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Troglitazone Downregulates -6 Desaturase Gene Expression in Human Skeletal Muscle Cell Cultures

From the Department of Endocrinology and Metabolism, University of Tübingen, Tübingen, Germany

-6 Desaturase, one of the rate-limiting enzymes, catalyzes the conversion of linoleic acid (C18:2 6) into -linolenic acid (C18:3 6), arachidonic acid (C20:4 6), and further metabolites. Recently, it has been shown that human -6 desaturase is expressed not only in liver but in a variety of human tissues, including muscle. Skeletal muscle is a major site of insulin action, and insulin sensitivity may be related to the fatty acid composition of muscle lipids. We examined the effects of troglitazone on the regulation of -6 desaturase gene expression in human muscle cell cultures obtained from muscle biopsies (n = 15). -6 Desaturase mRNA and peroxisome proliferator–activated receptor 2 (PPAR2) mRNA were quantified by two-step RT-PCR, and the activity of the -6 desaturase enzyme was estimated by gas chromatographic analysis of the 6-C18:3/C18:2 fatty acids ratio. In cells treated with 11.5 µmol troglitazone for 4 days, PPAR2 mRNA levels were significantly increased (301.0 ± 51.5%, P < 0.05) and -6 desaturase mRNA levels were significantly decreased (41.7 ± 5.9%, P < 0.0005) compared with the untreated controls. In accordance with the decrease of -6 desaturase mRNA, there was a significant decrease in the 6-C18:3/C18:2 ratio down to 47.4 ± 7.5% in cholesterol esters, 54.2 ± 7.4% in phospholipids, 56.7 ± 6.5% in nonesterified fatty acids, and 67.7 ± 5.9% in triglycerides. The troglitazone-induced decrease in -6 desaturase mRNA is associated with a change in the unsaturated fatty acid composition of the muscle cells. These results add new aspects to the known thiazolidinedione effects on lipid metabolism.

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