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Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity.


ABSTRACT: Obesity is associated with blunted ?-adrenoreceptor (?-AR)-mediated lipolysis and lipid oxidation in adipose tissue, but the mechanisms linking nutrient overload to catecholamine resistance are poorly understood. We report that targeted disruption of TGF-? superfamily receptor ALK7 alleviates diet-induced catecholamine resistance in adipose tissue, thereby reducing obesity in mice. Global and fat-specific Alk7 knock-out enhanced adipose ?-AR expression, ?-adrenergic signaling, mitochondrial biogenesis, lipid oxidation, and lipolysis under a high fat diet, leading to elevated energy expenditure, decreased fat mass, and resistance to diet-induced obesity. Conversely, activation of ALK7 reduced ?-AR-mediated signaling and lipolysis cell-autonomously in both mouse and human adipocytes. Acute inhibition of ALK7 in adult mice by a chemical-genetic approach reduced diet-induced weight gain, fat accumulation, and adipocyte size, and enhanced adipocyte lipolysis and ?-adrenergic signaling. We propose that ALK7 signaling contributes to diet-induced catecholamine resistance in adipose tissue, and suggest that ALK7 inhibitors may have therapeutic value in human obesity.

SUBMITTER: Guo T 

PROVIDER: S-EPMC4139062 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity.

Guo Tingqing T   Marmol Patricia P   Moliner Annalena A   Björnholm Marie M   Zhang Chao C   Shokat Kevan M KM   Ibanez Carlos F CF  

eLife 20140825


Obesity is associated with blunted β-adrenoreceptor (β-AR)-mediated lipolysis and lipid oxidation in adipose tissue, but the mechanisms linking nutrient overload to catecholamine resistance are poorly understood. We report that targeted disruption of TGF-β superfamily receptor ALK7 alleviates diet-induced catecholamine resistance in adipose tissue, thereby reducing obesity in mice. Global and fat-specific Alk7 knock-out enhanced adipose β-AR expression, β-adrenergic signaling, mitochondrial biog  ...[more]

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