It has recently been discovered that G protein-coupled receptors (GPCR) 41 and 43 are characterized by having the short chain fatty acids acetate and propionate as their ligands. The objective of this study was to investigate the involvement of GPCR41, GPCR43, and their ligands in the process of adipogenesis. We measured the levels of GPCR41 and GPCR43 mRNA in both adipose and other tissues of the mouse. GRP43 mRNA expression was higher in four types of adipose tissue than in other tissues, whereas GPCR41 mRNA was not detected in any adipose tissues. A high level of GPCR43 expression was found in isolated adipocytes, but expression level was very low in stromal-vascular cells. Expression of GPCR43 was up-regulated in adipose tissues of mice fed a high-fat diet compared with those fed a normal-fat diet. GPCR43 mRNA could not be detected in confluent and undifferentiated 3T3-L1 adipocytes; however, the levels rose with time after the initiation of differentiation. GPCR41 expression was not detected in confluent and differentiated adipocytes. Acetate and propionate treatments increased lipids present as multiple droplets in 3T3-L1 adipocytes. Propionate significantly elevated the level of GPCR43 expression during adipose differentiation, with up-regulation of PPAR-gamma2. Small interfering RNA mediated a reduction of GPCR43 mRNA in 3T3-L1 cells and blocked the process of adipocyte differentiation. In addition, both acetate and propionate inhibited isoproterenol-induced lipolysis in a dose-dependent manner. We conclude that acetate and propionate short chain fatty acids may have important physiological roles in adipogenesis through GPCR43, but not through GPCR41.

The factors that control fat deposition in adipose tissues are poorly understood. It is known that visceral adipose tissues display a range of biochemical properties that distinguish them from adipose tissues of subcutaneous origin. However, we have little information on gene expression, either in relation to fat deposition or on interspecies variation in fat deposition. The first step in this study was to identify genes expressed in fat depot of cattle using the differential display RT-PCR method. Among the transcripts identified as having differential expression in the two adipose tissues were cell division cycle 42 homolog (CDC42), prefoldin-5, decorin, phosphate carrier, 12S ribosomal RNA gene, and kelch repeat and BTB domain containing 2 (Kbtbd2). In subsequent experiments, we determined the expression levels of these latter genes in the pig and in mice fed either a control or high-fat diet to compare the regulation of fat accumulation in other animal species. The levels of CDC42 and decorin mRNA were found to be higher in visceral adipose tissue than in subcutaneous adipose tissue in cattle, pig, and mice. However, the other genes studied did not show consistent expression patterns between the two tissues in cattle, pigs, and mice. Interestingly, all genes were upregulated in subcutaneous and/or visceral adipose tissues of mice fed the high-fat diet compared with the control diet. The data presented here extend our understanding of gene expression in fat depots and provide further proof that the mechanisms of fat accumulation differ significantly between animal species. differential display and reverse transcriptase-polymerase chain reaction; fat depot THERE ARE TWO TYPES OF ADIPOSE TISSUE, subcutaneous and visceral. Recent studies indicate that adipocytes in these two fat depots show differences in basal metabolic properties, for example, in regulating volume, lipid composition, and so on (22,24). There is considerable current interest in visceral adipose tissue because of its relationship with various diseases such as cardiovascular disease, type 2 diabetes mellitus, hyperlipidemia, and syndrome X. There are a number of potential reasons why visceral adipose tissue may contribute to abnormalities in metabolism; among these are its anatomical site and pattern of venous drainage, and the presence of intrinsic and unique features of visceral adipocytes. The venous drainage of visceral adipose tissue is via the portal system, directly providing free fatty acid as a substrate for hepatic lipoprotein metabolism and glucose production (16,22,24). Additionally, in vitro studies using labeled tracers have demonstrated that visceral adipocytes have higher rates of lipid turnover than subcutaneous adipose tissue (19,20).Fat depot metabolism is also of importance in the commercial rearing of livestock such as cattle and pigs. One of the most important themes in the animal industry is the production of high quality meat at low cost. A better understanding of the specific accumulation mechanisms of fat depots should c...

Until now, the various proteins highly expressed in adipose tissues have been identified and characterized by traditional gene cloning techniques.However, methods of computer analysis have been developed that compare levels of expression among various tissues, and genes whose expression levels differ significantly between tissues have been found. Among these genes, we Confocal image analyses of green-fluorescent protein-adipogenin (pEGFP-adipogenin) transiently expressed in 3T3-L1 adipocytes showed that adipogenin was strictly localized to membranes and was absent from the cytosol.-3 -Moreover, small interfering RNA (siRNA) mediated a reduction of adipogenin mRNA in 3T3-L1 cells and blocked the process of adipocyte differentiation.These results indicate that adipogenin, an adipocyte-specific membrane protein, may be involved with adipogenesis, as one of the regulators of adipose tissue development.

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