Please use this identifier to cite or link to this item: https://doi.org/10.7554/eLife.03245
Title: Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity
Authors: Guo, T 
Marmol, P
Moliner, A 
Bj”rnholm, M
Zhang, C 
Shokat, K.M
Ibanez, C.F 
Keywords: 1-tert-butyl-3-naphthalen-1-ylmethyl-1H-pyrazolo(3,4-d)pyrimidin-4-ylemine
activin receptor 1
Acvr1c protein, mouse
adenosine triphosphate
beta adrenergic receptor
catecholamine
fat intake
pyrazole derivative
pyrimidine derivative
transforming growth factor beta
adipocyte
adipose tissue
adverse effects
animal
antagonists and inhibitors
deficiency
drug effects
fat intake
gene expression regulation
genetics
human
knockout mouse
lipid diet
lipid peroxidation
lipolysis
metabolism
mitochondrial dynamics
mouse
obesity
pathology
primary cell culture
signal transduction
Activin Receptors, Type I
Adenosine Triphosphate
Adipocytes
Adipose Tissue
Animals
Catecholamines
Diet, High-Fat
Dietary Fats
Gene Expression Regulation
Humans
Lipid Peroxidation
Lipolysis
Mice
Mice, Knockout
Mitochondrial Turnover
Obesity
Primary Cell Culture
Pyrazoles
Pyrimidines
Receptors, Adrenergic, beta
Signal Transduction
Transforming Growth Factor beta
Issue Date: 2014
Citation: Guo, T, Marmol, P, Moliner, A, Bj”rnholm, M, Zhang, C, Shokat, K.M, Ibanez, C.F (2014). Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity. eLife 3 : e03245. ScholarBank@NUS Repository. https://doi.org/10.7554/eLife.03245
Abstract: 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 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 β-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 β-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. Copyright © 2014, Guo et al.
Source Title: eLife
URI: https://scholarbank.nus.edu.sg/handle/10635/176018
ISSN: 2050-084X
DOI: 10.7554/eLife.03245
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