Prolonged inorganic arsenic exposure via drinking water impairs brown adipose tissue function in mice

Although epidemiologic studies show an association between long-term environmental inorganic arsenic (iAs) exposure and various disorders of glucose and lipid metabolism, the mechanisms of these ailments remain unclear. While white adipose tissue (WAT) essentially acts as a storage tissue for energy and is key to energy homeostasis, brown adipose tissue (BAT) consumes excess energy via uncoupling protein 1-mediated non-shivering thermogenesis in mitochondria and helps maintain the steady state of glucose and lipid metabolism. Our previous in vitro work found that iAs may inhibit adipogenesis and glucose uptake in adipocytes, leading us to hypothesize that chronic exposure to iAs in vivo may also affect the development and function of BAT, which plays a part in iAs-induced metabolic disorders. Thus, adult C57BL/6J female mice were provided drinking water containing 5 or 20 ppm of inorganic arsenicals (iAs³⁺ and iAs⁵⁺) for 17 weeks and control mice were given unaltered water. In these mice, iAs exposure induced cold intolerance and lipid accretion in BAT. In addition, iAs exposure impaired expression of various genes related to thermogenesis, mitochondrial function, adipocyte differentiation, as well as lipolysis in BAT of the exposed mice. These findings suggest a novel toxicity of iAs in BAT occurring via induction of BAT malfunction and impairment of thermogenesis. This novel toxicological linkage helps explain the mechanisms linking iAs exposure to increased risk of disorders of glucose and lipid metabolism.