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

The nuclear receptor peroxisome proliferator-activated receptor gamma regulates adipose differentiation and systemic insulin signaling via ligand-dependent transcriptional activation of target genes. However, the identities of the biologically relevant target genes are largely unknown. Here we describe the isolation and characterization of a novel target gene induced by PPARgamma ligands, termed PGAR (for PPARgamma angiopoietin related), which encodes a novel member of the angiopoietin family of secreted proteins. The transcriptional induction of PGAR follows a rapid time course typical of immediate-early genes and occurs in the absence of protein synthesis. The expression of PGAR is predominantly localized to adipose tissues and placenta and is consistently elevated in genetic models of obesity. Hormone-dependent adipocyte differentiation coincides with a dramatic early induction of the PGAR transcript. Alterations in nutrition and leptin administration are found to modulate the PGAR expression in vivo. Taken together, these data suggest a possible role for PGAR in the regulation of systemic lipid metabolism or glucose homeostasis.
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PMID:Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. 1086 90

The traditional role attributed to white adipose tissue is energy storage, fatty acids being released when fuel is required. The metabolic role of white fat is, however, complex. For example, the tissue is needed for normal glucose homeostasis and a role in inflammatory processes has been proposed. A radical change in perspective followed the discovery of leptin; this critical hormone in energy balance is produced principally by white fat, giving the tissue an endocrine function. Leptin is one of a number of proteins secreted from white adipocytes, which include angiotensinogen, adipsin, acylation-stimulating protein, adiponectin, retinol-binding protein, tumour neorosis factor a, interleukin 6, plasminogen activator inhibitor-1 and tissue factor. Some of these proteins are inflammatory cytokines, some play a role in lipid metabolism, while others are involved in vascular haemostasis or the complement system. The effects of specific proteins maybe autocrine or paracrine, or the site of action maybe distant from adipose tissue. The most recently described adipocyte secretory proteins are fasting-induced adipose factor, a fibrinogen-angiopoietin-related protein, metallothionein and resistin. Resistin is an adipose tissue-specific factor which is reported to induce insulin resistance, linking diabetes to obesity. Metallothionein is a metal-binding and stress-response protein which may have an antioxidant role. The key challenges in establishing the secretory functions of white fat are to identify the complement of secreted proteins, to establish the role of each secreted protein, and to assess the pathophysiological consequences of changes in adipocyte protein production with alterations in adiposity (obesity, fasting, cachexia). There is already considerable evidence of links between increased production of some adipocyte factors and the metabolic and cardiovascular complications of obesity. In essence, white adipose tissue is a major secretory and endocrine organ involved in a range of functions beyond simple fat storage.
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PMID:Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. 1168 7

The traditional function attributed to white adipose tissue of energy storage in the form of triglycerides has been challenged by results from recent studies, showing that adipose tissue is, in fact, a highly active metabolic and endocrine organ. A radical change in perspective followed the discovery of a large number of proteins secreted from white adipocytes, such as leptin, resistin, adiponectin, adipsin, acylation-stimulating protein, angiotensinogen, tumour necrosis factor a, interleukin-6, retinol-binding protein, plasminogen activator inhibitor-1, tissue factor, fasting-induced adipose factor, fibrinogen/angiopoetin-related protein, and metallothionein. The effects of specific proteins may be either autocrine or paracrine, meaning that they might act in adipose tissue itself or in more distant target tissues. Some of these proteins induce insulin resistance, some play a role in glucose and lipid metabolism, some are inflammatory cytokines, while others are involved in vascular haemostasis. The key challenges for future investigations of adipose tissue's secretory functions will be to identify all of its secreted proteins, to establish the function of each secreted protein, and to assess the pathophysiological consequences of changes in adipocyte protein production due to problems, such as obesity, fasting, or diabetes mellitus type 2.
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PMID:[Adipose tissue as an endocrine organ]. 1664 Jan 91

The trillions of microbes that colonize our adult intestines function collectively as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. Given the worldwide epidemic in obesity, there is interest in how interactions between human and microbial metabolomes may affect our energy balance. Here we report that, in contrast to mice with a gut microbiota, germ-free (GF) animals are protected against the obesity that develops after consuming a Western-style, high-fat, sugar-rich diet. Their persistently lean phenotype is associated with increased skeletal muscle and liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its downstream targets involved in fatty acid oxidation (acetylCoA carboxylase; carnitine-palmitoyltransferase). Moreover, GF knockout mice lacking fasting-induced adipose factor (Fiaf), a circulating lipoprotein lipase inhibitor whose expression is normally selectively suppressed in the gut epithelium by the microbiota, are not protected from diet-induced obesity. Although GF Fiaf-/- animals exhibit similar levels of phosphorylated AMPK as their wild-type littermates in liver and gastrocnemius muscle, they have reduced expression of genes encoding the peroxisomal proliferator-activated receptor coactivator (Pgc-1alpha) and enzymes involved in fatty acid oxidation. Thus, GF animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1alpha; and (ii) increased AMPK activity. Together, these findings support the notion that the gut microbiota can influence both sides of the energy balance equation, and underscore the importance of considering our metabolome in a supraorganismal context.
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PMID:Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. 1721 Sep 19

Cardiovascular and metabolic risk depends not only on the overall obesity but also fat distribution is more powerfull predictor for risk factors. Adipose tissue produces and secretes a variety of bioactive peptides - adipokines The most recently described adipocyte secretory proteins contribute to the pathogenesis of impaired insulin secretion and insulin resistance, endothelial dysfunction, a proinflammatory state and promote progression of atherosclerosis. This review presents an overview of the adipose tissue secreted proteins (leptin, TNF-alpha, IL-6, adiponectin, resistin, visfatin, ASP, FIAF, MT) role and their regulation in the context of abdominal obesity and the adverse metabolic consequences.
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PMID:Metabolic effects associated with adipose tissue distribution. 1735 88

The effect of hypoxia, induced by incubation under low (1%) oxygen tension or by exposure to CoCl(2), on the expression and secretion of inflammation-related adipokines was examined in human adipocytes. Hypoxia led to a rapid and substantial increase (greater than sevenfold by 4 h of exposure to 1% O(2)) in the hypoxia-sensitive transcription factor, HIF-1alpha, in human adipocytes. This was accompanied by a major increase (up to 14-fold) in GLUT1 transporter mRNA level. Hypoxia (1% O(2) or CoCl(2)) led to a reduction (up to threefold over 24 h) in adiponectin and haptoglobin mRNA levels; adiponectin secretion also decreased. No changes were observed in TNFalpha expression. In contrast, hypoxia resulted in substantial increases in FIAF/angiopoietin-like protein 4, IL-6, leptin, MIF, PAI-1 and vascular endothelial growth factor (VEGF) mRNA levels. The largest increases were with FIAF (maximum 210-fold), leptin (maximum 29-fold) and VEGF (maximum 23-fold); these were reversed on return to normoxia. The secretion of IL-6, leptin, MIF and VEGF from the adipocytes was also stimulated by exposure to 1% O(2). These results demonstrate that hypoxia induces extensive changes in human adipocytes in the expression and release of inflammation-related adipokines. Hypoxia may underlie the development of the inflammatory response in adipocytes, leading to obesity-associated diseases.
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PMID:Dysregulation of the expression and secretion of inflammation-related adipokines by hypoxia in human adipocytes. 1760 76

Gut microflora is now considered as a key organ involved in host energy homeostasis. Recent data suggest that the alterations of the gut bacteria ecosystem could contribute to the development of metabolic disorders such as type 2 diabetes and obesity. First, gut microflora may increase energy efficiency of non digested food via the fermentation, thus providing more energy to the host. Secondly, fatty acids flux and storage in the adipose tissue is under the control of the fasting-induced adipocyte factor FIAF, which expression depends on gut microflora. Third, high-fat diet feeding changes gut bacteria profile, leading to a drop in bifidobacteria content, which correlates with a higher LPS plasma levels, thereby participating to the onset of inflammation, insulin resistance and type 2 diabetes associated with obesity. Changing gut microflora composition could be a useful tool to prevent or to treat high-fat/low fibres diet-induced metabolic syndrome. double dagger.
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PMID:[Gut microflora is a key player in host energy homeostasis]. 1846 28

Recent data reported that chitosan reduces high-fat (HF) diet-induced obesity in mice without describing the metabolic consequences of such an effect. The aim of this study was to investigate the capacity of chitosan derived from edible mushrooms to modify adipocytokine levels and to assess the relevance of this effect on the development of fat mass, and on glucose and lipid metabolism in obese mice. Mice were fed a HF diet or a HF diet supplemented with 5% fungal chitosan for ten weeks. HF-induced hypertriglyceridaemia, fasting hyperinsulinaemia and fat accumulation in liver, muscle and white adipose tissue (WAT) were reduced after chitosan treatment. The higher lipid content in the caecum following treatment with chitosan suggested that this dietary fiber reduced lipid absorption. We postulated that the lower triglyceridaemia observed upon chitosan treatment could also be the result of the lower FIAF (fasting-induced adipose factor) expression observed in visceral adipose tissue. IL-6, resistin and leptin levels decreased in the serum after chitosan supplementation. We conclude that fungal chitosan counteracts some inflammatory disorders and metabolic alterations occurring in diet-induced obese mice since it decreases feed efficiency, fat mass, adipocytokine secretion and ectopic fat deposition in the liver and the muscle.
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PMID:Dietary supplementation with chitosan derived from mushrooms changes adipocytokine profile in diet-induced obese mice, a phenomenon linked to its lipid-lowering action. 1928 82

Glucocorticoids are important regulators of lipid homeostasis, and chronically elevated glucocorticoid levels induce hypertriglyceridemia, hepatic steatosis, and visceral obesity. The occupied glucocorticoid receptor (GR) is a transcription factor. However, those genes regulating lipid metabolism under GR control are not fully known. Angiopoietin-like 4 (ANGPTL4, fasting-induced adipose factor), a protein inhibitor of lipoprotein lipase, is synthesized and secreted during fasting, when circulating glucocorticoid levels are physiologically increased. We therefore tested whether the ANGPTL4 gene (Angptl4) is transcriptionally controlled by GR. We show that treatment with the synthetic glucocorticoid dexamethasone increased Angptl4 mRNA levels in primary hepatocytes and adipocytes (2-3-fold) and in the livers and white adipose tissue of mice (approximately 4-fold). We tested the mechanism of this increase in H4IIE hepatoma cells and found that dexamethasone treatment increased the transcriptional rate of Angptl4. Using bioinformatics and chromatin immunoprecipitation, we identified a GR binding site within the rat Angptl4 sequence. A reporter plasmid containing this site was markedly activated by dexamethasone, indicative of a functional glucocorticoid response element. Dexamethasone treatment also increased histone H4 acetylation and DNase I accessibility in genomic regions near this site, further supporting that it is a glucocorticoid response element. Glucocorticoids promote the flux of triglycerides from white adipose tissue to liver. We found that mice lacking ANGPTL4 (Angptl4(-/-)) had reductions in dexamethasone-induced hypertriglyceridemia and hepatic steatosis, suggesting that ANGPTL4 is required for this flux. Overall, we establish that ANGPTL4 is a direct GR target that participates in glucocorticoid-regulated triglyceride metabolism.
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PMID:Angiopoietin-like 4 (ANGPTL4, fasting-induced adipose factor) is a direct glucocorticoid receptor target and participates in glucocorticoid-regulated triglyceride metabolism. 1962 74

The gut microbiota has been implicated in host nutrient absorption and energy homeostasis. We studied the influence of different diets on body composition in germ-free (GF) and conventional (CV) mice. GF and CV male adult C3H mice were fed ad libitum a semi-synthetic low-fat diet (LFD; carbohydrate-protein-fat ratio: 41:42:17; 19.8 kJ/g), a high-fat diet (HFD; 41:16:43; 21.4 kJ/g) or a commercial Western diet (WD; 41:19:41; 21.5 kJ/g). There was no difference in body weight gain between GF and CV mice on the LFD. On the HFD, GF mice gained more body weight and body fat than CV mice, and had lower energy expenditure. GF mice on the WD gained significantly less body fat than GF mice on the HFD. GF mice on both HFD and WD showed increased intestinal mRNA expression of fasting-induced adipose factor/angiopoietin-like protein 4 (Fiaf/Angptl4), but they showed no major changes in circulating Fiaf/Angptl4 compared with CV mice. The faecal microbiota composition of the CV mice differed between diets: the proportion of Firmicutes increased on both HFD and WD at the expense of the Bacteroidetes. This increase in the Firmicutes was mainly due to the proliferation of one family within this phylum: the Erysipelotrichaceae. We conclude that the absence of gut microbiota does not provide a general protection from diet-induced obesity, that intestinal production of Fiaf/Angptl4 does not play a causal role in gut microbiota-mediated effects on fat storage and that diet composition affects gut microbial composition to larger extent than previously thought.
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PMID:Absence of intestinal microbiota does not protect mice from diet-induced obesity. 2044 70


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