Disease relevance of FFAR3

• They exhibited, however, a differential coupling to G proteins; GPR41 coupled exclusively though the Pertussis toxin-sensitive Gi/o family, whereas GPR43 displayed a dual coupling through Gi/o and Pertussis toxin-insensitive Gq protein families [1].
• The expression of GPR41 and 43, which have recently been identified as G-protein-coupled cell-surface receptors for short-chain fatty acids (SCFAs), was detected in a human breast cancer cell line (MCF-7) by RT-PCR [2].
• These common themes implicate GPR40, GPR41 and GPR43 in playing significant roles in metabolic diseases, such as diabetes, obesity and the metabolic syndrome [3].

High impact information on FFAR3

• A third family member, GPR42, is most likely a recent gene duplication of GPR41 and may be a pseudogene [4].
• GPR41 is related to GPR43 (52% similarity; 43% identity) and was activated by similar ligands but with differing specificity for carbon chain length, with pentanoate being the most potent agonist [4].
• In the present work, we have identified two previously orphan G protein-coupled receptors, GPR41 and GPR43, as receptors for SCFAs [1].
• The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids [4].
• Acetate was more selective for GPR43, whereas butyrate and isobutyrate were more active on GPR41 [1].

Biological context of FFAR3

• A search for open reading frames (ORF) in the non-coding CD22 sequence resulted in identification of two novel putative intronless genes, GPR40 and GPR41 [5].
• GPR41 and GPR43 have been reported to stimulate leptin release and adipogenesis respectively via activation by short-chain fatty acids [3].

Anatomical context of FFAR3

• GPR41 was expressed primarily in adipose tissue, whereas the highest levels of GPR43 were found in immune cells [4].
• These results suggest that GPR41 and 43 mediate SCFA signaling in mammary epithelial cells and thereby play an important role in their stress management [2].
• The expression of GPR41 appears to be the highest in brain and lung tissues, with lesser expression in heart, skeletal muscle, and kidney, as assayed by northern blotting [6].

Associations of FFAR3 with chemical compounds

• Propionate was the most potent agonist for both GPR41 and GPR43 [1].

Other interactions of FFAR3

• Since agonists of GPR40 are medium to longchain fatty acids and those for GPR41 and 43 are short-chain fatty acids, the family clearly provides an intriguing example of how the ligand specificity, patterns of expression, and function of GPCRs can diverge through evolution [7].

References