Disease relevance of Adipocytes

• Resistin, obesity and insulin resistance--the emerging role of the adipocyte as an endocrine organ [1].
• We conclude that mutations in AGPAT2 may cause congenital generalized lipodystrophy by inhibiting triacylglycerol synthesis and storage in adipocytes [2].
• Leptin, a hormone secreted by fat cells, suppresses food intake and promotes weight loss [3].
• Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity [4].
• When pertussis vaccine was used to functionally inactivate adenosine receptors in adipocytes from the younger and older rats, the ability of isoproterenol to activate lipolysis was restored in the older group [5].

Psychiatry related information on Adipocytes

• After alcohol consumption, the number of lipocytes (as assessed by light microscopy) was significantly decreased in fatty livers and at various stages of hepatic fibrosis; this was associated with a decreased hepatic vitamin A content [6].
• Leptin is a hormone secreted by adipocytes with an important role in the control of feeding behavior and neuroendocrine function [7].
• Comparing fed and fasted rats for the antilipolytic effect of insulin in adipocytes revealed that short-term food deprivation resulted in a substantial deterioration of the ability of insulin to suppress epinephrine-induced lipolysis [8].
• Effects of testosterone and estrogens on deltoid and trochanter adipocytes in two cases of transsexualism [9].
• In vitro adipocyte IS and TNF-alpha production was measured following dietary modification [10].

High impact information on Adipocytes

• The nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) is a transcription factor that is activated by polyunsaturated fatty acids and their metabolites and is essential for fat cell formation [11].
• OT receptors have also been identified in other tissues, including the kidney, heart, thymus, pancreas, and adipocytes [12].
• This is accompanied by a dramatic increase in expression of adipocyte genes including adipocyte fatty acid binding protein and lipid-metabolizing enzymes [13].
• Herein, we demonstrate that the membrane-anchored metalloproteinase, MT1-MMP, coordinates adipocyte differentiation in vivo [14].
• Moreover, adjusting Rho activity is sufficient to alter the differentiation program of adipocyte and myocyte precursors [15].

Chemical compound and disease context of Adipocytes

• In fat cells obtained from acromegaly patients after an overnight fast, insulin binding at low hormone concentrations was significantly reduced by 20-30%, insulin-induced antilipolysis was unchanged, but glucose oxidation was unresponsive to insulin [16].
• To examine the relevance of these effects in vivo, we studied white adipocytes from ob/ob mice during the development of obesity and after treatment with rosiglitazone [17].
• Several cell lines were derived from hibernomas; among them, the T37i cells can undergo terminal differentiation into brown adipocytes, which remain capable of expressing ucp1 upon adrenergic or retinoic acid stimulation [18].
• We conclude that lipocytes are an important source of proteoglycan in normal liver and may be the principal source of dermatan sulfate associated with hepatic fibrosis [19].
• RESULTS: Control livers remained normal, whereas 10 of 12 baboons fed alcohol without PC developed septal fibrosis or cirrhosis with transformation of 81% +/- 3% of the hepatic lipocytes to collagen-producing transitional cells [20].

Biological context of Adipocytes

• Characterization of regulatory regions of adipose-specific genes has led to the identification of the transcription factors peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer binding protein (C/EBP), which play a key role in the complex transcriptional cascade during adipocyte differentiation [13].
• Increased FOXC2 expression, in adipocytes, has a pleiotropic effect on gene expression, which leads to a lean and insulin sensitive phenotype [21].
• We show that haploinsufficiency of the Foxo1 gene, encoding a forkhead transcription factor (forkhead box transcription factor O1), restores insulin sensitivity and rescues the diabetic phenotype in insulin-resistant mice by reducing hepatic expression of glucogenetic genes and increasing adipocyte expression of insulin-sensitizing genes [22].
• Our results suggest that the physiologic role of PPAR gamma 2 is to regulate development of the adipose lineage in response to endogenous lipid activators and that this factor may serve to link the process of adipocyte differentiation to systemic lipid metabolism [23].
• These findings suggest a pivotal role for PPAR gamma and its endogenous ligand in adipocyte development and glucose homeostasis and as a target for intervention in metabolic disorders [24].

Anatomical context of Adipocytes

• Lipoprotein lipase is an enzyme in adipose tissue that hydrolyzes circulating triglycerides and thereby generates the fatty acids used in the synthesis of triglyceride in fat cells [25].
• Immunocytochemistry and subcellular fractionation of 3T3-L1 adipocytes show that FATP is localized to the plasma membrane [26].
• Pik3r1-/- mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes [27].
• Here, we report the PGJ2 and its derivatives are efficacious activators of peroxisome proliferator-activated receptors alpha and gamma (PPAR alpha and PPAR gamma, respectively), orphan nuclear receptors implicated in lipid homeostasis and adipocyte differentiation [28].
• The well-characterized erythrocyte glucose transporter is also expressed in brain, adipocytes, kidney, muscle, and certain transformed cells, but not in liver, intestine, or the islets of Langerhans [29].

Associations of Adipocytes with chemical compounds

• Similarly, the thiazolidinedione class of antidiabetic drugs also bind to PPAR gamma and act as potent regulators of adipocyte development [24].
• Monobutyrin levels increase at least 200-fold during adipocyte differentiation and represent a major fraction of the total angiogenic activity [30].
• 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma [24].
• A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation [28].
• Human serum lipoproteins activate adipocyte plasma membrane adenylate cyclase [31].

Gene context of Adipocytes

• Perilipin (encoded by the gene Plin), an adipocyte protein, has been postulated to modulate HSL activity [32].
• We have identified the human winged helix/forkhead transcription factor gene FOXC2 as a key regulator of adipocyte metabolism [21].
• Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase-deficient mice [33].
• Leptin has so far been reported to be secreted only by adipocytes and the placenta [34].
• Secretion of leptin from adipocytes communicates body energy status to the brain by activating the leptin receptor long form (LRb) [35].

Analytical, diagnostic and therapeutic context of Adipocytes

• By Northern analysis, freshly isolated human lipocytes exhibited low levels of mRNA expression for TIMP-1, but this increased markedly relative to beta-actin expression with lipocyte activation during cell culture [36].
• Pulse-chase labeling followed by immunoprecipitation demonstrated that C/EBP is a rapidly turning over protein in adipocytes and that cytokine treatment led to a specific, time dependent decrease in its rate of synthesis [37].
• The relative quantity of the 66-kD protein correlated with body mass index at r = 0.72. bFGF-related proteins probably function normally to maintain an appropriate complement of adipocyte precursors [38].
• TIMP-1 was immunolocalized to human lipocytes, and secretion of TIMP-1 was confirmed by ELISA of culture media; (mean +/- SD) 159 +/- 79 ng of TIMP-1/10(6) cells per 24 h [36].
• Oral administration of the cAMP phosphodiesterase inhibitor, aminophylline, was also effective in inhibiting the development of desensitization in fat cells [39].

References