title: Inhibition of stearoyl-CoA desaturase-1 in differentiating 3T3-L1 preadipocytes upregulates elongase 6 and downregulates genes affecting triacylglycerol synthesis.
abstract: BACKGROUND
  Stearoyl-CoA desaturase-1 (SCD1) is rate limiting for the conversion of saturated fatty acids palmitate (16:0) and stearate (18:0) to monounsaturated fatty acids palmitoleate (16:1n7) and oleate (18:1n9), respectively. Given that reduced SCD1 activity is associated with improved insulin sensitivity and decreased body weight, there is considerable interest to elucidate the role of this enzyme in adipocytes. During adipogenesis, SCD1 levels increase concomitantly with the accumulation of triacylglycerol (TG); however, the extent to which reduced SCD1 activity can influence TG synthesis and metabolic pathways in differentiating adipocytes remains relatively unexplored.
  
  
  OBJECTIVE
  The aim of this work was to delineate how reduced SCD1 activity affects gene expression, protein content and cellular fatty acids in differentiating murine preadipocytes.
  
  
  METHODS
  3T3-L1 preadipocytes were treated with an SCD1 inhibitor (10 nM) throughout differentiation. After 7 days, global gene expression, protein content and fatty acid profiles were examined using microarrays, western blotting and gas chromatography, respectively.
  
  
  RESULTS
  SCD1 inhibition increased the abundance of 16:0 and 18:0 (45% and 194%, respectively) and decreased 16:1n7 and 18:1n7 (61% and 35%, respectively) in differentiated preadipocytes. Interestingly, 18:1n9 levels increased by 61%. The augmented 18:0 suggested a possible increase in elongase activity. Elongase 6 (Elovl6) gene expression was increased 2.8-fold (P = 0.04); however, changes were not detected for ELOVL6 protein content. Microarray analysis revealed that genes affecting TG synthesis were downregulated with SCD1 inhibition, which coincided with a 33% decrease in cellular TG content.
  
  
  CONCLUSIONS
  These results provide new mechanistic insight into the role of SCD1 as a regulator of fatty acid profiles and TG synthesis in adipocytes, and reinforce that modulating SCD1 activity may help reduce the risk of obesity-related complications.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Ralston
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Badoud
authors.affiliation: Department of Mathematics and Statistics, University of Guelph, Guelph, ON, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Cattrysse
authors.affiliation: Department of Mathematics and Statistics, University of Guelph, Guelph, ON, Canada.
authors.forename: P D
authors.initials: PD
authors.lastname: McNicholas
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: D M
authors.initials: DM
authors.lastname: Mutch
mesh_terms: D041721:3T3-L1 Cells / Q000201:enzymology*; D000123:Acetyltransferases / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D002849:Chromatography, Gas; D015536:Down-Regulation; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D046888:Tissue Array Analysis; D014280:Triglycerides / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: C000630968:Elovl6 protein, mouse; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D014280:Triglycerides; C008757:palmitoleic acid; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases