Taurine-mediated browning of white adipose tissue is involved in its anti-obesity effect in mice
Taurine-mediated browning of white adipose tissue is involved in its anti-obesity effect in mice
复制标题
牛磺酸介导的白色脂肪组织褐变与其对小鼠的抗肥胖作用有关
DOI：
10.1074/jbc.ra119.009936
复制
发表时间：
2019-10-11
影响因子：
4.8
通讯作者：
Tang, Qi-Qun
中科院分区：
文献类型：
--
作者：
Guo, Ying-Ying;Li, Bai-Yu;Tang, Qi-Qun
牛磺酸是一种非蛋白质氨基酸，广泛存在于几乎所有动物组织中。摄入牛磺酸有助于改善肥胖及其相关的代谢紊乱。然而，牛磺酸对肥胖的保护作用的分子机制尚未完全了解。在这项研究中，发现用牛磺酸腹腔内治疗小鼠减轻了高脂饮食（HFD）诱导的肥胖，改善了胰岛素敏感性，增加了小鼠的能量消耗和适应性产热。同时，给予牛磺酸可显著诱导小鼠腹股沟白色脂肪组织（iWAT）的布朗宁，并显著增加iWAT中PGC 1 α、UCP 1等产热基因的表达。体外研究表明，牛磺酸还诱导C3 H 10 T1/2白色脂肪细胞中棕色样脂肪细胞的发育。抑制PGC 1 α表达可减弱牛磺酸促进C3 H10 T1/2细胞棕色样脂肪细胞表型的作用。此外，牛磺酸处理增强AMPK磷酸化在体外和体内，AMPKα1的敲低阻止牛磺酸介导的PGC 1 α在C3 H10 T1/2细胞中的诱导。因此，HFD小鼠iWAT中PGC 1 α的特异性敲低抑制了牛磺酸诱导的iWAT布朗宁，牛磺酸在增强适应性产热、预防肥胖和改善胰岛素敏感性方面的作用部分受损。这些结果揭示了牛磺酸在促进白色脂肪组织的布朗宁中的功能作用，这取决于PGC 1 α的诱导。我们的研究还表明了牛磺酸对肥胖的保护作用的潜在机制，这涉及牛磺酸介导的白色脂肪组织的布朗宁。
Taurine, a nonprotein amino acid, is widely distributed in almost all animal tissues. Ingestion of taurine helps to improve obesity and its related metabolic disorders. However, the molecular mechanism underlying the protective role of taurine against obesity is not completely understood. In this study, it was found that intraperitoneal treatment of mice with taurine alleviated high-fat diet (HFD)-induced obesity, improved insulin sensitivity, and increased energy expenditure and adaptive thermogenesis of the mice. Meanwhile, administration of the mice with taurine markedly induced the browning of inguinal white adipose tissue (iWAT) with significantly elevated expression of PGC1α, UCP1, and other thermogenic genes in iWAT. In vitro studies indicated that taurine also induced the development of brown-like adipocytes in C3H10T1/2 white adipocytes. Knockdown of PGC1α blunted the role of taurine in promoting the brown-like adipocyte phenotypes in C3H10T1/2 cells. Moreover, taurine treatment enhanced AMPK phosphorylation in vitro and in vivo, and knockdown of AMPKα1 prevented taurine-mediated induction of PGC1α in C3H10T1/2 cells. Consistently, specific knockdown of PGC1α in iWAT of the HFD-fed mice inhibited taurine-induced browning of iWAT, with the role of taurine in the enhancement of adaptive thermogenesis, the prevention of obesity, and the improvement of insulin sensitivity being partially impaired. These results reveal a functional role of taurine in facilitating the browning of white adipose tissue, which depends on the induction of PGC1α. Our studies also suggest a potential mechanism for the protective role of taurine against obesity, which involves taurine-mediated browning of white adipose tissue.