Influence of dietary fats on ecstasy-induced hyperthermia

Background and purpose: Studies were designed to examine the effects of dietary fats on metabolic effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy). These effects included hyperthermia, expression of uncoupling protein (UCP1 and 3) in brown adipose tissue or skeletal muscle and plasma free fatty acid (FFA) levels. Experimental approach: Male Sprague-Dawley rats were fed either a high-fat diet (HFD, 60% kcal) or a lower fat isocaloric controlled diet (LFD, 10% kcal) for 28 days before MDMA challenge. Key results: No significant differences were observed between LFD and HFD groups in terms of body weight, plasma thyroxine (T4) levels and expression of brown fat UCP1 or skeletal muscle UCP3 protein. HFD significantly raised levels of circulating FFA and potentiated the thermogenesis induced by MDMA (10 mg kg−1, s.c.), compared to the effects of the LFD. Moreover, 30 and 60 min after MDMA administration, plasma FFA levels decreased in HFD animals, but were markedly elevated in the LFD group. Conclusions and implications: These results indicate that high-fat feeding regulates MDMA-induced thermogenesis by augmenting the activation of UCP rather than its expression. British Journal of Pharmacology (2007) 151, 1103–1108; doi:10.1038/sj.bjp.0707312