Free Fatty Acid Receptors 2 and 3 as Microbial Metabolite Sensors to Shape Host Health: Pharmacophysiological View

Biomedicines
Sidharth P. MishraHariom Yadav

Abstract

The role of the gut microbiome in human health is becoming apparent. The major functional impact of the gut microbiome is transmitted through the microbial metabolites that are produced in the gut and interact with host cells either in the local gut environment or are absorbed into circulation to impact distant cells/organs. Short-chain fatty acids (SCFAs) are the major microbial metabolites that are produced in the gut through the fermentation of non-digestible fibers. SCFAs are known to function through various mechanisms, however, their signaling through free fatty acid receptors 2 and 3 (FFAR2/3; type of G-coupled protein receptors) is a new therapeutic approach. FFAR2/3 are widely expressed in diverse cell types in human and mice, and function as sensors of SCFAs to change several physiological and cellular functions. FFAR2/3 modulate neurological signaling, energy metabolism, intestinal cellular homeostasis, immune response, and hormone synthesis. FFAR2/3 function through Gi and/or Gq signaling, that is mediated through specific structural features of SCFAs-FFAR2/3 bindings and modulating specific signaling pathway. In this review, we discuss the wide-spread expression and structural homologies between human and mice FFAR...Continue Reading

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Citations

Nov 1, 2020·The Journal of Clinical Endocrinology and Metabolism·Sidharth P MishraHariom Yadav
Jan 27, 2021·Trends in Pharmacological Sciences·Graeme MilliganAndrew B Tobin
Oct 4, 2020·Biochemical and Biophysical Research Communications·John Jackson YangChun-Ming Huang
Jan 23, 2021·Current Opinion in Endocrinology, Diabetes, and Obesity·Natasha K LeeuwendaalHarriët Schellekens
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May 1, 2021·Biomedicines·Anna KiepuraRafał Olszanecki
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Jul 4, 2021·European Journal of Pharmacology·Jasmin BalloutMartin Diener
Oct 7, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qiang-Jun WangZhong-Hong Wu

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Methods Mentioned

BETA
IECs
GTPase
RNAseq
gastric bypass
transgenic

Software Mentioned

TASSER
SASA
Google Scholar

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