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 A(1)receptor (pADORA(1)) signaling; however, it remains unclear whether systemic and adipose tissue metabolism would also be under the control of central (c) ADORA(1)signaling. Here, we use tissue-specific pharmacology and metabolic tools to clarify the roles of cADORA(1)signaling in energy and adipocyte physiology. We found that cADORA(1)signaling reduces body weight while also inducing adipose tissue lipolysis. cADORA(1)signaling also increases adipose tissue sympathetic norepinephrine content. In contrast, pADORA(1)signaling facilitates a high-fat diet-induced obesity (DIO). We propose here a novel mechanism in which cADORA(1)and pADORA(1)signaling hinder and aggravate DIO, respectively.

Automated summary

Understanding the interaction between brain and adipocytes is crucial for regulating energy and glucose homeostasis. Central ADORA(1) signaling reduces body weight and induces adipose tissue lipolysis, while peripheral ADORA(1) signaling may contribute to obesity. This study proposes a novel mechanism where central and peripheral ADORA(1) signaling play opposite roles in modulating diet-induced obesity.