High-fat feeding reduced muscle uncoupling protein 3 expression in rats.

Uncoupling Protein 3 (UCP3), largely expressed in skeletal muscle, is modulated by cold, thyroid hormones, leptin, fasting-refeeding and exercise training among other factors in a tissue-specific manner. In brown adipose tissue, there is an increase in UCP3 levels after high-fat feeding and beta3-adrenergic agonist treatment. Controversial effects of these agents have been reported in skeletal muscle. The aim of this experimental trial was to evaluate the effect of high-fat feeding and beta3-adrenergic agent treatment on skeletal muscle UCP3 expression levels. Lean rats were fed a cafeteria diet for 30 days and found to have significantly higher fat stores and body weight than control rats at the end of the experimental period. When cafeteria-diet rats were daily i.p. injected with Tertatolol for 30 days; a decrease in total fat mass and body weight was found. Such an effect was not observed in fa/fa rats. Interestingly, gastrocnemius muscle UCP3 mRNA levels were significantly reduced in cafeteria-diet rats when compared to lean animals. Likewise, mitochondrial O2 consumption in gastrocnemius muscle was also significantly decreased (-31%) in cafeteria-diet rats as compared to the control group. It is suggested that the down-regulation of UCP3 gene expression together with the lower O2 consumption observed in high fat fed rats may be linked to lower fatty oxidation, which would promote triglyceride accumulation.