Loss of Stearoyl-CoA desaturase-1 attenuates adipocyte inflammation: effects of adipocyte-derived oleate.
OBJECTIVE
Adipose inflammation is crucial to the pathogenesis of metabolic disorders. This study aimed at identify the effects of stearoyl-CoA desaturase-1 (SCD1) on the inflammatory response of a paracrine network involving adipocytes, macrophages, and endothelial cells.


RESULTS
Loss of SCD1 in both genetic (Agouti) and diet-induced obesity (high-fat diet) mouse models prevented inflammation in white adipose tissue and improved its basal insulin signaling. In SCD1-deficient mice, white adipose tissue exhibited lower inflammation, with a reduced response to lipopolysaccharide in isolated adipocytes, but not in peritoneal macrophages. Mimicking the in vivo paracrine regulation of white adipose tissue inflammation, SCD1-deficient adipocyte-conditioned medium attenuated the induction of tumor necrosis factor (TNF) alpha/interleukin 1beta gene expression in RAW264.7 macrophages and reduced the adhesion response in endothelial cells. We further demonstrated that the adipocyte-derived oleate (18:1n9), but not palmitoleate (16:1n7), mediated the inflammation in macrophages and adhesion responses in endothelial cells.


CONCLUSIONS
Loss of SCD1 attenuates adipocyte inflammation and its paracrine regulation of inflammation in macrophages and endothelial cells. The reduced oleate level is linked to the inflammation-modulating effects of SCD1 deficiency.
Liu
Xueqing
X
Department of Biochemistry, University of Wisconsin, Madison, 433 Babcock Dr, Madison, WI 53706, USA.
Miyazaki
Makoto
M
Flowers
Matthew T
MT
Sampath
Harini
H
Zhao
Minghui
M
Chu
Kiki
K
Paton
Chad M
CM
Joo
Diane Seohee
DS
Ntambi
James M
JM
D052438:Adipocytes, White / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D005229:Fatty Acids, Monounsaturated / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000276:immunology; D019301:Oleic Acid / Q000276:immunology* / Q000378:metabolism; D019899:Paracrine Communication / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology
D017077:Culture Media, Conditioned; D005229:Fatty Acids, Monounsaturated; C008757:palmitoleic acid; D019301:Oleic Acid; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase