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

Jia Zhang, Yanjun Hou, Xue liang Du, Dan Chen, Guangzhi Sui, Yong Qi, Julio Licinio, Ma Li Wong, Yunlei Yang

Research output: Contribution to journalArticlepeer-review

Abstract

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 A1 receptor (pADORA1) signaling; however, it remains unclear whether systemic and adipose tissue metabolism would also be under the control of central (c) ADORA1 signaling. Here, we use tissue-specific pharmacology and metabolic tools to clarify the roles of cADORA1 signaling in energy and adipocyte physiology. We found that cADORA1 signaling reduces body weight while also inducing adipose tissue lipolysis. cADORA1 signaling also increases adipose tissue sympathetic norepinephrine content. In contrast, pADORA1 signaling facilitates a high-fat diet-induced obesity (DIO). We propose here a novel mechanism in which cADORA1 and pADORA1 signaling hinder and aggravate DIO, respectively.

Original languageEnglish (US)
Pages (from-to)2805-2819
Number of pages15
JournalMolecular Psychiatry
Volume26
Issue number7
DOIs
StatePublished - Jul 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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