Compartmentalization of stearoyl-coenzyme A desaturase 1 activity in HepG2 cells*
| Autor: | Shu Lim, Wai-Nang Paul Lee, Virender K. Rehan, Sharon Sugano, Gary Xiao, Catherine S. Mao, Jennifer K. Yee, Heidi S. Hummel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Conjugated linoleic acid
Coenzyme A desaturation index QD415-436 Biology Biochemistry Gene Expression Regulation Enzymologic chemistry.chemical_compound Endocrinology Isotopes Stearate Cell Line Tumor stable isotope Humans Linoleic Acids Conjugated Enzyme Inhibitors HepG2 cells chemistry.chemical_classification Staining and Labeling Fatty acid metabolism Lipogenesis Fatty Acids Fatty acid Cell Biology Peroxisome chemistry fatty acid metabolism Saturated fatty acid lipids (amino acids peptides and proteins) Stearoyl-CoA Desaturase Research Article |
| Zdroj: | Journal of Lipid Research, Vol 49, Iss 10, Pp 2124-2134 (2008) |
| ISSN: | 0022-2275 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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