G-protein-coupled receptors as fat sensors

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 15, Issue 2, 2012, Pages 112-116

  Vinolo, Marco A R ^a   Hirabara, Sandro M ^b   Curi, Rui ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b University Cruzeiro do Sul   (Brazil)

Author keywords

fatty acids; GPR119; GPR120; GPR40; GPR43

Indexed keywords

FAT; FATTY ACID; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 119; G PROTEIN COUPLED RECEPTOR 120; G PROTEIN COUPLED RECEPTOR 40; G PROTEIN COUPLED RECEPTOR 41; G PROTEIN COUPLED RECEPTOR 43; G PROTEIN COUPLED RECEPTOR 84; GLUCAGON; INCRETIN; INSULIN; UNCLASSIFIED DRUG;

CARDIOVASCULAR DISEASE; DYSLIPIDEMIA; GLUCAGON RELEASE; HORMONAL REGULATION; HUMAN; INFLAMMATION; INSULIN RELEASE; INSULIN RESISTANCE; LEUKOCYTE ACTIVATION; METABOLIC SYNDROME X; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS INSUFFICIENCY; RECEPTOR UPREGULATION; REVIEW; SENSOR;

ANIMALS; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; DYSLIPIDEMIAS; FATTY ACIDS; FEEDING BEHAVIOR; GASTROINTESTINAL TRACT; HUMANS; INCRETINS; INFLAMMATION; INSULIN; INSULIN RESISTANCE; INSULIN-SECRETING CELLS; LEUKOCYTES; LIGANDS; OBESITY; RECEPTORS, G-PROTEIN-COUPLED;

EID: 84857041125     PISSN: 13631950     EISSN: 14736519     Source Type: Journal    
DOI: 10.1097/MCO.0b013e32834f4598     Document Type: Review

References (47)

1. Takahashi HK, Cambiaghi, TD, Luchessi A, et al. Activation of survival and apoptotic signaling pathways in lymphocytes exposed to palmitic acid. J Cell Physiol 2012; 227:339-350.
2. Rodrigues HG, Vinolo MA, Magdalon J, et al. Dietary free oleic and linoleic acid enhances neutrophil function and modulates the inflammatory response in rats. Lipids 2010; 45:809-819.
3. Hansen KB, Rosenkilde MM, Knop FK, et al. 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J Clin Endocr Metab 2011; 96:E1409-E1417.
4. Keane DC, Takahashi HK, Dhayal S, et al. Arachidonic acid actions on functional integrity and attenuation of the negative effects of palmitic acid in a clonal pancreatic beta-cell line. Clin Sci (Lond) 2011; 120:195-206.
5. Martins de Lima T, Gorjao R, Hatanaka E, et al. Mechanisms by which fatty acids regulate leucocyte function. Clin Sci (Lond) 2007; 113:65-77. (Pubitemid 47066026)
6. Wellendorph P, Johansen LD, Brauner-Osborne H. Molecular pharmacology of promiscuous seven transmembrane receptors sensing organic nutrients. Mol Pharmacol 2009; 76:453-465.
7. Sawzdargo M, George SR, Nguyen T, et al. A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1. Biochem Biophys Res Commun 1997; 239: 543-547. (Pubitemid 27489000)
8. Briscoe CP, Tadayyon M, Andrews JL, et al. The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J Biol Chem 2003; 278:11303-11311. (Pubitemid 36792687)
9. Kotarsky K, Nilsson NE, Olde B, et al. Progress in methodology. Improved reporter gene assays used to identify ligands acting on orphan seventransmembrane receptors. Pharmacol Toxicol 2003; 93:249-258.
10. Brown AJ, Goldsworthy SM, Barnes AA, et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 2003; 278:11312-11319. (Pubitemid 36792688)
11. Nilsson NE, Kotarsky K, Owman C, et al. Identification of a free fatty acid receptor, FFA2R, expressed on leukocytes and activated by short-chain fatty acids. Biochem Biophys Res Commun 2003; 303:1047-1052. (Pubitemid 36390250)
12. Itoh Y, Kawamata Y, Harada M, et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40. Nature 2003; 422:173-176. (Pubitemid 36362750)
13. Edfalk S, Steneberg P, Edlund H. Gpr40 is expressed in enteroendocrine cells and mediates free fatty acid stimulation of incretin secretion. Diabetes 2008; 57:2280-2287.
14. Hara T, Hirasawa A, Sun Q, et al. Novel selective ligands for free fatty acid receptors GPR120 and GPR40. Naunyn Schmiedebergs Arch Pharmacol 2009; 380:247-255.
15. Hirasawa A, Tsumaya K, Awaji T, et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 2005; 11: 90-94. (Pubitemid 40215843)
16. Cox HM, Tough IR, Woolston AM, et al. Peptide YY is critical for acylethanolamine receptor Gpr119-induced activation of gastrointestinal mucosal responses. Cell Metab 2010; 11:532-542.
17. Lauffer LM, Iakoubov R, Brubaker PL. GPR119 is essential for oleoylethanolamide-induced glucagon-like peptide-1 secretion from the intestinal enteroendocrine L-cell. Diabetes 2009; 58:1058-1066.
18. Kaji I, Karaki S, Tanaka R, et al. Density distribution of free fatty acid receptor 2 (FFA2)-expressing and GLP-1-producing enteroendocrine L cells in human and rat lower intestine, and increased cell numbers after ingestion of fructooligosaccharide. J Mol Histol 2010; 42:27-38.
19. Girard J. The incretins: From the concept to their use in the treatment of type 2 diabetes. Part A. Incretins: Concept and physiological functions. Diabetes Metab 2008; 34:550-559.
20. Freeland KR, Wolever TM. Acute effects of intravenous and rectal acetate on glucagon-like peptide-1, peptide YY, ghrelin, adiponectin and tumour necrosis factor-Alpha. Br J Nutr 2010; 103:460-466.
21. Karaki S, Tazoe H, Hayashi H, et al. Expression of the short-chain fatty acid receptor, GPR43, in the human colon. J Mol Histol 2008; 39:135-142. (Pubitemid 351422023)
22. Liou AP, Lu X, Sei Y, et al. The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology 2010; 140:903-912.
23. Tanaka T, Katsuma S, Adachi T, et al. Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn Schmiedebergs Arch Pharmacol 2008; 377:523-527.
24. Kebede MA, Alquier T, Latour MG, et al. Lipid receptors and islet function: Therapeutic implications? Diabetes Obes Metab 2009; 11 (Suppl. 4):10-20.
25. Ning Y, O'Neill K, Lan H, et al. Endogenous and synthetic agonists of GPR119 differ in signalling pathways and their effects on insulin secretion in MIN6c4 insulinoma cells. Br J Pharmacol 2008; 155:1056-1065.
26. Semple G, Ren A, Fioravanti B, et al. Discovery of fused bicyclic agonists of the orphan G-protein coupled receptor GPR119 with in vivo activity in rodent models of glucose control. Bioorg Med Chem Lett 2011; 21:3134-3141. These authors developed and tested several GPR119 agonists. They found some agonists were able to decrease blood glucose and glycated hemoglobin (HbA1c) in a rat diabetic model, suggesting clinical relevance of these compounds.
27. Yoshida S, Ohishi T, Matsui T, et al. The role of small molecule GPR119 agonist, AS1535907, in glucose-stimulated insulin secretion and pancreatic beta-cell function. Diabetes Obes Metab 2011; 13:34-41. This article evaluated the effects of AS1535907, a GPR119 agonist, on isolated and 'in-vivo' beta-cell function. This compound was effective in improving the first phase of glucose-mediated insulin secretion, as well as the expression of genes involved in beta-cell function and insulin production.
28. Flodgren E, Olde B, Meidute-Abaraviciene S, et al. GPR40 is expressed in glucagon producing cells and affects glucagon secretion. Biochem Biophys Res Commun 2007; 354:240-245. (Pubitemid 46123225)
29. Flock G, Holland D, Seino Y, et al. GPR119 regulates murine glucose homeostasis through incretin receptor-dependent and independent mechanisms. Endocrinology 2011; 152:374-383. This study showed that GPR119 activation participates in the glucose homeostasis by its effects on enteroendocrine cells (by increasing incretin secretion) and on pancreatic beta-cells (by improving insulin secretion).
30. Yoshida S, Tanaka H, Oshima H, et al. AS1907417, a novel GPR119 agonist, as an insulinotropic and beta-cell preservative agent for the treatment of type 2 diabetes. Biochem Biophys Res Commun 2010; 400:745-751.
31. Overton HA, Fyfe MC, Reynet C. GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity. Br J Pharmacol 2008; 153 (Suppl. 1):S76-S81. (Pubitemid 351340991)
32. Ge H, Li X, Weiszmann J, et al. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology 2008; 149:4519-4526.
33. Ferchaud-Roucher V, Pouteau E, Piloquet H, et al. Colonic fermentation from lactulose inhibits lipolysis in overweight subjects. Am J Physiol Endocrinol Metab 2005; 289:E716-E720. (Pubitemid 41356096)
34. Zaibi MS, Stocker CJ, O'Dowd J, et al. Roles of GPR41 and GPR43 in leptin secretory responses of murine adipocytes to short chain fatty acids. FEBS Lett 2010; 584:2381-2386.
35. Xiong Y, Miyamoto N, Shibata K, et al. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc Natl Acad Sci 2004; 101:1045-1050. (Pubitemid 38160581)
36. Al-Lahham SH, Roelofsen H, Priebe M, et al. Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Invest 2010; 40:401-407.
37. Oh DY, Talukdar S, Bae EJ, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010; 142:687-698. This is the first article that shows the insulin-sensitizing effects of omega-3 fatty acids mediated by GPR120 activation in leukocytes and adipocytes. The involved mechanisms are identified and described, introducing new directions for the development of therapeutic interventions based on omega-3 fatty acids.
38. Kimura I, Inoue D, Maeda T, et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci 2011; 108:8030-8035. This was the first study to show how short-chain fatty acids and ketone bodies can modulate energy expenditure by activation of GPR41 and regulation of SNS activity. The relevance of these effects in different conditions is discussed.
39. Samuel BS, Shaito A, Motoike T, et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-Acid binding G proteincoupled receptor, Gpr41. Proc Natl Acad Sci 2008; 105:16767-16772.
40. Maslowski KM, Vieira AT, Ng A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 2009; 461:1282-1286. These authors describe and discuss the role of short-chain fatty acids produced by gut microbiota on inflammatory resolution through GPR43 activation, establishing a molecular link among diet, gut microbiota, and immune and inflammatory responses.
41. Sina C, Gavrilova O, Forster M, et al. G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol 2009; 183:7514-7522.
42. Vinolo MA, Ferguson GJ, Kulkarni S, et al. SCFAs induce mouse neutrophil chemotaxis through the GPR43 receptor. PLoS One 2011; 6:e21205.
43. Vinolo MA, Rodrigues HG, Hatanaka E, et al. Suppressive effect of shortchain fatty acids on production of proinflammatory mediators by neutrophils. J Nutr Biochem 2011; 22:849-855.
44. Vinolo MA, Rodrigues HG, Hatanaka E, et al. Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites. Clin Sci (Lond) 2009; 117:331-338.
45. Wang J, Wu X, Simonavicius N, et al. Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84. J Biol Chem 2006; 281:34457-34464. (Pubitemid 46036653)
46. Fujita T, Matsuoka T, Honda T, et al. A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J Investig Dermatol 2011; 131:1660-1667. These authors showed that GW9508, a GPR40 agonist, is able to inhibit the production of cytokines and chemokines induced by TNF-A and IFN-g by keratinocytes, suggesting an important role of GPR40 activation in the control of inflammatory response in the skin.
47. Rodrigues HG, Vinolo MA, Magdalon J, et al. Oral administration of oleic or linoleic acid accelerates the inflammatory phase of wound healing. J Invest Dermatol 2012; 132:208-215.