Troglitazone downregulates delta-6 desaturase gene expression in human skeletal muscle cell cultures

Diabetes
Hans Günther WahlHans-Ulrich Häring

Abstract

Delta-6 Desaturase, one of the rate-limiting enzymes, catalyzes the conversion of linoleic acid (C18:2 omega6) into gamma-linolenic acid (C18:3 omega6), arachidonic acid (C20:4 omega6), and further metabolites. Recently, it has been shown that human Delta-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 Delta-6 desaturase gene expression in human muscle cell cultures obtained from muscle biopsies (n = 15). Delta-6 Desaturase mRNA and peroxisome proliferator-activated receptor gamma2 (PPARgamma2) mRNA were quantified by two-step RT-PCR, and the activity of the Delta-6 desaturase enzyme was estimated by gas chromatographic analysis of the omega 6-C18:3/C18:2 fatty acids ratio. In cells treated with 11.5 micromol troglitazone for 4 days, PPARgamma2 mRNA levels were significantly increased (301.0 +/- 51.5%, P < 0.05) and Delta-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 Delta-6 de...Continue Reading

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