| First Author | Guo T | Year | 2014 |
| Journal | Elife | Volume | 3 |
| Pages | e03245 | PubMed ID | 25161195 |
| Mgi Jnum | J:269067 | Mgi Id | MGI:6203852 |
| Doi | 10.7554/eLife.03245 | Citation | Guo T, et al. (2014) Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity. Elife 3:e03245 |
| abstractText | Obesity is associated with blunted beta-adrenoreceptor (beta-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-beta 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 beta-AR expression, beta-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 beta-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 beta-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. |
