Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids
Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids
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DOI：
10.1210/en.2008-0059
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发表时间：
2008-09-01
期刊：
影响因子：
4.8
通讯作者：
Li, Yang
中科院分区：
文献类型：
--
作者：
Ge, Hongfei;Li, Xiaofan;Li, Yang
G蛋白偶联受体43（GPR 43）已被鉴定为短链脂肪酸（包括乙酸酯和丙酸酯）的受体。先前已经提出GPR 43在免疫和炎症反应中的潜在参与，因为其表达在免疫细胞中高度富集。GPR 43也在许多其他组织中表达，包括脂肪细胞;然而，GPR 43在这些其他组织中激活的功能后果尚不清楚。在这份报告中，我们专注于GPR 43在脂肪细胞中的潜在功能。我们表明，脂肪细胞与GPR 43天然配体，乙酸盐和丙酸盐处理，表现出脂肪分解活性的减少。这种脂解的抑制是GPR 43激活的结果，因为这种作用在从GPR 43敲除动物分离的脂肪细胞中被消除。在小鼠体内模型中，我们表明，通过乙酸盐激活GPR 43导致血浆游离脂肪酸水平降低，而不会诱导通过激活烟酸受体GPR 109 A观察到的潮红副作用。这些结果表明GPR 43在调节血脂谱和代谢综合征方面可能具有潜在作用。
G protein-coupled receptor 43 (GPR43) has been identified as a receptor for short-chain fatty acids that include acetate and propionate. A potential involvement of GPR43 in immune and inflammatory response has been previously suggested because its expression is highly enriched in immune cells. GPR43 is also expressed in a number of other tissues including adipocytes; however, the functional consequences of GPR43 activation in these other tissues are not clear. In this report, we focus on the potential functions of GPR43 in adipocytes. We show that adipocytes treated with GPR43 natural ligands, acetate and propionate, exhibit a reduction in lipolytic activity. This inhibition of lipolysis is the result of GPR43 activation, because this effect is abolished in adipocytes isolated from GPR43 knockout animals. In a mouse in vivo model, we show that the activation of GPR43 by acetate results in the reduction in plasma free fatty acid levels without inducing the flushing side effect that has been observed by the activation of nicotinic acid receptor, GPR109A. These results suggest a potential role for GPR43 in regulating plasma lipid profiles and perhaps aspects of metabolic syndrome.