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http://dx.doi.org/10.4062/biomolther.2020.213

Development of Free Fatty Acid Receptor 4 (FFA4/GPR120) Agonists in Health Science  

Son, So-Eun (Department of Pharmacy, College of Pharmacy, and Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University)
Kim, Nam-Jung (Department of Pharmacy, College of Pharmacy, and Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University)
Im, Dong-Soon (Department of Pharmacy, College of Pharmacy, and Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University)
Publication Information
Biomolecules & Therapeutics / v.29, no.1, 2021 , pp. 22-30 More about this Journal
Abstract
Till the 21st century, fatty acids were considered as merely building blocks for triglycerides, phospholipids, or cholesteryl esters. However, the discovery of G protein-coupled receptors (GPCRs) for free fatty acids at the beginning of the 21st century challenged that idea and paved way for a new field of research, merged into the field of receptor pharmacology for intercellular lipid mediators. Among the GPCRs for free fatty acids, free fatty acid receptor 4 (FFA4, also known as GPR120) recognizes long-chain polyunsaturated fatty acids such as DHA and EPA. It is significant in drug discovery because it regulates obesity-induced metaflammation and GLP-1 secretion. Our study reviews information on newly developed FFA4 agonists and their application in pathophysiologic studies and drug discovery. It also offers a potency comparison of the FFA4 agonists in an AP-TGF-α shedding assay.
Keywords
GPR120; FFA4; G protein-coupled receptor; Agonist; Drug development;
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1 Wang, C., Liu, Y., Pan, Y. and Jin, H. (2020) Effect of GSK-137647A, the first non-carboxylic FFA4 agonist, on the osteogenic and adipogenic differentiation of bone mesenchymal stem cells in db/db mice. J. Pharm. Pharmacol. 72, 461-469.   DOI
2 Wang, Y., Xie, T., Zhang, D. and Leung, P. S. (2019) GPR120 protects lipotoxicity-induced pancreatic β-cell dysfunction through regulation of PDX1 expression and inhibition of islet inflammation. Clin. Sci. (Lond.) 133, 101-116.   DOI
3 Watterson, K. R., Hansen, S. V., Hudson, B. D., Alvarez-Curto, E., Raihan, S. Z., Azevedo, C. M., Martin, G., Dunlop, J., Yarwood, S. J. and Ulven, T. (2017) Probe-dependent negative allosteric modulators of the long-chain free fatty acid receptor FFA4. Mol. Pharmacol. 91, 630-641.   DOI
4 Wellhauser, L. and Belsham, D. D. (2014) Activation of the omega-3 fatty acid receptor GPR120 mediates anti-inflammatory actions in immortalized hypothalamic neurons. J. Neuroinflammation 11, 60.   DOI
5 Oh, D. Y., Walenta, E., Akiyama, T. E., Lagakos, W. S., Lackey, D., Pessentheiner, A. R., Sasik, R., Hah, N., Chi, T. J., Cox, J. M., Powels, M. A., Di Salvo, J., Sinz, C., Watkins, S. M., Armando, A. M., Chung, H., Evans, R. M., Quehenberger, O., McNelis, J., BognerStrauss, J. G. and Olefsky, J. M. (2014) A Gpr120-selective agonist improves insulin resistance and chronic inflammation in obese mice. Nat. Med. 20, 942-947.   DOI
6 Patnaik, S. S., Lagana, A. S., Vitale, S. G., Buttice, S., Noventa, M., Gizzo, S., Valenti, G., Rapisarda, A. M. C., La Rosa, V. L. and Magno, C. (2017) Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome. Arch. Gynecol. Obstet. 295, 1341-1359.   DOI
7 Raptis, D. A., Limani, P., Jang, J. H., Ungethum, U., Tschuor, C., Graf, R., Humar, B. and Clavien, P. A. (2014) GPR120 on Kupffer cells mediates hepatoprotective effects of omega3-fatty acids. J. Hepatol. 60, 625-632.   DOI
8 Gong, Z., Yoshimura, M., Aizawa, S., Kurotani, R., Zigman, J. M., Sakai, T. and Sakata, I. (2014) G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro. Am. J. Physiol. Endocrinol. Metab. 306, E28-E35.   DOI
9 Fredriksson, R., Lagerstrom, M. C., Lundin, L. and Schioth, H. B. (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 63, 1256-1272.   DOI
10 Garrel, G., Simon, V., Denoyelle, C., Cruciani-Guglielmacci, C., Migrenne, S., Counis, R., Magnan, C. and Cohen-Tannoudji, J. (2011) Unsaturated fatty acids stimulate LH secretion via novel PKCepsilon and -theta in gonadotrope cells and inhibit GnRH-induced LH release. Endocrinology 152, 3905-3916.   DOI
11 Gozal, D., Qiao, Z., Almendros, I., Zheng, J., Khalyfa, A., Shimpukade, B. and Ulven, T. (2016) Treatment with TUG891, a free fatty acid receptor 4 agonist, restores adipose tissue metabolic dysfunction following chronic sleep fragmentation in mice. Int. J. Obes. (Lond.) 40, 1143-1149.   DOI
12 Graciano, M. F., Valle, M. M., Curi, R. and Carpinelli, A. R. (2013) Evidence for the involvement of GPR40 and NADPH oxidase in palmitic acid-induced superoxide production and insulin secretion. Islets 5, 139-148.   DOI
13 Han, L., Song, S., Niu, Y., Meng, M. and Wang, C. (2017) Eicosapentaenoic acid (EPA) induced macrophages activation through GPR120-mediated Raf-ERK1/2-IKKβ-NF-κB p65 signaling pathways. Nutrients 9, 937.   DOI
14 Hansen, K. B., Rosenkilde, M. M., Knop, F. K., Wellner, N., Diep, T. A., Rehfeld, J. F., Andersen, U. B., Holst, J. J. and Hansen, H. S. (2011) 2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans. J. Clin. Endocrinol. Metab. 96, E1409-E1417.   DOI
15 Hansen, S. V. and Ulven, T. (2017) Pharmacological tool compounds for the free fatty acid receptor 4 (FFA4/GPR120). Handb. Exp. Pharmacol. 236, 33-56.   DOI
16 Serhan, C. N., Chiang, N. and Dalli, J. (2018) New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration. Mol. Aspects Med. 64, 1-17.   DOI
17 Zhao, C., Zhou, J., Meng, Y., Shi, N., Wang, X., Zhou, M., Li, G. and Yang, Y. (2020) DHA sensor GPR120 in host defense exhibits the dual characteristics of regulating dendritic cell function and skewing the balance of Th17/Tregs. Int. J. Biol. Sci. 16, 374-387.   DOI
18 Zhao, J., Wang, H., Shi, P., Wang, W. and Sun, Y. (2017) GPR120, a potential therapeutic target for experimental colitis in IL-10 deficient mice. Oncotarget 8, 8397-8405.   DOI
19 Zhao, Y. Y., Fu, H., Liang, X. Y., Zhang, B. L., Wei, L. L., Zhu, J. X., Chen, M. W. and Zhao, Y. F. (2019) Lipopolysaccharide inhibits GPR120 expression in macrophages via Toll-like receptor 4 and p38 MAPK activation. Cell Biol. Int. doi: 10.1002/cbin.11204 [Online ahead of print].   DOI
20 Schilperoort, M., van Dam, A. D., Hoeke, G., Shabalina, I. G., Okolo, A., Hanyaloglu, A. C., Dib, L. H., Mol, I. M., Caengprasath, N., Chan, Y. W., Damak, S., Miller, A. R., Coskun, T., Shimpukade, B., Ulven, T., Kooijman, S., Rensen, P. C. and Christian, M. (2018) The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat. EMBO Mol. Med. 10, e8047.   DOI
21 Shimpukade, B., Hudson, B. D., Hovgaard, C. K., Milligan, G. and Ulven, T. (2012) Discovery of a potent and selective GPR120 agonist. J. Med. Chem. 55, 4511-4515.   DOI
22 Son, S. E., Park, S. J., Koh, J. M. and Im, D. S. (2020) Free fatty acid receptor 4 (FFA4) activation ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by increasing regulatory T cells in mice. Acta Pharmacol. Sin. 41, 1337-1347.   DOI
23 Song, T., Zhou, Y., Peng, J., Tao, Y. X., Yang, Y., Xu, T., Peng, J., Ren, J., Xiang, Q. and Wei, H. (2016) GPR120 promotes adipogenesis through intracellular calcium and extracellular signal-regulated kinase 1/2 signal pathway. Mol. Cell. Endocrinol. 434, 1-13.   DOI
24 Sparks, S. M., Chen, G., Collins, J. L., Danger, D., Dock, S. T., Jayawickreme, C., Jenkinson, S., Laudeman, C., Leesnitzer, M. A., Liang, X., Maloney, P., McCoy, D. C., Moncol, D., Rash, V., Rimele, T., Vulimiri, P., Way, J. M. and Ross, S. (2014) Identification of diarylsulfonamides as agonists of the free fatty acid receptor 4 (FFA4/GPR120). Bioorg. Med. Chem. Lett. 24, 3100-3103.   DOI
25 Huang, Z., Guo, F., Xia, Z., Liang, Y., Lei, S., Tan, Z., Ma, L. and Fu, P. (2020) Activation of GPR120 by TUG891 ameliorated cisplatininduced acute kidney injury via repressing ER stress and apoptosis. Biomed. Pharmacother. 126, 110056.   DOI
26 Hara, T., Hirasawa, A., Sun, Q., Sadakane, K., Itsubo, C., Iga, T., Adachi, T., Koshimizu, T. A., Hashimoto, T., Asakawa, Y. and Tsujimoto, G. (2009) Novel selective ligands for free fatty acid receptors GPR120 and GPR40. Naunyn Schmiedebergs Arch. Pharmacol. 380, 247-255.   DOI
27 Hasan, A. U., Ohmori, K., Hashimoto, T., Kamitori, K., Yamaguchi, F., Noma, T., Igarashi, J., Tsuboi, K., Tokuda, M., Nishiyama, A. and Kohno, M. (2017) GPR120 in adipocytes has differential roles in the production of pro-inflammatory adipocytokines. Biochem. Biophys. Res. Commun. 486, 76-82.   DOI
28 Hirasawa, A., Tsumaya, K., Awaji, T., Katsuma, S., Adachi, T., Yamada, M., Sugimoto, Y., Miyazaki, S. and Tsujimoto, G. (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat. Med. 11, 90-94.   DOI
29 Hudson, B. D., Shimpukade, B., Mackenzie, A. E., Butcher, A. J., Pediani, J. D., Christiansen, E., Heathcote, H., Tobin, A. B., Ulven, T. and Milligan, G. (2013) The pharmacology of TUG-891, a potent and selective agonist of the free fatty acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism. Mol. Pharmacol. 84, 710-725.   DOI
30 Ichimura, A., Hirasawa, A., Poulain-Godefroy, O., Bonnefond, A., Hara, T., Yengo, L., Kimura, I., Leloire, A., Liu, N. and Iida, K. (2012) Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature 483, 350-354.   DOI
31 Im, D. S. (2012) Omega-3 fatty acids in anti-inflammation (pro-resolution) and GPCRs. Prog. Lipid Res. 51, 232-237.   DOI
32 Kern, P. A., Finlin, B. S., Ross, D., Boyechko, T., Zhu, B., Grayson, N., Sims, R. and Bland, J. S. (2017) Effects of KDT501 on metabolic parameters in insulin-resistant prediabetic humans. J. Endocr. Soc. 1, 650-659.   DOI
33 Wu, Q., Wang, H., Zhao, X., Shi, Y., Jin, M., Wan, B., Xu, H., Cheng, Y., Ge, H. and Zhang, Y. (2013) Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma. Oncogene 32, 5541-5550.   DOI
34 Yore, M. M., Syed, I., Moraes-Vieira, P. M., Zhang, T., Herman, M. A., Homan, E. A., Patel, R. T., Lee, J., Chen, S. and Peroni, O. D. (2014) Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159, 318-332.   DOI
35 Suckow, A. T. and Briscoe, C. P. (2017) Key questions for translation of FFA receptors: from pharmacology to medicines. Handb. Exp. Pharmacol. 236, 101-131.   DOI
36 Stone, V. M., Dhayal, S., Brocklehurst, K. J., Lenaghan, C., Sorhede Winzell, M., Hammar, M., Xu, X., Smith, D. M. and Morgan, N. G. (2014) GPR120 (FFAR4) is preferentially expressed in pancreatic d cells and regulates somatostatin secretion from murine islets of Langerhans. Diabetologia 57, 1182-1191.   DOI
37 Im, D. S. (2013) Intercellular lipid mediators and GPCR drug discovery. Biomol. Ther. (Seoul) 21, 411-422.   DOI
38 Inoue, A., Ishiguro, J., Kitamura, H., Arima, N., Okutani, M., Shuto, A., Higashiyama, S., Ohwada, T., Arai, H., Makide, K. and Aoki, J. (2012) TGFa shedding assay: an accurate and versatile method for detecting GPCR activation. Nat. Methods 9, 1021-1029.   DOI
39 Janssen, S., Laermans, J., Iwakura, H., Tack, J. and Depoortere, I. (2012) Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein. PLoS ONE 7, e40168.   DOI
40 Kang, S., Huang, J., Lee, B. K., Jung, Y. S., Im, E., Koh, J. M. and Im, D. S. (2018) Omega-3 polyunsaturated fatty acids protect human hepatoma cells from developing steatosis through FFA4 (GPR120). Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1863, 105-116.   DOI
41 Kim, H. J., Yoon, H. J., Kim, B. K., Kang, W. Y., Seong, S. J., Lim, M. S., Kim, S. Y. and Yoon, Y. R. (2016) G protein-coupled receptor 120 signaling negatively regulates osteoclast differentiation, survival, and function. J. Cell. Physiol. 231, 844-851.   DOI
42 Konda, V. R., Desai, A., Darland, G., Grayson, N. and Bland, J. S. (2014) KDT501, a derivative from hops, normalizes glucose metabolism and body weight in rodent models of diabetes. PLoS ONE 9, e87848.   DOI
43 Konno, Y., Ueki, S., Takeda, M., Kobayashi, Y., Tamaki, M., Moritoki, Y., Oyamada, H., Itoga, M., Kayaba, H., Omokawa, A. and Hirokawa, M. (2015) Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis. PLoS ONE 10, e0120386.   DOI
44 Li, Z., Zhou, Z. and Zhang, L. (2020) Current status of GPR40/FFAR1 modulators in medicinal chemistry (2016-2019): a patent review. Expert Opin. Ther. Pat. 30, 27-38.   DOI
45 Azevedo, C. M., Watterson, K. R., Wargent, E. T., Hansen, S. V., Hudson, B. D., Kepczynska, M. A., Dunlop, J., Shimpukade, B., Christiansen, E., Milligan, G., Stocker, C. J. and Ulven, T. (2016) Nonacidic free fatty acid receptor 4 agonists with antidiabetic activity. J. Med. Chem. 59, 8868-8878.   DOI
46 Sun, Q., Hirasawa, A., Hara, T., Kimura, I., Adachi, T., Awaji, T., Ishiguro, M., Suzuki, T., Miyata, N. and Tsujimoto, G. (2010) Structureactivity relationships of GPR120 agonists based on a docking simulation. Mol. Pharmacol. 78, 804-810.   DOI
47 Suzuki, T., Igari, S., Hirasawa, A., Hata, M., Ishiguro, M., Fujieda, H., Itoh, Y., Hirano, T., Nakagawa, H., Ogura, M., Makishima, M., Tsujimoto, G. and Miyata, N. (2008) Identification of G protein-coupled receptor 120-selective agonists derived from PPARg agonists. J. Med. Chem. 51, 7640-7644.   DOI
48 Takahashi, K., Fukushima, K., Onishi, Y., Minami, K., Otagaki, S., Ishimoto, K., Fukushima, N., Honoki, K. and Tsujiuchi, T. (2018) Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. Exp. Cell Res. 369, 54-60.   DOI
49 Su, X. L., Liu, Y. G., Shi, M., Zhao, Y. Y., Liang, X. Y., Zhang, L. J., Wei, L. L. and Zhao, Y. F. (2020) The GPR120 agonist TUG-891 inhibits the motility and phagocytosis of mouse alveolar macrophages. Biomed. Res. Int. 2020, 1706168.
50 Ahn, S. H., Park, S. Y., Baek, J. E., Lee, S. Y., Baek, W. Y., Lee, S. Y., Lee, Y. S., Yoo, H. J., Kim, H., Lee, S. H., Im, D. S., Lee, S. K., Kim, B. J. and Koh, J. M. (2016) Free fatty acid receptor 4 (GPR120) stimulates bone formation and suppresses bone resorption in the presence of elevated n-3 fatty acid levels. Endocrinology 157, 2621-2635.   DOI
51 Villegas-Comonfort, S., Takei, Y., Tsujimoto, G., Hirasawa, A. and Garcia-Sainz, J. A. (2017) Effects of arachidonic acid on FFA4 receptor: Signaling, phosphorylation and internalization. Prostaglandins Leukot. Essent. Fatty Acids 117, 1-10.   DOI
52 Takahashi, K., Fukushima, K., Onishi, Y., Node, Y., Inui, K., Fukushima, N., Honoki, K. and Tsujiuchi, T. (2017) Different effects of Gprotein-coupled receptor 120 (GPR120) and GPR40 on cell motile activity of highly migratory osteosarcoma cells. Biochem. Biophys. Res. Commun. 484, 675-680.   DOI
53 Tan, J. K., McKenzie, C., Marino, E., Macia, L. and Mackay, C. R. (2017) Metabolite-sensing G protein-coupled receptors-facilitators of diet-related immune regulation. Annu. Rev. Immunol. 35, 371-402.   DOI
54 Ulven, T. and Christiansen, E. (2015) Dietary fatty acids and their potential for controlling metabolic diseases through activation of FFA4/GPR120. Annu. Rev. Nutr. 35, 239-263.   DOI
55 Sun, M., Wu, W., Liu, Z. and Cong, Y. (2017) Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J. Gastroenterol. 52, 1-8.   DOI
56 Christian, M. (2020) Elucidation of the roles of brown and brite fat genes: GPR120 is a modulator of brown adipose tissue function. Exp. Physiol. 105, 1201-1205.   DOI
57 Briscoe, C. P., Peat, A. J., McKeown, S. C., Corbett, D. F., Goetz, A. S., Littleton, T. R., McCoy, D. C., Kenakin, T. P., Andrews, J. L., Ammala, C., Fornwald, J. A., Ignar, D. M. and Jenkinson, S. (2006) Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br. J. Pharmacol. 148, 619-628.   DOI
58 Chen, Y. L., Lin, Y. P., Sun, C. K., Huang, T. H., Yip, H. K. and Chen, Y. T. (2018a) Extracorporeal shockwave against inflammation mediated by GPR120 receptor in cyclophosphamide-induced rat cystitis model. Mol. Med. 24, 60.   DOI
59 Chen, Y., Zhang, D., Ho, K. W., Lin, S., Suen, W. C., Zhang, H., Zha, Z., Li, G. and Leung, P. S. (2018b) GPR120 is an important inflammatory regulator in the development of osteoarthritis. Arthritis Res. Ther. 20, 163.   DOI
60 Mo, Z., Tang, C., Li, H., Lei, J., Zhu, L., Kou, L., Li, H., Luo, S., Li, C., Chen, W. and Zhang, L. (2020) Eicosapentaenoic acid prevents inflammation induced by acute cerebral infarction through inhibition of NLRP3 inflammasome activation. Life Sci. 242, 117133.   DOI
61 Moran, B. M., Abdel-Wahab, Y. H., Flatt, P. R. and McKillop, A. M. (2014) Evaluation of the insulin-releasing and glucose-lowering effects of GPR120 activation in pancreatic β-cells. Diabetes Obes. Metab. 16, 1128-1139.   DOI
62 Murtaza, B., Hichami, A., Khan, A. S., Shimpukade, B., Ulven, T., Ozdener, M. H. and Khan, N. A. (2020) Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice. J. Lipid Res. 61, 133-142.   DOI
63 Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K. and Matsukura, S. (2001) A role for ghrelin in the central regulation of feeding. Nature 409, 194-198.   DOI
64 Oh, D. Y., Talukdar, S., Bae, E. J., Imamura, T., Morinaga, H., Fan, W., Li, P., Lu, W. J., Watkins, S. M. and Olefsky, J. M. (2010) GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 142, 687-698.   DOI
65 Finlin, B. S., Zhu, B., Kok, B. P., Godio, C., Westgate, P. M., Grayson, N., Sims, R., Bland, J. S., Saez, E. and Kern, P. A. (2017) The influence of a KDT501, a novel isohumulone, on adipocyte function in humans. Front. Endocrinol. 8, 255.   DOI
66 Christiansen, E., Watterson, K. R., Stocker, C. J., Sokol, E., Jenkins, L., Simon, K., Grundmann, M., Petersen, R. K., Wargent, E. T., Hudson, B. D., Kostenis, E., Ejsing, C. S., Cawthorne, M. A., Milligan, G. and Ulven, T. (2015) Activity of dietary fatty acids on FFA1 and FFA4 and characterisation of pinolenic acid as a dual FFA1/FFA4 agonist with potential effect against metabolic diseases. Br. J. Nutr. 113, 1677-1688.   DOI
67 Cornish, J., MacGibbon, A., Lin, J. M., Watson, M., Callon, K. E., Tong, P. C., Dunford, J. E., van der Does, Y., Williams, G. A., Grey, A. B., Naot, D. and Reid, I. R. (2008) Modulation of osteoclastogenesis by fatty acids. Endocrinology 149, 5688-5695.   DOI
68 Davenport, A. P., Alexander, S. P., Sharman, J. L., Pawson, A. J., Benson, H. E., Monaghan, A. E., Liew, W. C., Mpamhanga, C. P., Bonner, T. I. and Neubig, R. R. (2013) International union of basic and clinical pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol. Rev. 65, 967-986.   DOI
69 Egerod, K. L., Engelstoft, M. S., Lund, M. L., Grunddal, K. V., Zhao, M., Barir-Jensen, D., Nygaard, E. B., Petersen, N., Holst, J. J. and Schwartz, T. W. (2015) Transcriptional and functional characterization of the g protein-coupled receptor repertoire of gastric somatostatin cells. Endocrinology 156, 3909-3923.   DOI
70 Engelstoft, M. S., Park, W. M., Sakata, I., Kristensen, L. V., Husted, A. S., Osborne-Lawrence, S., Piper, P. K., Walker, A. K., Pedersen, M. H., Nohr, M. K., Pan, J., Sinz, C. J., Carrington, P. E., Akiyama, T. E., Jones, R. M., Tang, C., Ahmed, K., Offermanns, S., Egerod, K. L., Zigman, J. M. and Schwartz, T. W. (2013) Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells. Mol. Metab. 2, 376-392.   DOI