Dietary Lactate Supplementation Protects against Obesity by Promoting Adipose Browning in Mice
Dietary Lactate Supplementation Protects against Obesity by Promoting Adipose Browning in Mice
复制标题
DOI：
10.1021/acs.jafc.0c05899
复制
发表时间：
2020-12-16
影响因子：
6.1
通讯作者：
Chen, Wei
中科院分区：
文献类型：
--
作者：
Yao, Zhijie;Yan, Yongheng;Chen, Wei
酸奶已被广泛用于减肥食品，以防止肥胖，但其分子性质仍不清楚。乳酸盐是酸奶的主要成分，而其同源细胞表面受体GPR 81在哺乳动物的脂肪组织中高度表达。在此，我们假设膳食中补充乳酸盐可能会激活GPR 81以促进脂肪布朗宁。通过研究小鼠模型，我们观察到肥胖小鼠脂肪组织中的GPR 81显著低于瘦小鼠，而β 3-肾上腺素能受体（β 3-AR）激动剂显著上调了其表达。GPR 81的缺乏大大减弱了实验性脂肪布朗宁和产热。重要的是，口服乳酸盐有效地诱导脂肪布朗宁，增强产热，改善血脂异常，并保护小鼠免受高脂饮食诱导的肥胖。从机制上讲，p38丝裂原活化蛋白激酶可能是GPR 81的关键下游效应。总的来说，我们的研究结果揭示了GPR 81在脂肪布朗宁中的关键作用，并为通过调节乳酸-GPR 81信号传导轴来控制肥胖提供了新的见解。
Yogurt has been widely used in weight-loss foods to prevent obesity, but its molecular nature remains unclear. Lactate is a major ingredient of yogurt, while its cognate cell surface receptor GPR81 is highly expressed in adipose tissues in mammals. Here we hypothesized that dietary lactate supplementation might activate GPR81 to promote adipose browning. Studying mouse models, we observed that GPR81 was substantially lowered in adipose tissue of obese mice compared with that for lean ones, whereas its expression was markedly up-regulated by a beta 3-adrenergic receptor (beta 3-AR) agonist. The deficiency of GPR81 greatly attenuated experimental adipose browning and thermogenesis. Importantly, oral administration of lactate effectively induced adipose browning, enhanced thermogenesis, improved dyslipidemia, and protected mice against high-fat-diet-induced obesity. Mechanistically, p38 mitogen-activated protein kinase might serve as a key downstream effect or of GPR81. Collectively, our findings revealed a critical role of GPR81 in adipose browning and provided a new insight into obesity management by modulating lactate-GPR81 signaling axis.