内分泌学
脂解
脂肪组织
内科学
脂肪细胞
FGF21型
脂肪甘油三酯脂肪酶
生物
过氧化物酶体增殖物激活受体γ
过氧化物酶体增殖物激活受体
医学
受体
成纤维细胞生长因子
作者
René Adam,D. M. Pryce,Joseph S. Lee,Yuanqi Zhao,Ivory J. Mintah,Soo Kee Min,Gabor Halasz,Jason Mastaitis,Gurinder S. Atwal,Senem Aykul,Vincent Idone,Aris N. Economides,Luca A. Lotta,Andrew J. Murphy,George D. Yancopouloš,Mark W. Sleeman,Viktoria Gusarova
标识
DOI:10.1073/pnas.2309967120
摘要
Body fat distribution is a heritable risk factor for cardiovascular and metabolic disease. In humans, rare Inhibin beta E ( INHBE , activin E) loss-of-function variants are associated with a lower waist-to-hip ratio and protection from type 2 diabetes. Hepatic fatty acid sensing promotes INHBE expression during fasting and in obese individuals, yet it is unclear how the hepatokine activin E governs body shape and energy metabolism. Here, we uncover activin E as a regulator of adipose energy storage. By suppressing β-agonist-induced lipolysis, activin E promotes fat accumulation and adipocyte hypertrophy and contributes to adipose dysfunction in mice. Mechanistically, we demonstrate that activin E elicits its effect on adipose tissue through ACVR1C, activating SMAD2/3 signaling and suppressing PPARG target genes. Conversely, loss of activin E or ACVR1C in mice increases fat utilization, lowers adiposity, and drives PPARG-regulated gene signatures indicative of healthy adipose function. Our studies identify activin E–ACVR1C as a metabolic rheostat promoting liver–adipose cross talk to restrain excessive fat breakdown and preserve fat mass during prolonged fasting, a mechanism that is maladaptive in obese individuals.
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