title: Stearoyl-CoA desaturase enzyme 1 inhibition reduces glucose utilization for de novo fatty acid synthesis and cell proliferation in 3T3-L1 adipocytes.
abstract: Stearoyl-CoA desaturase enzyme 1 (SCD1) is a lipogenic enzyme that is upregulated in obesity, insulin resistance, and cancer. Since glucose is a substrate for both de novo fatty acid synthesis and deoxyribose synthesis, we hypothesized that SCD1 affects these multiple synthetic pathways through changes in glucose utilization. This study determined glucose utilization for fatty acid synthesis and cell proliferation in 3T3-L1 preadipocytes during SCD1 inhibition. The effects of SCD1 on cellular metabolism as mediated by its monounstaurated fatty acid products (palmitoleate and oleate) were also observed. 3T3-L1 preadipocytes underwent differentiation induction in conjunction with one of the following treatments for 4 days: (A) no treatment, (B) SCD1 inhibitor CGX0290, (C) CGX0290 + palmitoleate, or (D) CGX0290 + oleate. All cells received medium with 50 % [U13C]-glucose. Cells were harvested on day 7 for studies of fatty acid metabolism, tricarboxylic acid (TCA) cycle activities, and deoxyribose synthesis. CGX0290 decreased fatty acid desaturation, glucose utilization for fatty acid synthesis (acetyl-CoA enrichment), and de novo synthesis. CGX0290 treatment also led to decreased cell density through increased cell death. Further analysis showed that deoxyribose new synthesis and oxidative pentose phosphate pathway activity were unchanged, while non-oxidative transketolase pathway activity was stimulated. Palmitoleate and oleate supplementation each partially ameliorated the effects of CGX0290. In 3T3-L1 cells, SCD1 promotes glucose utilization for fatty acid synthesis. In cell proliferation, SCD1 may promote cell survival, but does not impact the oxidative pathway of deoxyribose production. These effects may be mediated through the production of palmitoleate and oleate.
authors.affiliation: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Walter Martin Research Building, Torrance, CA 90502, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Yee
authors.forename: Paulin N
authors.initials: PN
authors.lastname: Wahjudi
authors.forename: Juan
authors.initials: J
authors.lastname: Vega
authors.forename: Shu
authors.initials: S
authors.lastname: Lim
authors.forename: Ashley
authors.initials: A
authors.lastname: Martin
authors.forename: Mary E
authors.initials: ME
authors.lastname: Patterson
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Cohen
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Mao
authors.forename: Wai-Nang P
authors.initials: WN
authors.lastname: Lee
keywords: Cell proliferation; Glucose utilization; Lipogenesis; Pentose phosphate pathway; Stable isotopes; Stearoyl-CoA desaturase enzyme 1
references.citation: PLoS One. 2010 Jun 30;5(6):e11394
references.pmid: 20613975
references.citation: Annu Rev Biochem. 2012;81:715-36
references.pmid: 22463691
references.citation: J Biol Chem. 2008 Feb 1;283(5):2906-16
references.pmid: 18032385
references.citation: Biol Mass Spectrom. 1992 Feb;21(2):114-22
references.pmid: 1606182
references.citation: PLoS One. 2009 Aug 27;4(8):e6812
references.pmid: 19710915
references.citation: Am J Clin Nutr. 2005 Oct;82(4):747-50
references.pmid: 16210702
references.citation: Biol Mass Spectrom. 1991 Aug;20(8):451-8
references.pmid: 1768701
references.citation: Anal Biochem. 2001 Nov 15;298(2):189-95
references.pmid: 11700973
references.citation: Anal Biochem. 1987 Apr;162(1):156-9
references.pmid: 2440339
references.citation: J Biol Chem. 1989 Sep 5;264(25):14755-61
references.pmid: 2570068
references.citation: J Lipid Res. 2008 Oct;49(10):2124-34
references.pmid: 18599738
references.citation: J Lipid Res. 2000 Aug;41(8):1310-6
references.pmid: 10946019
references.citation: Dev Neurosci. 1996;18(5-6):469-77
references.pmid: 8940620
references.citation: Nutr Metab Cardiovasc Dis. 2006 Mar;16(2):128-36
references.pmid: 16487913
references.citation: Biochem Biophys Res Commun. 2010 Sep 3;399(4):480-6
references.pmid: 20655875
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11482-6
references.pmid: 12177411
references.citation: Curr Opin Lipidol. 2010 Jun;21(3):192-7
references.pmid: 20216310
references.citation: Anal Chem. 1998 May 1;70(9):1664-9
references.pmid: 9599574
references.citation: Int J Oncol. 2008 Oct;33(4):839-50
references.pmid: 18813799
references.citation: Arterioscler Thromb Vasc Biol. 2009 Mar;29(3):341-7
references.pmid: 19095997
references.citation: Methods Enzymol. 1975;35:279-87
references.pmid: 1121283
references.citation: Mol Cancer Ther. 2010 Jun;9(6):1740-54
references.pmid: 20530718
references.citation: Nutr Metab (Lond). 2009 Jun 11;6:27
references.pmid: 19519902
references.citation: Carcinogenesis. 2010 Sep;31(9):1509-15
references.pmid: 20595235
references.citation: J Biol Chem. 2010 Feb 26;285(9):6044-52
references.pmid: 20032470