A stress signaling pathway in adipose tissue regulates hepatic insulin resistance.

Abstract	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.
Authors	Guadalupe Sabio, Madhumita Das, Alfonso Mora, Zhiyou Zhang, John Y Jun, Hwi Jin Ko, Tamera Barrett, Jason K Kim, Roger J Davis
Journal	Science (New York, N.Y.) (Science) Vol. 322 Issue 5907 Pg. 1539-43 (Dec 05 2008) ISSN: 1095-9203 [Electronic] United States
PMID	19056984 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Dietary Fats Insulin Insulin Receptor Substrate Proteins Interleukin-6 Irs1 protein, mouse Socs3 protein, mouse Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins Proto-Oncogene Proteins c-akt Mitogen-Activated Protein Kinase 8 Glucose
Topics	Adipocytes (enzymology, metabolism) Adipose Tissue (enzymology, metabolism) Animals Dietary Fats (administration & dosage) Enzyme Activation Glucose (metabolism) Insulin (metabolism) Insulin Receptor Substrate Proteins (metabolism) Insulin Resistance Interleukin-6 (administration & dosage, metabolism) Liver (metabolism) MAP Kinase Signaling System Mice Mitogen-Activated Protein Kinase 8 (deficiency, genetics, metabolism) Phosphorylation Proto-Oncogene Proteins c-akt (metabolism) Signal Transduction Stress, Physiological Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!