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Obesity results from a caloric imbalance between energy intake, absorption and expenditure. In both rodents and humans, diet-induced thermogenesis contributes to energy expenditure and involves the activation of brown adipose tissue (BAT). We hypothesize that environmental toxicants commonly used as food additives or pesticides might reduce BAT thermogenesis through suppression of uncoupling protein 1 (UCP1) and this may contribute to the development of obesity. Using a step-wise screening approach, we discover that the organophosphate insecticide chlorpyrifos suppresses UCP1 and mitochondrial respiration in BAT at concentrations as low as 1 pM. In mice housed at thermoneutrality and fed a high-fat diet, chlorpyrifos impairs BAT mitochondrial function and diet-induced thermogenesis, promoting greater obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This is associated with reductions in cAMP; activation of p38MAPK and AMPK; protein kinases critical for maintaining UCP1 and mitophagy, respectively in BAT. These data indicate that the commonly used pesticide chlorpyrifos, suppresses diet-induced thermogenesis and the activation of BAT, suggesting its use may contribute to the obesity epidemic. Chlorpyrifos is a widely-used pesticide and a common residue on vegetables and fruits. Here the authors show that at non-neurotoxic doses, chlorpyrifos reduces energy expenditure, by inhibiting diet induced thermogenesis, and promotes obesity and insulin resistance. [ABSTRACT FROM AUTHOR]

Obesity is a leading cause of morbidity, mortality and health care expenditure whose incidence is rapidly rising across the globe. Although the cause of the obesity epidemic is typically viewed as a product of an increased availability of high calorie foods and/or a reduction in physical activity, there is mounting evidence that exposure to synthetic chemicals in our environment may play an important role. Pesticides, are a class of chemicals whose widespread use has coincided with the global rise of obesity over the past two decades. Importantly, given their lipophilic nature many pesticides have been shown to accumulate with adipose tissue depots, suggesting they may be disrupting the function of white adipose tissue (WAT), brown adipose tissue (BAT) and beige adipose tissue to promote obesity and metabolic diseases such as type 2 diabetes. In this review, we discuss epidemiological evidence linking pesticide exposure with body mass index (BMI) and the incidence of diabetes. We then review preclinical studies in rodent models which have directly evaluated the effects of different classes of insecticides and herbicides on obesity and metabolic dysfunction. Lastly, we review studies conducted in adipose tissue cells lines and the purported mechanisms by which pesticides may induce alterations in adipose tissue function. The review of the literature reveals major gaps in our knowledge regarding human exposure to pesticides and our understanding of whether physiologically relevant concentrations promote obesity and elicit alterations in key signaling pathways vital for maintaining adipose tissue metabolism. [ABSTRACT FROM AUTHOR]

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]