Fatty Acid Cycling in Human Hepatoma Cells and the Effects of Troglitazone
| Autor: | W.-N. P. Lee, Shu Lim, John Edmond, Sara Bassilian, E. A. Bergner |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Carcinoma
Hepatocellular Biochemistry Gas Chromatography-Mass Spectrometry Troglitazone chemistry.chemical_compound Stearate Mole Tumor Cells Cultured medicine Humans Chromans Molecular Biology chemistry.chemical_classification Fatty Acids Liver Neoplasms food and beverages Fatty acid Cell Biology Peroxisome Thiazoles chemistry Lipogenesis Thiazolidinediones lipids (amino acids peptides and proteins) Oxidation-Reduction Saponification Homeostasis medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 273:20929-20934 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.273.33.20929 |
| Popis: | Fatty acid cycling by chain shortening/elongation in the peroxisomes is an important source of fatty acids for membrane lipid synthesis. Its role in the homeostasis of nonessential fatty acids is poorly understood. We report here a study on the cycling of saturated fatty acids and the effects of troglitazone in HepG2 cells in culture using [U-13C]stearate or [U-13C]oleate and mass isotopomer analysis. HepG2 cells were grown in the presence of 0.7 mmol/liter [U-13C]stearate or [U-13C]oleate, and in the presence and absence of 50 microM troglitazone for 72 h. Fatty acids extracted from cell pellets after saponification were analyzed by gas chromatography/mass spectrometry. Peroxisomal beta-oxidation of uniformly 13C-labeled stearate (C18:0) and oleate (C18:1) resulted in chain shortening and produced uniformly labeled palmitate (C16:0) and palmitoleate (C16:1). In untreated cells, 16% of C16:0 was derived from C18:0 and 26% of C16:1 from C18:1 by chain shortening. Such contributions were significantly increased by troglitazone to 23.6 and 36.6%, respectively (p < 0.001). Desaturation of stearate contributed 67% of the oleate, while reduction of oleate contributed little to stearate (2%). The desaturation of C18:0 to C18:1 was not affected by troglitazone. Our results demonstrated a high degree of recycling of C18:0 and C18:1 to C16:0 and C16:1 through chain shortening and desaturation. Chain shortening was accompanied by chain elongation in the synthesis of other long chain fatty acids. Troglitazone specifically increased recycling by peroxisomal beta-oxidation of C18 to C16 fatty acids, and the interconversion of long chain fatty acids was associated with reduced de novo lipogenesis. |
| Databáze: | OpenAIRE |
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