A stress signaling pathway in adipose tissue regulates hepatic insulin resistance.
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.
Sabio
Guadalupe
G
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Das
Madhumita
M
Mora
Alfonso
A
Zhang
Zhiyou
Z
Jun
John Y
JY
Ko
Hwi Jin
HJ
Barrett
Tamera
T
Kim
Jason K
JK
Davis
Roger J
RJ
D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000008:administration & dosage / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D048055:Mitogen-Activated Protein Kinase 8 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
D004041:Dietary Fats; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; C526295:Irs1 protein, mouse; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051057:Proto-Oncogene Proteins c-akt; D048055:Mitogen-Activated Protein Kinase 8; D005947:Glucose