Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai, China.
Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai, China
Diabetes. 2021 Jul;70(7):1458-1472. doi: 10.2337/db20-1210. Epub 2021 Apr 16.
l-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with l-theanine (100 mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1, and other thermogenic genes. Meanwhile, administration of the mice with l-theanine increased energy expenditure. In vitro studies indicated that l-theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of l-theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. l-theanine treatment enhanced AMPKα phosphorylation both in adipocytes and iWAT. Knockdown of AMPKα abolished l-theanine-induced upregulation of Prdm16 and adipocyte browning. l-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for l-theanine-induced increase of α-KG and DNA demethylation on the Prdm16 promoter. Moreover, intraperitoneal administration with l-theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol, and free fatty acids in the high-fat diet-fed mice. Our results suggest a potential role of l-theanine in combating diet-induced obesity in mice, which may involve l-theanine-induced browning of WAT.
茶氨酸是一种具有多种有益功效的非蛋白氨基酸。我们发现，腹腔内给予茶氨酸（100mg/kg/天）可增强适应性产热，并诱导腹股沟白色脂肪组织（iWAT）褐变，同时上调 Prdm16、Ucp1 和其他产热基因。此外，给予小鼠茶氨酸可增加能量消耗。体外研究表明，茶氨酸可诱导脂肪细胞向棕色样特征发展。shRNA 介导的 Prdm16 耗竭削弱了茶氨酸在促进脂肪细胞和小鼠 iWAT 中向棕色样表型转变的作用。茶氨酸处理可增强 AMPKα 在脂肪细胞和 iWAT 中的磷酸化。AMPKα 的敲低可消除茶氨酸诱导的 Prdm16 上调和脂肪细胞褐变。茶氨酸增加了脂肪细胞中的α-酮戊二酸（α-KG）水平，这可能通过诱导其启动子上的活性 DNA 去甲基化来增加 Prdm16 的转录。AMPK 激活是茶氨酸诱导α-KG 增加和 Prdm16 启动子 DNA 去甲基化所必需的。此外，腹腔内给予茶氨酸可改善肥胖、改善葡萄糖耐量和胰岛素敏感性，并降低高脂肪饮食喂养小鼠的血浆甘油三酯、总胆固醇和游离脂肪酸。我们的研究结果表明，茶氨酸在对抗肥胖症方面具有潜在作用，这可能涉及茶氨酸诱导的 WAT 褐变。
