Oncostatin M decreases adiponectin expression and induces dedifferentiation of adipocytes by JAK3- and MEK-dependent pathways.
Adiponectin, an adipokine secreted from adipocytes, plays a crucial role in the regulation of glucose and lipid metabolism. In the present study, we examine the role of the IL-6 family of cytokines in the expression of adiponectin in human adipocytes derived from human adipose tissue-derived stromal cells. Oncostatin M (OSM), but not IL-6, attenuated the expression level of adiponectin dose- and time-dependently, and the inhibitory effect of OSM on adiponectin expression was as potent as that of TNF-alpha. The OSM-induced down-regulation of adiponectin expression was correlated with the down-regulation of PPARgamma2 and lipoprotein lipase, markers for adipogenic differentiation, and depletion of intracellular lipid droplets, suggesting dedifferentiation of adipocytes in response to OSM. OSM induced phosphorylation of STAT1, and treatment of adipocytes with JAK3 inhibitor WHI-P131 or MEK inhibitor U0126, but not with JAK2 inhibitor AG490, prevented the activation of STAT1. Furthermore, the OSM-induced suppression of adiponectin expression and dedifferentiation of adipocytes were ameliorated by WHI-P131 or U0126, but not by AG490. These results suggest that OSM inhibits adiponectin expression by inducing dedifferentiation of adipocytes through signaling pathways involving JAK3 and MEK, but not JAK2.
Song
Hae Young
HY
Medical Research Center for Ischemic Tissue Regeneration & Medical Research Institute, Pusan National University, Busan 602-739, Republic of Korea.
Kim
Mi Ra
MR
Lee
Mi Jeong
MJ
Jeon
Eun Su
ES
Bae
Yong Chan
YC
Jung
Jin Sup
JS
Kim
Jae Ho
JH
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics*; D002454:Cell Differentiation; D015536:Down-Regulation; D006801:Humans; D053616:Janus Kinase 3 / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D053683:Oncostatin M / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D052242:Adiponectin; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D020930:MAP Kinase Kinase Kinases