Document Detail


Compartmentalization of stearoyl-coenzyme A desaturase 1 activity in HepG2 cells.
MedLine Citation:
PMID:  18599738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the conversion of stearate (18:0) to oleate (18:1n-9) and of palmitate (16:0) to palmitoleate (16:1), which are key steps in triglyceride synthesis in the fatty acid metabolic network. This study investigated the role of SCD1 in fatty acid metabolism in HepG2 cells using SCD1 inhibitors and stable isotope tracers. HepG2 cells were cultured with [U-(13)C]stearate, [U-(13)C]palmitate, or [1,2-(13)C]acetate and (1) DMSO, (2) compound CGX0168 or CGX0290, or (3) trans-10,cis-12 conjugated linoleic acid (CLA). (13)C incorporation into fatty acids was determined by GC-MS and desaturation indices calculated from the respective ion chromatograms. FAS, SCD1, peroxisome proliferator-activated receptor alpha, and peroxisome proliferator-activated receptor gamma mRNA levels were assessed by semiquantitative RT-PCR. The addition of CGX0168 and CGX0290 decreased the stearate and palmitate desaturation indices in HepG2 cells. CLA led to a decrease in the desaturation of stearate only, but not palmitate. Comparison of desaturation indices based on isotope enrichment ratios differed, depending on the origin of saturated fatty acid. SCD1 gene expression was not affected in any group. In conclusion, the differential effects of SCD1 inhibitors and CLA on SCD1 activity combined with the dependence of desaturation indices on the source of saturated fatty acid strongly support the compartmentalization of desaturation systems. The effects of SCD1 inhibition on fatty acid composition in HepG2 cells occurred through changes in the dynamics of the fatty acid metabolic network and not through transcriptional regulatory mechanisms.
Authors:
Jennifer K Yee; Catherine S Mao; Heidi S Hummel; Shu Lim; Sharon Sugano; Virender K Rehan; Gary Xiao; Wai-Nang Paul Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-07-03
Journal Detail:
Title:  Journal of lipid research     Volume:  49     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-09-15     Completed Date:  2008-10-22     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2124-34     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Enzyme Inhibitors / pharmacology
Fatty Acids / chemistry,  metabolism
Gene Expression Regulation, Enzymologic / drug effects
Humans
Isotopes
Linoleic Acids, Conjugated / pharmacology
Lipogenesis / drug effects
Staining and Labeling
Stearoyl-CoA Desaturase / antagonists & inhibitors,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
1P01 AT-003960/AT/NCCAM NIH HHS; 2 K12 HD-034610/HD/NICHD NIH HHS; M01 RR-00425/RR/NCRR NIH HHS; P01 CA-042710/CA/NCI NIH HHS; T32 DK-007571/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Fatty Acids; 0/Isotopes; 0/Linoleic Acids, Conjugated; EC 1.14.19.1/SCD1 protein, human; EC 1.14.19.1/Stearoyl-CoA Desaturase
Comments/Corrections

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