Acetate and Propionate Short Chain Fatty Acids Stimulate Adipogenesis via GPCR43

Abstract

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.

Control of appetite and energy intake by SCFA: what are the potential underlying mechanisms?

“…Both FFAR2 and FFAR3 are activated by physiological concentrations of SCFA, although a preference of FFAR2 for acetate and propionate and of FFAR3 for propionate and butyrate has been reported (29)(30)(31) . These receptors have been shown to be expressed not only in the gut epithelium (32,33) where SCFA are produced and are at their highest concentrations, but also at multiple tissue sites, including adipose tissue (34)(35)(36) , immune cells (29) , skeletal muscle (31) and within the peripheral nervous system (37,38) . A possible role for these receptors in energy intake regulation emerged with the identification that FFAR2 and FFAR3 are present on colonic endocrine L-cells (32,33) .…”

“…Furthermore, it was found in vivo that elevating circulating levels of propionate increased leptin levels in mice. Nevertheless, not all researchers have been able to detect FFAR3 in different adipose tissue sites (34,36,37) , thus the role of FFAR3 in adipose tissue function is currently a contentious topic. It has been …”

“…consistently reported that FFAR2 is abundantly expressed in white adipose tissue (34)(35)(36) and suggested that FFAR2 may be responsible for stimulating leptin release from adipocytes. It was found that leptin secretion from wild-type adipocytes was increased by acetate, yet butyrate had no significant effect (35) .…”

Les récepteurs membranaires des acides gras de la cellule β

“…De plus, GPR43 est exprimé par les polynucléaires neutrophiles et éosinophiles [7,36], et les souris dont le gène gpr43 est invalidé ont un profil inflammatoire [37]. L'expression de GPR43 est aussi détectable dans les adipocytes blancs [38], mais celle de GPR41 reste controversée [39]. Diverses publications suggèrent que ces récepteurs jouent un rôle dans la régulation de l'adipogenèse [38], la lipolyse [40] et la sécrétion de leptine [39] par les adipocytes.…”

“…L'expression de GPR43 est aussi détectable dans les adipocytes blancs [38], mais celle de GPR41 reste controversée [39]. Diverses publications suggèrent que ces récepteurs jouent un rôle dans la régulation de l'adipogenèse [38], la lipolyse [40] et la sécrétion de leptine [39] par les adipocytes. Ximenes et al [41] ont par ailleurs montré que l'acide propionique, un ligand de GPR41 et GPR43, inhibe la sécrétion d'insuline en réponse au glucose dans les îlots de rats.…”