Title

Prevention of steatosis by hepatic JNK1

UMMS Affiliation

Program in Molecular Medicine

Date

12-1-2009

Document Type

Article

Medical Subject Headings

Animals; Fatty Liver; Glucose Intolerance; Hepatocytes; Insulin Resistance; Mice; Mice, Transgenic; Mitogen-Activated Protein Kinase 8; Organ Specificity; Signal Transduction

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology

Abstract

Nonalcoholic steatosis (fatty liver) is a major cause of liver dysfunction that is associated with insulin resistance and metabolic syndrome. The cJun NH(2)-terminal kinase 1 (JNK1) signaling pathway is implicated in the pathogenesis of hepatic steatosis and drugs that target JNK1 may be useful for treatment of this disease. Indeed, mice with defects in JNK1 expression in adipose tissue are protected against hepatic steatosis. Here we report that mice with specific ablation of Jnk1 in hepatocytes exhibit glucose intolerance, insulin resistance, and hepatic steatosis. JNK1 therefore serves opposing actions in liver and adipose tissue to both promote and prevent hepatic steatosis. This finding has potential implications for the design of JNK1-selective drugs for the treatment of metabolic syndrome.

Rights and Permissions

Citation: Cell Metab. 2009 Dec;10(6):491-8. doi: 10.1016/j.cmet.2009.09.007. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

19945406