High Fat Diet (HFD) Induced Inhibition of Sympathetic Outflow to Brown Adipose Tissue (BAT): Role of the Nucleus Tractus Solitarius (NTS)

Abstract

The lack of radio labeled glucose uptake in BAT in obese humans has been interpreted to suggest that these individuals lack significant depots of active BAT. This seemingly contradicts the observation in rodent models of diet‐induced obesity that BAT (UCP‐1 expression) is upregulated, a state that is typically associated with increased activity of BAT. In the current studies rats made obese by maintenance on a HFD failed to increase BAT sympathetic nerve activity (SNA) in response to cooling. In contrast, mRNA for UCP‐1 was up regulated by a HFD. In addition, activation of the sympathetic premotor neurons in the raphe pallidus with the GABAA receptor antagonist, bicuculline, increased BAT SNA and thermogenesis in both rats maintained on a HFD and those on control diet; suggesting that the sympathetic pathway from the level of the sympathetic premotor neurons to the BAT is not impaired in rats maintained on a HFD. Stimulation of vagal afferent activity or activation of neurons in the NTS (the site of vagal afferent terminals) inhibits cooling‐evoked sympathetic outflow to BAT, therefore this study also sought to test whether glutamatergic activation of neurons in the NTS plays a role in HFD‐induced inhibition of BAT SNA. Blockade of glutamatergic receptors in the NTS reversed the HFD‐induced inhibition of BAT SNA and thermogenesis. Finally, lipid metabolites that may be altered in animals on a high fat diet act on TRPV‐1 receptors in the NTS to enhance glutamatergic neurotransmission. The current study investigated whether activation of TRPV‐1 receptors in the NTS also play a role in the HFD‐induced inhibition of BAT SNA. Blockade of TRPV‐1 receptors in the NTS reversed the HFD‐induced impairment of cooling‐evoked BAT SNA. These data suggest that plasticity in the NTS during maintenance on a HFD may contribute to weight gain by impairing metabolism in adipose tissue.Support or Funding InformationSupported by American Diabetes Association Basic Science grant #1‐13‐BS‐120 and NIH R01 NS091066.