Loss of Oncostatin M Signaling in Adipocytes Induces Insulin Resistance and Adipose Tissue Inflammation in Vivo.
Oncostatin M (OSM) is a multifunctional gp130 cytokine. Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor β (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. In vivo, we generated a mouse line lacking Osmr in adiponectin-expressing cells (OSMR(FKO) mice). The effects of OSM on gene expression were also assessed in vitro and in vivo OSM exerts proinflammatory effects on cultured adipocytes that are partially rescued by Osmr knockdown. Osm expression is significantly increased in adipose tissue T cells of high fat-fed mice. In addition, adipocyte Osmr expression is increased following high fat feeding. OSMR(FKO) mice exhibit increased insulin resistance and adipose tissue inflammation and have increased lean mass, femoral length, and bone volume. Also, OSMR(FKO) mice exhibit increased expression of Osm, the T cell markers Cd4 and Cd8, and the macrophage markers F4/80 and Cd11c Interestingly, the same proinflammatory genes induced by OSM in adipocytes are induced in the adipose tissue of the OSMR(FKO) mouse, suggesting that increased expression of proinflammatory genes in adipose tissue arises both from adipocytes and other cell types. These findings suggest that adipocyte OSMR signaling is involved in the regulation of adipose tissue homeostasis and that, in obesity, OSMR ablation may exacerbate insulin resistance by promoting adipose tissue inflammation.
From the Matrix Biology Laboratory.
Carrie M
0000-0001-8521-7046
CM
Elks
Department of Medicine, University of California, San Diego, California 92093.
Peng
P
Zhao
Department of Nutrition Science, Purdue University, West Lafayette, Indiana 47907.
Ryan W
RW
Grant
Adipocyte Biology Laboratory.
Hardy
H
Hang
From the Matrix Biology Laboratory.
Jennifer L
JL
Bailey
Cell Biology and Bioimaging Core, and.
David H
DH
Burk
Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana 70803, and.
Margaret A
MA
McNulty
Transgenics Core, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808.
Randall L
0000-0003-4399-0019
RL
Mynatt
Adipocyte Biology Laboratory, Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana 70803 jsteph1@lsu.edu.
Jacqueline M
0000-0002-3796-9531
JM
Stephens
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D016827:CD8 Antigens / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D055785:Gene Knockdown Techniques; D007333:Insulin Resistance; D051379:Mice; D008817:Mice, Mutant Strains; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism*; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D015434:Panniculitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
D039521:CD11c Antigen; D015704:CD4 Antigens; D016827:CD8 Antigens; D053681:Oncostatin M Receptor beta Subunit; C508352:Osm protein, mouse; C508349:Osmr protein, mouse; D053683:Oncostatin M
STATs; adipocyte; adipose tissue; inflammation; insulin resistance; obesity; oncostatin M