ADORA1-driven brain-sympathetic neuro-adipose connections control body weight and adipose lipid metabolism

It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripheral adenosine A1receptor (pADORA1) signaling; however, it remains unclear whether systemic and adipose tissue metabolism would also be under the control of central (c) ADORA1signaling. Here, we use tissue-specific pharmacology and metabolic tools to clarify the roles of cADORA1signaling in energy and adipocyte physiology. We found that cADORA1signaling reduces body weight while also inducing adipose tissue lipolysis. cADORA1signaling also increases adipose tissue sympathetic norepinephrine content. In contrast, pADORA1signaling facilitates a high-fat diet-induced obesity (DIO). We propose here a novel mechanism in which cADORA1and pADORA1signaling hinder and aggravate DIO, respectively.