L-Theanine Activates the Browning of White Adipose Tissue Through the AMPK/a-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-Induced Obesity in Mice
L-Theanine Activates the Browning of White Adipose Tissue Through the AMPK/a-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-Induced Obesity in Mice
复制标题
L-茶氨酸通过 AMPK/a-酮戊二酸/Prdm16 轴激活白色脂肪组织的褐变，并改善小鼠饮食引起的肥胖
作者：
Wan-Qiu Peng;Gang Xiao;Bai-Yu Li;Ying-Ying Guo;Liang Guo;Qi-Qun Tang
L-茶氨酸是一种具有多种功效的非蛋白质氨基酸。我们发现，经L茶氨酸(100 mg/kg/d)腹腔注射后，小鼠的适应性产热能力增强，腹股沟白色脂肪组织发生褐变，Prdm16、ucp1等生热基因表达增加。同时，给予L茶氨酸可增加小鼠的能量消耗。体外研究表明，L茶氨酸可诱导脂肪细胞形成棕色样特征。ShRNA介导的Prdm16缺失减弱了L茶氨酸在促进脂肪细胞和小鼠IWAT中棕色样表型的作用。L-茶氨酸处理促进脂肪细胞和IWAT中AMPKα的磷酸化。敲除AMPKα基因可阻断L茶氨酸诱导的Prdm16表达上调和脂肪细胞褐变。L茶氨酸增加脂肪细胞内α-酮戊二酸(α-KG)水平，可能通过诱导Prdm16启动子上活性脱甲基化来促进Prdm16的转录。在L-茶氨酸诱导的Prdm16启动子上α-KG增加和DNA去甲基化过程中，需要AMPK的激活。此外，腹腔注射L茶氨酸可改善高脂饮食小鼠的肥胖，改善糖耐量和胰岛素敏感性，降低血浆甘油三酯、总胆固醇和游离脂肪酸。我们的结果提示L-茶氨酸在对抗饮食诱导的小鼠肥胖方面具有潜在的作用，这可能涉及L-茶氨酸诱导的Wat褐变。
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 AMPKalpha phosphorylation both in adipocytes and iWAT. Knockdown of AMPKalpha abolished l-theanine-induced upregulation of Prdm16 and adipocyte browning. l-Theanine increased the alpha-ketoglutarate (alpha-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 alpha-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.