Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43
Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43
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DOI：
10.1210/en.2005-0545
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发表时间：
2005-12-01
期刊：
影响因子：
4.8
通讯作者：
Sasaki, S
中科院分区：
文献类型：
--
作者：
Hong, YH;Nishimura, Y;Sasaki, S
最近发现G蛋白偶联受体（GPCR）41和43的特征在于具有短链脂肪酸乙酸酯和丙酸酯作为它们的配体。本研究的目的是研究GPCR 41、GPCR 43及其配体在脂肪形成过程中的作用。我们测量了小鼠脂肪和其他组织中GPCR 41和GPCR 43 mRNA的水平。GRP 43 mRNA在四种脂肪组织中的表达均高于其他组织，而GPCR 41 mRNA在所有脂肪组织中均未检测到。GPCR 43在分离的脂肪细胞中有高水平的表达，而在基质血管细胞中表达水平很低。与正常脂肪饮食的小鼠相比，高脂肪饮食的小鼠脂肪组织中GPCR 43的表达上调。在融合和未分化的3 T3-L1脂肪细胞中不能检测到GPCR 43 mRNA;然而，在分化开始后，GPCR 43 mRNA的水平随时间而升高。GPCR 41在融合和分化的脂肪细胞中未检测到表达。乙酸盐和丙酸盐处理增加了3 T3-L1脂肪细胞中作为多个液滴存在的脂质。丙酸盐显著提高了脂肪分化过程中GPCR 43的表达水平，并上调了PPAR-gamma 2。小分子干扰RNA（siRNA）可抑制3 T3-L1细胞中GPCR 43 mRNA的表达，阻断脂肪细胞的分化。此外，醋酸盐和丙酸盐均以剂量依赖性方式抑制异丙肾上腺素诱导的脂解。我们的结论是，乙酸和丙酸短链脂肪酸可能有重要的生理作用，脂肪形成通过GPCR 43，但不是通过GPCR 41。
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-gamma 2. 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.