| First Author | Tsukita S | Year | 2012 |
| Journal | Cell Metab | Volume | 16 |
| Issue | 6 | Pages | 825-32 |
| PubMed ID | 23217261 | Mgi Jnum | J:195098 |
| Mgi Id | MGI:5476418 | Doi | 10.1016/j.cmet.2012.11.006 |
| Citation | Tsukita S, et al. (2012) Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals. Cell Metab 16(6):825-32 |
| abstractText | Considering the explosive increase in obesity worldwide, there must be an unknown mechanism(s) promoting energy accumulation under conditions of overnutrition. We identified a feed-forward mechanism favoring energy storage, originating in hepatic glucokinase (GK) upregulation. High-fat feeding induced hepatic GK upregulation, and hepatic GK overexpression dose-dependently decreased adaptive thermogenesis by downregulating thermogenesis-related genes in brown adipose tissue (BAT). This intertissue (liver-to-BAT) system consists of the afferent vagus from the liver and sympathetic efferents from the medulla and antagonizes anti-obesity effects of leptin on thermogenesis. Furthermore, upregulation of endogenous GK in the liver by high-fat feeding was more marked in obesity-prone than in obesity-resistant strains and was inversely associated with BAT thermogenesis. Hepatic GK overexpression in obesity-resistant mice promoted weight gain, while hepatic GK knockdown in obesity-prone mice attenuated weight gain with increased adaptive thermogenesis. Thus, this intertissue energy-saving system may contribute to determining obesity predisposition. |
