Endogenous metabolites as ligands for G protein-coupled receptors modulating risk factors for metabolic and cardiovascular disease

Sarah Tonack, Cong Tang, Stefan Offermanns


During the last decade, several G protein-coupled receptors activated by endogenous metabolites have been described. These receptors respond to fatty acids, mono- and disaccharides, amino acids, or various intermediates and products of metabolism, including ketone bodies, lactate, succinate, or bile acids. Receptors of endogenous metabolites are expressed in taste cells, the gastrointestinal tract, adipose tissue, endocrine glands, immune cells, or the kidney and are therefore in a position to sense food intake in the gastrointestinal tract or to link metabolite levels to the appropriate responses of metabolic organs. Some of the receptors appear to provide a link between metabolic and neuronal or immune functions. Given that many of these metabolic processes are dysregulated under pathological conditions, including diabetes, dyslipidemia, and obesity, receptors of endogenous metabolites have also been recognized as potential drug targets to prevent and/or treat metabolic and cardiovascular diseases. This review describes G protein-coupled receptors activated by endogenous metabolites and summarizes their physiological, pathophysiological, and potential pharmacological roles.

  • fatty acid
  • carbohydrates
  • ketone bodies
  • lactate
  • bile acid
  • G protein-coupled receptors
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