Title:Free Fatty Acids-Sensing G Protein-Coupled Receptors in Drug Targeting and Therapeutics
Volume: 20
Issue: 31
Author(s): Tomo Yonezawa, Riho Kurata, Kaori Yoshida, Masanori A. Murayama, Xiaofeng Cui and Akihiko Hasegawa
Affiliation:
Keywords:
GPR40, GPR41, GPR43, GPR84, GPR120, free fatty acids.
Abstract: G protein-coupled receptor (GPCR) (also known as seven-transmembrane domain receptor) superfamily represents
the largest protein family in the human genome. These receptors respond to various physiological ligands such as
photons, odors, pheromones, hormones, ions, and small molecules including amines, amino acids to large peptides and
steroids. Thus, GPCRs are involved in many diseases and the target of around half of all conventional drugs. The physiological
roles of free fatty acids (FFAs), in particular, long-chain FFAs, are important for the development of many metabolic
disease including obesity, diabetes, and atherosclerosis. In the past half decade, deorphanization of several GPCRs
has revealed that GPR40, GPR41, GPR43, GPR84 and GPR120 sense concentration of extracellular FFAs with various
carbon chain lengths. GPR40 and GPR120 are activated by medium- and long-chain FFAs. GPR84 is activated by medium-
chain, but not long-chain, FFAs. GPR41 and GPR43 are activated by short-chain FFAs. GPR40 is highly expressed
in pancreatic beta cells and plays a crucial role in FFAs-induced insulin secretion. GPR120 is mainly expressed in enteroendocrine
cells and plays an important role for FFAs-induced glucagon-like peptide-1. GPR43 is abundant in leukocytes
and adipose tissue, whilst GPR41 is highly expressed in adipose tissue, the pancreas and leukocytes. GPR84 is expressed
in leukocytes and monocyte/macrophage. This review aims to shed light on the physiological roles and development
of drugs targeting these receptors.
