2-Aminoadipic acid protects against obesity and diabetes.

Autor: Wang-Yang Xu, Yan Shen, Houbao Zhu, Junhui Gao, Chen Zhang, Lingyun Tang, Shun-Yuan Lu, Chun-Ling Shen, Hong-Xin Zhang, Ziwei Li, Peng Meng, Ying-Han Wan, Jian Fei, Zhu-Gang Wang
Předmět:
Zdroj: Journal of Endocrinology; Nov2019, Vol. 243 Issue 2, p111-123, 13p
Abstrakt: Obesity and type 2 diabetes (T2D) are both complicated endocrine disorders resulting from an interaction between multiple predisposing genes and environmental triggers, while diet and exercise have key influence on metabolic disorder s. Previous reports demonstrated that 2-aminoadipic acid (2-AAA), an intermediate metabolite of lysine metabolism, could modulate insulin secretion and predict T2D, suggesting the role of 2-AAA in glycolipid metabolism. Here, we showed that treatment of diet-induced obesity (DIO) mice with 2-AAA significantly reduced body weight, decreas ed fat accumulation and lowered fasting glucose. Furthermore, Dhtkd1-/- mice, in which the substrate of DHTKD1 2-AAA increased to a significant high level, were resistant to D IO and obesity-related insulin resistance. Further study showed that 2-AAA induced higher energy expenditure due to increased adipocyte thermogenesis via upregulating PGC1α and UCP1 mediated by β3AR activation, and stimulated lipolysis depending on enhanced expression of hormone-sensitive lipase (HSL) through activating β3AR signaling. Moreover, 2-AAA could alleviate the diabetic symptoms of db/db mice. Our data showed that 2-AAA played an important role in regulating glycolipid metabolism independent of diet and exercise, implying that improving the level of 2-AAA in vivo could be developed as a strategy in the treatment of obesity or diabetes. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index