Effects of the pesticide deltamethrin on high fat diet-induced obesity and insulin resistance in male mice.

Worldwide, rates of metabolic diseases are rapidly increasing and environmental exposure to pesticides, pollutants and/or other chemicals may play a role. Reductions in Brown Adipose Tissue (BAT) thermogenesis, mediated in part by uncoupling protein 1 (Ucp1), are associated with metabolic diseases. In the current study, we investigated whether the pesticide deltamethrin (0.01–1 mg/kg bw/day) incorporated into a high-fat diet and fed to mice housed at either room temperature (21°C) or thermoneutrality (29°C) would suppress BAT activity and accelerate the development of metabolic disease. Importantly, thermoneutrality allows for more accurate modeling of human metabolic disease. We found that, 0.01 mg/kg bw/day of deltamethrin induced weight loss, improved insulin sensitivity and increased energy expenditure, effects that were associated with increases in physical activity. In contrast, exposure to 0.1 and 1 mg/kg bw/day deltamethrin had no effect on any of the parameters examined. Deltamethrin treatment in mice did not alter molecular markers of BAT thermogenesis, despite observing suppression of UCP1 expression in cultured brown adipocytes. These data indicate that while deltamethrin inhibits UCP1 expression in vitro, 16wks exposure does not alter BAT thermogenesis markers nor exacerbates the development of obesity and insulin resistance in mice. • Thermoneutral housing of mice lowers basal metabolic rate and may reduce the threshold for chemicals to induce toxicity. • Deltamethrin is a widely used pyrethroid pesticide used in crop protection and mosquito control.. • Deltamethrin reduces uncoupling protein 1 and thermogenic capacity in cultured brown adipocytes. • Exposure of mice to 0.1 or 1 mg/kg bw/day deltamethrin mixed with a high-fat diet does not promote obesity or insulin resistance. • Surprisingly, exposure to 0.01 mg/kg bw/day deltamethrin increased physical activity and reduced adiposity. [ABSTRACT FROM AUTHOR]