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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
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In addition to multiple alleles at the same locus influencing traits, numerous genes or alleles at different locations may interact and influence phenotypes in a phenomenon called epistasis. For example, rabbit fur can be black or brown depending on whether the animal is homozygous dominant or heterozygous at a TYRP1 locus. However, if the rabbit is also homozygous recessive at a locus on the tyrosinase gene (TYR), it will have an unshaded coat that appears white, regardless of its TYRP1...
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The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
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Polymorphic Variation in FFA Receptors: Functions and Consequences.

Atsuhiko Ichimura1

  • 1Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29, Sakyo-ku, yoshidashimoadachi-cho, Kyoto, 606-8501, Japan. ichimura.atsuhiko.2r@kyoto-u.ac.jp.

Handbook of Experimental Pharmacology
|November 20, 2016
PubMed
Summary

Free fatty acid receptors (FFARs) are key to metabolic health, regulating energy balance. Understanding FFARs and their genetic variations offers new therapeutic targets for obesity and type 2 diabetes.

Keywords:
DiabetesEnergy homeostasisFFARsFree fatty acidsGPCRsGenetic variationsGeneticsGlucoseInsulinMutationPolymorphic variationsPolymorphismSNPs

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Area of Science:

  • Metabolic physiology
  • Pharmacology
  • Genetics

Background:

  • Dietary free fatty acids (FFAs) are crucial nutrients and signaling molecules.
  • G protein-coupled receptors (GPCRs), specifically FFA receptors (FFARs), mediate FFA functions.
  • FFARs regulate metabolic processes like hormone secretion and energy homeostasis.

Purpose of the Study:

  • To review the physiological roles of FFARs.
  • To examine genetic variations in FFARs.
  • To discuss FFARs as potential drug targets for metabolic disorders.

Main Methods:

  • Literature review of physiological and pharmacological studies.
  • Analysis of functional data on FFARs.
  • Examination of genetic polymorphism data related to FFARs.

Main Results:

  • FFARs mediate diverse physiological functions influencing energy balance.
  • FFA functions are dependent on FFA characteristics (chain length, unsaturation).
  • Genetic variations in FFARs may influence individual responses to ligands and drugs.

Conclusions:

  • FFARs are critical regulators of energy homeostasis.
  • FFARs represent promising pharmacological targets for metabolic disorders like obesity and type 2 diabetes.
  • Further research into FFAR genetic variations is needed to understand personalized therapeutic approaches.