PPARγ in Vagal Neurons Regulates High-Fat Diet Induced Thermogenesis

The vagus nerve innervates visceral organs and have long been suspected to play a role in surveying peripheral metabolic status and relaying it to the CNS. However, it remains unknown whether vagal sensory neurons can directly interact with dietary-derived nutrients and whether altered nutrient sensing by the vagus nerve would impair long-term energy balance. In this study, we systematically profiled nuclear receptor expression in vagal sensory neurons and found PPARγ expression is negatively regulated by high-fat-diet feeding (HFD). We demonstrate PPARγ in vagal neurons regulates HFD-induced thermogenesis that involves active re-programing of white adipocyte cell fate. Moreover, we show that PPARγ regulates the expression of a set of neuronal genes that are important for synaptic transmission. Altogether, our findings provide insights into how vagal afferents survey metabolic information from peripheral tissues and demonstrated that PPARγ-dependent lipid sensing in vagal sensory neurons is important for the maintenance of energy homeostasis.