G protein-coupled receptors and adipogenesis: a focus on adenosine receptors

Abstract

G-protein coupled receptors (GPCRs) are a large family of proteins that coordinate extracellular signals to produce physiologic outcomes. Adenosine receptors (AR) are one class of GPCRs that have been shown to regulate functions as diverse as inflammation, blood flow, and cellular differentiation. Adenosine signals through four GPCRs that either inhibit (A1AR and A3AR) or activate (A2aAR and A2bAR) adenylyl cyclase. This review will focus on the role of GPCRs, and in particular, adenosine receptors, in adipogenesis. Preadipocytes differentiate to mature adipocytes as the adipose tissue expands to compensate for the consumption of excess nutrients. These newly generated adipocytes contribute to maintaining metabolic homeostasis. Understanding the key drivers of this differentiation process can aid the development of therapeutics to combat the growing obesity epidemic and associated metabolic consequences. Although much literature has covered the transcriptional events that culminate in the formation of an adipocyte, less focus has been on receptor-mediated extracellular signals that direct this process. This review will highlight GPCRs and their downstream messengers as significant players controlling adipocyte differentiation.

Fig. 1

Adenosine production and signaling. Adenosine and ATP are released from cells during times of stress, inflammation, and cell damage. ATP can be converted to adenosine by CD39 and CD73 ectonucleotidases. Adenosine can also be released from cells by transporters, ENT1,2. Adenosine binds to receptors on the cell membrane that inhibit (A1AR and A3AR) or stimulate (A2aAR and A2bAR) adenylyl cyclase.