| Hepatocyte-specific deletion of Janus kinase 2 (JAK2) protects against diet-induced steatohepatitis and glucose intolerance. | |
| | |
MedLine Citation:
|
PMID: 22275361 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease and is now considered to be the hepatic manifestation of the metabolic syndrome. However, the role of steatosis per se and the precise factors required in the progression to steatohepatitis or insulin resistance remain elusive. The JAK-STAT pathway is critical in mediating signaling of a wide variety of cytokines and growth factors. Mice with hepatocyte-specific deletion of Janus kinase 2 (L-JAK2 KO mice) develop spontaneous steatosis as early as two weeks of age. In this study, we investigated the metabolic consequences of jak2 deletion in response to diet-induced metabolic stress. To our surprise, despite the profound hepatosteatosis, deletion of hepatic jak2 did not sensitize the liver to accelerated inflammatory injury on a prolonged high fat diet (HFD). This was accompanied by complete protection against HFD-induced whole-body insulin resistance and glucose intolerance. Improved glucose-stimulated insulin secretion and an increase in β-cell mass were also present in these mice. Moreover, L-JAK2 KO mice had progressively reduced adiposity in association with blunted hepatic growth hormone signaling. These mice also exhibited increased resting energy expenditure on both chow and high fat diet. In conclusion, our findings indicate a key role of hepatic JAK2 in metabolism such that its absence completely arrests steatohepatitis development and confers protection against diet-induced systemic insulin resistance and glucose intolerance. |
| | |
Authors:
|
Sally Yu Shi; Ruben Garcia Martin; Robin E Duncan; Diana Choi; Shun-Yan Lu; Stephanie A Schroer; Erica P Cai; Cynthia T Luk; Kathryn E Hopperton; Anthony F Domenichiello; Christine Tang; Mark Naples; Mark J Dekker; Adria Giacca; Khosrow Adeli; Kay-Uwe Wagner; Richard P Bazinet; Minna Woo |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-1-24 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
|
Created Date: 2012-1-25 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of Toronto, Canada; |
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: Picomolar concentrations of free zinc(II) ions regulate receptor protein tyrosine phosphatase beta a...
Next Document: C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemi...