The role of G-protein-coupled receptors in mediating the effect of fatty acids on inflammation and insulin sensitivity

Dayoung Oh, William S. Lagakos

Research output: Contribution to journalReview article

67 Scopus citations

Abstract

Purpose of Review: Chronic activation of inflammatory pathways mediates the pathogenesis of insulin resistance, and the macrophage/adipocyte nexus provides a key mechanism underlying decreased insulin sensitivity. Free fatty acids are important in the pathogenesis of insulin resistance, although their precise mechanisms of action have yet to be fully elucidated. Recently, a family of G-protein-coupled receptors has been identified that exhibits high affinity for fatty acids. This review summarizes recent findings on six of these receptors, their ligands, and their potential physiological functions in vivo. Recent Findings: Upon activation, the free fatty acid receptors affect inflammation, glucose metabolism, and insulin sensitivity. Genetic deletion of GPR40 and GPR41, receptors for long-chain and short-chain fatty acids, respectively, results in resistance to diet-induced obesity. Deletion of GPR43 and GPR84 exacerbates inflammation, and deletion of the long-chain fatty acid receptors GPR119 and GPR120 reduces or is predicted to reduce glucose tolerance. Summary: These studies provide a new understanding of the general biology of gastric motility and also shed valuable insight into some potentially beneficial therapeutic targets. Furthermore, highly selective agonists or antagonists for the free fatty acid receptors have been developed and look promising for treating various metabolic diseases.

Original languageEnglish (US)
Pages (from-to)322-327
Number of pages6
JournalCurrent Opinion in Clinical Nutrition and Metabolic Care
Volume14
Issue number4
DOIs
StatePublished - Jul 1 2011

Keywords

  • G-protein-coupled receptor
  • free fatty acid
  • glucose tolerance
  • inflammation
  • insulin resistance

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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