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Free fatty acid receptor 3 - Wikipedia Jump to content

Free fatty acid receptor 3

From Wikipedia, the free encyclopedia
FFAR3
Identifiers
AliasesFFAR3, FFA3R, GPR41, GPR42, free fatty acid receptor 3
External IDsOMIM: 603821; MGI: 2685324; HomoloGene: 82482; GeneCards: FFAR3; OMA:FFAR3 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2865

233080

Ensembl

ENSG00000185897

ENSMUSG00000019429

UniProt

O14843

Q3UFD7

RefSeq (mRNA)

NM_005304

NM_001033316

RefSeq (protein)

NP_005295

NP_001028488

Location (UCSC)Chr 19: 35.36 – 35.36 MbChr 7: 30.55 – 30.56 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Free fatty acid receptor 3 (FFAR3, also termed GPR41) protein is a G protein coupled receptor (i.e., GPR or GPCR) that in humans is encoded by the FFAR3 gene (i.e., GPR41 gene).[5] GPRs reside on cell surfaces, bind specific signaling molecules, and thereby are activated to trigger certain functional responses in their parent cells. FFAR3 is a member of the free fatty acid receptor group of GPRs that includes FFAR1 (i.e., GPR40), FFAR2 (i.e., GPR43), and FFAR4 (i.e., GPR120).[6] All of these FFARs are activated by fatty acids. FFAR3 and FFAR2 are activated by certain short-chain fatty acids (SC-FAs), i.e., fatty acids consisting of 2 to 6 carbon atoms[7] whereas FFFAR1 and FFAR4 are activated by certain fatty acids that are 6 to more than 21 carbon atoms long.[8][9][10] Hydroxycarboxylic acid receptor 2 is also activated by a SC-FA that activate FFAR3, i.e., butyric acid.[11]

The human FFAR3 gene is located next to the FFAR2 gene at locus 13.12 on the long (i.e., "q") arm of chromosome 19 (location abbreviated as 19q13.12). The human FFAR3 and FFAR2 proteins consist of 346 and 330 amino acids, respectively,[12] and share about a 40% amino acid sequence homology.[13] The two FFARs have been found to form a heteromer complex (i.e., FFAR3 and FFAR2 bind to each other and are activated together by a SC-FA) in human monocytes, macrophages, and the immortalized embryonic kidney cells, HEK 293 cells. When stimulated by a SC-FA, the cells expressing both FFAR3 and FFAR2 may form this heterodimer and thereby activate cell signaling pathways and mount responses that differ from those of cells expressing only one of these FFARs.[14] The formation of GPR43-GPR41 heterodimers has not been evaluated in most studies and may explain otherwise conflicting results on the roles of FFAR3 and FFAR2 in cell function.[10][15][16] Furthermore, SC-FAs can alter the function of cells independently of FFAR3 and FFAR2 by altering the activity of cellular histone deacetylases which regulate the transcription of various genes or by altering metabolic pathways which alter cell functions.[17][18] Given these alternate ways for SC-FAs to activate cells as wells at the ability of SC-FAs to activate FFAR2 or, in the case of butyric acid, hydroxycarboxylic acid receptor 2, the studies reported here focus on those showing that the examined action(s) of an SC-FA is absent or reduced in cells, tissues, or animals that have no or reduced FFAR3 activity due respectively to knockout (i.e., removal or inactivation) or knockdown (i.e., reduction) of the FFAR3 protein gene, i.e., the Ffar3 gene in animals or FFAR3 gene in humans.

Certain bacteria in the gastrointestinal tract ferment fecal fiber into SC-FAs and excrete them as waste products. The excreted SC-FAs enter the gastrointestinal walls, diffuse into the portal venous system, and ultimately flow into the systemic circulation. During this passage, they can activate the FFAR3 on cells in the intestinal wall as well as throughout the body.[19] This activation may: suppress the appetite for food and thereby reduce overeating and the development of obesity;[20][21] inhibit the liver's accumulation of fatty acids and thereby the development of fatty liver diseases;[22] decrease blood pressure and thereby the development of hypertension and hypertension-related cardiac diseases;[23] modulate insulin secretion and thereby the development and/or symptoms of type 2 diabetes;[24] reduce heart rate and blood plasma norepinephrine levels and thereby lower total body energy expenditures;[19] and suppress or delay the development of allergic asthma.[25]

The specific types of bacteria in the intestines can be modified to increase the number which make SC-FAs by using foods that stimulate the growth of these bacteria (i.e., prebiotics), preparations of SC-FA-producing bacteria (i.e., probiotics), or both methods (see synbiotics).[26] Individuals with disorders that are associated with low levels of the SC-FA-producing intestinal bacteria may show improvements in their conditions when treated with prebiotics, probiotics, or synbiotics while individuals with disorders associated with high levels of SC-FAs may show improvements in their conditions when treated with methods, e.g., antibiotics, that reduce the intestinal levels of these bacteria.[19][27] (For information on these treatments see Disorders treated by probiotics and Disorders treated by prebiotics). In addition, drugs are being tested for their ability to act more usefully, potently, and effectively than SC-FAs in stimulating or inhibiting FFAR3 and thereby for treating the disoders that are inhibited or stimulated, respectively, by SC-FAs.[28]

FFAR3-activating and inhibiting agents

[edit]

The SC-FAs that activate FFAR3 include proprionic, butyric, acetic,[29] valeric[19] caproic,[27] and formic acids.[30] (Confusingly, butyric acid also activates hydroxycarboxylic acid receptor 2[30] and βべーた-hydroxybutyric acid has been reported to stimulate or inhibit FFAR3.[31]) FFAR2 is activated by many of these same SC-FAs but differs from FFAR3 in its relative binding affinities for them. In humans, the binding affinity ranking of FFAR3 is: propionic = butyric = valeric > acetic > formic acids (acetic[29] and formic[30] acids have very low binding affinities for, and therefore must be at extremely high levels to activate, FFAR3); FFAR2's relative binding affinity ranking for these SC-FAs is: acetic = propionic > butyric > valeric = formic acids.[30] AR420626 (also termed 1-MCPC[12] or its chemical name, [(S)-2-(4-chlorophenyl)-3,3-dimethyl-N-(5-phenylthiazol-2-yl)butamide (CFMB)/AR420626][32]) has been reported to be a selective activator of FFAR3[33] but has also been reported to activate FFAR2[32] and to inhibit the activation of FFAR3.[19] Its actions require further characterizations.[19] AR399519 and CF3-MQC have been reported to inhibit the activation of mouse FFAR3; the actions of these agents also require further characterizations.[12]

Tissues and cells expressing FFAR3

[edit]

Studies have reported that humans express FFAR3 in their: a) enteroendocrine L cells and K cells of the intestines;[10] b) endothelium of blood vessels in the frontal cortex of the brain,[34] pancreatic βべーた-cells,[35] and adipose. i.e., fat, tissue (but not in mouse adipose tissue);[36] c) the vascular endothelium of the myometrium, the epithelium of the amnion, chorion and placenta, and certain immune cells in these tissues of pregnant women;[37] d) the hippocampus of the brain;[38] e) sympathetic ganglia, i.e., autonomic ganglia of the sympathetic nervous system;[12][39] f) certain types of immune cells, i.e., blood monocytes (but not mouse monocytes), basophils,[18][40][41] dendritic cells derived from human monocytes isolated from whole blood, and the tissues containing these blood cells, i.e., the bone marrow, spleen, lymph nodes, and thymus;[42] and g) alveolar macrophages, and macrophages in various other tissues;[18] and h) certain immortalised cell lines, i.e., MCF-7 breast cancer,[43] HCT116 colorectal cancer,[44] HEK293 embryonic kidney,[14][41] U937 leukemic promonocyte, THP-1 leukemic monocyte, EoL-1 leukemic eosinophil, Jurcat leukemic T lymphocyte, MOLT-4 T lymphoblast leukemic, and HL60 acute myeloid leukemia cells (but only when the HL60 cells are pre-treated with phorbol 12-myristate 13-acetate to promote their cellular differentiation).[41] As noted, the expression of FFAR3 in the cells and tissues of animals are not always the same as those in humans.

Functions

[edit]

Regulation of satiety and obesity

[edit]

L cells are enteroendocrine cells, i.e., specialized cells that secrete hormones directly into the circulation. L cells reside in the epithelium of the gastrointestinal tract, particularly the terminal ileum and colon. They are stimulated to secrete PYY (also termed peptide YY) and GLP-1 (also termed glucagon-like peptide-1) by the SC-FAs that accumulate inside the intestines after feeding. L cells express FFAR3 and/or FFAR2.[29] Ffar3 and Ffar2 gene knock out mice show reduced secretions of GLP-1 and PYY.[45] Studies have shown that Ffar3 gene knockout mice fed a high fat diet have significant increases in their food intake and body weights compared to wild-type (i.e., genetically unaltered) mice.[19] These and other studies in animals suggest that the activation of FFAR3 and FFAR2 on L cells by SC-FAs triggers the release of PYY and GLP-1 both of which, among various other activities, inhibit gastric emptying and thereby suppress appetite and the development of obesity.[19][21] Further studies are needed to determine if FFAR3 plays a similar role in human satiety and obesity.[19] It should be noted, however, that Semaglutide, also called Wegovy, is a peptide with a modified GLP-1-like structure. It strongly stimulates GLP-1 receptors and thereby suppresses appetite and promotes weight loss in obese individuals.[46]

Leptin is a peptide hormone released by adipose tissue that triggers satiety and thereby tends to reduce or stop further food intake and the development of obesity. It also plays a role in female reproductive function, lipolysis (e.g., the breakdown of triglycerides into their component free fatty acids and glycerol), the growth of fetuses, inflammation, and angiogenesis (i.e., the formation of new blood vessels from pre-existing blood vessels).[20] While studies have suggested that the SC-FA-induced activation of FFAR3 leads to the secretion of leptin from the white adipose tissue of intact animals and the fat tissue isolated from human tissues, other studies have suggested that FFAR2 rather than FFAR3 is responsible for the SC-FA-induced release of leptin form fat tissue. A systematic review of the published studies on this issue concluded that SC-FA-induced activation of FFAR3 is likely responsible for the SC-FA-induced release of leptin from cultured fat tissue taken from animals. However, the data were insufficient to support a role for FFAR3 in the release of leptin from cultured human fat tissues or the fat tissue of intact animals. The role of FFAR3 stimulation of leptin release in apatite suppression and obesity needs further study.[47]

Regulation of liver fatty acid storage and fatty liver disease

[edit]

In a high-fat diet-induced obesity model of fatty liver disease (i.e., excessive buildup of fat in the liver), mice fed a diet that increased intestinal levels of SC-FAs showed reductions in their livers' synthesis of lipids, triglyceride levels, and weights. These reductions did not occur in Ffar3 gene knockout mice but did occur in Ffar2 gene knocked-out mice. These results indicate that the SC-FA-induced activation of FFAR3 suppresses the liver's accumulation of fatty acids that underlies the development of fatty liver disease in this mouse model.[22] Other studies have found that Ffar3 gene knockout mice showed less weight gain than wild-type mice under standard laboratory conditions but this difference was lost in mice reared under germ-free conditions (i.e., which causes the mice to have lower intestinal and tissue levels of SC-FAs).[13] These findings indicated that the activation of FFAR3 but not FFAR2 by SC-FAs protects against developing fatty liver disease in mice;[13][30] they also support studies to determine if FFAR3 has these actions in humans and if FFAR3 activators can be used to treat or prevent human fatty liver diseases such as non-alcoholic fatty liver disease.[48]

Regulation of insulin secretion and diabetes

[edit]

Individuals with type 2 diabetes, which accounts for 90% of all diabetes cases, have decreases in the proliferation, maturation, and activity of their pancreatic islet insulin-secreting beta-cells as well as the potency of insulin's actions. These decreases result in reduced insulin secretion, hyperglycemia, and the many other afflictions associated with this disorder. Studies in the past have reported that the activation of FFAR3 reduced the insulin secreted by 1) human and mouse beta cells in vivo, 2) cultured human and murine beta cell-containing pancreatic islets, and 3) cultured beta cell lines.[12][24] These studies showed that acetic acid-induced inhibition of insulin secretion by mouse pancreatic islets did not occur in islets that had both of their Ffar3 and Ffar2 genes knocked out but had no effect on insulin secretion in islets that had only one of the two genes knocked out.[24] In contrast to this, however, a recent study of streptozotocin-induced and high-fat diet-induced murine models of diabetes found that the FFAR3-activating drug, AR420626, increased blood plasma insulin levels and stimulated skeletal muscle to take up glucose and thereby improved glucose tolerance test results.[49] Other recent studies have reported that activated FFAR3 may reduce, increase, or have little effect on insulin secretion depending on 1) the levels of ambient glucose and FFAR3 activators studied, 2) human or animal species studied, 3) age of the animals studied, and 4) variations in the proportions of alpha, beta, and delta cells in the pancreatic islets of humans. The role of FFAR3 in human as well as animal models of insulin secretion and diabetes requires further studies.[35]

Regulation of blood pressure and hypertension-induced cardiovascular disorders

[edit]

An early study showed that the intravenous injection of propionic acid into mice induced a brief (<5 min) hypotensive response as defined by drops in their mean arterial pressures. This response was reduced in mice that had one of their two Ffar3 genes knocked out and absent in mice that had both Ffar3 genes knocked out.[23][50] A subsequent study reported that Ffar3 gene knockout mice developed abnormally high diastolic blood pressuress and pulse pressures (i.e., systolic minus diastolic blood pressures) as well as increased amounts of cardiac collagen and elastin connective tissue and increased cardiac stiffness as evidenced by a reduce rate of heart muscle relaxation measured by pressure-volume loop analysis tau levels.[51][52] Taken together, these studies suggest that in mice SC-FA-activated FFAR3 functions to reduce blood pressure as well as some of the consequences of hypertension such as cardiac fibroses and poor myocardial contractility.[53] Studies in humans have found that individuals undergoing hemodialysis using dialysis solutions that contain acetic acid often develop hypotension; the role of FFAR3 in this response, if any, was not investigated.[23][50] And, a study of 69 individuals (55.1% women, mean age 59.8 years) found that arterial stiffness was associated with lower levels of FFAR3 and FFAR2 in circulating blood immune cells (particularly regulatory T cells which are known to be protective in murine models of hypertension[54]).[52] Overall. the mouse studies suggest that FFAR3 contributes to suppressing hypertension and its subsequent effects on the heart in mice[51] and that that SC-FA-activated FFAR3 and/or FFAR2 may have vasodilatory actions and thereby suppress the development of hypertension and hypertension-induced arterial stiffness in humans. Further studies in humans are needed to investigate the latter possibilities.[51][54]

Regulation of the sympathetic nervous system and its control of heart rate and energy expenditure

[edit]

Studies have shown that compared to wild type mice, Ffar3 gene knockout mice have: a) significantly smaller-sized sympathetic nervous system ganglia as judged by measurements of this systems' largest ganglia, the superior cervical ganglion; b) significantly slower heart rates; and c) significantly lower norepinephrine levels in their blood plasma. (Norepinephrine is a neurotransmitter that is released by sympathetic nervous system neurons and among other actions increases heart rate and total body energy expenditure.) Furthermore, the treatment of wild type mice with propionic acid increased their heart rates but did not do so in Ffar3 gene knockout mice.[19][39] Finally, the offspring of Ffar3-gene knockout mice had slower heart rates (as well as lower body temperatures) than the offspring of wild type mice.[10] These findings indicate that FFAR3 regulates heart rates and energy expenditure in mice. Studies are needed to determine if it does so in humans.[19][39]

Regulation of allergic asthma reactions

[edit]

Asthma may be atopic (i.e., symptoms triggered by allergens) or non-atopic (i.e., symptoms triggered by non-allergenic factors such as cold air). The studies reported here relate to allergen-induced asthma. Mice fed a diet that lowers their SC-FAs levels and then given intranasal injections of dust mite extract developed dust mite allergy asthma reactions to the injections. Their respiratory tract airways had increased numbers of eosinophils and goblet cells as well as excessive levels of mucus; their lung tissue levels of interleukin-4, interleukin-5, interleukin-13, and interleukin-17A and serum immunoglobulin E levels were elevated; and their airway resistance response to a bronchial challenge test was high. In contrast, mice fed a diet that increased their SC-FAs levels developed less of these responses to the extract. Furthermore, mice on the SC-FA lowering diet that were given propionic acid also had far less of these responses to the mite extract. And, Ffar3 (but not Ffar2) gene knockout mice on the low SF-FA diet did not show rises in their lung airway eosinophil levels in response to the mite extract (this was the only parameter of asthma reported in the knockout studies). These finding implicate propionic acid and FFAR3 in the suppression of asthma allergic reactions to mite extract in mice.[55]

A second study investigated the effects that an inulin-rich diet (which raises bodily SC-FA levels) feed to rats had on their offsprings' development of asthma. Pregnant rats were feed a normal or inulin-rich diet for 1 week. Their offspring were injected with ovalbumin on days 21 and 29 after birth, 7 days later challenged with aerosolized ovalbumin, and on the next day examined for their responses to the aerosol. Compared to the offspring of mothers on a normal diet, the offspring of mothers on the inulin diet had lower levels of lung inflammatory cells, less histological evidence of allergic lung disease, lower lung tissue levels of immunoglobulin E, interleukin-4, and interleukin-17, and significantly elevated lung levels of FFAR3 (Lung FFAR2 levels were not significantly elevated). These results indicate that a diet promoting the production of SC-FAs in pregnant rats suppresses the development of asthmatic disease in their offspring; this suppression may involve FFAR3.[25] In a similar study, newborn mice were feed breast milk from mothers who had drunk pure water or water containing a SC-FA. After 3 weeks, the newborns were weaned off the mothers' milk, feed plain water, and 3 weeks thereafter sensitized to and challenged by injection of mite extract into their tracheas. Mothers who drank pure water or water laced with acetic or butyric acid and sensitized to the mite extract had asthma signs after challenge with the extract whereas mothers who drank propionic acid-laced water had far less of these signs. Furthermore, Ffar3 gene knockout mothers who drank propionic acid-laced water and then sensitized to the mite extract had asthma signs similar to these in wild type mothers challenged with the extract. The study also found that the offspring of mothers who drank propionic acid-laced water had fewer eosinophils and T helper cells in their airways than the offsprings of mothers who drank pure water, acetic acid-laced water, or butyric acid-laced water. Propionic acid-laced water did not suppress the development of asthma in Ffar3 gene knockout offsprings. These results indicate that ingestion of propionic acid, but not acetic or butyric acid, suppresses the development of allergic asthma in adult as well as newborn rats and does so by a FFAR3-dependent mechanism. The studies also indicate that the milk of pregnant rats who consumed propionic acid-laced but not those who drank pure water reduced the susceptibility of newborn rats to developing allergic asthma by a mechanism dependent on FFAR3 in the mothers as well as the offsprings. These findings support further studies to determine if propionic acid or other FFAR3 activators would be useful for preventing and/or treating asthma in humans.[18][56]

A study of humans living on European farms or in non-farm rural areas reported that the fecal levels of butyric but not acetic acid in 12 month old children who had not develop asthma by the time they entered the first year of school were significantly higher than these levels in children who did develop asthma by the school entry age.[57] A study conducted in Canada reported that the levels of fecal acetic acid (but not butyric or propionic acid) were lower in 3 month old human infants who were predicted to have asthma by school age (based on a Phylogenetic Investigation of Communities by Reconstruction of Unobserved States prediction algorithm) compared to infants predicted not to do so.[58] Finally, a study conducted in Japan found that the fecal levels of propionic but not acetic or butyric acid trended lower in 1 month old human infants that developed asthma by age 5 than in infants that did not develop asthma. The fecal levels of propionic as well acetic and butyric acid obtained from 1 week-, 1 year, and 5-year-old infants did not show this trend.[56] The different SC-FA implicated in suppressing asthma in these three studies may reflect dietary or other differences between the populations of the three countries. In all events, the studies allow that, based on rodent studies, FFAR3 may mediate these SG-FA actions and, based on human studies, SC-FAs may act to suppress, or at least delay) the onset of, asthma in children Further studies are needed to determine if FFAR3 is involved in the apparent actions of the cited SC-FAs in the development of asthma in children.[56]

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000185897 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019429 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: FFAR3 free fatty acid receptor 3".
  6. ^ Sawzdargo M, George SR, Nguyen T, Xu S, Kolakowski LF, O'Dowd BF (October 1997). "A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1". Biochemical and Biophysical Research Communications. 239 (2): 543–7. doi:10.1006/bbrc.1997.7513. PMID 9344866.
  7. ^ Karmokar PF, Moniri NH (December 2022). "Oncogenic signaling of the free-fatty acid receptors FFA1 and FFA4 in human breast carcinoma cells". Biochemical Pharmacology. 206: 115328. doi:10.1016/j.bcp.2022.115328. PMID 36309079. S2CID 253174629.
  8. ^ Briscoe CP, Tadayyon M, Andrews JL, Benson WG, Chambers JK, Eilert MM, Ellis C, Elshourbagy NA, Goetz AS, Minnick DT, Murdock PR, Sauls HR, Shabon U, Spinage LD, Strum JC, Szekeres PG, Tan KB, Way JM, Ignar DM, Wilson S, Muir AI (March 2003). "The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids". The Journal of Biological Chemistry. 278 (13): 11303–11. doi:10.1074/jbc.M211495200. PMID 12496284.
  9. ^ Tunaru S, Bonnavion R, Brandenburger I, Preussner J, Thomas D, Scholich K, Offermanns S (January 2018). "20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner through FFAR1". Nature Communications. 9 (1): 177. Bibcode:2018NatCo...9..177T. doi:10.1038/s41467-017-02539-4. PMC 5766607. PMID 29330456.
  10. ^ a b c d Grundmann M, Bender E, Schamberger J, Eitner F (February 2021). "Pharmacology of Free Falsoatty Acid Receptors and Their Allosteric Modulators". International Journal of Molecular Sciences. 22 (4). doi:10.3390/ijms22041763. PMC 7916689. PMID 33578942.
  11. ^ Offermanns S (March 2017). "Hydroxy-Carboxylic Acid Receptor Actions in Metabolism". Trends in Endocrinology and Metabolism. 28 (3): 227–236. doi:10.1016/j.tem.2016.11.007. PMID 28087125. S2CID 39660018.
  12. ^ a b c d e Mishra SP, Karunakar P, Taraphder S, Yadav H (June 2020). "Free Fatty Acid Receptors 2 and 3 as Microbial Metabolite Sensors to Shape Host Health: Pharmacophysiological View". Biomedicines. 8 (6): 154. doi:10.3390/biomedicines8060154. PMC 7344995. PMID 32521775.
  13. ^ a b c Secor JD, Fligor SC, Tsikis ST, Yu LJ, Puder M (2021). "Free Fatty Acid Receptors as Mediators and Therapeutic Targets in Liver Disease". Frontiers in Physiology. 12: 656441. doi:10.3389/fphys.2021.656441. PMC 8058363. PMID 33897464.
  14. ^ a b Ang Z, Xiong D, Wu M, Ding JL (January 2018). "FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing". FASEB Journal. 32 (1): 289–303. doi:10.1096/fj.201700252RR. PMC 5731126. PMID 28883043.
  15. ^ Martin-Gallausiaux C, Marinelli L, Blottière HM, Larraufie P, Lapaque N (February 2021). "SCFA: mechanisms and functional importance in the gut". The Proceedings of the Nutrition Society. 80 (1): 37–49. doi:10.1017/S0029665120006916. PMID 32238208. S2CID 214772999.
  16. ^ Ang Z, Er JZ, Tan NS, Lu J, Liou YC, Grosse J, Ding JL (September 2016). "Human and mouse monocytes display distinct signalling and cytokine profiles upon stimulation with FFAR2/FFAR3 short-chain fatty acid receptor agonists". Scientific Reports. 6: 34145. Bibcode:2016NatSR...634145A. doi:10.1038/srep34145. PMC 5036191. PMID 27667443.
  17. ^ Carretta MD, Quiroga J, López R, Hidalgo MA, Burgos RA (2021). "Participation of Short-Chain Fatty Acids and Their Receptors in Gut Inflammation and Colon Cancer". Frontiers in Physiology. 12: 662739. doi:10.3389/fphys.2021.662739. PMC 8060628. PMID 33897470.
  18. ^ a b c d Tan JK, Macia L, Mackay CR (February 2023). "Dietary fiber and SCFAs in the regulation of mucosal immunity". The Journal of Allergy and Clinical Immunology. 151 (2): 361–370. doi:10.1016/j.jaci.2022.11.007. PMID 36543697. S2CID 254918066.
  19. ^ a b c d e f g h i j k Ikeda T, Nishida A, Yamano M, Kimura I (November 2022). "Short-chain fatty acid receptors and gut microbiota as therapeutic targets in metabolic, immune, and neurological diseases". Pharmacology & Therapeutics. 239: 108273. doi:10.1016/j.pharmthera.2022.108273. PMID 36057320. S2CID 251992642.
  20. ^ a b Obradovic M, Sudar-Milovanovic E, Soskic S, Essack M, Arya S, Stewart AJ, Gojobori T, Isenovic ER (2021). "Leptin and Obesity: Role and Clinical Implication". Frontiers in Endocrinology. 12: 585887. doi:10.3389/fendo.2021.585887. PMC 8167040. PMID 34084149.
  21. ^ a b Navalón-Monllor V, Soriano-Romaní L, Silva M, de Las Hazas ML, Hernando-Quintana N, Suárez Diéguez T, Esteve PM, Nieto JA (August 2023). "Microbiota dysbiosis caused by dietetic patterns as a promoter of Alzheimer's disease through metabolic syndrome mechanisms". Food & Function. 14 (16): 7317–7334. doi:10.1039/d3fo01257c. PMID 37470232. S2CID 259996464.
  22. ^ a b Shimizu H, Masujima Y, Ushiroda C, Mizushima R, Taira S, Ohue-Kitano R, Kimura I (November 2019). "Dietary short-chain fatty acid intake improves the hepatic metabolic condition via FFAR3". Scientific Reports. 9 (1): 16574. Bibcode:2019NatSR...916574S. doi:10.1038/s41598-019-53242-x. PMC 6851370. PMID 31719611.
  23. ^ a b c Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, Brunet I, Wan LX, Rey F, Wang T, Firestein SJ, Yanagisawa M, Gordon JI, Eichmann A, Peti-Peterdi J, Caplan MJ (March 2013). "Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation". Proceedings of the National Academy of Sciences of the United States of America. 110 (11): 4410–5. Bibcode:2013PNAS..110.4410P. doi:10.1073/pnas.1215927110. PMC 3600440. PMID 23401498.
  24. ^ a b c Ghislain J, Poitout V (March 2021). "Targeting lipid GPCRs to treat type2 diabetes mellitus - progress and challenges". Nature Reviews. Endocrinology. 17 (3): 162–175. doi:10.1038/s41574-020-00459-w. PMID 33495605. S2CID 231695737.
  25. ^ a b Yuan G, Wen S, Zhong X, Yang X, Xie L, Wu X, Li X (2023). "Inulin alleviates offspring asthma by altering maternal intestinal microbiome composition to increase short-chain fatty acids". PLOS ONE. 18 (4): e0283105. Bibcode:2023PLoSO..1883105Y. doi:10.1371/journal.pone.0283105. PMC 10072493. PMID 37014871.
  26. ^ Kim YA, Keogh JB, Clifton PM (June 2018). "Probiotics, prebiotics, synbiotics and insulin sensitivity". Nutrition Research Reviews. 31 (1): 35–51. doi:10.1017/S095442241700018X. PMID 29037268.
  27. ^ a b Kimura I, Ichimura A, Ohue-Kitano R, Igarashi M (January 2020). "Free Fatty Acid Receptors in Health and Disease". Physiological Reviews. 100 (1): 171–210. doi:10.1152/physrev.00041.2018. PMID 31487233. S2CID 201845937.
  28. ^ Loona DP, Das B, Kaur R, Kumar R, Yadav AK (2023). "Free Fatty Acid Receptors (FFARs): Emerging Therapeutic Targets for the Management of Diabetes Mellitus". Current Medicinal Chemistry. 30 (30): 3404–3440. doi:10.2174/0929867329666220927113614. PMID 36173072. S2CID 252598831.
  29. ^ a b c Kuwahara A, Kuwahara Y, Inui T, Marunaka Y (March 2018). "Regulation of Ion Transport in the Intestine by Free Fatty Acid Receptor 2 and 3: Possible Involvement of the Diffuse Chemosensory System". International Journal of Molecular Sciences. 19 (3): 735. doi:10.3390/ijms19030735. PMC 5877596. PMID 29510573.
  30. ^ a b c d e Zhang D, Jian YP, Zhang YN, Li Y, Gu LT, Sun HH, Liu MD, Zhou HL, Wang YS, Xu ZX (August 2023). "Short-chain fatty acids in diseases". Cell Communication and Signaling. 21 (1): 212. doi:10.1186/s12964-023-01219-9. PMC 10436623. PMID 37596634.
  31. ^ Won YJ, Lu VB, Puhl HL, Ikeda SR (December 2013). "βべーた-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3". The Journal of Neuroscience. 33 (49): 19314–25. doi:10.1523/JNEUROSCI.3102-13.2013. PMC 3850046. PMID 24305827.
  32. ^ a b Christiansen CB, Gabe MB, Svendsen B, Dragsted LO, Rosenkilde MM, Holst JJ (July 2018). "The impact of short-chain fatty acids on GLP-1 and PYY secretion from the isolated perfused rat colon". American Journal of Physiology. Gastrointestinal and Liver Physiology. 315 (1): G53–G65. doi:10.1152/ajpgi.00346.2017. PMID 29494208. S2CID 3633401.
  33. ^ Mikami D, Kobayashi M, Uwada J, Yazawa T, Kamiyama K, Nishimori K, Nishikawa Y, Nishikawa S, Yokoi S, Taniguchi T, Iwano M (2020). "AR420626, a selective agonist of GPR41/FFA3, suppresses growth of hepatocellular carcinoma cells by inducing apoptosis via HDAC inhibition". Therapeutic Advances in Medical Oncology. 12: 1758835920913432. doi:10.1177/1758835920913432. PMC 7517987. PMID 33014144.
  34. ^ Hoyles L, Snelling T, Umlai UK, Nicholson JK, Carding SR, Glen RC, McArthur S (March 2018). "Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier". Microbiome. 6 (1): 55. doi:10.1186/s40168-018-0439-y. PMC 5863458. PMID 29562936.
  35. ^ a b Teyani R, Moniri NH (August 2023). "Gut feelings in the islets: The role of the gut microbiome and the FFA2 and FFA3 receptors for short chain fatty acids on βべーた-cell function and metabolic regulation". British Journal of Pharmacology. 180 (24): 3113–3129. doi:10.1111/bph.16225. PMID 37620991. S2CID 261121846.
  36. ^ Al Mahri S, Malik SS, Al Ibrahim M, Haji E, Dairi G, Mohammad S (February 2022). "Free Fatty Acid Receptors (FFARs) in Adipose: Physiological Role and Therapeutic Outlook". Cells. 11 (4): 750. doi:10.3390/cells11040750. PMC 8870169. PMID 35203397.
  37. ^ Voltolini C, Battersby S, Etherington SL, Petraglia F, Norman JE, Jabbour HN (January 2012). "A novel antiinflammatory role for the short-chain fatty acids in human labor". Endocrinology. 153 (1): 395–403. doi:10.1210/en.2011-1457. hdl:20.500.11820/7035e8fd-062a-491a-9943-f20ad03844dd. PMID 22186417. S2CID 34431654.
  38. ^ Zamarbide M, Martinez-Pinilla E, Gil-Bea F, Yanagisawa M, Franco R, Perez-Mediavilla A (March 2022). "Genetic Inactivation of Free Fatty Acid Receptor 3 Impedes Behavioral Deficits and Pathological Hallmarks in the APPswe Alzheimer's Disease Mouse Model". International Journal of Molecular Sciences. 23 (7): 3533. doi:10.3390/ijms23073533. PMC 8999053. PMID 35408893.
  39. ^ a b c Kimura I, Inoue D, Maeda T, Hara T, Ichimura A, Miyauchi S, Kobayashi M, Hirasawa A, Tsujimoto G (May 2011). "Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41)". Proceedings of the National Academy of Sciences of the United States of America. 108 (19): 8030–5. Bibcode:2011PNAS..108.8030K. doi:10.1073/pnas.1016088108. PMC 3093469. PMID 21518883.
  40. ^ Cox MA, Jackson J, Stanton M, Rojas-Triana A, Bober L, Laverty M, Yang X, Zhu F, Liu J, Wang S, Monsma F, Vassileva G, Maguire M, Gustafson E, Bayne M, Chou CC, Lundell D, Jenh CH (November 2009). "Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines". World Journal of Gastroenterology. 15 (44): 5549–57. doi:10.3748/wjg.15.5549. PMC 2785057. PMID 19938193.
  41. ^ a b c Miyasato S, Iwata K, Mura R, Nakamura S, Yanagida K, Shindou H, Nagata Y, Kawahara M, Yamaguchi S, Aoki J, Inoue A, Nagamune T, Shimizu T, Nakamura M (January 2023). "Constitutively active GPR43 is crucial for proper leukocyte differentiation". FASEB Journal. 37 (1): e22676. doi:10.1096/fj.202201591R. PMID 36468834. S2CID 254244683.
  42. ^ Le Poul E, Loison C, Struyf S, Springael JY, Lannoy V, Decobecq ME, Brezillon S, Dupriez V, Vassart G, Van Damme J, Parmentier M, Detheux M (July 2003). "Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation". The Journal of Biological Chemistry. 278 (28): 25481–9. doi:10.1074/jbc.M301403200. PMID 12711604.
  43. ^ Yonezawa T, Kobayashi Y, Obara Y (January 2007). "Short-chain fatty acids induce acute phosphorylation of the p38 mitogen-activated protein kinase/heat shock protein 27 pathway via GPR43 in the MCF-7 human breast cancer cell line". Cellular Signalling. 19 (1): 185–93. doi:10.1016/j.cellsig.2006.06.004. PMID 16887331.
  44. ^ Al Mahri S, Al Ghamdi A, Akiel M, Al Aujan M, Mohammad S, Aziz MA (May 2020). "Free fatty acids receptors 2 and 3 control cell proliferation by regulating cellular glucose uptake". World Journal of Gastrointestinal Oncology. 12 (5): 514–525. doi:10.4251/wjgo.v12.i5.514. PMC 7235185. PMID 32461783.
  45. ^ de Vos WM, Tilg H, Van Hul M, Cani PD (May 2022). "Gut microbiome and health: mechanistic insights". Gut. 71 (5): 1020–1032. doi:10.1136/gutjnl-2021-326789. PMC 8995832. PMID 35105664.
  46. ^ Iacobucci G (March 2023). "Appetite suppressant semaglutide is to be made available to treat obesity in England". BMJ (Clinical Research Ed.). 380: 556. doi:10.1136/bmj.p556. PMID 36889753. S2CID 257379156.
  47. ^ Gabriel FC, Fantuzzi G (December 2019). "The association of short-chain fatty acids and leptin metabolism: a systematic review". Nutrition Research. 72: 18–35. doi:10.1016/j.nutres.2019.08.006. PMID 31669116. S2CID 155928278.
  48. ^ Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F (June 2016). "From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites". Cell. 165 (6): 1332–1345. doi:10.1016/j.cell.2016.05.041. PMID 27259147. S2CID 8562345.
  49. ^ Lee DH, Heo KS, Myung CS (July 2023). "Gαあるふぁi -coupled GPR41 activation increases Ca2+ influx in C2C12 cells and shows a therapeutic effect in diabetic animals". Obesity. 31 (7): 1871–1883. doi:10.1002/oby.23786. PMID 37309717. S2CID 259147907.
  50. ^ a b Pluznick JL (April 2017). "Microbial Short-Chain Fatty Acids and Blood Pressure Regulation". Current Hypertension Reports. 19 (4): 25. doi:10.1007/s11906-017-0722-5. PMC 5584783. PMID 28315048.
  51. ^ a b c Kaye DM, Shihata WA, Jama HA, Tsyganov K, Ziemann M, Kiriazis H, Horlock D, Vijay A, Giam B, Vinh A, Johnson C, Fiedler A, Donner D, Snelson M, Coughlan MT, Phillips S, Du XJ, El-Osta A, Drummond G, Lambert GW, Spector TD, Valdes AM, Mackay CR, Marques FZ (April 2020). "Deficiency of Prebiotic Fiber and Insufficient Signaling Through Gut Metabolite-Sensing Receptors Leads to Cardiovascular Disease". Circulation. 141 (17): 1393–1403. doi:10.1161/CIRCULATIONAHA.119.043081. hdl:10536/DRO/DU:30135388. PMID 32093510. S2CID 211476145.
  52. ^ a b Dinakis E, Nakai M, Gill PA, Yiallourou S, Sata Y, Muir J, Carrington M, Head GA, Kaye DM, Marques FZ (November 2021). "The Gut Microbiota and Their Metabolites in Human Arterial Stiffness". Heart, Lung & Circulation. 30 (11): 1716–1725. doi:10.1016/j.hlc.2021.07.022. PMID 34452845. S2CID 237340692.
  53. ^ Poll BG, Xu J, Jun S, Sanchez J, Zaidman NA, He X, Lester L, Berkowitz DE, Paolocci N, Gao WD, Pluznick JL (April 2021). "Acetate, a Short-Chain Fatty Acid, Acutely Lowers Heart Rate and Cardiac Contractility Along with Blood Pressure". The Journal of Pharmacology and Experimental Therapeutics. 377 (1): 39–50. doi:10.1124/jpet.120.000187. PMC 7985618. PMID 33414131.
  54. ^ a b R Muralitharan R, Marques FZ (February 2021). "Diet-related gut microbial metabolites and sensing in hypertension". Journal of Human Hypertension. 35 (2): 162–169. doi:10.1038/s41371-020-0388-3. PMID 32733062. S2CID 220881080.
  55. ^ Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, Blanchard C, Junt T, Nicod LP, Harris NL, Marsland BJ (February 2014). "Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis". Nature Medicine. 20 (2): 159–66. doi:10.1038/nm.3444. PMID 24390308. S2CID 35298402.
  56. ^ a b c Ito T, Nakanishi Y, Shibata R, Sato N, Jinnohara T, Suzuki S, Suda W, Hattori M, Kimura I, Nakano T, Yamaide F, Shimojo N, Ohno H (2023). "The propionate-GPR41 axis in infancy protects from subsequent bronchial asthma onset". Gut Microbes. 15 (1): 2206507. doi:10.1080/19490976.2023.2206507. PMC 10158560. PMID 37131293.
  57. ^ Depner M, Taft DH, Kirjavainen PV, Kalanetra KM, Karvonen AM, Peschel S, Schmausser-Hechfellner E, Roduit C, Frei R, Lauener R, Divaret-Chauveau A, Dalphin JC, Riedler J, Roponen M, Kabesch M, Renz H, Pekkanen J, Farquharson FM, Louis P, Mills DA, von Mutius E, Ege MJ (November 2020). "Maturation of the gut microbiome during the first year of life contributes to the protective farm effect on childhood asthma". Nature Medicine. 26 (11): 1766–1775. doi:10.1038/s41591-020-1095-x. hdl:2164/16359. PMID 33139948. S2CID 226244474.
  58. ^ Arrieta MC, Stiemsma LT, Dimitriu PA, Thorson L, Russell S, Yurist-Doutsch S, Kuzeljevic B, Gold MJ, Britton HM, Lefebvre DL, Subbarao P, Mandhane P, Becker A, McNagny KM, Sears MR, Kollmann T, Mohn WW, Turvey SE, Finlay BB (September 2015). "Early infancy microbial and metabolic alterations affect risk of childhood asthma". Science Translational Medicine. 7 (307): 307ra152. doi:10.1126/scitranslmed.aab2271. PMID 26424567. S2CID 206687974.
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