Hepatic Glucokinase Modulates Obesity Predisposition by Regulating BAT Thermogenesis via Neural Signals

作者：Tsukita Sohei; Yamada Tetsuya^*; Uno Kenji; Takahashi Kei; Kaneko Keizo; Ishigaki Yasushi; Imai Junta; Hasegawa Yutaka; Sawada Shojiro; Ishihara Hisamitsu; Oka Yoshitomo; Katagiri Hideki

来源：Cell Metabolism, 2012, 16(6): 825-832.

DOI：10.1016/j.cmet.2012.11.006

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 knock-down in obesity-prone mice attenuated weight gain with increased adaptive thermogenesis. Thus, this intertissue energy-saving system may contribute to determining obesity predisposition.

• 出版日期2012-12-5