Progress in FY2015 includes the following: We studied chronic BAT stimulation with CL316243, a beta3-adrenergic agonist in mice at thermoneutrality (30C) and at a typical vivarium temperature (22C). Vehicle-treated control mice at 30C, compared to 22C, had reduced food intake, metabolic rate, and brown adipose activity, as well as increased adiposity due to the minimal need for adaptive thermogenesis at 30C. At both temperatures, CL316243 treatment increased brown adipose activation and energy expenditure and improved glucose tolerance. At 30C, CL316243 increased energy expenditure disproportionately to changes in food intake, thus reducing adiposity, while at 22C these changes were matched, yielding unchanged adiposity. We conclude that beta3-adrenergic agonist treatment can have beneficial metabolic effects in the absence of adiposity changes.
