Consumption of a high fat diet inhibits sympathetic outflow to brown adipose tissue (BAT) via vagal afferent activation of neurons in the Nucleus Tractus Solitarius (NTS)

The recognition of significant depots of BAT in adult humans, the inverse correlation between active BAT and obesity, and the ability of white adipose to be “converted” to a more “brown-like” phenotype have reinvigorated research in this area. The lack of active BAT in obesity has been interpreted to suggest that obese adults lack significant depots of BAT. This seemingly contradicts the observation in rodent models of diet-induced obesity that BAT (UCP-1 expression) is upregulated. The current studies sought to resolve this contradiction by testing the hypotheses that BAT is upregulated in diet-induced obesity but that the sympathetic drive of this tissue is impaired in animals maintained on a high fat diet. Rats made obese by maintenance on a high fat diet failed to increase BAT sympathetic nerve activity in response to cooling. In contrast, mRNA for UCP-1 was up regulated by a high fat diet and activation of the sympathetic premotor neurons in the raphe pallidus with bicuculline resulted in exaggerated increases in BAT SNA and thermogenesis in rats maintained on a high fat diet compared to those on control diet. Furthermore, preliminary data suggest that vagal afferent activity and glutamatergic activation of neurons in the NTS is required for the high fat diet induced inhibition of BAT SNA and thermogenesis. These data suggest that plasticity in vagal afferent activity during maintenance on a high fat diet may contribute to weight gain by impairing metabolism in adipose tissue. Supported by American Diabetes Association Basic Science grant #1-13-BS-120.