title: SCD1 inhibition during 3T3-L1 adipocyte differentiation remodels triacylglycerol, diacylglycerol and phospholipid fatty acid composition.
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.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Electronic address: jralston@uoguelph.ca.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Ralston
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1. Electronic address: dmutch@uoguelph.ca.
authors.forename: David M
authors.initials: DM
authors.lastname: Mutch
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004075:Diglycerides / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005989:Glycerides / Q000096:biosynthesis*; D051379:Mice; D010743:Phospholipids / Q000096:biosynthesis*; D015398:Signal Transduction / Q000187:drug effects; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors*; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D004075:Diglycerides; D004791:Enzyme Inhibitors; D005989:Glycerides; D010743:Phospholipids; D014280:Triglycerides; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase
keywords: CAY10566; Diacylglycerol; Fatty acids; Gas chromatography; Phospholipid; Signalling pathways; Stearoyl-CoA desaturase 1; Triacylglycerol