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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipose tissue inflammation is a characteristic of obesity. However, the mechanisms that regulate this inflammatory response and link adipose inflammation to systemic metabolic consequences are not fully understood. In this study, we have taken advantage of the highly restricted coexpression of adipocyte/macrophage fatty acid-binding proteins (FABPs) aP2 (FABP4) and mal1 (FABP5) to examine the contribution of these lipid chaperones in macrophages and adipocytes to local and systemic inflammation and metabolic homeostasis in mice. Deletion of FABPs in adipocytes resulted in reduced expression of inflammatory cytokines in macrophages, whereas the same deletion in macrophages led to enhanced insulin signaling and glucose uptake in adipocytes. Using radiation chimerism through bone marrow transplantation, we generated mice with FABP deficiency in bone marrow and stroma-derived elements in vivo and studied the impact of each cellular target on local and systemic insulin action and glucose metabolism in dietary obesity. The results of these experiments indicated that neither macrophages nor adipocytes individually could account for the total impact of FABPs on systemic metabolism and suggest that interactions between these 2 cell types, particularly in adipose tissue, are critical for the inflammatory basis of metabolic deterioration.
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PMID:Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. 1855 Nov 91

This study evaluates the protective effect of Juniperus chinensis hot water extract (JCE) against high-fat-diet (HFD)-induced obesity and its molecular mechanisms in the visceral adipose tissue of rats. JCE supplementation significantly lowered body weight gain, visceral fat-pad weights, blood lipid levels, and blood insulin and leptin levels of rats rendered obese by an HFD. Feeding with JCE significantly reversed the HFD-induced down-regulation of the epididymal adipose tissue genes implicated in adipogenesis, such as the peroxisome proliferator-activated receptors gamma2 (PPARgamma2), adipocyte protein 2 (aP2), sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and HMG-CoA reductase (HMGR), as well as those involved in uncoupled respiration, such as the uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3). Dietary supplementation with JCE also reversed the HFD-induced decreases in the AMP-activated protein kinase (AMPK) and the acetyl-CoA carboxylase 2 (ACC2) expressions at both the mRNA and protein levels and restored the HFD-induced inhibitions in the AMPK and ACC2 phosphorylation, which are related to fatty acid beta-oxidation, in the epididymal adipose tissue. This study reports, for the first time, that the JCE can have an anti-obesity effect in a rodent model with HFD-induced obesity through an enhanced gene transcription of the uncoupling protein as well as an elevated AMPK protein expression and phosphorylation in the visceral adipose tissue.
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PMID:Anti-obesity effects of Juniperus chinensis extract are associated with increased AMP-activated protein kinase expression and phosphorylation in the visceral adipose tissue of rats. 1859 85

The aim of present study is to evaluate the effects of Garcinia cambogia on the mRNA levels of the various genes involved in adipogenesis, as well as on body weight gain, visceral fat accumulation, and other biochemical markers of obesity in obesity-prone C57BL/6J mice. Consumption of the Garcinia cambogia extract effectively lowered the body weight gain, visceral fat accumulation, blood and hepatic lipid concentrations, and plasma insulin and leptin levels in a high-fat diet (HFD)-induced obesity mouse model. The Garcinia cambogia extract reversed the HFD-induced changes in the expression pattern of such epididymal adipose tissue genes as adipocyte protein aP2 (aP2), sterol regulatory element-binding factor 1c (SREBP1c), peroxisome proliferator-activated receptor gamma2 (PPARgamma2), and CCAT/enhancer-binding protein alpha (C/EBPalpha). These findings suggest that the Garcinia cambogia extract ameliorated HFD-induced obesity, probably by modulating multiple genes associated with adipogenesis, such as aP2, SREBP1c, PPARgamma2, and C/EBPalpha in the visceral fat tissue of mice.
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PMID:Garcinia cambogia extract ameliorates visceral adiposity in C57BL/6J mice fed on a high-fat diet. 1860 10

Obesity and osteoporosis are major health issues affecting millions of individuals. Transgenic mice overexpressing DeltaFosB, an activator protein-1 transcription factor, under the control of the enolase 2 (ENO2) promoter exhibit both an increase in bone density and a decrease in adipose mass. Here we demonstrate that DeltaFosB overexpression increases fatty-acid oxidation and energy expenditure, leading to a decrease in adipocyte size and adipose mass. In addition, the ENO2-DeltaFosB mice exhibit increased insulin sensitivity and glucose tolerance. Targeted overexpression of DeltaFosB in adipocytes using the adipocyte protein 2 promoter failed to induce changes in fat or in bone, showing that the effect on metabolic activity is not due to cell-autonomous effects of DeltaFosB within adipocytes. Detailed analysis of the ENO2-DeltaFosB mice demonstrated that energy expenditure was increased in muscle, independent of locomotor activity. These findings provide evidence that signaling downstream of DeltaFosB is a potential target for not only osteoporosis but also obesity and diabetes.
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PMID:Increased energy expenditure and insulin sensitivity in the high bone mass DeltaFosB transgenic mice. 1877 35

MicroRNAs (miRNAs) are short non-coding RNA that post-transcriptionally regulates gene expression. miR-143 has been proposed to play a role in the differentiation of adipocytes in culture. However, the mechanism regulating the expression of miR-143 in adult adipose tissue during the development of obesity in vivo is unknown. Here in, we showed that the expression of miR-143 in the mesenteric fat was up-regulated in mice fed a high-fat diet. Increased miR-143 expression was associated with an elevated body weight and mesenteric fat weight. Furthermore, miR-143 levels were closely correlated with expression levels of adipocyte differentiation markers such as PPARgamma and aP2 as well as plasma levels of leptin, one of the important adipocytokines involved in insulin resistance. These findings provide the first evidence for the up-regulated expression of miR-143 in the mesenteric fat of high-fat diet-induced obese mice, which might contribute to the regulated expression of adipocyte genes involved in the pathophysiology of obesity.
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PMID:Up-regulated expression of microRNA-143 in association with obesity in adipose tissue of mice fed high-fat diet. 1880 85

Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders including diabetes, hypertension, and heart disease. It is generally accepted that the regulation of adipogenesis or adipokines expression prevents obesity. In this study, we show that isorhamnetin inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. At the molecular level, the mRNA expression levels of peroxidase proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), which are the major adipogenic transcription factors, were markedly reduced by isorhamnetin. However, the mRNA levels of C/EBP-beta and -delta, the upstream regulators of PPAR-gamma and C/EBP-alpha, were not reduced by isorhamnetin. Moreover, the mRNA levels of PPAR-gamma target genes such as lipoprotein lipase (LPL), CD36, aP2, and liver X receptor-alpha (LXR-alpha) were downregulated by isorhamnetin. We also showed that isorhamnetin inhibits the expression and secretion of adiponectin, and the results of adiponectin promoter assays suggest the inhibition of PPAR-gamma expression as a possible mechanism underlying the isorhamnetin-mediated effects. Taken together, these results indicate that isorhamnetin inhibits adipogenesis through downregulation of PPAR-gamma and C/EBP-alpha.
Obesity (Silver Spring) 2009 Feb
PMID:Isorhamnetin represses adipogenesis in 3T3-L1 cells. 1894 72

Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPARgamma full agonist COOH (30 mg.kg(-1).day(-1)) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (-30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPARgamma agonism, and suggests a key role for LPL therein.
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PMID:Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat. 1897 52

Fucoidan is a group of sulfated fucose-containing polysaccharides that derived from non-mammalian origin such as marine brown algae, the jelly coat from sea urchin eggs, and the sea cucumber body wall. However, potential biological activities against obesity from fucoidan were not reported in the literature. The objective of this study was to evaluate protective effect of fucoidan in 3T3-L1 adipocyte differentiation. Preadipocyte 3T3-L1 was treated with 100 and 200 microg/ml fucoidan during adipogenesis. Adipogenesis was determined through Oil Red O staining method and the expression of adipogenic genes aP2, ACC, and PPARgamma. Adipogenesis of 3T3-L1 treated with 100 and 200 microg/ml fucoidan were significantly inhibited at 32.8% and 39.7% using Oil Red O staining method, respectively (P < 0.05). Treating the 3T3-L1 cells with 100 and 200 microg/ml fucoidan significantly decreased the expression of aP2 gene by 6.2% and 27.2%, respectively, of ACC gene by 22.2% and 38.2%, respectively, and of PPARgamma gene by 44.2% and 69.4%, respectively, compared to adipocyte controls (P < 0.05). The results suggest that fucoidan could be used for inhibiting fat accumulation, which is mediated by decreasing aP2, ACC, and PPARgamma gene expression.
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PMID:Inhibitory effects of Fucoidan in 3T3-L1 adipocyte differentiation. 1906 76

Several metabolic abnormalities are associated with relative excess or deficiency of adipose tissue. Identifying the regulators of adipogenic differentiation is critical for its successful manipulation. Ad36, a human adenovirus, is a novel factor that promotes adipogenesis. We exploited the adipogenic potential of Ad36 to reveal exogenous modifiers of adipogenesis in rodent preadipocyte cell line in the presence or absence of differentiation inducers methyl-isobutyl-xanthine, dexamethasone, and insulin (M, D, and I; MDI). A nonadipogenic human adenovirus Ad2 was used as a negative control for viral infection. First, we confirmed that, Ad36, but not Ad2, increases lipid accumulation in the presence or absence of MDI. Time-course studies for expression of key genes of adipogenic cascade showed that it is Ad36, but not Ad2, which downregulated preadipocyte marker gene Wnt10b, and upregulated expression of early (C/EBPDelta and C/EBPbeta), intermediate (PPARgamma2), and late genes (aP2 and G3PDH) of adipogenic cascade even in the absence of MDI. In the presence of MDI, onset of expression of adipogenic genes coincided for Ad36 and control groups, but the expressions were significantly greater for the Ad36 group. Next, we observed that attenuation of Ad36 mRNA expression by an antiadenoviral agent reduced 3T3-L1 differentiation, indicating that viral mRNA expression is required for the process. Furthermore, with or without MDI or its components, Ad36 significantly increased lipid accumulation in 3T3-L1 cells. Cell confluency at the time of Ad36 infection positively influenced lipid accumulation. The results reveal that Ad36 is an MDI-independent exogenous regulator of the adipogenic process. Elucidating the molecular pathways involved may reveal novel regulatory controls of adipogenesis.
Obesity (Silver Spring) 2009 Apr
PMID:Adipogenic cascade can be induced without adipogenic media by a human adenovirus. 1916 54

Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old AOC3-KO males than in age-matched wild-type controls. However, WAT from AOC3-KO mice contained lower CD45 mRNA levels and fewer CD45(+) leukocytes. Subpopulation analyses revealed a diminished infiltration of WAT by T cells, macrophages, natural killer, and natural killer T cells. A decrease in leukocyte content in WAT was also detected in female AOC3-KO mice as early as 2 months of age, whereas increased fat mass was evident by 6 months of age. Reduced CD45(+) populations in WAT of AOC3-KO mice was not rescued by human SSAO/VAP-1 expression on adipocytes under the control of aP2, suggesting the importance of vascular AOC3 in leukocyte entrance into fat. Our results indicate that SSAO/VAP-1 is instrumental for the presence of leukocytes in WAT. Therefore, AOC3-KO mice present a unique model of mild obesity, characterized by increased WAT devoid of low-grade inflammation.
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PMID:Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition. 1921 46


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