Clore Laboratory, University of Buckingham, Buckingham MK18 1EG, UK.
Br J Nutr. 2013 May 28;109(10):1755-64. doi: 10.1017/S0007114512003923. Epub 2012 Oct 31.
SCFA are produced in the gut by bacterial fermentation of undigested carbohydrates. Activation of the Gαi-protein-coupled receptor GPR41 by SCFA in β-cells and sympathetic ganglia inhibits insulin secretion and increases sympathetic outflow, respectively. A possible role in stimulating leptin secretion by adipocytes is disputed. In the present study, we investigated energy balance and glucose homoeostasis in GPR41 knockout mice fed on a standard low-fat or a high-fat diet. When fed on the low-fat diet, body fat mass was raised and glucose tolerance was impaired in male but not female knockout mice compared to wild-type mice. Soleus muscle and heart weights were reduced in the male mice, but total body lean mass was unchanged. When fed on the high-fat diet, body fat mass was raised in male but not female GPR41 knockout mice, but by no more in the males than when they were fed on the low-fat diet. Body lean mass and energy expenditure were reduced in male mice but not in female knockout mice. These results suggest that the absence of GPR41 increases body fat content in male mice. Gut-derived SCFA may raise energy expenditure and help to protect against obesity by activating GPR41.
短链脂肪酸（SCFA）是肠道细菌未消化的碳水化合物发酵产生的。SCFA 激活 β 细胞和交感神经节中的 Gαi 蛋白偶联受体 GPR41，分别抑制胰岛素分泌和增加交感神经输出。其刺激脂肪细胞分泌瘦素的作用可能存在争议。在本研究中，我们研究了低脂或高脂饮食喂养的 GPR41 敲除小鼠的能量平衡和葡萄糖稳态。与野生型小鼠相比，低脂饮食喂养的雄性而非雌性 GPR41 敲除小鼠的体脂肪量增加，葡萄糖耐量受损。雄性小鼠的比目鱼肌和心脏重量减轻，但总体瘦体重不变。高脂饮食喂养时，雄性 GPR41 敲除小鼠的体脂肪量增加，但增加幅度不及低脂饮食喂养时。雄性小鼠的体瘦体重和能量消耗减少，但雌性敲除小鼠则没有。这些结果表明，GPR41 的缺失会增加雄性小鼠的体脂肪含量。肠道来源的 SCFA 可能通过激活 GPR41 来增加能量消耗并有助于预防肥胖。
