Loss of Stearoyl-CoA Desaturase-1 Attenuates Adipocyte Inflammation

Abstract

Background and Purpose— 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. Methods and 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) α/interleukin 1β 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. This study is the first demonstration of the role of stearoyl-CoA desaturase-1 (SCD1) in obesity-related white adipose tissue (WAT) inflammation. It further explores the function of SCD1 in the paracrine inflammatory regulation of a network containing adipocytes, macrophages, and endothelial cells. Oleate (18:1n9), but not palmitoleate (16:1n7), was shown to be the lipid inflammatory mediator.