Document Detail


Hepatic Glucokinase Modulates Obesity Predisposition by Regulating BAT Thermogenesis via Neural Signals.
MedLine Citation:
PMID:  23217261     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Sohei Tsukita; Tetsuya Yamada; Kenji Uno; Kei Takahashi; Keizo Kaneko; Yasushi Ishigaki; Junta Imai; Yutaka Hasegawa; Shojiro Sawada; Hisamitsu Ishihara; Yoshitomo Oka; Hideki Katagiri
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell metabolism     Volume:  16     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  825-32     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Department of Metabolic Diseases, Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan; Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Tyk2 and Stat3 regulate brown adipose tissue differentiation and obesity.
Next Document:  Circadian oscillations of protein-coding and regulatory RNAs in a highly dynamic mammalian liver epi...