SCD1 mediates the influence of exogenous saturated and monounsaturated fatty acids in adipocytes: Effects on cellular stress,inflammatory markers and fatty acid elongation

Palmitate (PA), stearate (SA), palmitoleate (PMA) and oleate (OA) are among the most abundant fatty acids (FAs) in adipose tissue (AT). These FAs differentially regulate AT inflammation by altering adipocyte signalling pathways and the secretion of proinflammatory cytokines. Intracellular levels of these FAs are controlled, in part, by stearoyl-CoA desaturase 1 (SCD1). Therefore, SCD1 may have an important role mediating FA-regulation of adipocyte inflammation. Given this, we hypothesized that the influence of PA, SA, PMA and OA on inflammation and cellular stress, as well as FA metabolism, would be exacerbated with reduced SCD1 activity. Real-time RT-PCR, immunoassays, gas chromatography and western blotting were used to examine the expression and secretion of common inflammatory markers, as well as FA profiles and markers of cellular stress, in 3T3-L1 adipocytes. FA treatments differentially affected inflammatory markers and FA profiles in SCD1-inhibited adipocytes. Specifically, SA significantly increased the expression of Ccl5 (5.3-fold) and Mcp-1 (3.2-fold), and the secretion of IL-6 (17.8-fold) and MCP-1 (4.0-fold) in SCD1-inhibited adipocytes compared to controls. The proinflammatory effects observed with SA are particularly notable given that SCD1-inhibited adipocytes increased elongation of PA to SA, as determined using U-¹³C-PA. The effects of PA, PMA and OA were not as substantial as those of SA, although PA did significantly increase Ccl5 (2.7-fold) and Mcp-1 (1.2-fold) expression in SCD1-inhibited adipocytes. None of the FAs altered markers of cellular stress. Collectively, these results emphasize the differential effects of individual FAs and highlight how SCD1 influences their regulation of adipocyte inflammation.