While the role of BAT in maintaining body temperature is unambiguous, BATs contribution to body weight regulation is not well understood. Rothwell and Stock (Nature, 1979) showed that overfeeding rodents a high fat diet stimulated BAT, suggesting a role for BAT in limiting weight gain. However, the idea that BAT has this function is far from universally accepted. Progress in FY2014 includes the following: We published the effects of intermittent cold exposure (4 C for one to eight hours three times a week) on C57BL/6J mice fed a high fat diet. Cold exposure increased metabolic rate approximately twofold during the challenge and activated brown fat. In response, food intake increased to compensate fully for the increased energy expenditure;thus, the mice showed no reduction in body weight or adiposity. Despite the unchanged adiposity, the cold-treated mice showed transient improvements in glucose homeostasis. Administration of the cannabinoid receptor-1 inverse agonist AM251 caused weight loss and improvements in glucose homeostasis, but showed no further improvements when combined with cold exposure. These data suggest that intermittent cold exposure causes transient, meaningful improvements in glucose homeostasis, but without synergy when combined with AM251. Since energy expenditure is significantly increased during cold exposure, a drug that dissociates food intake from metabolic demand during cold exposure may achieve weight loss and further metabolic improvements.
