant. Decreases or increases in LOP concentrations amounted to 100% change versus controls.

Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages.

PubMed

Lichtenstein, Laeticia; Mattijssen, Frits; de Wit, Nicole J; Georgiadi, Anastasia; Hooiveld, Guido J; van der Meer, Roelof; He, Yin; Qi, Ling; Köster, Anja; Tamsma, Jouke T; Tan, Nguan Soon; Müller, Michael; Kersten, Sander

2010-12-01

Dietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we study the role of the lipoprotein lipase inhibitor Angptl4 in the response to dietary saturated fat. Strikingly, in mice lacking Angptl4, saturated fat induces a severe and lethal phenotype characterized by fibrinopurulent peritonitis, ascites, intestinal fibrosis, and cachexia. These abnormalities are preceded by a massive acute phase response induced by saturated but not unsaturated fat or medium-chain fat, originating in mesenteric lymph nodes (MLNs). MLNs undergo dramatic expansion and contain numerous lipid-laden macrophages. In peritoneal macrophages incubated with chyle, Angptl4 dramatically reduced foam cell formation, inflammatory gene expression, and chyle-induced activation of ER stress. Induction of macrophage Angptl4 by fatty acids is part of a mechanism that serves to reduce postprandial lipid uptake from chyle into MLN-resident macrophages by inhibiting triglyceride hydrolysis, thereby preventing macrophage activation and foam cell formation and protecting against progressive, uncontrolled saturated fat-induced inflammation. Copyright © 2010 Elsevier Inc. All rights reserved.

Injection Laryngoplasty Using Autologous Fat Enriched with Adipose-Derived Regenerative Stem Cells: A Safe Therapeutic Option for the Functional Reconstruction of the Glottal Gap after Unilateral Vocal Fold Paralysis

PubMed Central

Poletti, Daniel; Scola, Batolomé; Gómez-Vilda, Pedro; García-Martín, Ana I.; Fernández-Santos, María Eugenia

2018-01-01

Background Paralysis of one vocal fold leads to glottal gap and vocal fold insufficiency that has significant impact upon a patient's quality of life. Fillers have been tested to perform intracordal injections, but they do not provide perdurable results. Early data suggest that enriching fat grafts with adipose-derived regenerative cells (ADRCs) promote angiogenesis and modulate the immune response, improving graft survival. The aim of this study is to propose ADRC-enriched adipose tissue grafts as effective filler for the paralyzed vocal fold to use it for functional reconstruction of the glottal gap. Method This is the first phase I-IIA clinical trial (phase I/IIA clinical trial, unicentric, randomized, controlled, and two parallel groups), to evaluate the safety of a new therapy with ADRC-enriched fat grafting (ADRC: group I) for laryngoplasty after unilateral vocal fold paralysis. Control group patients received centrifuged autologous fat (CAF: group II) grafts. Overall mean age is 52.49 ± 16.60 years. Group I (ADRC): 7 patients (3 males and 4 females), 52.28 ± 20.95 year. Group II (CAF): 7 patients (3 males and 4 females), 52.71 ± 12.59 year. Results VHI-10 test showed that preoperative mean score was 24.21 ± 8.28. Postoperative mean score was 6.71 ± 6.75. Preoperative result in group I was 21.14 ± 3.58 and postoperative result was 3.14 ± 3.53. Preoperative result for group II was 27.29 ± 10.66. Postoperative score in group II was 10.29 ± 7.52. Wilcoxon and the Student t-tests showed that the patient's self-perception of posttreatment improvement is larger when ADRCs are used. Comparing pre- and posttreatment voice quality analysis, group I showed a p = 0.053. Group II showed a p = 0.007. There would be no significant differentiation between pre- and posttreatment results. This is true for group II and limited for group I. Conclusions This prospective trial demonstrates the safety and efficacy of the treatment of glottal gap defects utilizing ADRC-enriched fat grafts. This trial is registered with NCT02904824. PMID:29760737

Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1

PubMed Central

Sideri, Aristea; Stavrakis, Dimitris; Bowe, Collin; Shih, David Q.; Fleshner, Phillip; Arsenescu, Violeta; Arsenescu, Razvan; Turner, Jerrold R.; Pothoulakis, Charalabos

2015-01-01

In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis. PMID:25591865

Circadian and feeding cues integrate to drive rhythms of physiology in Drosophila insulin-producing cells.

PubMed

Barber, Annika F; Erion, Renske; Holmes, Todd C; Sehgal, Amita

2016-12-01

Circadian clocks regulate much of behavior and physiology, but the mechanisms by which they do so remain poorly understood. While cyclic gene expression is thought to underlie metabolic rhythms, little is known about cycles in cellular physiology. We found that Drosophila insulin-producing cells (IPCs), which are located in the pars intercerebralis and lack an autonomous circadian clock, are functionally connected to the central circadian clock circuit via DN1 neurons. Insulin mediates circadian output by regulating the rhythmic expression of a metabolic gene (sxe2) in the fat body. Patch clamp electrophysiology reveals that IPCs display circadian clock-regulated daily rhythms in firing event frequency and bursting proportion under light:dark conditions. The activity of IPCs and the rhythmic expression of sxe2 are additionally regulated by feeding, as demonstrated by night feeding-induced changes in IPC firing characteristics and sxe2 levels in the fat body. These findings indicate circuit-level regulation of metabolism by clock cells in Drosophila and support a role for the pars intercerebralis in integrating circadian control of behavior and physiology. © 2016 Barber et al.; Published by Cold Spring Harbor Laboratory Press.

Use of Taiwanese ropy fermented milk (TRFM) and Lactococcus lactis subsp. cremoris isolated from TRFM in manufacturing of functional low-fat cheeses.

PubMed

Chiang, Ming-Lun; Chen, Hsi-Chia; Wang, Sheng-Yao; Hsieh, Yueh-Ling; Chen, Ming-Ju

2011-09-01

The purpose of this study was to manufacture new functional low-fat cheeses using Taiwanese ropy fermented milk (TRFM) and Lactococcus lactis subsp. cremoris strains isolated from TRFM. After 28 d of ripening and storage, the viable populations of lactic acid bacteria (LAB) in the low-fat cheeses made with L. lactis subsp. cremoris TL1 (TL1), L. lactis subsp. cremoris TL4 (TL4), and TRFM still maintained above 10(8) CFU/g. The low-fat cheeses made with TL1 and TRFM showed higher moisture contents than the cheeses made with TL4, full-fat, and low-fat cheese controls. The low-fat cheeses made with TL1 and TL4 had higher customer preferential scores similar to full-fat cheese control in the sensory evaluation. Additionally, the low-fat cheeses fermented with TL1, TL4, and TRFM for 4 h had higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging and ferrous ion-chelating abilities than the cheeses fermented with the starters for 8 h, full-fat, and low-fat cheese controls. A better angiotensin-converting enzyme (ACE) inhibition activity was also observed in the low-fat cheeses made with TL1, TL4, and TRFM than that in the full-fat and low-fat cheese controls during ripening and storage period. As health-conscious consumers continue to seek low-fat alternatives in their diets, there remain strong interests for the dairy industry to develop low-fat cheeses to meet the demands. This study clearly demonstrated that the low-fat cheeses fermented with TL1 for 4 h showed a better overall acceptability and possessed antioxidative abilities and ACE inhibitory activities than other cheeses tested in this study. By improving its flavor and investigating the possible mechanisms of its functionalities in the future, this low-fat cheese might possibly be commercialized and give a positive impact on cheese consumption in the future. © 2011 Institute of Food Technologists®

Functional foods for the prevention and treatment of cardiovascular diseases: cholesterol and beyond.

PubMed

Rudkowska, Iwona; Jones, Peter J H

2007-05-01

Cardiovascular disease (CVD) is a major cause of death and disability in many developed countries. The purpose of this literature review is to establish a recommendation for the intake of functional food ingredients in a healthy diet--such as plant sterols (PSs) in low-fat and functional matrices, fatty acid composition and other nutrients of tree nuts and flavonoids in dark chocolate--for the prevention and treatment of CVD. These three specific functional foods are explored in this review, since there is a higher potential for their increased consumption by the population to prevent CVD. First, PS have been added to various nontraditional matrices, such as low-fat products and functional oils, which have shown cholesterol-lowering effects in most clinical trials. Secondly, a growing number of clinical studies indicate that the beneficial effect of tree nuts may not only be due to their fatty acid composition but to other key nutrients, which may provide supplementary health benefits, such as endothelial cell function, as well as decreasing total cholesterol and low-density lipoprotein cholesterol (LDL-C). Lastly, flavonoids in dark chocolate may protect LDL-C particles from undergoing oxidative modification. However, some gaps in our knowledge need to be filled before firm recommendations can be made for habitual dark chocolate consumption. Overall, these functional foods should be considered as an addition to current lipid-lowering recommendations for improving CVD risk.

Predicting Functional Capacity From Measures of Muscle Mass in Postmenopausal Women.

PubMed

Orsatti, Fábio Lera; Nunes, Paulo Ricardo Prado; Souza, Aletéia de Paula; Martins, Fernanda Maria; de Oliveira, Anselmo Alves; Nomelini, Rosekeila Simões; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Cândido

2017-06-01

Menopause increases body fat and decreases muscle mass and strength, which contribute to sarcopenia. The amount of appendicular muscle mass has been frequently used to diagnose sarcopenia. Different measures of appendicular muscle mass have been proposed. However, no studies have compared the most salient measure (appendicular muscle mass corrected by body fat) of the appendicular muscle mass to physical function in postmenopausal women. To examine the association of 3 different measurements of appendicular muscle mass (absolute, corrected by stature, and corrected by body fat) with physical function in postmenopausal women. Cross-sectional descriptive study. Outpatient geriatric and gynecological clinic. Forty-eight postmenopausal women with a mean age (standard deviation [SD]) of 62.1 ± 8.2 years, with mean (SD) length of menopause of 15.7 ± 9.8 years and mean (SD) body fat of 43.6% ± 9.8%. Not applicable. Appendicular muscle mass measure was measured with dual-energy x-ray absorptiometry. Physical function was measured by a functional capacity questionnaire, a short physical performance battery, and a 6 minute-walk test. Muscle quality (leg extensor strength to lower-body mineral-free lean mass ratio) and sum of z scores (sum of each physical function tests z score) were performed to provide a global index of physical function. The regression analysis showed that appendicular muscle mass corrected by body fat was the strongest predictor of physical function. Each increase in the standard deviation of appendicular muscle mass corrected by body fat was associated with a mean sum of z score increase of 59% (standard deviation), whereas each increase in absolute appendicular muscle mass and appendicular muscle mass corrected by stature were associated with a mean sum of z scores decrease of 23% and 36%, respectively. Muscle quality was associated with appendicular muscle mass corrected by body fat. These findings indicate that appendicular muscle mass corrected by body fat is a better predictor of physical function than the other measures of appendicular muscle mass in postmenopausal women. I. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Adipose tissue lymphocytes: types and roles.

PubMed

Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

2009-12-01

Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

Leptin expression in human mammary epithelial cells and breast milk.

PubMed

Smith-Kirwin, S M; O'Connor, D M; De Johnston, J; Lancey, E D; Hassink, S G; Funanage, V L

1998-05-01

Leptin has recently been shown to be produced by the human placenta and potentially plays a role in fetal and neonatal growth. Many functions of the placenta are replaced by the mammary gland in terms of providing critical growth factors for the newborn. In this study, we show that leptin is produced by human mammary epithelial cells as revealed by RT/PCR analysis of total RNA from mammary gland and immunohistochemical staining of breast tissue, cultured mammary epithelial cells, and secretory epithelial cells present in human milk. We also verify that immunoreactive leptin is present in whole milk at 30- to 150-fold higher concentrations than skim milk. We propose that leptin is secreted by mammary epithelial cells in milk fat globules, which partition into the lipid portion of breast milk.

Replacement of dietary saturated fat with unsaturated fats increases numbers of circulating endothelial progenitor cells and decreases numbers of microparticles: findings from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study.

PubMed

Weech, Michelle; Altowaijri, Hana; Mayneris-Perxachs, Jordi; Vafeiadou, Katerina; Madden, Jacqueline; Todd, Susan; Jackson, Kim G; Lovegrove, Julie A; Yaqoob, Parveen

2018-06-01

Endothelial progenitor cells (EPCs) and microparticles are emerging as novel markers of cardiovascular disease (CVD) risk, which could potentially be modified by dietary fat. We have previously shown that replacing dietary saturated fatty acids (SFAs) with monounsaturated or n-6 (ω-6) polyunsaturated fatty acids (MUFAs or PUFAs, respectively) improved lipid biomarkers, blood pressure, and markers of endothelial activation, but their effects on circulating EPCs and microparticles are unclear. The Dietary Intervention and VAScular function (DIVAS) Study investigated the replacement of 9.5-9.6% of total energy (%TE) contributed by SFAs with MUFAs or n-6 PUFAs for 16 wk on EPC and microparticle numbers in United Kingdom adults with moderate CVD risk. In this randomized, controlled, single-blind, parallel-group dietary intervention, men and women aged 21-60 y (n = 190) with moderate CVD risk (≥50% above the population mean) consumed 1 of three 16-wk isoenergetic diets. Target compositions for total fat, SFAs, MUFAs, and n-6 PUFAs (%TE) were as follows: SFA-rich diet (36:17:11:4; n = 64), MUFA-rich diet (36:9:19:4; n = 62), and n-6 PUFA-rich diet (36:9:13:10; n = 66). Circulating EPC, endothelial microparticle (EMP), and platelet microparticle (PMP) numbers were analyzed by flow cytometry. Dietary intake, vascular function, and other cardiometabolic risk factors were determined at baseline. Relative to the SFA-rich diet, MUFA- and n-6 PUFA-rich diets decreased EMP (-47.3%, -44.9%) respectively and PMP (-36.8%, -39.1%) numbers (overall diet effects, P < 0.01). The MUFA-rich diet increased EPC numbers (+28.4%; P = 0.023). Additional analyses that used stepwise regression models identified the augmentation index (measuring arterial stiffness determined by pulse-wave analysis) as an independent predictor of baseline EPC and microparticle numbers. Replacement of 9.5-9.6%TE dietary SFAs with MUFAs increased EPC numbers, and replacement with either MUFAs or n-6 PUFAs decreased microparticle numbers, suggesting beneficial effects on endothelial repair and maintenance. Further studies are warranted to determine the mechanisms underlying the favorable effects on EPC and microparticle numbers after SFA replacement. This trial was registered at www.clinicaltrials.gov as NCT01478958.

Obesity induced by a high-fat diet is associated with increased immune cell entry into the central nervous system.

PubMed

Buckman, Laura B; Hasty, Alyssa H; Flaherty, David K; Buckman, Christopher T; Thompson, Misty M; Matlock, Brittany K; Weller, Kevin; Ellacott, Kate L J

2014-01-01

Obesity is associated with chronic low-grade inflammation in peripheral tissues caused, in part, by the recruitment of inflammatory monocytes into adipose tissue. Studies in rodent models have also shown increased inflammation in the central nervous system (CNS) during obesity. The goal of this study was to determine whether obesity is associated with recruitment of peripheral immune cells into the CNS. To do this we used a bone marrow chimerism model to track the entry of green-fluorescent protein (GFP) labeled peripheral immune cells into the CNS. Flow cytometry was used to quantify the number of GFP(+) immune cells recruited into the CNS of mice fed a high-fat diet compared to standard chow fed controls. High-fat feeding resulted in obesity associated with a 30% increase in the number of GFP(+) cells in the CNS compared to control mice. Greater than 80% of the GFP(+) cells recruited to the CNS were also CD45(+) CD11b(+) indicating that the GFP(+) cells displayed characteristics of microglia/macrophages. Immunohistochemistry further confirmed the increase in GFP(+) cells in the CNS of the high-fat fed group and also indicated that 93% of the recruited cells were found in the parenchyma and had a stellate morphology. These findings indicate that peripheral immune cells can be recruited to the CNS in obesity and may contribute to the inflammatory response. Copyright © 2013 Elsevier Inc. All rights reserved.

[Estimation of the biological age in taiga tick females (Ixodes persulcatus:Ixodidae) by the fat reserves in organism].

PubMed

Balashov, Iu S; Grigor'eva, L A

2010-01-01

The method of estimation of the biological age in non-feeding tick females by the level of adipose inclusions in the cells of the midgut and fat body is developed. In order to estimate the fat reserves in non-feeding females, alive ticks were dissected and fragments of their internal were vitally stained with the pregnant solution of sudan III in 70 % ethanol. Three age-specific groups were established: I, young females whose intestines and fat body were filled with fat inclusions; II, mature females whose fat reserves were partially expended; III, old females having isolated fat inclusions in their midgut and fat body.

Ral GTPase and the exocyst regulate autophagy in a tissue-specific manner.

PubMed

Tracy, Kirsten; Velentzas, Panagiotis D; Baehrecke, Eric H

2016-01-01

Autophagy traffics cellular components to the lysosome for degradation. Ral GTPase and the exocyst have been implicated in the regulation of stress-induced autophagy, but it is unclear whether they are global regulators of this process. Here, we investigate Ral function in different cellular contexts in Drosophila and find that it is required for autophagy during developmentally regulated cell death in salivary glands, but does not affect starvation-induced autophagy in the fat body. Furthermore, knockdown of exocyst subunits has a similar effect, preventing autophagy in dying cells but not in cells of starved animals. Notch activity is elevated in dying salivary glands, this change in Notch signaling is influenced by Ral, and decreased Notch function influences autophagy. These data indicate that Ral and the exocyst regulate autophagy in a context-dependent manner, and that in dying salivary glands, Ral mediates autophagy, at least in part, by regulation of Notch. © 2015 The Authors.

Dietary Nutrients and Bioactive Substances Modulate Heat Shock Protein (HSP) Expression: A Review.

PubMed

Moura, Carolina Soares; Lollo, Pablo Christiano Barboza; Morato, Priscila Neder; Amaya-Farfan, Jaime

2018-05-28

Interest in the heat shock proteins (HSPs), as a natural physiological toolkit of living organisms, has ranged from their chaperone function in nascent proteins to the remedial role following cell stress. As part of the defence system, HSPs guarantee cell tolerance against a variety of stressors, including exercise, oxidative stress, hyper and hypothermia, hyper and hypoxia and improper diets. For the past couple of decades, research on functional foods has revealed a number of substances likely to trigger cell protection through mechanisms that involve the induction of HSP expression. This review will summarize the occurrence of the most easily inducible HSPs and describe the effects of dietary proteins, peptides, amino acids, probiotics, high-fat diets and other food-derived substances reported to induce HSP response in animals and humans studies. Future research may clarify the mechanisms and explore the usefulness of this natural alternative of defense and the modulating mechanism of each substance.

Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes

PubMed Central

Fuente-Martín, Esther; García-Cáceres, Cristina; Granado, Miriam; de Ceballos, María L.; Sánchez-Garrido, Miguel Ángel; Sarman, Beatrix; Liu, Zhong-Wu; Dietrich, Marcelo O.; Tena-Sempere, Manuel; Argente-Arizón, Pilar; Díaz, Francisca; Argente, Jesús; Horvath, Tamas L.; Chowen, Julie A.

2012-01-01

Glial cells perform critical functions that alter the metabolism and activity of neurons, and there is increasing interest in their role in appetite and energy balance. Leptin, a key regulator of appetite and metabolism, has previously been reported to influence glial structural proteins and morphology. Here, we demonstrate that metabolic status and leptin also modify astrocyte-specific glutamate and glucose transporters, indicating that metabolic signals influence synaptic efficacy and glucose uptake and, ultimately, neuronal function. We found that basal and glucose-stimulated electrical activity of hypothalamic proopiomelanocortin (POMC) neurons in mice were altered in the offspring of mothers fed a high-fat diet. In adulthood, increased body weight and fasting also altered the expression of glucose and glutamate transporters. These results demonstrate that whole-organism metabolism alters hypothalamic glial cell activity and suggest that these cells play an important role in the pathology of obesity. PMID:23064363

Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats.

PubMed

Peng, Qiuxian; Zhang, Qin; Xiao, Wei; Shao, Meng; Fan, Qin; Zhang, Hongwei; Zou, Yukai; Li, Xin; Xu, Wenxue; Mo, Zhixian; Cai, Hongbing

2014-07-18

Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertn group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver. Copyright © 2014. Published by Elsevier Inc.

Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

PubMed

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

2012-03-01

The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities. Copyright © 2010 Elsevier GmbH. All rights reserved.

Low-fat and fat-free pleomorphic lipomas: a diagnostic challenge.

PubMed

Sachdeva, Mandi P; Goldblum, John R; Rubin, Brian P; Billings, Steven D

2009-07-01

Pleomorphic lipomas are benign tumors that most commonly present as subcutaneous masses in the head and neck, shoulder, or back region of middle-aged to elderly men. They are related to spindle cell lipomas based on shared cytogenetic aberrations and histologic features. When little or no fat is present, the diagnosis can be challenging. A review of 38 pleomorphic lipomas seen in consultation revealed 7 cases in which fat was present in reduced (<5%) amounts (n = 5) or absent (n = 2). Six of 7 cases were from men with a mean age of 59 years. Excluding 1 case where the site was not specified, they all presented as solitary well-circumscribed subcutaneous masses in the head and neck (n = 3) or shoulder (n = 2) region. The seventh case was an intradermal tumor from the nose of a 48-year-old woman. All displayed pleomorphic and multinucleated floret cells interspersed among bland spindle cells and ropey collagen. They were diffusely immunoreactive for CD34. Referring diagnoses, when provided, included myxofibrosarcoma, giant cell fibroblastoma, and granulomatous rosacea for the tumor from the nose; none considered pleomorphic lipomas. When fat is absent or present in reduced amounts, clinical context and identification of classic nonlipogenic components are essential for the diagnosis of pleomorphic lipomas.

Dynamics of Adipocyte Turnover in Humans

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

Spalding, K; Arner, E; Westermark, P

2007-07-16

Obesity is increasing in an epidemic fashion in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells is thought to be most important. We show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fatmore » cells stays constant in adulthood in lean and obese and even under extreme conditions, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analyzing the integration of {sup 14}C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in obesity, suggesting a tight regulation of fat cell number that is independent of metabolic profile in adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.« less

An increase in visceral fat is associated with a decrease in the taste and olfactory capacity

PubMed Central

Fernandez-Garcia, Jose Carlos; Alcaide, Juan; Santiago-Fernandez, Concepcion; Roca-Rodriguez, MM.; Aguera, Zaida; Baños, Rosa; Botella, Cristina; de la Torre, Rafael; Fernandez-Real, Jose M.; Fruhbeck, Gema; Gomez-Ambrosi, Javier; Jimenez-Murcia, Susana; Menchon, Jose M.; Casanueva, Felipe F.; Fernandez-Aranda, Fernando; Tinahones, Francisco J.; Garrido-Sanchez, Lourdes

2017-01-01

Introduction Sensory factors may play an important role in the determination of appetite and food choices. Also, some adipokines may alter or predict the perception and pleasantness of specific odors. We aimed to analyze differences in smell–taste capacity between females with different weights and relate them with fat and fat-free mass, visceral fat, and several adipokines. Materials and methods 179 females with different weights (from low weight to morbid obesity) were studied. We analyzed the relation between fat, fat-free mass, visceral fat (indirectly estimated by bioelectrical impedance analysis with visceral fat rating (VFR)), leptin, adiponectin and visfatin. The smell and taste assessments were performed through the "Sniffin’ Sticks" and "Taste Strips" respectively. Results We found a lower score in the measurement of smell (TDI-score (Threshold, Discrimination and Identification)) in obese subjects. All the olfactory functions measured, such as threshold, discrimination, identification and the TDI-score, correlated negatively with age, body mass index (BMI), leptin, fat mass, fat-free mass and VFR. In a multiple linear regression model, VFR mainly predicted the TDI-score. With regard to the taste function measurements, the normal weight subjects showed a higher score of taste functions. However a tendency to decrease was observed in the groups with greater or lesser BMI. In a multiple linear regression model VFR and age mainly predicted the total taste scores. Discussion We show for the first time that a reverse relationship exists between visceral fat and sensory signals, such as smell and taste, across a population with different body weight conditions. PMID:28158237

STUDIES UPON CALCAREOUS DEGENERATION

PubMed Central

Klotz, Oskar

1905-01-01

It will be seen from the above that we have studied the conditions associated with the deposit of calcareous salts: (I) in connection with normal and pathological ossification, and (2) in pathological calcification as exhibited in (a) atheroma of the vessels; (b) calcification of caseating tubercular lesions; (c) calcification of inflammatory new growth, and (d) degenerating tumors; and we have induced experimentally deposits of calcareous salts in the lower animals: (a) within celloidin capsules containing fats and soaps; (b) in the kidney, and (c) in connection with fat necrosis. I. We have found that bone formation and pathological calcareous infiltration are wholly distinct processes. In the former there is no evidence of associated fatty change, and the cells associated with the process of deposition of calcium are functionally active. In the latter there is an antecedent fatty change in the affected areas, and the cells involved present constant evidences of degeneration. The view that would seem to account best for the changes observed in the latter case is that with lowered vitality the cells are unable to utilize the products brought to them by the blood, or which they continue to absorb, so that the normal series of decompositions associated with their metabolism fails to take place and hence they interact among themselves in the cytoplasm with the result that insoluble compounds replace soluble ones. II. Besides the fact that calcification is always preceded by fatty change within the cells, another fact should be emphasized. namely: that combination of the fats present with calcium salts to form calcium soaps tends to occur. The stages immediately preceding these are difficult to follow with anything approaching certainty, perhaps because the earlier stages vary under different conditions. In fat necrosis, for instance, the cells affected are normally storehouses for neutral fats, and as long as they remain healthy neutral fats alone are present in them. When they are subjected to the action of the pancreatic juice with its fat-splitting ferment the cells are killed and coincidently the neutral fats are decomposed, fatty acids being deposited. The fatty acids now slowly combine with the calcium salts. In degenerating lipomata the process would seem to be similar. But in other cases the cells are not obviously fat-containing in the normal state; nevertheless prior to calcification they undergo so-called fatty degeneration, which is really a form of cell degeneration accompanied by fat infiltration. As regards the source of the cell fats in general we may safely accept: 1. That fats are transported in the blood as diffusible soaps. 2. That taken up by the cells these soaps may either— (a) Be reconverted into neutral fats and become stored in the cytoplasm as such, or (b) undergo assimilation proper, becoming part and parcel of the cell substance, in which case they are not recognizable by the ordinary microchemical tests. 3. If these two possibilities be accepted it follows that the appearance of fats and soaps in the degenerating cell may be due to either— (a) Absorption or infiltration of soaps from the surrounding medium, the degenerating cell retaining the power of splitting off the fat but being unable to utilize this in metabolism. (b) Cytoplasmic disintegration with dissociation of the soap-albumen combination or, more broadly, liberation of the fats from their combination with the cytoplasm. The appearances seen in the cells of atheromatous areas indicate that the first of these does occur. III. In areas undergoing calcareous infiltration we have demonstrated. the presence of soaps, and this often in such quantities that they can be isolated and estimated by gross chemical methods. By microchemical methods also we have been able to show that after removing all the neutral fats and fatty acids by petroleum ether there remains behind a substance giving with Sudan III the reaction we associate with the presence of soap. And experimentally we have produced these soaps within the organism, more particularly by placing capsules containing fats and fatty acids within the tissues and after several days finding that the capsules contain calcium soaps and possess a calcium content far in excess of that of the normal blood and lymph. IV. While these are the facts, certain of the details of this reaction demand elucidation. The existence of sodium and it may be potassium soaps in the degenerated cells is comprehensible if we accept that these are present in the circulating lymph and simply undergoing absorption. But even then, as these are diffusible substances how is it to be explained that they become stored up in these particular areas? We have found that, as a matter of fact, in regions which give the reaction for soaps, but which give no reaction for calcium (which therefore presumably contain at most amounts of the insoluble calcium soap too small to need consideration, the ordinary solvents for potassium and sodium soaps do not forthwith remove the stainable material; they are relatively insoluble. The reason for this insolubility is suggested by the observations made in the test tube, that soap solutions mixed with solutions of white of egg or blood serum form a precipitate of combined soap and albumen, which likewise is insoluble in water and alcohol. The indications are therefore that in cells undergoing degeneration, with degeneration of the cytoplasm, certain albuminous molecules unite with the soaps present to form relatively insoluble soap-albuminate. V. With regard to calcium soaps, these are also present and in certain stages appear to be the dominating form in the affected tissues. Two questions suggest themselves, viz.: what is the source of calcium, and what is the process by which they become formed? As to the source, the amount present in well-marked calcification is far in excess of the normal calcium contents of the affected tissue. If in the kidneys of experimental calcification three hundred times as much calcium may be present as in the normal kidney (von Kossa), the calcium must be conveyed to the part by the blood and lymph, and that this is so is demonstrated, as we have pointed out, by the distribution of the infiltration in solid organs, that like ovarian fibroids have undergone necrosis, in which the earliest deposits are superficial. As to the process, there are three possibilities: 1. That sodium and potassium soaps and soap albuminates are first formed and that interaction occurs between them and the diffused calcium salts from the lymph, the less soluble-calcium replacing the sodium and potassium. 2. That under certain conditions the calcium salts act directly on the neutral fats present in the degenerating cells. 3. That the neutral fats are first broken down into fatty acids and that these react with the calcium salts to form the soaps. We are assured that the first process occurs and that because in the boundary zone of areas of calcification we can detect soapy particles devoid of calcium, identical in position and arrangement with the particles more deeply placed which give the calcium reactions. But this is not the only reaction. In case of fat necrosis we see clearly that the third process is in evidence. And we are far from being convinced that the second does not also obtain. We have been impressed by the large accumulation of neutral fats in the cells in cases of early atheroma and the absence at any stage of the process of recognizable fatty acid. While soaps, it is true, are compounds of fatty acids with alkalies, it is recognized in ordinary domestic life that they can be formed by the direct action of strong lye upon ordinary fats, and this even in the cold. It is quite possible therefore that there occurs a similar direct process in the organism. The point is worth noting, however, that this does not occur in healthy cells the seat of fatty infiltration. We therefore leave this an open question, only laying down that, as indicated by the hyalin albuminous matrix left when calcium salts are dissolved out of an area of calcification, there must exist a calcium soap- or fat-albuminate similar to the potassium and sodium soap-albuminates already mentioned—such an albuminate as we can form with calcium soaps in the test tube. VI. In old areas of calcification soaps are largely if not entirely wanting, although these are to be detected at the periphery, when the process is still advancing. The reactions given by these older areas are almost entirely those of calcium phosphate, though some calcium carbonate is at times to be made out. This seems surely to indicate that the final stage in calcification is an interaction between the calcium soap-albuminates and substances containing phosphoric and carbonic acids. Such substances, it is needless to say, are present in considerable amounts in the lymph and blood. We must conclude that the acid sodium phosphates of the lymph act on the calcium soap, the highly insoluble calcium phosphates being formed (plus the albuminous moiety of the original compound) and diffusible sodium soap being liberated, while similarly alkaline carbonates form calcium carbonate and liberate sodium and potassium soaps. Calcium phosphate and calcium carbonate thus become the insoluble earthy salts of old crystalline areas of calcification. VII. As already stated very little soap is to be found in these old areas. It is possibly worth suggestion that the soaps liberated in this last reaction, as they diffuse out, again react with diffusible calcium salts and form calcium soaps which once more react with the alkaline salts to produce the phosphates and carbonates; that, in short, they have a katalytic action. Certain it is that old calcareous areas are extraordinarily dense, and have a coarse crystalline structure, wholly at variance with the finely granular appearance of the more recent areas, and these large crystalline masses, it would seem, can only be formed by successive deposition of new material and eventual fusion, as the interspaces become filled in between the original masses. PMID:19867016

Dynamic changes in lipid droplet-associated proteins in the "browning" of white adipose tissues.

PubMed

Barneda, David; Frontini, Andrea; Cinti, Saverio; Christian, Mark

2013-05-01

The morphological and functional differences between lipid droplets (LDs) in brown (BAT) and white (WAT) adipose tissues will largely be determined by their associated proteins. Analysing mRNA expression in mice fat depots we have found that most LD protein genes are expressed at higher levels in BAT, with the greatest differences observed for Cidea and Plin5. Prolonged cold exposure, which induces the appearance of brown-like adipocytes in mice WAT depots, was accompanied with the potentiation of the lipolytic machinery, with changes in ATGL, CGI-58 and G0S2 gene expression. However the major change detected in WAT was the enhancement of Cidea mRNA. Together with the increase in Cidec, it indicates that LD enlargement through LD-LD transference of fat is an important process during WAT browning. To study the dynamics of this phenotypic change, we have applied 4D confocal microscopy in differentiated 3T3-L1 cells under sustained β-adrenergic stimulation. Under these conditions the cells experienced a LD remodelling cycle, with progressive reduction on the LD size by lipolysis, followed by the formation of new LDs, which were subjected to an enlargement process, likely to be CIDE-triggered, until the cell returned to the basal state. This transformation would be triggered by the activation of a thermogenic futile cycle of lipolysis/lipogenesis and could facilitate the molecular mechanism for the unilocular to multilocular transformation during WAT browning. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

High-fat, high-fructose, high-cholesterol feeding causes severe NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine.

PubMed

Panasevich, M R; Meers, G M; Linden, M A; Booth, F W; Perfield, J W; Fritsche, K L; Wankhade, Umesh D; Chintapalli, Sree V; Shankar, K; Ibdah, J A; Rector, R S

2018-01-01

Pediatric obesity and nonalcoholic steatohepatitis (NASH) are on the rise in industrialized countries, yet our ability to mechanistically examine this relationship is limited by the lack of a suitable higher animal models. Here, we examined the effects of high-fat, high-fructose corn syrup, high-cholesterol Western-style diet (WD)-induced obesity on NASH and cecal microbiota dysbiosis in juvenile Ossabaw swine. Juvenile female Ossabaw swine (5 wk old) were fed WD (43.0% fat; 17.8% high-fructose corn syrup; 2% cholesterol) or low-fat diet (CON/lean; 10.5% fat) for 16 wk ( n = 6 each) or 36 wk ( n = 4 each). WD-fed pigs developed obesity, dyslipidemia, and systemic insulin resistance compared with CON pigs. In addition, obese WD-fed pigs developed severe NASH, with hepatic steatosis, hepatocyte ballooning, inflammatory cell infiltration, and fibrosis after 16 wk, with further exacerbation of histological inflammation and fibrosis after 36 wk of WD feeding. WD feeding also resulted in robust cecal microbiota changes including increased relative abundances of families and genera in Proteobacteria ( P < 0.05) (i.e., Enterobacteriaceae, Succinivibrionaceae, and Succinivibrio) and LPS-containing Desulfovibrionaceae and Desulfovibrio and a greater ( P < 0.05) predicted microbial metabolic function for LPS biosynthesis, LPS biosynthesis proteins, and peptidoglycan synthesis compared with CON-fed pigs. Overall, juvenile Ossabaw swine fed a high-fat, high-fructose, high-cholesterol diet develop obesity and severe microbiota dysbiosis with a proinflammatory signature and a NASH phenotype directly relevant to the pediatric/adolescent and young adult population.

Feasibility of obtaining breast epithelial cells from healthy women for studies of cellular proliferation.

PubMed

Miller, N A; Thomas, M; Martin, L J; Hedley, D W; Michal, S; Boyd, N F

1997-05-01

Increased dietary fat intake and rate of breast epithelial cell proliferation have each been associated with the development of breast cancer. The goal of this study was to measure the effect of a low fat, high carbohydrate diet on the rate of breast epithelial cell proliferation in women at high risk for breast cancer. Women were recruited from the intervention and control groups of a randomized low fat dietary intervention trial, breast epithelial cells were obtained by fine needle aspiration, and cell proliferation was assessed in these samples using immunofluorescent detection of Ki-67 and PCNA. The effects of needle size and study group on cell yield and cytologic features of the cells were also examined. Fifty three women (20 in the intervention group and 33 in the control group) underwent the biopsy procedure. Slides from 38 subjects were stained for Ki-67 and from 14 subjects for PCNA. No cell proliferation (fluorescence) was detected for either Ki-67 or PCNA in any of the slides. Epithelial cell yield and number of stromal fragments were greater with a larger needle size. Numbers of stromal fragments and bipolar naked nuclei were greater in the low fat as compared to the control group but no differences in epithelial cell yield were observed between the two groups. This study confirms that fine needle aspiration biopsy is a feasible method of obtaining epithelial cells from women without discrete breast masses, but suggests that cell proliferation cannot be assessed using Ki-67 and PCNA in such samples.

Autologous Adipose-Derived Tissue Matrix Part I: Biologic Characteristics.

PubMed

Schendel, Stephen A

2017-10-01

Autologous collagen is an ideal soft tissue filler and may serve as a matrix for stem cell implantation and growth. Procurement of autologous collagen has been limited, though, secondary to a sufficient source. Liposuction is a widely performed and could be a source of autologous collagen. The amount of collagen and its composition in liposuctioned fat remains unknown. The purpose of this research was to characterize an adipose-derived tissue-based product created using ultrasonic cavitation and cryo-grinding. This study evaluated the cellular and protein composition of the final product. Fat was obtained from individuals undergoing routine liposuction and was processed by a 2 step process to obtain only the connective tissue. The tissue was then evaluated by scanning electronic microscope, Western blot analysis, and flow cytometry. Liposuctioned fat was obtained from 10 individuals with an average of 298 mL per subject. After processing an average of 1 mL of collagen matrix was obtained from each 100 mL of fat. Significant viable cell markers were present in descending order for adipocytes > CD90+ > CD105+ > CD45+ > CD19+ > CD144+ > CD34+. Western blot analysis showed collagen type II, III, IV, and other proteins. Scanning electronic microscope study showed a regular pattern of cross-linked, helical collagen. Additionally, vital staing demonstrated that the cells were still viable after processing. Collagen and cells can be easily obtained from liposuctioned fat by ultrasonic separation without alteration of the overall cellular composition of the tissue. Implantation results in new collagen and cellular growth. Collagen matrix with viable cells for autologous use can be obtained from liposuctioned fat and may provide long term results. 5. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells

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

Chiou, Michael; Xu Yue; Longaker, Michael T.

2006-05-05

Adipose-derived mesenchymal cells (AMCs) have demonstrated a great capacity for differentiating into bone, cartilage, and fat. Studies using bone marrow-derived mesenchymal cells (BMSCs) have shown that fibroblast growth factor (FGF)-2, a potent mitogenic factor, plays an important role in tissue engineering due to its effects in proliferation and differentiation for mesenchymal cells. The aim of this study was to investigate the function of FGF-2 in AMC chondrogenic differentiation and its possible contributions to cell-based therapeutics in skeletal tissue regeneration. Data demonstrated that FGF-2 significantly promoted the proliferation of AMCs and enhanced chondrogenesis in three-dimensional micromass culture. Moreover, priming AMCs withmore » treatment of FGF-2 at 10 ng/ml demonstrated that cells underwent chondrogenic phenotypic differentiation, possibly by inducing N-Cadherin, FGF-receptor 2, and transcription factor Sox9. Our results indicated that FGF-2 potentiates chondrogenesis in AMCs, similar to its functions in BMSCs, suggesting the versatile potential applications of FGF-2 in skeletal regeneration and cartilage repair.« less

Rapid development of cardiac dysfunction in a canine model of insulin resistance and moderate obesity.

PubMed

Broussard, Josiane L; Nelson, Michael D; Kolka, Cathryn M; Bediako, Isaac Asare; Paszkiewicz, Rebecca L; Smith, Laura; Szczepaniak, Edward W; Stefanovski, Darko; Szczepaniak, Lidia S; Bergman, Richard N

2016-01-01

The worldwide incidence of obesity and diabetes continues to rise at an alarming rate. A major cause of the morbidity and mortality associated with obesity and diabetes is heart disease, yet the mechanisms that lead to cardiovascular complications remain unclear. We performed cardiac MRI to assess left ventricular morphology and function during the development of moderate obesity and insulin resistance in a well-established canine model (n = 26). To assess the influence of dietary fat composition, we randomised animals to a traditional lard diet (rich in saturated and monounsaturated fat; n = 12), a salmon oil diet (rich in polyunsaturated fat; n = 8) or a control diet (n = 6). High-fat feeding with lard increased body weight and fasting insulin and markedly reduced insulin sensitivity. Lard feeding also significantly reduced left ventricular function, evidenced by a worsening of circumferential strain and impairment in left ventricular torsion. High-fat feeding with salmon oil increased body weight; however, salmon oil feeding did not impair insulin sensitivity or cardiac function. These data emphasise the importance of dietary fat composition on both metabolic and cardiac function, and have important implications for the relationship between diet and health.

Utility of human embryonic kidney cell line HEK-293 for rapid isolation of fixed and street rabies viruses: comparison with Neuro-2a and BHK-21 cell lines.

PubMed

Madhusudana, Shampur Narayan; Sundaramoorthy, Subha; Ullas, Padinjaremattatthil Thankappan

2010-12-01

A confirmatory rabies diagnosis can be achieved by rapid virus isolation in cell culture using brain tissue from the suspect animal. Several cell lines have been used for this purpose and the murine neuroblastoma cell line Neuro-2a has been found to be the most sensitive. The human embryonic kidney cell line HEK-293 is known to express several neuronal proteins and is believed to be of neuronal origin. We hypothesized that this cell line could be susceptible to rabies virus, which is highly neurotropic. First we tested the sensitivity of HEK-293 cells to the laboratory strain, challenge virus standard (CVS). We then tested 120 brain samples from different animals and humans suspected to have died of rabies by fluorescent antibody test (FAT). Both FAT-positive and FAT-negative brains were tested for virus isolation using Neuro-2a, BHK-21, and HEK-293 cell lines and also by mouse inoculation. There was 100% correlation between FAT, virus isolation in Neuro-2a and HEK-293 cells, and mouse inoculation. However, the rate of virus isolation in the BHK-21 cell line was only 28% when compared to the other cell lines. The sensitivity of HEK-293 to CVS strain of virus was similar to that of Neuro-2a. We conclude that the HEK-293 cell line is as sensitive as the Neuro-2a cell line for the rapid isolation of rabies virus and may serve as an alternative cell line for rabies diagnosis and future research. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Impact of high-fat diet and voluntary running on body weight and endothelial function in LDL receptor knockout mice.

PubMed

Langbein, Heike; Hofmann, Anja; Brunssen, Coy; Goettsch, Winfried; Morawietz, Henning

2015-05-01

Obesity and physical inactivity are important cardiovascular risk factors. Regular physical exercise has been shown to mediate beneficial effects in the prevention of cardiovascular diseases. However, the impact of physical exercise on endothelial function in proatherosclerotic low-density lipoprotein receptor deficient (LDLR(-/-)) mice has not been studied so far. Six-week-old male LDLR(-/-) mice were fed a standard diet or a high-fat diet (39 kcal% fat diet) for 20 weeks. The impact of high-fat diet and voluntary running on body weight and amount of white adipose tissue was monitored. Basal tone and endothelial function was investigated in aortic rings using a Mulvany myograph. LDLR(-/-) mice on high-fat diet had increased cumulative food energy intake, but also higher physical activity compared to mice on control diet. Body weight and amount of visceral and retroperitoneal white adipose tissue of LDLR(-/-) mice were significantly increased by high-fat diet and partially reduced by voluntary running. Endothelial function in aortae of LDLR(-/-) mice was impaired after 20 weeks on standard and high-fat diet and could not be improved by voluntary running. Basal tone showed a trend to be increased by high-fat diet. Voluntary running reduced body weight and amount of white adipose tissue in LDLR(-/-) mice. Endothelial dysfunction in LDLR(-/-) mice could not be improved by voluntary running. In a clinical context, physical exercise alone might not have an influence on functional parameters and LDL-C levels in patients with familial hypercholesterolemia. However, physical activity in these patients may be in general beneficial and should be performed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Assessment of body fat based on potential function clustering segmentation of computed tomography images

NASA Astrophysics Data System (ADS)

Zhang, Lixin; Lin, Min; Wan, Baikun; Zhou, Yu; Wang, Yizhong

2005-01-01

In this paper, a new method of body fat and its distribution testing is proposed based on CT image processing. As it is more sensitive to slight differences in attenuation than standard radiography, CT depicts the soft tissues with better clarity. And body fat has a distinct grayness range compared with its neighboring tissues in a CT image. An effective multi-thresholds image segmentation method based on potential function clustering is used to deal with multiple peaks in the grayness histogram of a CT image. The CT images of abdomens of 14 volunteers with different fatness are processed with the proposed method. Not only can the result of total fat area be got, but also the differentiation of subcutaneous fat from intra-abdominal fat has been identified. The results show the adaptability and stability of the proposed method, which will be a useful tool for diagnosing obesity.

Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control

PubMed Central

Zhao, Bin; Wei, Xiaomu; Li, Weiquan; Udan, Ryan S.; Yang, Qian; Kim, Joungmok; Xie, Joe; Ikenoue, Tsuneo; Yu, Jindan; Li, Li; Zheng, Pan; Ye, Keqiang; Chinnaiyan, Arul; Halder, Georg; Lai, Zhi-Chun; Guan, Kun-Liang

2007-01-01

The Hippo pathway plays a key role in organ size control by regulating cell proliferation and apoptosis in Drosophila. Although recent genetic studies have shown that the Hippo pathway is regulated by the NF2 and Fat tumor suppressors, the physiological regulations of this pathway are unknown. Here we show that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway. Phosphorylation by the Lats tumor suppressor kinase leads to cytoplasmic translocation and inactivation of the YAP oncoprotein. Furthermore, attenuation of this phosphorylation of YAP or Yorkie (Yki), the Drosophila homolog of YAP, potentiates their growth-promoting function in vivo. Moreover, YAP overexpression regulates gene expression in a manner opposite to cell density, and is able to overcome cell contact inhibition. Inhibition of YAP function restores contact inhibition in a human cancer cell line bearing deletion of Salvador (Sav), a Hippo pathway component. Interestingly, we observed that YAP protein is elevated and nuclear localized in some human liver and prostate cancers. Our observations demonstrate that YAP plays a key role in the Hippo pathway to control cell proliferation in response to cell contact. PMID:17974916

A high fat diet containing saturated but not unsaturated fatty acids enhances T cell receptor clustering on the nanoscale.

PubMed

Shaikh, Saame Raza; Boyle, Sarah; Edidin, Michael

2015-09-01

Cell culture studies show that the nanoscale lateral organization of surface receptors, their clustering or dispersion, can be altered by changing the lipid composition of the membrane bilayer. However, little is known about similar changes in vivo, which can be effected by changing dietary lipids. We describe the use of a newly developed method, k-space image correlation spectroscopy, kICS, for analysis of quantum dot fluorescence to show that a high fat diet can alter the nanometer-scale clustering of the murine T cell receptor, TCR, on the surface of naive CD4(+) T cells. We found that diets enriched primarily in saturated fatty acids increased TCR nanoscale clustering to a level usually seen only on activated cells. Diets enriched in monounsaturated or n-3 polyunsaturated fatty acids had no effect on TCR clustering. Also none of the high fat diets affected TCR clustering on the micrometer scale. Furthermore, the effect of the diets was similar in young and middle aged mice. Our data establish proof-of-principle that TCR nanoscale clustering is sensitive to the composition of dietary fat. Copyright © 2015 Elsevier Ltd. All rights reserved.

Physicochemical and functional properties of micronized jincheng orange by-products (Citrus sinensis Osbeck) dietary fiber and its application as a fat replacer in yogurt.

PubMed

Yi, Tian; Huang, Xingjian; Pan, Siyi; Wang, Lufeng

2014-08-01

Orange by-products from juice extraction are generally discarded or used in animal feed due to their low market value. However, orange by-products show potential as dietary fiber (DF) and fat replacers in products such as yogurt. This study assessed the benefits of using orange by-products in DF-enriched materials such as DF powders (OP) and micronized DF with ball-milling (MDF). The study also investigated the effects of adding different levels of OP and MDF on the quality of low-fat yogurt. Results show that MDF showed better physicochemical and functional properties than OP, and that 2% MDF as a fat replacer in yogurt retained most of the textural and sensory properties of full-fat yogurt. Therefore, this study showed that MDF is a promising alternative as a fat replacer in low-fat yogurt, without sacrificing good taste and other qualities of full-fat yogurt.

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

PubMed Central

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

2015-01-01

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

Effect of N-Acetylcysteine on Adipose-Derived Stem Cell and Autologous Fat Graft Survival in a Mouse Model.

PubMed

Gillis, Joshua; Gebremeskel, Simon; Phipps, Kyle D; MacNeil, Lori A; Sinal, Christopher J; Johnston, Brent; Hong, Paul; Bezuhly, Michael

2015-08-01

Autologous fat grafting is a popular reconstructive technique, but is limited by inconsistent graft retention. The authors examined whether a widely available, clinically safe antioxidant, N-acetylcysteine, could improve adipose-derived stem cell survival and graft take when added to tumescent solution during fat harvest. Inguinal fat pads were harvested from C57BL/6 mice using tumescent solution with or without N-acetylcysteine. Flow cytometric, proliferation, and differentiation assays were performed on isolated primary adipose-derived stem cells and 3T3-L1 preadipocytes treated with or without hydrogen peroxide and/or N-acetylcysteine. N-Acetylcysteine-treated or control grafts were injected under recipient mouse scalps and assessed by serial micro-computed tomographic volumetric analysis. Explanted grafts underwent immunohistochemical analysis. In culture, N-acetylcysteine protected adipose-derived stem cells from oxidative stress and improved cell survival following hydrogen peroxide treatment. Combined exposure to both N-acetylcysteine and hydrogen peroxide led to a 200-fold increase in adipose-derived stem cell proliferation, significantly higher than with either agent alone. N-Acetylcysteine decreased differentiation of adipose-derived stem cells into mature adipocytes, as evidenced by decreased transcription of adipocyte differentiation markers and reduced Oil Red-O staining. In vivo, N-acetylcysteine treatment resulted in improved graft retention at 3 months compared with control (46 versus 17 percent; p = 0.027). N-Acetylcysteine-treated grafts demonstrated less fibrosis and inflammation, and a 33 percent increase in adipocyte density compared with controls (p < 0.001) that was not associated with increased vascularity. These findings provide proof of principle for the addition of N-acetylcysteine to tumescent harvest solution in the clinical setting to optimize fat graft yields.

Diet, exercise and gut mucosal immunity.

PubMed

Valdés-Ramos, Roxana; Martínez-Carrillo, Beatriz E; Aranda-González, Irma I; Guadarrama, Ana Laura; Pardo-Morales, Rosa Virgen; Tlatempa, Patricia; Jarillo-Luna, Rosa A

2010-11-01

Diet and exercise are primary strategies recommended for the control of the obesity epidemic. Considerable attention is being paid to the effect of both on the immune system. However, little research has been done on the effect of diet, nutrients or exercise on the mucosal immune system. The gastrointestinal tract (gut) is not only responsible for the entry of nutrients into the organism, but also for triggering the primary immune response to orally ingested antigens. The gut-associated lymphoid tissue contains a large amount of immune cells, disseminated all along the intestine in Peyer's patches and lamina propria. Specific nutrients or their combinations, as well as the microflora, are capable of modulating the immune system through cell activation, production of signalling molecules or gene expression. We have observed an increase in T-cells as well as a decrease in B-cells from Peyer's patches, induced by diets high in fats or carbohydrates in Balb/c mice. It has also been demonstrated that exercise modulates the immune system, where moderate levels may improve its function by increasing the proliferation of lymphocytes from various sites, including gut-associated lymphoid tissue, whereas exhaustive acute exercise may cause immunosuppression. High-fat diets combined with exercise are able to induce an increase in CD3+ lymphocytes due to increased CD8+ cells and a decrease in B-cells. Explanations and consequences of the effects of diet and exercise on the gut mucosal immunity are still being explored.

Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

PubMed

Jonker, Jacqueline T; de Mol, Pieter; de Vries, Suzanna T; Widya, Ralph L; Hammer, Sebastiaan; van Schinkel, Linda D; van der Meer, Rutger W; Gans, Rijk O B; Webb, Andrew G; Kan, Hermien E; de Koning, Eelco J P; Bilo, Henk J G; Lamb, Hildo J

2013-11-01

To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P < .01), and subcutaneous abdominal fat volume remained unchanged (P = .9). Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P < .01) and paracardial fat volume from 4.6 mL ± 0.9 to 3.7 mL ± 0.8 (P = .02). Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

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

PubMed

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

2016-03-01

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

Left ventricular function impairment in patients with normal-weight obesity: contribution of abdominal fat deposition, profibrotic state, reduced insulin sensitivity, and proinflammatory activation.

PubMed

Kosmala, Wojciech; Jedrzejuk, Diana; Derzhko, Roksolana; Przewlocka-Kosmala, Monika; Mysiak, Andrzej; Bednarek-Tupikowska, Grazyna

2012-05-01

Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. One hundred sixty-eight subjects (age, 38±7 years) with BMI <25kg/m(2) and no history of any disease affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (β=-0.17, P<0.006), C-reactive protein (β=-0.20, P<0.002) and abdominal fat deposit (β=-0.20, P<0.003); for tissue S velocity, PICP (β=-0.21, P<0.002) and abdominal fat deposit (β=-0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (β=-0.30, P<0.0001), PICP (β=-0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; β=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both β=0.18, P<0.01) and HOMA IR (β=0.16, P<0.04). In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

Maternal high fat diet promotion of mammary tumor risk in adult progeny is associated with early expansion of mammary cancer stem-like cells and increased maternal oxidative environment

USDA-ARS?s Scientific Manuscript database

Many adult chronic diseases might be programmed during early life by maternal nutritional history. Here, we evaluated effects of maternal high fat diet on mammary gland development and tumor formation in adult progeny. Female Wnt-1 transgenic mice exposed to high fat (HFD, 45% kcal fat) or control C...

High-fat diet exposure from pre-pubertal age induces polycystic ovary syndrome (PCOS) in rats.

PubMed

Patel, Roshni; Shah, Gaurang

2018-02-01

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, oligo-anovulation, polycystic ovaries and metabolic syndrome. Many researchers reported that PCOS often starts with menarche in adolescents. Presently available animal model focuses on ovarian but not metabolic features of PCOS. Therefore, we hypothesized that high-fat diet feeding to pre-pubertal female rats results in both reproductive and metabolic features of PCOS. Pre-pubertal female rats were divided into two groups: group I received normal pellet diet and group II received high-fat diet (HFD). In the letrozole study, adult female rats were divided into two groups: group I received 1% carboxy methyl cellulose and group II received 1 mg/kg letrozole orally. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, luteinizing hormone (LH) receptor and follicle-stimulating hormone receptor expression were measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Feeding of HFD gradually increase glucose intolerance and fasting insulin levels. Triglyceride level was higher in HFD study while total cholesterol level was higher in the letrozole study. Alteration in testosterone and estrogen levels was observed in both studies. LH receptor expression was upregulated only in HFD study. Histopathological changes like increase cystic follicle, diminished granulosa cell layer and thickened theca cell layer were observed in letrozole as well as HFD study. High-fat diet initiated at pre-puberty age in rats produces both metabolic disturbances and ovarian changes similar to that observed clinically in PCOS patients. Letrozole on the other hand induces change in ovarian structure and function. © 2018 Society for Reproduction and Fertility.

Pasture v. standard dairy cream in high-fat diet-fed mice: improved metabolic outcomes and stronger intestinal barrier.

PubMed

Benoit, Bérengère; Plaisancié, Pascale; Géloën, Alain; Estienne, Monique; Debard, Cyrille; Meugnier, Emmanuelle; Loizon, Emmanuelle; Daira, Patricia; Bodennec, Jacques; Cousin, Olivier; Vidal, Hubert; Laugerette, Fabienne; Michalski, Marie-Caroline

2014-08-28

Dairy products derived from the milk of cows fed in pastures are characterised by higher amounts of conjugated linoleic acid and α-linolenic acid (ALA), and several studies have shown their ability to reduce cardiovascular risk. However, their specific metabolic effects compared with standard dairy in a high-fat diet (HFD) context remain largely unknown; this is what we determined in the present study with a focus on the metabolic and intestinal parameters. The experimental animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver, white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice, despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG concentrations, and inflammation in the adipose tissue than the SDC mice. Furthermore, they exhibited a higher expression of hepatic PPARα mRNA and adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative activity of the tissues. These results might be explained, in part, by the higher amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC mice. Moreover, the PDC diet was found to increase the proportions of two strategic cell populations involved in the protective function of the intestinal epithelium, namely Paneth and goblet cells in the small intestine and colon, compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due, at least in part, to the protective mechanisms induced by specific lipids.

Reduced Triglyceride Secretion in Response to an Acute Dietary Fat Challenge in Obese Compared to Lean Mice

PubMed Central

Uchida, Aki; Whitsitt, Mary C.; Eustaquio, Trisha; Slipchenko, Mikhail N.; Leary, James F.; Cheng, Ji-Xin; Buhman, Kimberly K.

2012-01-01

Obesity results in abnormally high levels of triglyceride (TG) storage in tissues such as liver, heart, and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism. More specifically we asked whether TG storage in and secretion from the intestine are altered in obesity. We investigated these questions in diet-induced obese (DIO) and leptin-deficient (ob/ob) mice. We found greater levels of TG storage in the intestine of DIO mice compared to lean mice in the fed state, but similar levels of TG storage after a 6-h fast. In addition, we found similar TG storage in the intestine of lean and DIO mice at multiple time points after an acute dietary fat challenge. Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice compared to lean controls in response to an acute dietary fat challenge. Furthermore, we found altered mRNA levels for genes involved in regulation of intestinal TG metabolism in lean and DIO mice at 6 h fasting and in response to an acute dietary fat challenge. More specifically, we found that many of the genes related to TG synthesis, chylomicron synthesis, TG storage, and lipolysis were induced in response to an acute dietary fat challenge in lean mice, but this induction was not observed in DIO mice. In fact, we found a significant decrease in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation in DIO mice in response to an acute dietary fat challenge. Our findings demonstrate altered TG handling by the small intestine of obese compared to lean mice. PMID:22375122

m6A demethylase FTO facilitates tumor progression in lung squamous cell carcinoma by regulating MZF1 expression.

PubMed

Liu, Jiqin; Ren, Dangli; Du, Zhenhua; Wang, Hekong; Zhang, Hua; Jin, Ying

2018-08-25

N 6 -Methyladenosine (m 6 A) represents the most prevalent internal modification in mammalian mRNAs. Emerging evidences suggest that m 6 A modification is profoundly implicated in many biological processes, including cancer development. However, limited knowledge is available about the functional importance of m 6 A in lung cancer. In this study, by data mining The Cancer Genome Atlas (TCGA) database, we first identified fat mass- and obesity-associated protein (FTO) as a prognostic factor for lung squamous cell carcinoma (LUSC). Then we showed that FTO, but not other m 6 A modification genes including METTL3, METTL14 and ALKBH5, was the major dysregulated factor responsible for aberrant m 6 A modification in LUSC. Loss-of-function studies suggested that FTO knockdown effectively inhibited cell proliferation and invasion, while promoted cell apoptosis of L78 and NCI-H520 cells. Furthermore, overexpression of FTO, but not its mutant form, facilitated the malignant phenotypes of CHLH-1 cells. Mechanistically, FTO enhanced MZF1 expression by reducing m 6 A levels and mRNA stability in MZF1 mRNA transcript, leading to oncogenic functions. Taken together, our study demonstrates the functional importance of FTO in the tumor progression of LUSC and provides a potential therapeutic target for LUSC treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

Metabolic syndrome alters expression of insulin signaling-related genes in swine mesenchymal stem cells.

PubMed

Conley, Sabena M; Zhu, Xiang-Yang; Eirin, Alfonso; Tang, Hui; Lerman, Amir; van Wijnen, Andre J; Lerman, Lilach O

2018-02-20

Metabolic syndrome (MetS) is associated with insulin resistance (IR) and impaired glucose metabolism in muscle, fat, and other cells, and may induce inflammation and vascular remodeling. Endogenous reparative systems, including adipose tissue-derived mesenchymal stem/stromal cells (MSC), are responsible for repair of damaged tissue. MSC have also been proposed as an exogenous therapeutic intervention in patients with cardiovascular and chronic kidney disease (CKD). The feasibility of using autologous cells depends on their integrity, but whether in MetS IR involves adipose tissue-derived MSC remains unknown. The aim of this study was to examine the expression of mRNA involved in insulin signaling in MSC from subjects with MetS. Domestic pigs consumed a lean or obese diet (n=6 each) for 16weeks. MSC were collected from subcutaneous abdominal fat and analyzed using high-throughput RNA-sequencing for expression of genes involved in insulin signaling. Expression profiles for enriched (fold change>1.4, p<0.05) and suppressed (fold change<0.7, p<0.05) mRNAs in MetS pigs were functionally interpreted by gene ontology analysis. The most prominently upregulated and downregulated mRNAs were further probed. We identified in MetS-MSC 168 up-regulated and 51 down-regulated mRNAs related to insulin signaling. Enriched mRNAs were implicated in biological pathways including hepatic glucose metabolism, adipocyte differentiation, and transcription regulation, and down-regulated mRNAs in intracellular calcium signaling and cleaving peptides. Functional analysis suggested that overall these alterations could increase IR. MetS alters mRNA expression related to insulin signaling in adipose tissue-derived MSC. These observations mandate caution during administration of autologous MSC in subjects with MetS. Copyright © 2017. Published by Elsevier B.V.

Paternal Diet-Induced Obesity Retards Early Mouse Embryo Development, Mitochondrial Activity and Pregnancy Health

PubMed Central

Binder, Natalie K.; Hannan, Natalie J.; Gardner, David K.

2012-01-01

Worldwide, 48% of adult males are overweight or obese. An association between infertility and excessive body weight is now accepted, although focus remains primarily on females. It has been shown that parental obesity results in compromised embryo development, disproportionate changes in embryo metabolism and reduced blastocyst cell number. The aim of this study was to determine whether paternal obesity has negative effects on the resultant embryo. Specifically, using in vitro fertilisation (IVF), we wanted to isolate the functional effects of obesity on sperm by examining the subsequent embryo both pre- and post-implantation. Epididymal sperm was collected from age matched normal and obese C57BL/6 mice and cryopreserved for subsequent IVF with oocytes collected from Swiss females (normal diet/weight). Obesity was induced in male mice by feeding a high fat diet of 22% fat for 10 weeks. Resultant embryos were cultured individually and development monitored using time-lapse microscopy. Paternal obesity resulted in a significant delay in preimplantation embryo development as early as syngamy (P<0.05). Metabolic parameters were measured across key developmental stages, demonstrating significant reduction in mitochondrial membrane potential (P<0.01). Blastocysts were stained to determine trophectoderm (TE) and inner cell mass (ICM) cell numbers, revealing significant differences in the ratio of cell allocation to TE and ICM lineages (P<0.01). Functional studies examining blastocyst attachment, growth and implantation demonstrated that blastocysts derived from sperm of obese males displayed significantly reduced outgrowth on fibronectin in vitro (P<0.05) and retarded fetal development in vivo following embryo transfer (P<0.05). Taken together, these data clearly demonstrate that paternal obesity has significant negative effects on the embryo at a variety of key early developmental stages, resulting in delayed development, reduced placental size and smaller offspring. PMID:23300638

Chemical composition of fat and oil products

USDA-ARS?s Scientific Manuscript database

Fats and oils are an important dietary component, and contribute to the nutritional and sensory quality of foods. This chapter focuses on the chemical composition of fats and oils, and how these compositions affect the functional properties of fats and oils in foods. The focus will remain on the mos...

Liver injury in hypervitaminosis A: Evidence for activation of Kupffer cell function

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

Sim, W.L.W.

1988-01-01

The most important and novel finding of this work was enhanced liver Kupffer cell phagocytic and metabolic function by hypervitaminosis A. An animal model of hypervitaminosis A was developed in male Sprague-Dawley rats gavaged with 250,000 I.U. retinol/kg body weight/day for 3 weeks. Presence of hypervitaminosis A was indicated by characteristic changes in the fur coat, presence of brittle bones and spontaneous fractures and a significant increase in plasma and liver concentrations of retinyl palmitate while retinol levels remained the same as in controls. Hypervitaminosis A did not cause severe liver abnormalities as reflected by normal plasma glutamate pyruvate transaminasemore » activity and bilirubin. The main change was a marked increase in size of the fat or Vitamin A storing cells. Measurement of clearance from blood of indocyanine green and {sup 99m}Tc-disofenin indicated this hepatocyte function was normal. Kupffer cell phagocytic function was enhanced in hypervitaminosis A as determined by clearance from blood of {sup 99m}Tc-sulfur colloid. In vitro, there was also evidence that treatment with high doses of Vitamin A activated or enhanced Kupffer cell function. Kupffer cells from control and Vitamin A treated rats were isolated by enzymatic dispersion, purified by centrifugal elutriation, and placed in culture. Activation was indicated by (1) increased phagocytosis of {sup 51}Cr-labeled opsonized sheep red blood cells (2) enhanced release of superoxide anion and (3) enhanced production of tumor cytolytic factor by Kupffer cells from Vitamin A treated rats.« less

Correlation between lumbar dysfunction and fat infiltration in lumbar multifidus muscles in patients with low back pain.

PubMed

Hildebrandt, Markus; Fankhauser, Gabriela; Meichtry, André; Luomajoki, Hannu

2017-01-10

Lumbar multifidus muscles (LMM) are important for spinal motion and stability. Low back pain (LBP) is often associated with fat infiltration in LMM. An increasing fat infiltration of LMM may lead to lumbar dysfunction. The purpose of this study was to investigate whether there is a correlation between the severity of lumbar dysfunction and the severity of fat infiltration of LMM. In a cross-sectional study, 42 patients with acute or chronic LBP were recruited. Their MRI findings were visually rated and graded using three criteria for fat accumulation in LMM: Grade 0 (0-10%), Grade 1 (10-50%) and Grade 2 (>50%). Lumbar sagittal range of motion, dynamic upright and seated posture control, sagittal movement control, body awareness and self-assessed functional disability were measured to determine the patients' low back dysfunction. The main result of this study was that increased severity of fat infiltration in the lumbar multifidus muscles correlated significantly with decreased range of motion of lumbar flexion (p = 0.032). No significant correlation was found between the severity of fat infiltration in LMM and impaired movement control, posture control, body awareness or self-assessed functional disability. This is the first study investigating the relationship between the severity of fat infiltration in LMM and the severity of lumbar dysfunction. The results of this study will contribute to the understanding of the mechanisms leading to fat infiltration of LMM and its relation to spinal function. Further studies should investigate whether specific treatment strategies are effective in reducing or preventing fat infiltration of LMM.

Association of C49620T ABCC8 polymorphism with anthropometric and metabolic parameters in patients with autosomal dominant polycystic kidney disease: a preliminary study.

PubMed

Pietrzak-Nowacka, Maria; Safranow, Krzysztof; Bińczak-Kuleta, Agnieszka; Rózański, Jacek; Ciechanowski, Kazimierz; Ciechanowicz, Andrzej

2012-01-01

The aim of the study was to evaluate an association between the C49620T ABCC8 gene polymorphism and anthropometric, biochemical parameters, pancreatic β-cell function and insulin sensitivity among autosomal dominant polycystic kidney disease (ADPKD) patients. Forty-nine ADPKD patients (M/F: 19/30) and fifty healthy controls (M/F: 22/28) aged above 18 years, with normal kidney function and no diagnosis of diabetes, were enrolled into the study. The ABCC8 (SUR1) C49620T (IVS15-3C/T, rs1799854) genotypes were determined using a PCR-RFLP technique. In the ADPKD group among TT homozygous patients, total body fat content and percentage of fat in body weight were significantly lower than among C allele carriers (16.1 +/- 7.7 vs 22.9 +/- 7.1kg, p=0.04 and 22.8 +/- 6.5 vs 30.0 +/- 6.1%, p=0.001, respectively) while total body water was higher (58.4 +/- 4.3 vs 53.7 +/- 4.0kg, p=0.003). Among TT homozygous controls higher BMI values and LDL-cholesterol levels were observed if compared to C variant carriers (26.3 +/- 3.9 vs 23.8 +/3.4kg/m2 p=0.04 and 133.1 +/- 27.0 vs 114.3 +/- 35.2mg/dL, p=0.05, respectively), as well as higher area under curve of glucose concentrations (115.9 +/- 23.9 vs 102.7 +/- 25.2 mmol*h/L, p=0.046) during an oral glucose tolerance test. In the ADPKD group and among controls no association between the investigated polymorphism and secretory function of the pancreatic β-cells or insulin sensitivity was found. The C49620T ABCC8 polymorphism is associated with anthropometric risk factors for type 2 diabetes among ADPKD patients, with a protective effect of the TT genotype, but without influence on pancreatic β-cell secretory function or insulin sensitivity.

Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice

PubMed Central

Yoshizaki, Yumiko; Kawasaki, Chihiro; Cheng, Kai-Chun; Ushikai, Miharu; Amitani, Haruka; Asakawa, Akihiro; Okutsu, Kayu; Sameshima, Yoshihiro; Takamine, Kazunori

2014-01-01

Rice koji is considered a readily accessible functional food that may have health-promoting effects. We investigated whether white, yellow, and red koji have the anti-obesity effect in C57BL/6J mice fed a high-fat diet (HFD), which is a model for obesity. Mice were fed HFD containing 10% (w/w) of rice koji powder or steamed rice for 4 weeks. Weight gain, epididymal white adipose tissue, and total adipose tissue weight were significantly lower in all rice koji groups than in the HFD-rice group after 4 weeks. Feed efficiency was significantly reduced in the yellow koji group. Blood glucose levels were significantly lower in the white and red koji groups with HOMA-R and leptin levels being reduced in the white koji group. White and red koji increased glucose uptake and GLUT4 protein expression in L6 myotube cells. These results showed that all rice koji have the anti-obesity or anti-diabetes effects although the mechanisms may differ depending on the type of rice koji consumed. PMID:25237599

Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice.

PubMed

Yoshizaki, Yumiko; Kawasaki, Chihiro; Cheng, Kai-Chun; Ushikai, Miharu; Amitani, Haruka; Asakawa, Akihiro; Okutsu, Kayu; Sameshima, Yoshihiro; Takamine, Kazunori; Inui, Akio

2014-01-01

Rice koji is considered a readily accessible functional food that may have health-promoting effects. We investigated whether white, yellow, and red koji have the anti-obesity effect in C57BL/6J mice fed a high-fat diet (HFD), which is a model for obesity. Mice were fed HFD containing 10% (w/w) of rice koji powder or steamed rice for 4 weeks. Weight gain, epididymal white adipose tissue, and total adipose tissue weight were significantly lower in all rice koji groups than in the HFD-rice group after 4 weeks. Feed efficiency was significantly reduced in the yellow koji group. Blood glucose levels were significantly lower in the white and red koji groups with HOMA-R and leptin levels being reduced in the white koji group. White and red koji increased glucose uptake and GLUT4 protein expression in L6 myotube cells. These results showed that all rice koji have the anti-obesity or anti-diabetes effects although the mechanisms may differ depending on the type of rice koji consumed.

High-fat diet exacerbates inflammation and cell survival signals in the skin of ultraviolet B-irradiated C57BL/6 mice

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

Meeran, Syed M.; Singh, Tripti; Nagy, Tim R.

Inflammation induced by chronic exposure to ultraviolet (UV) radiation has been implicated in various skin diseases. We formulated the hypothesis that a high-fat diet may influence the UV-induced inflammatory responses in the skin. C57BL/6 mice were fed a high-fat diet or control diet and exposed to UVB radiation (120 mJ/cm{sup 2}) three times/week for 10 weeks. The mice were then sacrificed and skin and plasma samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. We found that the levels of inflammatory biomarkers were increased in the UVB-exposed skin of the mice fedmore » the high-fat diet than the UVB-exposed skin of the mice fed the control diet. The levels of inflammatory biomarkers of early responses to UVB exposure (e.g., myeloperoxidase, cyclooxygenase-2, prostaglandin-E{sub 2}), proinflammatory cytokines (i.e., tumor necrosis factor-alpha, interleukin-1beta, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser{sup 473}) were higher in high-fat-diet-fed mouse skin than control-diet-fed mouse skin. The plasma levels of insulin growth factor-1 were greater in the UVB-irradiated mice fed the high-fat diet than the UVB-irradiated mice fed the control diet, whereas the levels of plasma adiponectin were significantly lower. This pronounced exacerbation of the UVB-induced inflammatory responses in the skin of mice fed a high-fat diet suggests that high-fat diet may increase susceptibility to inflammation-associated skin diseases, including the risk of skin cancer.« less

Improved fat graft survival by different volume fractions of platelet-rich plasma and adipose-derived stem cells.

PubMed

Li, Feng; Guo, Weihua; Li, Kun; Yu, Mei; Tang, Wei; Wang, Hang; Tian, Weidong

2015-03-01

The success of soft-tissue augmentation is offset by the low survival rates of grafted fat tissue. Research shows that adipose-derived stem cells (ASCs) and platelet-rich plasma (PRP) are beneficial to tissue healing. To evaluate the long-term effects of different volume fractions of PRP combined with ASCs on fat graft. ASCs were isolated from human fat tissue, and PRP was obtained from human blood. Cell count kit-8 and real-time polymerase chain reaction (PCR) were used to evaluate the influence of PRP (0%, 10%, 20%, and 30%; volume/volume [v/v]) in medium on ASC proliferation and adipogenic differentiation, respectively. A novel lipoinjection consisting of granular fat, PRP, and ASCs was subcutaneously transplanted into nude mice. The grafts were volumetrically and histologically evaluated 10, 30, 60, and 90 days after transplantation. The addition of PRP improved ASC proliferation. Expression of adipogenic-related genes, peroxisome proliferator-activated receptor-γ, lipoprotein lipase, and adipophilin were up-regulated in PRP-induced ASCs. Compared with other groups, granular fat grafts formed with 20% (v/v) and 30% (v/v) PRP significantly improved residual volumes. More intact adipocytes and capillary formation, but less vacuolization, were observed in the 20% (v/v) and 30% (v/v) PRP groups at 30, 60, and 90 days. However, no significant difference was observed between the 20% (v/v) and 30% (v/v) PRP groups in retaining fat grafts and improving histology. Fat grafting with 20% (v/v) PRP and ASCs constitutes an appropriate transplantation strategy for improving graft survival and provides a potential approach for soft-tissue restoration in plastic and reconstructive surgery. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Inhibition of lipolysis in the novel transgenic quail model overexpressing G0/G1 switch gene 2 in the adipose tissue during feed restriction.

PubMed

Shin, Sangsu; Choi, Young Min; Han, Jae Yong; Lee, Kichoon

2014-01-01

In addition to the issue of obesity in humans, the production of low-fat meat from domestic animals is important in the agricultural industry to satisfy consumer demand. Understanding the regulation of lipolysis in adipose tissue could advance our knowledge to potentially solve both issues. Although the G0/G1 switch gene 2 (G0S2) was recently identified as an inhibitor of adipose triglyceride lipase (ATGL) in vitro, its role in vivo has not been fully clarified. This study was conducted to investigate the role of G0S2 gene in vivo by using two independent transgenic quail lines during different energy conditions. Unexpectedly, G0S2 overexpression had a negligible effect on plasma NEFA concentration, fat cell size and fat pad weight under ad libitum feeding condition when adipose lipolytic activity is minimal. A two-week feed restriction in non-transgenic quail expectedly caused increased plasma NEFA concentration and dramatically reduced fat cell size and fat pad weight. Contrary, G0S2 overexpression under a feed restriction resulted in a significantly less elevation of plasma NEFA concentration and smaller reductions in fat pad weights and fat cell size compared to non-transgenic quail, demonstrating inhibition of lipolysis and resistance to loss of fat by G0S2. Excessive G0S2 inhibits lipolysis in vivo during active lipolytic conditions, such as food restriction and fasting, suggesting G0S2 as a potential target for treatment of obesity. In addition, transgenic quail are novel models for studying lipid metabolism and mechanisms of obesity.

Dietary fat intake, circulating and membrane fatty acid composition of healthy Norwegian men and women.

PubMed

Min, Y; Blois, A; Geppert, J; Khalil, F; Ghebremeskel, K; Holmsen, H

2014-02-01

The present study aimed to assess the dietary fat intake and blood fatty acid status of healthy Norwegian men and women living in Bergen whose habitual diet is known to be high in long-chain omega-3 fat. Healthy men (n = 41) and women (n = 40) aged 20-50 years who were regular blood donors completed 7-day food diaries and their nutrient intake was analysed by Norwegian food database software, kbs, version 4.9 (kostberegningssystem; University of Oslo, Oslo, Norway). Blood samples were obtained before blood donation and assessed for the fatty acid composition of plasma triglycerides and cholesterol esters, phosphatidylcholine, and red cell phosphatidylcholine and phosphatidylethanolamine. There was no difference in dietary fat intake between men and women. Total and saturated fat intakes exceeded the upper limits of the recommendations of the National Nutrition Council of Norway. Although polyunsaturated fat intake was close to the lower limit of the recommended level, the intake varied greatly among individuals, partly as a result of the use of supplementary fish oil. Moreover, the proportional fatty acid composition of plasma and red cell lipids was similar between men and women. Enrichment of docosahexaenoic acid in red cell phosphatidylethanolamine was found in fish oil users. The results of the present study provide a snapshot of the current nutritional status of healthy Norwegian adults. Moreover, the detailed blood fatty acid composition of men and women whose habitual diet constitutes high long-chain polyunsaturated omega-3 fat as well as saturated fat could be used as reference value for population studies. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

Quantitative proteomic analysis of milk fat globule membrane (MFGM) proteins in human and bovine colostrum and mature milk samples through iTRAQ labeling.

PubMed

Yang, Mei; Cong, Min; Peng, Xiuming; Wu, Junrui; Wu, Rina; Liu, Biao; Ye, Wenhui; Yue, Xiqing

2016-05-18

Milk fat globule membrane (MFGM) proteins have many functions. To explore the different proteomics of human and bovine MFGM, MFGM proteins were separated from human and bovine colostrum and mature milk, and analyzed by the iTRAQ proteomic approach. A total of 411 proteins were recognized and quantified. Among these, 232 kinds of differentially expressed proteins were identified. These differentially expressed proteins were analyzed based on multivariate analysis, gene ontology (GO) annotation and KEGG pathway. Biological processes involved were response to stimulus, localization, establishment of localization, and the immune system process. Cellular components engaged were the extracellular space, extracellular region parts, cell fractions, and vesicles. Molecular functions touched upon were protein binding, nucleotide binding, and enzyme inhibitor activity. The KEGG pathway analysis showed several pathways, including regulation of the actin cytoskeleton, focal adhesion, neurotrophin signaling pathway, leukocyte transendothelial migration, tight junction, complement and coagulation cascades, vascular endothelial growth factor signaling pathway, and adherens junction. These results enhance our understanding of different proteomes of human and bovine MFGM across different lactation phases, which could provide important information and potential directions for the infant milk powder and functional food industries.

Prenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure and insulin resistance in offspring rats.

PubMed

Hao, Xue-Qin; Du, Jing-Xia; Li, Yan; Li, Meng; Zhang, Shou-Yan

2014-01-01

Adult metabolic syndrome may in part have origins in fetal or early life. This study was designed to explore the effect of prenatal exposure to lipopolysaccharide and high-fat diet on metabolic syndrome in offspring rats. 32 pregnant rats were randomly divided into four groups, including Control group; LPS group (pregnant rats were injected with LPS 0.4 mg/kg intraperitoneally on the 8(th), 10(th) and 12(th) day of pregnancy); High-fat group (maternal rats had high-fat diet during pregnancy and lactation period, and their pups also had high-fat diet up to the third month of life); LPS + High-fat group (rats were exposed to the identical experimental scheme with LPS group and High-fat group). Blood pressure elevated in LPS group and High-fat group, reduced in LPS+High-fat group, accompanied by the increase of serum leptin level in LPS and High-fat group and increase of serum IL-6, TNF-a in High-fat group; both serum insulin and cholesterol increased in High-fat and LPS+High-fat group, as well as insulin in LPS group. HOMA-IR value increased in LPS, High-fat and LPS+High-fat group, and QUICKI decreased in these groups; H-E staining showed morphologically pathological changes in thoracic aorta and liver tissue in the three groups. Increased serum alanine and aspartate aminotransferase suggest impaired liver function in LPS+High-fat group. Prenatal exposure to lipopolysaccharide combined with pre- and postnatal high-fat diet result in lowered blood pressure, insulin resistance and impaired liver function in three-month old offspring rats. The lowered blood pressure might benefit from the predictive adaptive response to prenatal inflammation.

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

PubMed

Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues, this review addresses the originality of the BMAT with regard to its development, anatomy, metabolic properties, and response to physiological cues.

Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

PubMed Central

Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

2016-01-01

Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone–fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues – subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT – is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues, this review addresses the originality of the BMAT with regard to its development, anatomy, metabolic properties, and response to physiological cues. PMID:27445987

Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.

PubMed

Yuan, Fang; Lei, Yonghong; Wang, Qiurong; Esberg, Lucy B; Huang, Zaixing; Scott, Glenda I; Li, Xue; Ren, Jun

2015-03-18

Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Influence of selected dietary components on the functioning of the human nervous system

PubMed

Wendołowicz, Agnieszka; Stefańska, Ewa; Ostrowska, Lucyna

The diet is directly connected not only with the physical status but also with the functioning of the brain and the mental status. The potentially beneficial nutrients with a protective effect on the nervous system function include amino acids (tryptophan, phenylalanine, tyrosine, taurine), glucose and vitamins C, E, D and beta-carotene, B group vitamins (vitamin B12, vitamin B6, vitamin B4, vitamin B1) and minerals (selenium, zinc, magnesium, sodium, iron, copper, manganese, iodine). The presence of antioxidants in the diet protects against oxidative damage to nervous system cells. Biochemical data indicate that polyunsaturated fatty acids such as arachidonic acid (AA), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) as structural components of the nervous system play a key role in its function. The nutrition of the entire body also influences the production of neurotransmitters in the brain. A diet without an appropriate supply of protein, mineral nutrients or vitamins may result in a failure to form appropriately balanced numbers of neurotransmitters, which, as a result, may lead to neurotransmission dysfunction. This is the reason why proper nutrition is based on vegetables, fruits, whole-grain cereal products supplemented with products providing full-value protein (dairy products, fish, lean meat) and high-quality fat products (vegetable oils, fish fats).

Phosphate cycling on the basic protein of Plodia interpunctella granulosis virus

NASA Technical Reports Server (NTRS)

Funk, C. J.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

1993-01-01

The presence of infected cell-specific phosphoproteins was investigated in Plodia interpunctella granulosis virus (PiGV)-infected fat body using [32P]orthophosphoric acid labeling. One infected cell-specific phosphoprotein had a mobility similar to that of the basic protein (VP12) of PiGV. Further analysis, using immunoblotting and acid-urea gel analysis of infected fat body, confirmed that this phosphoprotein was VP12. However we did not detect phosphorylated VP12 in 32P-labeled nucleocapsids. Phosphoamino acid analysis of 32P-labeled VP12 revealed that phosphoserine was present in the basic protein. Since VP12 is phosphorylated in the infected cell, but not in the nucleocapsid, it appears that dephosphorylation of VP12 is a critical event in the life cycle of the virus. We therefore assayed virus nucleocapsids and infected fat body for the presence of phosphatase activity. Phosphatase activity was not detected in the virus, but the infected fat body had more activity than uninfected fat body. A model for nucleocapsid assembly and uncoating is presented which takes into account the phosphorylation state of VP12, the role of Zn2+ in the nucleocapsid, and the role of the capsid-associated kinase.

Neither Good nor Useful: Looking Ad Vivum in Children's Assessments of Fat and Healthy Bodies

ERIC Educational Resources Information Center

Harwood, Valerie

2012-01-01

Fat bodies are not, fait accompli, bad. Yet in our international research, we found overwhelmingly that fat functioned as a marker to indicate health or lack of health. A body with fat was simply and conclusively unhealthy. This article reports on how this unbalanced view of fat was tied to assessments of healthy bodies that were achieved by…

Composition, yield, and functionality of reduced-fat Oaxaca cheese: effects of using skim milk or a dry milk protein concentrate.

PubMed

Caro, I; Soto, S; Franco, M J; Meza-Nieto, M; Alfaro-Rodríguez, R H; Mateo, J

2011-02-01

The effect of adding either skim milk or a commercial dry milk protein concentrate (MPC) to whole milk on the composition, yield, and functional properties of Mexican Oaxaca cheese were investigated. Five batches of Oaxaca cheeses were produced. One batch (the control) was produced from whole milk containing 3.5% fat and 9% nonfat solids (SNF). Two batches were produced from milk standardized with skim milk to 2.7 and 1.8% fat, maintaining the SNF content at 9%. In the other 2 batches, an MPC (40% protein content) was used to standardize the milk to a SNF content of 10 and 11%, maintaining the milk fat content at 3.5%. The use of either skim milk or MPC caused a significant decrease in the fat percentage in cheese. The use of skim milk or MPC showed a nonsignificant tendency to lower total solids and fat recoveries in cheese. Actual, dry matter, and moisture-adjusted cheese yields significantly decreased with skim milk addition, but increased with MPC addition. However, normalized yields adjusted to milk fat and protein reference levels did not show significant differences between treatments. Considering skim milk-added and control cheeses, actual yield increased with cheese milk fat content at a rate of 1.34 kg/kg of fat (R=0.88). In addition, cheese milk fat and SNF:fat ratio proved to be strong individual predictors of cheese moisture-adjusted yield (r(2) ≈ 0.90). Taking into account the results obtained from control and MPC-added cheeses, a 2.0-kg cheese yield increase rate per kg of milk MPC protein was observed (R=0.89), with TS and SNF being the strongest predictors for moisture adjusted yield (r(2) ≈ 0.77). Reduced-fat Oaxaca cheese functionality differed from that of controls. In unmelted reduced-fat cheeses, hardness and springiness increased. In melted reduced-fat cheeses, meltability and free oil increased, but stretchability decreased. These changes were related to differences in cheese composition, mainly fat in dry matter and calcium in SNF. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells

PubMed Central

Okumura, Takashi; Ohuchida, Kenoki; Sada, Masafumi; Abe, Toshiya; Endo, Sho; Koikawa, Kazuhiro; Iwamoto, Chika; Miura, Daisuke; Mizuuchi, Yusuke; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Manabe, Tatsuya; Ohtsuka, Takao; Nagai, Eishi; Mizumoto, Kazuhiro; Oda, Yoshinao; Hashizume, Makoto; Nakamura, Masafumi

2017-01-01

Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion. Mice fed a high fat diet had significantly larger primary pancreatic tumors and a significantly higher rate of distant organ metastasis than mice fed a standard diet. In the organotypic fat invasion model, pancreatic cancer cell clusters were smaller and more elongated in shape and showed increased fibrosis. Adipose tissue-derived conditioned medium enhanced pancreatic cancer cell invasiveness and gemcitabine resistance, as well as inducing morphologic changes in cancer cells and increasing the numbers of lipid droplets in their cytoplasm. The concentrations of oleic, palmitoleic, and linoleic acids were higher in adipose tissue-derived conditioned medium than in normal medium, with these fatty acids significantly enhancing the migration of cancer cells. Mature adipocytes were smaller and the concentration of fatty acids in the medium higher when these cells were co-cultured with cancer cells. These findings indicate that lipolytic and fibrotic changes in peripancreatic adipose tissue enhance local invasiveness and metastasis via adipocyte-released fatty acids. Inhibition of fatty acid uptake by cancer cells may be a novel therapy targeting interactions between cancer and stromal cells. PMID:28407685

Soy protein isolate inhibits high fat diet-induced senescence pathways in osteoblasts to maintain bone acquisition in rats

USDA-ARS?s Scientific Manuscript database

Chronic consumption by experimental animals of a typical Western diet high in saturated fats and cholesterol during postnatal life has been demonstrated to impair skeletal development. However, the underlying mechanism by which high fat, energy dense diets affect bone-forming cell phenotypes is poor...

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

Smirnov, Sergey V.; Harbacheuski, Ryhor; Lewis-Antes, Anita

Mesenchymal stem cells (MSCs) in bone marrow (BM) regulate the differentiation and proliferation of adjacent hematopoietic precursor cells and contribute to the regeneration of mesenchymal tissues, including bone, cartilage, fat and connective tissue. BM is an important site for the pathogenesis of human cytomegalovirus (HCMV) where the virus establishes latency in hematopoietic progenitors and can transmit after reactivation to neighboring cells. Here we demonstrate that BM-MSCs are permissive to productive HCMV infection, and that HCMV alters the function of MSCs: (i) by changing the repertoire of cell surface molecules in BM-MSCs, HCMV modifies the pattern of interaction between BM-MSCs andmore » hematopoietic cells; (ii) HCMV infection of BM-MSCs undergoing adipogenic or osteogenic differentiation impaired the process of differentiation. Our results suggest that by altering BM-MSC biology, HCMV may contribute to the development of various diseases.« less

The influence of major dietary fatty acids on insulin secretion and action.

PubMed

López, Sergio; Bermúdez, Beatriz; Abia, Rocío; Muriana, Francisco J G

2010-02-01

To briefly summarize recent advances towards understanding the influence of major dietary fatty acids on beta-cell function and evaluate their implications for insulin resistance. Studies in humans have shown that beta-cell function and insulin sensitivity improve progressively in the postprandial period as the proportion of monounsaturated fatty acids (MUFAs) with respect to saturated fatty acids (SFAs) in dietary fats increases. However, cell-culture experiments have revealed a dichotomy in the ability of fatty acids to moderate hyperactivity of, and induce lipotoxicity in, beta-cells. There are also some novel findings regarding the ability of HDL to protect beta-cells against oxidized LDL-induced apoptosis in vitro and of reconstituted HDL to attenuate insulin resistance in vivo. These findings raise new questions regarding the contribution of dietary fatty acids to insulin secretion and action. These new findings point to a critical role for major dietary fatty acids in the etiology and pathogenesis of diabetes, which appears to be of particular relevance during postprandial periods and mainly depends on the fatty acid type. This underscores the importance of dietary fatty acids in standard diabetes management.

Conservation of Planar Polarity Pathway Function Across the Animal Kingdom.

PubMed

Hale, Rosalind; Strutt, David

2015-01-01

Planar polarity is a well-studied phenomenon resulting in the directional coordination of cells in the plane of a tissue. In invertebrates and vertebrates, planar polarity is established and maintained by the largely independent core and Fat/Dachsous/Four-jointed (Ft-Ds-Fj) pathways. Loss of function of these pathways can result in a wide range of developmental or cellular defects, including failure of gastrulation and problems with placement and function of cilia. This review discusses the conservation of these pathways across the animal kingdom. The lack of vital core pathway components in basal metazoans suggests that the core planar polarity pathway evolved shortly after, but not necessarily alongside, the emergence of multicellularity.

Central fat influences cardiac autonomic function in obese and overweight girls.

PubMed

Soares-Miranda, Luisa; Alves, Alberto J; Vale, Susana; Aires, Luisa; Santos, Rute; Oliveira, José; Mota, Jorge

2011-10-01

It has been suggested that upper-body fat compared with lower-body fat is more closely associated with cardiovascular abnormalities. Our objective was to analyze the relationship between central fat (CF) and cardiac autonomic (cANS) function in obese and overweight girls. Children were classified in two groups based on CF: those above (CFa(50)) and those below the 50th percentile (CFb(50)) of the entire sample. This study included 16 female children who were diagnosed as being overweight or obese (age: 14.3 ± 2.8 years; weight: 75.0 ± 15.8 kg; height: 157.1 ± 8.9 cm; body mass index: 30.1 ± 5.4; and total body fat: 40.5 ± 5.0%; Tanner stage: 4). cANS function was assessed through heart rate variability (HRV) and CF parameters by dual-energy X-ray absorptiometry. Female children with higher CF exhibited significantly higher sympathetic and lower parasympathetic modulation than those with lower CF, independently of total body fat. The data of the present study indicate that CF is associated with less favorable indexes of HRV. In addition, our findings suggest that CF might be an important measure to assess the effect of obesity on cANS function in female children.

Metabolic mechanisms of drug-nutrient interactions.

PubMed

Hathcock, J N

1985-01-01

Metabolic mechanisms of nutrition and drug interactions include 1) the effects of diet on drug metabolism and action and 2) the effects of drugs on nutritional processes. The type, amount, and timing of foods consumed influence drug dissolution, absorption, distribution, metabolism, and excretion. High-fat meals enhance the absorption of griseofulvin and some other drugs. Milk and other sources of calcium inhibit absorption of tetracycline. High-fat meals increase plasma concentrations of free fatty acids and thereby displace many drugs from binding sites on plasma albumin. High-protein diets increase the activity of the mixed-function oxidase system and enhance the metabolism of numerous drugs. High-electrolyte intakes increase excretion of lithium and also diminish the action of diuretic agents. Bile acid sequestrants and some laxatives decrease lipid digestion and absorption, as well as absorption of the fat-soluble vitamins. Numerous drugs, including tetracycline and cholestyramine, bind iron and decrease its absorption. Coumarins inhibit the function of vitamin K. Phenobarbital and other anticonvulsants are inducers of cytochrome P-450 and the mixed-function oxidase system. Long-term treatment with these inducers can cause excessive metabolism and deficiency of vitamin D. Prooxidant drugs such as chloroquine, drugs detoxified by conjugation with glutathione, and alcohol can deplete reduced glutathione with consequent effects on amino acid transport and the redox status of cells. Acid-forming foods acidify the urine and increase the loss of alkaline drugs such as the amphetamines. Base-forming drugs increase the loss of acidic drugs such as barbiturates. The range of metabolic interactions of drugs and nutrients includes the full scope of physiological processes to which drugs and nutrients are subject.

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

PubMed

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

2017-01-01

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

Controlled cellular energy conversion in brown adipose tissue thermogenesis

NASA Technical Reports Server (NTRS)

Horowitz, J. M.; Plant, R. E.

1978-01-01

Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

A Novel Mammary Fat Pad Transplantation Technique to Visualize the Vessel Generation of Vascular Endothelial Stem Cells.

PubMed

Yu, Qing Cissy; Song, Wenqian; Lai, Dengwen; Zeng, Yi Arial

2017-08-03

Endothelial cells (ECs) are the fundamental building blocks of the vascular architecture and mediate vascular growth and remodeling to ensure proper vessel development and homeostasis. However, studies on endothelial lineage hierarchy remain elusive due to the lack of tools to gain access as well as to directly evaluate their behavior in vivo. To address this shortcoming, a new tissue model to study angiogenesis using the mammary fat pad has been developed. The mammary gland develops mostly in the postnatal stages, including puberty and pregnancy, during which robust epithelium proliferation is accompanied by extensive vascular remodeling. Mammary fat pads provide space, matrix, and rich angiogenic stimuli from the growing mammary epithelium. Furthermore, mammary fat pads are located outside the peritoneal cavity, making them an easily accessible grafting site for assessing the angiogenic potential of exogenous cells. This work also describes an efficient tracing approach using fluorescent reporter mice to specifically label the targeted population of vascular endothelial stem cells (VESCs) in vivo. This lineage tracing method, coupled with subsequent tissue whole-mount microscopy, enable the direct visualization of targeted cells and their descendants, through which the proliferation capability can be quantified and the differentiation commitment can be fate-mapped. Using these methods, a population of bipotent protein C receptor (Procr) expressing VESCs has recently been identified in multiple vascular systems. Procr + VESCs, giving rise to both new ECs and pericytes, actively contribute to angiogenesis during development, homeostasis, and injury repair. Overall, this manuscript describes a new mammary fat pad transplantation and in vivo lineage tracing techniques that can be used to evaluate the stem cell properties of VESCs.

Human blood and marrow side population stem cell and Stro-1 positive bone marrow stromal cell numbers decline with age, with an increase in quality of surviving stem cells: correlation with cytokines.

PubMed

Brusnahan, S K; McGuire, T R; Jackson, J D; Lane, J T; Garvin, K L; O'Kane, B J; Berger, A M; Tuljapurkar, S R; Kessinger, M A; Sharp, J G

2010-01-01

Hematological deficiencies increase with aging leading to anemias, reduced hematopoietic stress responses and myelodysplasias. This study tested the hypothesis that side population hematopoietic stem cells (SP-HSC) would decrease with aging, correlating with IGF-1 and IL-6 levels and increases in bone marrow fat. Marrow was obtained from the femoral head and trochanteric region of the femur at surgery for total hip replacement (N=100). Whole trabecular marrow samples were ground in a sterile mortar and pestle and cellularity and fat content determined. Marrow and blood mononuclear cells were stained with Hoechst dye and the SP-HSC profiles acquired. Marrow stromal cells (MSC) were enumerated flow cytometrically employing the Stro-1 antibody, and clonally in the colony forming unit fibroblast (CFU-F) assay. Plasma levels of IGF-1 (ng/ml) and IL-6 (pg/ml) were measured by ELISA. SP-HSC in blood and bone marrow decreased with age but the quality of the surviving stem cells increased. MSC decreased non-significantly. IGF-1 levels (mean=30.7, SEM=2) decreased and IL-6 levels (mean=4.4, SEM=1) increased with age as did marrow fat (mean=1.2mmfat/g, SEM=0.04). There were no significant correlations between cytokine levels or fat and SP-HSC numbers. Stem cells appear to be progressively lost with aging and only the highest quality stem cells survive. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

A Unique Case of Allogeneic Fat Grafting Between Brothers

PubMed Central

Kim, Samuel; Edelson, Richard L.; Sumpio, Brandon; Kwei, Stephanie

2016-01-01

Summary: We present a case of a 65-year-old man with cutaneous T-cell lymphoma treated with radiation therapy and an allogeneic hematopoietic stem cell transplant from his human leukocyte antigen-matched brother. Engraftment was successful, but the patient went on to develop painful, radiation-induced ulcers. The ulcers were fat-allografted using liposuctioned fat from his brother because of the patient’s unique chimeric state. Postprocedure follow-up revealed epithelialization of the ulcer sites and significant improvement in neuropathic pain. Our unique case study supports the use of fat grafting for its restorative purposes and for its ability to alleviate chronic neuropathic pain. Additionally, it appears that our case provides a basis of a general approach to the treatment of radiation-induced ulcers in chimeric patients with lymphoid malignancies. PMID:27757347

Survival of Listeria monocytogenes in vanilla-flavored soy and dairy products stored at 8 degrees C.

PubMed

Tipparaju, Sireesha; Ravishankar, Sadhana; Slade, Peter J

2004-02-01

The survival of Listeria monocytogenes V37 in vanilla-flavored yogurt (low-fat and nonfat) and soy milk (low-fat and Plus) stored at 8 degrees C for 31 days was investigated. Commercial samples of yogurt and soy milk were used. These samples were inoculated with either 10(4) or 10(7) CFU of L. monocytogenes per ml. Sampling was carried out every 3 to 4 days initially and was then carried out weekly, for a total storage time of 31 days. Each time a sample was collected, the pH of the sample was measured. After 31 days, low-fat plain, low-fat vanilla, and nonfat plain yogurt samples inoculated with 10(4) CFU/ml showed 2.5-log reductions in viable cell populations, and nonfat vanilla yogurt showed a 3.5-log reduction. For yogurt inoculated with 10(7) CFU/ml, reductions of 2.5 log CFU/ml were observed for plain low-fat and nonfat yogurts, and reductions of 5 log CFU/ml were observed for vanilla-flavored low-fat and nonfat yogurts. In vanilla-flavored and plain low-fat and Plus soy milk samples, cell counts increased from 10(4) and 10(7) CFU/ml to 10(9) CFU/ml at 7 and 3 days of storage, respectively, at 8 degrees C. Coagulation in soy milk samples was observed when the cell population reached 10(9) CFU/ml. In soy milk, the L. monocytogenes population did not change for up to 31 days. Vanillin had an inhibitory effect on L. monocytogenes in yogurt but not in soy milk.

High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis.

PubMed

Relling, David P; Esberg, Lucy B; Fang, Cindy X; Johnson, W Thomas; Murphy, Eric J; Carlson, Edward C; Saari, Jack T; Ren, Jun

2006-03-01

Obesity is associated with dyslipidemia, which leads to elevated triglyceride and ceramide levels, apoptosis and compromised cardiac function. To determine the role of high-fat diet-induced obesity on cardiomyocyte function, weanling male Sprague-Dawley rats were fed diets incorporating 10% of kcal or 45% of kcal from fat. Mechanical function of ventricular myocytes was evaluated including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of shortening and relengthening (+/- dl/dt). Intracellular Ca properties were assessed using fluorescent microscopy. High-fat diet induced hyperinsulinemic insulin-resistant obesity with depressed PS, +/- dl/dt, prolonged TPS/TR90 reduced intracellular Ca release and Ca clearing rate in the absence of hypertension, diabetes, lipotoxicity and apoptosis. Myocyte responsiveness to increased stimulus frequency and extracellular Ca was compromised. SERCA2a and phospholamban levels were increased, whereas phosphorylated phospholamban and potassium channel (Kv1,2) were reduced in high-fat diet group. High-fat diet upregulated the forkhead transcription factor Foxo3a, and suppressed mitochondrial aconitase activity without affecting expression of the caloric sensitive gene silent information regulator 2 (Sir2), protein nitrotyrosine formation, lipid peroxidation and apoptosis. Levels of endothelial nitric oxide synthase (NOS), inducible NOS, triglycerides and ceramide were similar between the two groups. Collectively, our data show that high-fat diet-induced obesity resulted in impaired cardiomyocyte function, upregulated Foxo3a transcription factor and mitochondrial damage without overt lipotoxicity or apoptosis.

Cytoplasmic and nuclear localization of cadherin in honey bee (Apis mellifera L.) gonads.

PubMed

Florecki, Mônica M; Hartfelder, Klaus

2011-01-01

Cadherins are crucial molecules mediating cell-cell interactions between somatic and germline cells in insect and mammalian male and female gonads. We analysed the presence and localization of cadherins in ovaries of honeybee queens and in testes of drones. Transcripts representing two classical cadherins, E-cadherin (shotgun) and N-cadherin, as well as three protocadherins (Starry night, Fat and Fat-like) were detected in gonads of both sexes. Pan-cadherin antibodies, which most probably detect a honeybee N-cadherin, were used in immunolocalization analyses. In the germarium of ovarioles, cadherin-IR (cadherin immunoreactivity) was evidenced as homogeneously distributed in the cytoplasm and as nuclear foci, in both germline and somatic cells. It was also detected in polyfusomes and ring canals. In testiolar tubules, cadherin-IR showed a cytoplasmic and nuclear distributon alike in ovaries. The unexpected nuclear localization and cytoplasmic distribution in ovaries and testes were corroborated by immunogold electron microscopy, which revealed cadherin aggregates associated with electron-dense nuclear structures. With respect to cadherin localization, the honeybee differs from Drosophila, the model for gametogenesis in insects, raising the question as to how differences among solitary and social species may be built into and generated from the general architecture of polytrophic meroistic ovaries. It also indicates the possibility of divergent roles for cadherin in the functional architecture of insect gonads, in general, especially in taxa with high reproductive output.

Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue1

PubMed Central

Lumeng, Carey N.; Liu, Jianhua; Geletka, Lynn; Delaney, Colin; DelProposto, Jennifer; Desai, Anjali; Oatmen, Kelsie; Martinez-Santibanez, Gabriel; Julius, Annabelle; Garg, Sanjay; Yung, Raymond L.

2011-01-01

Age-related adiposity has been linked to chronic inflammatory diseases in late-life. To date, the studies on adipose tissue leukocytes and aging have not taken into account the heterogeneity of adipose tissue macrophages (ATMs), nor have they examined how age impacts other leukocytes such as T cell in fat. Therefore, we have performed a detailed examination of ATM subtypes in young and old mice using state of the art techniques. Our results demonstrate qualitative changes in ATMs with aging that generate a decrease in resident Type 2 (M2) ATMs. The profile of ATMs in old fat shifts towards a pro-inflammatory environment with increased numbers of CD206-CD11c- (double negative) ATMs. The mechanism of this aging-induced shift in the phenotypic profile of ATMs was found to be related to a decrease in PPARγ expression in ATMs and alterations in chemokine/chemokine receptor expression profiles. Furthermore, we have revealed a profound and unexpected expansion of adipose tissue T (ATT) cells in visceral fat with aging that includes a significant induction of regulatory T cells (Tregs) in fat. Our findings demonstrate a unique inflammatory cell signature in the physiologic context of aging adipose tissue that differs from those induced in setting of diet-induced obesity. PMID:22075699

Dynamic, M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high-fat diet--induced obesity in mice.

PubMed

Shaul, Merav E; Bennett, Grace; Strissel, Katherine J; Greenberg, Andrew S; Obin, Martin S

2010-05-01

To identify, localize, and determine M1/M2 polarization of epidydimal adipose tissue (eAT) macrophages (Phis) during high-fat diet (HFD)-induced obesity. Male C57BL/6 mice were fed an HFD (60% fat kcal) or low-fat diet (LFD) (10% fat kcal) for 8 or 12 weeks. eATMPhis (F4/80(+) cells) were characterized by in vivo fluorescent labeling, immunohistochemistry, fluorescence-activated cell sorting, and quantitative PCR. Recruited interstitial macrophage galactose-type C-type lectin (MGL)1(+)/CD11c(-) and crown-like structure-associated MGL1(-)/CD11c(+) and MGL1(med)/CD11c(+) eATMPhis were identified after 8 weeks of HFD. MGL1(med)/CD11c(+) cells comprised approximately 65% of CD11c(+) eATMPhis. CD11c(+) eATMPhis expressed a mixed M1/M2 profile, with some M1 transcripts upregulated (IL-12p40 and IL-1beta), others downregulated (iNOS, caspase-1, MCP-1, and CD86), and multiple M2 and matrix remodeling transcripts upregulated (arginase-1, IL-1Ra, MMP-12, ADAM8, VEGF, and Clec-7a). At HFD week 12, each eATMPhi subtype displayed an enhanced M2 phenotype as compared with HFD week 8. CD11c(+) subtypes downregulated IL-1beta and genes mediating antigen presentation (I-a, CD80) and upregulated the M2 hallmark Ym-1 and genes promoting oxidative metabolism (PGC-1alpha) and adipogenesis (MMP-2). MGL1(med)/CD11c(+) eATMPhis upregulated additional M2 genes (IL-13, SPHK1, CD163, LYVE-1, and PPAR-alpha). MGL1(med)/CD11c(+) ATMPhis expressing elevated PGC-1alpha, PPAR-alpha, and Ym-1 transcripts were selectively enriched in eAT of obese mice fed pioglitazone for 6 days, confirming the M2 features of the MGL1(med)/CD11c(+) eATMPhi transcriptional profile and implicating PPAR activation in its elicitation. These results 1) redefine the phenotypic potential of CD11c(+) eATMPhis and 2) suggest previously unappreciated phenotypic and functional commonality between murine and human ATMPhis in the development of obesity and its complications.

Arteriogenesis in murine adipose tissue is contingent on CD68+/CD206+ macrophages

PubMed Central

Seaman, Scott A.; Cao, Yiqi; Campbell, Chris A.; Peirce, Shayn M.

2016-01-01

Objective The surgical transfer of skin, fat, and/or muscle from a donor site to a recipient site within the same patient, is a widely performed procedure in reconstructive surgeries. A surgical pre-treatment strategy that is intended to increase perfusion in the flap, termed “flap delay”, is a commonly employed technique by plastic surgeons prior to flap transplantation. Here, we explored whether CD68+/CD206+ macrophages are required for arteriogenesis within the flap by performing gain-of-function and loss-of-function studies in a previously published flap delay murine model. Methods and Results Local injection of M2-polarized macrophages into the flap resulted in an increase in collateral vessel diameter. Application of a thin biomaterial film loaded with a pharmacological agent (FTY720), which has been previously shown to recruit CD68+/CD206+ macrophages to remodeling tissue, increased CD68+/CD206+ cell recruitment and collateral vessel enlargement. Conversely, when local macrophage populations were depleted within the inguinal fat pad via clodronate liposome delivery, we observed fewer CD68+ cells accompanied by diminished collateral vessel enlargement. Conclusions Our study underscores the importance of macrophages during microvascular adaptations that are induced by flap delay. These studies suggest a mechanism for a translatable therapeutic target that may be used to enhance the clinical flap delay procedure. PMID:27976451

Skeletal muscle tissue transcriptome differences in lean and obese female beagle dogs.

PubMed

Grant, R W; Vester Boler, B M; Ridge, T K; Graves, T K; Swanson, K S

2013-08-01

Skeletal muscle is a large and insulin-sensitive tissue that is an important contributor to metabolic homeostasis and energy expenditure. Many metabolic processes are altered with obesity, but the contribution of muscle tissue in this regard is unclear. A limited number of studies have compared skeletal muscle gene expression of lean and obese dogs. Using microarray technology, our objective was to identify genes and functional classes differentially expressed in skeletal muscle of obese (14.6 kg; 8.2 body condition score; 44.5% body fat) vs. lean (8.6 kg; 4.1 body condition score; 22.9% body fat) female beagle adult dogs. Alterations in 77 transcripts was observed in genes pertaining to the functional classes of signaling, transport, protein catabolism and proteolysis, protein modification, development, transcription and apoptosis, cell cycle and differentiation. Genes differentially expressed in obese vs. lean dog skeletal muscle indicate oxidative stress and altered skeletal muscle cell differentiation. Many genes traditionally associated with lipid, protein and carbohydrate metabolism were not altered in obese vs. lean dogs, but genes pertaining to endocannabinoid metabolism, insulin signaling, type II diabetes mellitus and carnitine transport were differentially expressed. The relatively small response of skeletal muscle could indicate that changes are occurring at a post-transcriptional level, that other tissues (e.g., adipose tissue) were buffering skeletal muscle from metabolic dysfunction or that obesity-induced changes in skeletal muscle require a longer period of time and that the length of our study was not sufficient to detect them. Although only a limited number of differentially expressed genes were detected, these results highlight genes and functional classes that may be important in determining the etiology of obesity-induced derangement of skeletal muscle function. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.

PubMed

Liu, Hong; Yang, Li-xia; Guo, Rui-wei; Zhu, Guo-Fu; Shi, Yan-Kun; Wang, Xian-mei; Qi, Feng; Guo, Chuan-ming; Ye, Jin-shan; Yang, Zhi-hua; Liang, Xing

2013-10-09

Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody. EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions. EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Circadian Disruption and Diet-Induced Obesity Synergize to Promote Development of β-Cell Failure and Diabetes in Male Rats

PubMed Central

Qian, Jingyi; Yeh, Bonnie; Rakshit, Kuntol; Colwell, Christopher S.

2015-01-01

There are clear epidemiological associations between circadian disruption, obesity, and pathogenesis of type 2 diabetes. The mechanisms driving these associations are unclear. In the current study, we hypothesized that continuous exposure to constant light (LL) compromises pancreatic β-cell functional and morphological adaption to diet-induced obesity leading to development of type 2 diabetes. To address this hypothesis, we studied wild type Sprague Dawley as well as Period-1 luciferase reporter transgenic rats (Per1-Luc) for 10 weeks under standard light-dark cycle (LD) or LL with concomitant ad libitum access to either standard chow or 60% high-fat diet (HFD). Exposure to HFD led to a comparable increase in food intake, body weight, and adiposity in both LD- and LL-treated rats. However, LL rats displayed profound loss of behavioral circadian rhythms as well as disrupted pancreatic islet clock function characterized by the impairment in the amplitude and the phase islet clock oscillations. Under LD cycle, HFD did not adversely alter diurnal glycemia, diurnal insulinemia, β-cell secretory function as well as β-cell survival, indicating successful adaptation to increased metabolic demand. In contrast, concomitant exposure to LL and HFD resulted in development of hyperglycemia characterized by loss of diurnal changes in insulin secretion, compromised β-cell function, and induction of β-cell apoptosis. This study suggests that circadian disruption and diet-induced obesity synergize to promote development of β-cell failure, likely mediated as a consequence of impaired islet clock function. PMID:26348474

Effect of fat type in baked bread on amylose-lipid complex formation and glycaemic response.

PubMed

Lau, Evelyn; Zhou, Weibiao; Henry, Christiani Jeyakumar

2016-06-01

The formation of amylose-lipid complexes (ALC) had been associated with reduced starch digestibility. A few studies have directly characterised the extent of ALC formation with glycaemic response. The objectives of this study were to investigate the effect of using fats with varying degree of saturation and chain length on ALC formation as well as glycaemic and insulinaemic responses after consumption of bread. Healthy men consumed five test breads in a random order: control bread without any added fats (CTR) and breads baked with butter (BTR), coconut oil (COC), grapeseed oil (GRP) or olive oil (OLV). There was a significant difference in glycaemic response between the different test breads (P=0·002), primarily due to COC having a lower response than CTR (P=0·016), but no significant differences between fat types were observed. Insulinaemic response was not altered by the addition of fats/oils. Although BTR was more insulinotropic than GRP (P<0·05), postprandial β-cell function did not differ significantly. The complexing index (CI), a measure of ALC formation, was significantly higher for COC and OLV compared with BTR and GRP (P<0·05). CI was significantly negatively correlated with incremental AUC (IAUC) of change in blood glucose concentrations over time (IAUCglucose) (r -0·365, P=0·001). Linear regression analysis showed that CI explained 13·3 % of the variance and was a significant predictor of IAUCglucose (β=-1·265, P=0·001), but IAUCinsulin did not predict IAUCglucose. Our study indicated that a simple way to modulate glycaemic response in bread could lie in the choice of fats/oils, with coconut oil showing the greatest attenuation of glycaemic response.

Developmental conditioning of endothelium-derived hyperpolarizing factor-mediated vasorelaxation

PubMed Central

Stead, Rebecca; Musa, Moji G.; Bryant, Claire L.; Lanham, Stuart A.; Johnston, David A.; Reynolds, Richard; Torrens, Christopher; Fraser, Paul A.; Clough, Geraldine F.

2016-01-01

Objectives: The endothelium maintains vascular homeostasis through the release of endothelium-derived relaxing factors (EDRF) and endothelium-derived hyperpolarization (EDH). The balance in EDH : EDRF is disturbed in cardiovascular disease and may also be susceptible to developmental conditioning through exposure to an adverse uterine environment to predispose to later risk of hypertension and vascular disease. Methods: Developmentally conditioned changes in EDH : EDRF signalling pathways were investigated in cremaster arterioles (18–32 μm diameter) and third-order mesenteric arteries of adult male mice offspring of dams fed either a fat-rich (high fat, HF, 45% energy from fat) or control (C, 10% energy from fat) diet. After weaning, offspring either continued on high fat or were placed on control diets to give four dietary groups (C/C, HF/C, C/HF, and HF/HF) and studied at 15 weeks of age. Results: EDH via intermediate (IKCa) and small (SKca) conductance calcium-activated potassium channels contributed less than 10% to arteriolar acetylcholine-induced relaxation in in-situ conditioned HF/C offspring compared with ∼60% in C/C (P < 0.01). The conditioned reduction in EDH signalling in HF/C offspring was reversed in offspring exposed to a high-fat diet both before and after weaning (HF/HF, 55%, P < 0.01 vs. HF/C). EDH signalling was unaffected in arterioles from C/HF offspring. The changes in EDH : EDRF were associated with altered endothelial cell expression and localization of IKCa channels. Conclusion: This is the first evidence that EDH-mediated microvascular relaxation is susceptible to an adverse developmental environment through down-regulation of the IKCa signalling pathway. Conditioned offspring exposed to a ‘second hit’ (HF/HF) exhibit adaptive vascular mechanisms to preserve dilator function. PMID:26682783

Developmental conditioning of endothelium-derived hyperpolarizing factor-mediated vasorelaxation.

PubMed

Stead, Rebecca; Musa, Moji G; Bryant, Claire L; Lanham, Stuart A; Johnston, David A; Reynolds, Richard; Torrens, Christopher; Fraser, Paul A; Clough, Geraldine F

2016-03-01

The endothelium maintains vascular homeostasis through the release of endothelium-derived relaxing factors (EDRF) and endothelium-derived hyperpolarization (EDH). The balance in EDH : EDRF is disturbed in cardiovascular disease and may also be susceptible to developmental conditioning through exposure to an adverse uterine environment to predispose to later risk of hypertension and vascular disease. Developmentally conditioned changes in EDH : EDRF signalling pathways were investigated in cremaster arterioles (18-32  μm diameter) and third-order mesenteric arteries of adult male mice offspring of dams fed either a fat-rich (high fat, HF, 45% energy from fat) or control (C, 10% energy from fat) diet. After weaning, offspring either continued on high fat or were placed on control diets to give four dietary groups (C/C, HF/C, C/HF, and HF/HF) and studied at 15 weeks of age. EDH via intermediate (IKCa) and small (SKca) conductance calcium-activated potassium channels contributed less than 10% to arteriolar acetylcholine-induced relaxation in in-situ conditioned HF/C offspring compared with ∼60% in C/C (P < 0.01). The conditioned reduction in EDH signalling in HF/C offspring was reversed in offspring exposed to a high-fat diet both before and after weaning (HF/HF, 55%, P < 0.01 vs. HF/C). EDH signalling was unaffected in arterioles from C/HF offspring. The changes in EDH : EDRF were associated with altered endothelial cell expression and localization of IKCa channels. This is the first evidence that EDH-mediated microvascular relaxation is susceptible to an adverse developmental environment through down-regulation of the IKCa signalling pathway. Conditioned offspring exposed to a 'second hit' (HF/HF) exhibit adaptive vascular mechanisms to preserve dilator function.

Characterization of stem cells in Dupuytren's disease.

PubMed

Hindocha, S; Iqbal, S A; Farhatullah, S; Paus, R; Bayat, A

2011-02-01

Dupuytren's disease (DD) is a common fibroproliferative disease of unknown origin. The source of abnormal cells leading to DD formation remains underexplored. In addition to fascia, palmar skin and fat-derived cells may be a potential source of cells causing DD. This study aimed to profile haematopoietic and mesenchymal stem cells in different DD tissue components compared with tissue removed at carpal tunnel surgery (control). Biopsies were taken from the diseased cord, nodule, perinodular fat and skin overlying the nodule of ten patients with DD and compared with control tissue from seven patients having surgery for carpal tunnel syndrome. Fluorescence-activated cell sorting (FACS), immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR) were used to identify expression of selected stem cell markers. FACS and QRT-PCR analysis identified the highest RNA expression and number of cells positive for adipocyte stem cell markers (CD13 and CD29) in the DD nodule in comparison with carpal tunnel control tissue (P = 0·053). CD34 RNA was overexpressed, and a higher percentage of these cells was present in DD skin compared with carpal tunnel skin (P = 0·001). Each structural component of DD (cord, nodule, perinodular fat and skin) had distinct stem cell populations. These findings support the hypothesis that DD may result from mesenchymal progenitor cell expansion.