Open AccessAKAP1 Deficiency Attenuates Diet‐Induced Obesity and Insulin Resistance by Promoting Fatty Acid Oxidation and Thermogenesis in Brown Adipocytes
Author(s) -
Ji Lele,
Zhao Ya,
He Linjie,
Zhao Jing,
Gao Tian,
Liu Fengzhou,
Qi Bingchao,
Kang Fei,
Wang Gang,
Zhao Yilin,
Guo Haitao,
He Yuanfang,
Li Fei,
Huang Qichao,
Xing Jinliang
Publication year - 2021
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202002794
Subject(s) - thermogenesis , endocrinology , medicine , insulin resistance , brown adipose tissue , obesity , appetite , beta oxidation , adipose tissue , uncoupling protein , knockout mouse , biology , chemistry , metabolism , receptor
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 of AKAP1 , 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.