Autocrine Regulation of Metabolic Functions Through Metabolite GPCRs

抄録

G-protein-coupled receptors (GPCRs) have traditionally been regarded as receptors for hormones, neurotransmitters, and other mediators which are produced solely for the purpose of carrying a signal and to serve cell-cell communication. This view has changed during the last decade, as a growing number of GPCRs are being identified, for which the ligands are energy substrates or metabolic intermediates. Among these ligands are saturated and unsaturated free fatty acids (FFAs) as well as hydroxy carboxylic acids (HCAs), such as lactate and ketone bodies, which exert cellular effects through GPCRs named FFA1-FFA4 and HCA1-HCA3, respectively. These receptors are widely expressed in the human body and regulate the metabolic, endocrine or immune system to maintain homeostasis under changing dietary conditions. Data will be presented on the role of FFA1, FFA2 and FFA3 in the regulation of beta-cell function and of the lactate receptor HCA1 in adipocyte function and body weight regulation by natural ligands acting in part in an autocrine manner.