Biomaterial Database

AKAP1 Deficiency Attenuates Diet-Induced Obesity and Insulin Resistance by Promoting Fatty Acid Oxidation and Thermogenesis in Brown Adipocytes. 2021

Lele Ji, and Ya Zhao, and Linjie He, and Jing Zhao, and Tian Gao, and Fengzhou Liu, and Bingchao Qi, and Fei Kang, and Gang Wang, and Yilin Zhao, and Haitao Guo, and Yuanfang He, and Fei Li, and Qichao Huang, and Jinliang Xing

State Key Laboratory of Cancer Biology and Department of Physiology and Pathophysiology Fourth Military Medical University Xi'an Shaanxi 710032 China.

Altering the balance between energy intake and expenditure is a major strategy for treating obesity. Nonetheless, despite the progression in antiobesity drugs on appetite suppression, therapies aimed at increasing energy expenditure are limited. Here, knockout ofAKAP1, a signaling hub on outer mitochondrial membrane, renders mice resistant to diet-induced obesity.AKAP1 knockout significantly enhances energy expenditure and thermogenesis in brown adipose tissues (BATs) of obese mice. Restoring AKAP1 expression in BAT clearly reverses the beneficial antiobesity effect in AKAP1 mice. Mechanistically, AKAP1 remarkably decreases fatty acid β-oxidation (FAO) by phosphorylating ACSL1 to inhibit its activity in a protein-kinase-A-dependent manner and thus inhibits thermogenesis in brown adipocytes. Importantly, AKAP1 peptide inhibitor effectively alleviates diet-induced obesity and insulin resistance. Altogether, the findings demonstrate that AKAP1 functions as a brake of FAO to promote diet-induced obesity, which may be used as a potential therapeutic target for obesity.