A stress signaling pathway in adipose tissue regulates hepatic insulin resistance
Program in Molecular Medicine
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
A high-fat diet causes activation of the regulatory protein c-Jun NH2-terminal kinase 1 (JNK1) and triggers development of insulin resistance. JNK1 is therefore a potential target for therapeutic treatment of metabolic syndrome. We explored the mechanism of JNK1 signaling by engineering mice in which the Jnk1 gene was ablated selectively in adipose tissue. JNK1 deficiency in adipose tissue suppressed high-fat diet-induced insulin resistance in the liver. JNK1-dependent secretion of the inflammatory cytokine interleukin-6 by adipose tissue caused increased expression of liver SOCS3, a protein that induces hepatic insulin resistance. Thus, JNK1 activation in adipose tissue can cause insulin resistance in the liver.
DOI of Published Version
Science. 2008 Dec 5;322(5907):1539-43. Link to article on publisher's site
Science (New York, N.Y.)
Sabio, Guadalupe; Das, Madhumita; Mora, Alfonso; Zhang, Zhiyou; Jun, John Y.; Ko, Hwi Jin; Barrett, Tamera; Kim, Jason K.; and Davis, Roger J., "A stress signaling pathway in adipose tissue regulates hepatic insulin resistance" (2008). Open Access Articles. 2023.