Chronic Arsenic Exposure Impairs Adaptive Thermogenesis in Male C57BL/6J Mice
Castriota, Felicia (2019), Chronic Arsenic Exposure Impairs Adaptive Thermogenesis in Male C57BL/6J Mice, Dryad, Dataset, https://doi.org/10.6078/D1V10C
The global prevalence of type 2 diabetes (T2D) has doubled since 1980. Human epidemiological studies support arsenic exposure as a risk factor for T2D, although the precise mechanism is unclear. We hypothesized that chronic arsenic ingestion alters glucose homeostasis by impairing adaptive thermogenesis, i.e. body heat production in cold environments. Arsenic is a pervasive environmental contaminant, with more than 200 million people worldwide currently exposed to arsenic-contaminated drinking water. Male C57BL/6J mice exposed to sodium arsenite in drinking water at 300 parts per billion (ppb) for 9 weeks experienced significantly decreased metabolic heat production when acclimated to chronic cold tolerance testing, as evidenced by indirect calorimetry, despite no change in physical activity. Arsenic exposure increased total fat mass, and unilocular lipid droplet size in both subcutaneous inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT). This hypertrophy appeared to be specific to BAT and WAT, as no lipidosis was observed in liver. RNA sequencing analysis of iWAT indicated that arsenic dysregulated mitochondrial processes, including fatty acid metabolism. Western blotting confirmed that arsenic significantly decreased TOMM20 in both BAT and WAT, a correlate of mitochondrial abundance; PGC1A, a master regulator of mitochondrial biogenesis; and, CPT1B,the rate limiting step of fatty acid oxidation (FAO). Our findings show that chronic arsenic exposure impacts the mitochondria of thermogenic tissues involved in energy expenditure and glucose regulation, providing novel mechanistic evidence for arsenic’s role in T2D development.