PPAR? in vagal neurons regulates high-fat diet induced thermogenesis.

ABSTRACT: The vagus nerve innervates visceral organs providing a link between key metabolic cues and the CNS. However, it is not clear whether vagal neurons can directly respond to changing lipid levels and whether altered "lipid sensing" by the vagus nerve regulates energy balance. In this study, we systematically profiled the expression of all known nuclear receptors in laser-captured nodose ganglion (NG) neurons. In particular, we found PPAR? expression was reduced by high-fat-diet feeding. Deletion of PPAR? in Phox2b neurons promoted HFD-induced thermogenesis that involved the reprograming of white adipocyte into a brown-like adipocyte cell fate. Finally, we showed that PPAR? in NG neurons regulates genes necessary for lipid metabolism and those that are important for synaptic transmission. Collectively, our findings provide insights into how vagal afferents survey peripheral metabolic cues and suggest that the reduction of PPAR? in NG neurons may serve as a protective mechanism against diet-induced weight gain.

SUBMITTER: Liu C 

PROVIDER: S-EPMC4046333 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature