biostudies-literatureJi LNational Natural Science Foundation of China2002794https://www.ebi.ac.uk/biostudies/studies/S-EPMC7967052biostudies-literatureUnknown8(6)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<i>AKAP1</i>, a signaling hub on outer mitochondrial membrane, renders mice resistant to diet-induced obesity.<i>AKAP1</i> 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 <i>AKAP1^-/-</i> 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 inhibitAdvanced science (Weinheim, Baden-Wurttemberg, Germany)<i>AKAP1</i> Deficiency Attenuates Diet-Induced Obesity and Insulin Resistance by Promoting Fatty Acid Oxidation and Thermogenesis in Brown Adipocytes.PMC7967052818702848183007081772935Li FJi LWang GHe LHuang QZhao YKang FXing JHe YGuo HQi BZhao JLiu FGao Tfalse<i>AKAP1</i> Deficiency Attenuates Diet-Induced Obesity and Insulin Resistance by Promoting Fatty Acid Oxidation and Thermogenesis in Brown Adipocytes.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<i>AKAP1</i>, a signaling hub on outer mitochondrial membrane, renders mice resistant to diet-induced obesity.<i>AKAP1</i> 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 <i>AKAP1^-/-</i> 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 inhibit2021-01-01T00:00:00Z2021 Mar2025-04-18T13:27:28.364Z2025-04-06T23:13:11.65ZS-EPMC79670523374772310.1002/advs.202002794