SCD1 inhibition during 3T3-L1 adipocyte differentiation remodels triacylglycerol, diacylglycerol and phospholipid fatty acid composition. (July 2015)

• Record Type: Journal Article
• Authors: Ralston, Jessica C.; Mutch, David M.
• Is Part Of: Prostaglandins, leukotrienes, and essential fatty acids. Volume 98(2015:Jul.)
• Page Start: 29
• Page End: 37
• Publication Date: 2015-07
• Subjects: SCD1 stearoyl-CoA desaturase 1 -- SCD1inhib SCD1 inhibitor -- FA fatty acid -- SFA saturated fatty acid -- MUFA monounsaturated fatty acid -- PUFA polyunsaturated fatty acid -- AT adipose tissue -- PL phospholipid -- TAG triacylglycerol -- DAG diacylglycerol -- CE cholesteryl ester -- FFA free fatty acid -- DMSO dimethyl sulfoxide -- DMEM Dulbecco׳s modified Eagle׳s medium -- IBMX 3-isobutyl-1-methylxanthine -- Dex dexamethasone -- FBS fetal bovine serum -- TLC thin layer chromatography -- Agpat acylglycerol-3-phosphate acyltransferase -- Dgkδ diacylglycerol kinase delta -- GPAT glycerol-3-phosphate acyltransferase -- PA phosphatidic acid -- JNK c-Jun N-terminal kinase -- AKT protein kinase B.; Fatty acids -- Stearoyl-CoA desaturase 1 -- CAY10566 -- Gas chromatography -- Phospholipid -- Triacylglycerol -- Diacylglycerol -- Signalling pathways; Lipids -- Periodicals; Unsaturated fatty acids -- Periodicals; Prostaglandins -- Periodicals; Leukotrienes -- Periodicals; Fatty Acids, Unsaturated -- Periodicals; Acides gras insaturés -- Périodiques; Prostaglandines -- Périodiques; Leucotriènes -- Périodiques; Lipides -- Périodiques; 612.01577
• DOI: 10.1016/j.plefa.2015.04.008
• Languages: English
• ISSNs: 0952-3278

Abstract

Abstract: The conversion of saturated fatty acids (FAs) palmitate (16:0) and stearate (18:0) into monounsaturated FAs palmitoleate (16:1n-7) and oleate (18:1n-9) is catalyzed by stearoyl-CoA desaturase 1 (SCD1). These FAs represent the dominant constituents of adipocyte triacylglycerols (TAGs) and phospholipids (PLs). Given the critical role of SCD1 in lipid metabolism and the notable increase in its expression during adipogenesis, reductions in SCD1 activity have the potential to compromise the adipocyte's ability to accumulate lipid. The current study used thin-layer and gas chromatography to examine the content and FA composition of TAGs, PLs, cholesteryl esters, diacylglycerols and free fatty acids in SCD1-inhibited differentiating 3T3-L1 adipocyte cells. SCD1 inhibition reduced total cellular PL and TAG content concurrent with the down-regulation of genes involved in TAG and PL biosynthesis; however, the relative amount of PL was unaltered. While total DAG levels were increased ~2.7-fold in SCD1-inhibited adipocytes, this did not induce JNK activation; however, phosphorylated (Ser473) AKT was significantly reduced. As expected, total SFA and MUFA content were increased (~1.3-fold) and decreased (~4.0-fold). Further, SCD1 inhibition caused a ~2.2-fold increase and a ~8.3-fold decrease in total cellular 18:0 and 16:1n-7 levels, respectively. Similar changes were also seen in other lipid fractions. The levels of other FAs, including polyunsaturated FAs, were also changed in SCD1-inhibited adipocytes. Together, these results add to the existing body of knowledge regarding SCD1 function in adipocytes and highlight its important role in regulating global adipocyte lipid composition.