Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals

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

研究成果: Article査読

65 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)825-832
ページ数8
ジャーナルCell Metabolism
16
6
DOI
出版ステータスPublished - 2012 12 5

ASJC Scopus subject areas

  • 生理学
  • 分子生物学
  • 細胞生物学

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