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Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

  • Namkung, Jun (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology) ;
  • Kim, Hail (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology) ;
  • Park, Sangkyu (Department of Biochemistry, College of Medicine, Catholic Kwandong University)
  • Received : 2015.09.30
  • Accepted : 2015.11.26
  • Published : 2015.12.31

Abstract

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment.

Keywords

References

  1. Alenina, N., Kikic, D., Todiras, M., Mosienko, V., Qadri, F., Plehm, R., Boye, P., Vilianovitch, L., Sohr, R., Tenner, K., et al. (2009). Growth retardation and altered autonomic control in mice lacking brain serotonin. Proc. Natl. Acad. Sci. USA 106, 10332-10337. https://doi.org/10.1073/pnas.0810793106
  2. Arase, K., Sakaguchi, T., and Bray, G.A. (1988). Effect of fenfluramine on sympathetic firing rate. Pharmacol. Biochem. Behav. 29, 675-680. https://doi.org/10.1016/0091-3057(88)90186-4
  3. Bertrand, R.L., Senadheera, S., Markus, I., Liu, L., Howitt, L., Chen, H., Murphy, T.V., Sandow, S.L., and Bertrand, P.P. (2011). A Western diet increases serotonin availability in rat small intestine. Endocrinology 152, 36-47. https://doi.org/10.1210/en.2010-0377
  4. Bouwknecht, J.A., van der Gugten, J., Hijzen, T.H., Maes, R.A., Hen, R., and Olivier, B. (2001). Male and female 5-HT(1B) receptor knockout mice have higher body weights than wildtypes. Physiol. Behav. 74, 507-516. https://doi.org/10.1016/S0031-9384(01)00589-3
  5. Brand, T., and Anderson, G.M. (2011). The measurement of plateletpoor plasma serotonin: a systematic review of prior reports and recommendations for improved analysis. Clin. Chem. 57, 1376-1386. https://doi.org/10.1373/clinchem.2011.163824
  6. Breisch, S.T., Zemlan, F.P., and Hoebel, B.G. (1976). Hyperphagia and obesity following serotonin depletion by intraventricular pchlorophenylalanine. Science 192, 382-385. https://doi.org/10.1126/science.130678
  7. Collins, S., Yehuda-Shnaidman, E., and Wang, H. (2010). Positive and negative control of Ucp1 gene transcription and the role of [beta]-adrenergic signaling networks. Int. J. Obes. 34, S28-S33. https://doi.org/10.1038/ijo.2010.180
  8. Colman, E., Golden, J., Roberts, M., Egan, A., Weaver, J., and Rosebraugh, C. (2012). The FDA's assessment of two drugs for chronic weight management. N Eng. J. Med. 367, 1577-1579. https://doi.org/10.1056/NEJMp1211277
  9. Crane, J.D., Palanivel, R., Mottillo, E.P., Bujak, A.L., Wang, H., Ford, R.J., Collins, A., Blumer, R.M., Fullerton, M.D., Yabut, J.M., et al. (2015). Inhibiting peripheral serotonin synthesis reduces obesity and metabolic dysfunction by promoting brown adipose tissue thermogenesis. Nat. Med. 21, 166-172. https://doi.org/10.1038/nm.3766
  10. Feldman, J.M. (1988). Effect of the monoamine oxidase inhibitors clorgyline and pargyline on the hyperphagia of obese mice. Behav. Brain Res. 29, 147-158. https://doi.org/10.1016/0166-4328(88)90062-9
  11. Gershon, M.D., and Ross, L.L. (1966). Location of sites of 5-hydroxytryptamine storage and metabolism by radioautography. J. Physiol. 186, 477-492. https://doi.org/10.1113/jphysiol.1966.sp008047
  12. Gershon, M.D., and Tack, J. (2007). The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 132, 397-414. https://doi.org/10.1053/j.gastro.2006.11.002
  13. Gres, S., Canteiro, S., Mercader, J., and Carpene, C. (2013). Oxidation of high doses of serotonin favors lipid accumulation in mouse and human fat cells. Mol. Nutr. Food Res. 57, 1089-1099. https://doi.org/10.1002/mnfr.201200681
  14. Gutknecht, L., Araragi, N., Merker, S., Waider, J., Sommerlandt, F.M., Mlinar, B., Baccini, G., Mayer, U., Proft, F., Hamon, M., et al. (2012). Impacts of brain serotonin deficiency following Tph2 inactivation on development and raphe neuron serotonergic specification. PLoS One 7, e43157. https://doi.org/10.1371/journal.pone.0043157
  15. Halford, J.C.G., and Blundell, J.E. (1996). The 5-HT1B receptor agonist CP-94,253 reduces food intake and preserves the behavioural satiety sequence. Physiol. Behav. 60, 933-939. https://doi.org/10.1016/0031-9384(96)00073-X
  16. Hannon, J., and Hoyer, D. (2008). Molecular biology of 5-HT receptors. Behav. Brain Res. 195, 198-213. https://doi.org/10.1016/j.bbr.2008.03.020
  17. Haub, S., Ritze, Y., Ladel, I., Saum, K., Hubert, A., Spruss, A., Trautwein, C., and Bischoff, S.C. (2011). Serotonin receptor type 3 antagonists improve obesity-associated fatty liver disease in mice. J. Pharmacol. Exp. Ther. 339, 790-798. https://doi.org/10.1124/jpet.111.181834
  18. Heal, D.J., Aspley, S., Prow, M.R., Jackson, H.C., Martin, K.F., and Cheetham, S.C. (1998). Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from d-amphetamine and d-fenfluramine. Int. J. Obes. Relat. Metab. Disord. 22 Suppl 1, S18-28; discussion S29.
  19. Heisler, L.K., Kanarek, R.B., and Gerstein, A. (1997). Fluoxetine decreases fat and protein intakes but not carbohydrate intake in male rats. Pharmacol. Biochem. Behav. 58, 767-773. https://doi.org/10.1016/S0091-3057(97)00036-1
  20. Heisler, L.K., Cowley, M.A., Tecott, L.H., Fan, W., Low, M.J., Smart, J.L., Rubinstein, M., Tatro, J.B., Marcus, J.N., Holstege, H., et al. (2002). Activation of central melanocortin pathways by fenfluramine. Science 297, 609-611. https://doi.org/10.1126/science.1072327
  21. Kennett, G.A., and Curzon, G. (1988). Evidence that hypophagia induced by mCPP and TFMPP requires 5-HT1C and 5-HT1B receptors; hypophagia induced by RU 24969 only requires 5-HT1B receptors. Psychopharmacology (Berl) 96, 93-100. https://doi.org/10.1007/BF02431539
  22. Keszthelyi, D., Troost, F.J., and Masclee, A.A.M. (2009). Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function. Neurogastroenterol. Motil. 21, 1239-1249. https://doi.org/10.1111/j.1365-2982.2009.01370.x
  23. Kim, H., Toyofuku, Y., Lynn, F.C., Chak, E., Uchida, T., Mizukami, H., Fujitani, Y., Kawamori, R., Miyatsuka, T., Kosaka, Y., et al. (2010). Serotonin regulates pancreatic beta cell mass during pregnancy. Nat. Med. 16, 804-808. https://doi.org/10.1038/nm.2173
  24. Kim, H.J., Kim, J.H., Noh, S., Hur, H.J., Sung, M.J., Hwang, J.T., Park, J.H., Yang, H.J., Kim, M.S., Kwon, D.Y., et al. (2011). Metabolomic analysis of livers and serum from high-fat diet induced obese mice. J. Proteome Res. 10, 722-731. https://doi.org/10.1021/pr100892r
  25. Kim, K., Oh, C.M., Ohara-Imaizumi, M., Park, S., Namkung, J., Yadav, V.K., Tamarina, N.A., Roe, M.W., Philipson, L.H., Karsenty, G., et al. (2015). Functional role of serotonin in insulin secretion in a diet-induced insulin-resistant state. Endocrinology 156, 444-452. https://doi.org/10.1210/en.2014-1687
  26. Kinoshita, M., Ono, K., Horie, T., Nagao, K., Nishi, H., Kuwabara, Y., Takanabe-Mori, R., Hasegawa, K., Kita, T., and Kimura, T. (2010). Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5. Mol. Endocrinol. 24, 1978-1987. https://doi.org/10.1210/me.2010-0054
  27. Lam, D.D., and Heisler, L.K. (2007). Serotonin and energy balance: molecular mechanisms and implications for type 2 diabetes. Exp. Rev. Mol. Med. 9, 1-24.
  28. Lam, D.D., Przydzial, M.J., Ridley, S.H., Yeo, G.S.H., Rochford, J.J., O'Rahilly, S., and Heisler, L.K. (2008). Serotonin 5-HT2C receptor agonist rromotes hypophagia via downstream activation of melanocortin 4 receptors. Endocrinology 149, 1323-1328. https://doi.org/10.1210/en.2007-1321
  29. Lam, D.D., Garfield, A.S., Marston, O.J., Shaw, J., and Heisler, L.K. (2010). Brain serotonin system in the coordination of food intake and body weight. Pharmacol. Biochem. Behav. 97, 84-91. https://doi.org/10.1016/j.pbb.2010.09.003
  30. Le Feuvre, R.A., Aisenthal, L., and Rothwell, N.J. (1991). Involvement of corticotrophin releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) and related compounds. Brain Res. 555, 245-250. https://doi.org/10.1016/0006-8993(91)90348-Y
  31. Lesurtel, M., Graf, R., Aleil, B., Walther, D.J., Tian, Y., Jochum, W., Gachet, C., Bader, M., and Clavien, P.A. (2006). Platelet-derived serotonin mediates liver regeneration. Science 312, 104-107. https://doi.org/10.1126/science.1123842
  32. Martin, C.K., Redman, L.M., Zhang, J., Sanchez, M., Anderson, C.M., Smith, S.R., and Ravussin, E. (2010). Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J. Clin. Endocrinol. Metab. 96, 837-845.
  33. Matsuda, M., Imaoka, T., Vomachka, A.J., Gudelsky, G.A., Hou, Z., Mistry, M., Bailey, J.P., Nieport, K.M., Walther, D.J., Bader, M., et al. (2004). Serotonin regulates mammary gland development via an autocrine-paracrine loop. Dev. Cell 6, 193-203. https://doi.org/10.1016/S1534-5807(04)00022-X
  34. Merens, W., Willem Van der Does, A.J., and Spinhoven, P. (2007). The effects of serotonin manipulations on emotional information processing and mood. J. Affect. Disord. 103, 43-62. https://doi.org/10.1016/j.jad.2007.01.032
  35. Monti, J.M. (2011). Serotonin control of sleep-wake behavior. Sleep Med. Rev. 15, 269-281. https://doi.org/10.1016/j.smrv.2010.11.003
  36. Moore, M.C., DiCostanzo, C.A., Dardevet, D., Lautz, M., Farmer, B., Neal, D.W., and Cherrington, A.D. (2004). Portal infusion of a selective serotonin reuptake inhibitor enhances hepatic glucose disposal in conscious dogs. Am. J. Physiol. Endocrinol. Metab. 287, E1057-1063. https://doi.org/10.1152/ajpendo.00313.2004
  37. Murphy, D.L., and Lesch, K.P. (2008). Targeting the murine serotonin transporter: insights into human neurobiology. Nat. Rev. Neurosci. 9, 85-96.
  38. Nomura, S., Shouzu, A., Omoto, S., Nishikawa, M., and Iwasaka, T. (2005). 5-HT2A receptor antagonist increases circulating adiponectin in patients with type 2 diabetes. Blood Coagul. Fibrinolysis 16, 423-428. https://doi.org/10.1097/01.mbc.0000176197.48134.08
  39. Nonogaki, K., Strack, A.M., Dallman, M.F., and Tecott, L.H. (1998). Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat. Med. 4, 1152-1156. https://doi.org/10.1038/2647
  40. Oh, C.M., Namkung, J., Go, Y., Shong, K.E., Kim, K., Kim, H., Park, B.Y., Lee, H.W., Jeon, Y.H., Song, J., et al. (2015). Regulation of systemic energy homeostasis by serotonin in adipose tissues. Nat. Commun. 6, 6794. https://doi.org/10.1038/ncomms7794
  41. Ohara-Imaizumi, M., Kim, H., Yoshida, M., Fujiwara, T., Aoyagi, K., Toyofuku, Y., Nakamichi, Y., Nishiwaki, C., Okamura, T., and Uchida, T. (2013). Serotonin regulates glucose-stimulated insulin secretion from pancreatic ${\beta}$ cells during pregnancy. Proc. Natl. Acad. Sci. USA 110, 19420-19425. https://doi.org/10.1073/pnas.1310953110
  42. Rothwell, N.J., and Stock, M.J. (1987). Effect of diet and fenfluramine on thermogenesis in the rat: possible involvement of serotonergic mechanisms. Int. J. Obes. 11, 319-324.
  43. Sakaguchi, T., and Bray, G.A. (1989). Effect of norepinephrine, serotonin and tryptophan on the firing rate of sympathetic nerves. Brain Res. 492, 271-280. https://doi.org/10.1016/0006-8993(89)90910-4
  44. Savelieva, K.V., Zhao, S., Pogorelov, V.M., Rajan, I., Yang, Q., Cullinan, E., and Lanthorn, T.H. (2008). Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. PLoS One 3, e3301. https://doi.org/10.1371/journal.pone.0003301
  45. Serretti, A., and Mandelli, L. (2010). Antidepressants and body weight: a comprehensive review and meta-analysis. J. Clin. Psychiatry 71, 1259-1272. https://doi.org/10.4088/JCP.09r05346blu
  46. Sohn, J.W., Elmquist, J.K., and Williams, K.W. (2013). Neuronal circuits that regulate feeding behavior and metabolism. Trends Neurosci. 36, 504-512. https://doi.org/10.1016/j.tins.2013.05.003
  47. Sumara, G., Sumara, O., Kim, Jason K., and Karsenty, G. (2012). Gut-derived serotonin is a multifunctional determinant to fasting adaptation. Cell Metab. 16, 588-600. https://doi.org/10.1016/j.cmet.2012.09.014
  48. Tecott, L.H., Sun, L.M., Akana, S.F., Strack, A.M., Lowenstein, D.H., Dallman, M.F., and Julius, D. (1995). Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 374, 542-546. https://doi.org/10.1038/374542a0
  49. Uchida-Kitajima, S., Yamauchi, T., Takashina, Y., Okada-Iwabu, M., Iwabu, M., Ueki, K., and Kadowaki, T. (2008). 5-Hydroxytryptamine 2A receptor signaling cascade modulates adiponectin and plasminogen activator inhibitor 1 expression in adipose tissue. FEBS Lett. 582, 3037-3044. https://doi.org/10.1016/j.febslet.2008.07.044
  50. Vickers, S.P., Clifton, P.G., Dourish, C.T., and Tecott, L.H. (1999). Reduced satiating effect of d-fenfluramine in serotonin 5-HT2C receptor mutant mice. Psychopharmacology 143, 309-314. https://doi.org/10.1007/s002130050952
  51. Wade, P.R., Chen, J., Jaffe, B., Kassem, I.S., Blakely, R.D., and Gershon, M.D. (1996). Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J. Neurosci. 16, 2352-2364. https://doi.org/10.1523/JNEUROSCI.16-07-02352.1996
  52. Walther, D.J., and Bader, M. (2003). A unique central tryptophan hydroxylase isoform. Biochem. Pharmacol. 66, 1673-1680. https://doi.org/10.1016/S0006-2952(03)00556-2
  53. Watanabe, H., Akasaka, D., Ogasawara, H., Sato, K., Miyake, M., Saito, K., Takahashi, Y., Kanaya, T., Takakura, I., Hondo, T., et al. (2010). Peripheral serotonin enhances lipid metabolism by accelerating bile acid turnover. Endocrinology 151, 4776-4786. https://doi.org/10.1210/en.2009-1349
  54. Yadav, V.K., Ryu, J.H., Suda, N., Tanaka, K.F., Gingrich, J.A., Schutz, G., Glorieux, F.H., Chiang, C.Y., Zajac, J.D., Insogna, K.L., et al. (2008). Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135, 825-837. https://doi.org/10.1016/j.cell.2008.09.059
  55. Yamakawa, J., Takahashi, T., Itoh, T., Kusaka, K., Kawaura, K., Wang, X.Q., and Kanda, T. (2003). A novel serotonin blocker, sarpogrelate, increases circulating adiponectin levels in diabetic patients with arteriosclerosis obliterans. Diabetes Care 26, 2477-2478. https://doi.org/10.2337/diacare.26.8.2477
  56. Young, S.N., and Leyton, M. (2002). The role of serotonin in human mood and social interaction: Insight from altered tryptophan levels. Pharmacol. Biochem. Behav. 71, 857-865. https://doi.org/10.1016/S0091-3057(01)00670-0
  57. Zhang, X., Beaulieu, J.M., Sotnikova, T.D., Gainetdinov, R.R., and Caron, M.G. (2004). Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science 305, 217. https://doi.org/10.1126/science.1097540
  58. Zhou, L., Sutton, G.M., Rochford, J.J., Semple, R.K., Lam, D.D., Oksanen, Laura J., Thornton-Jones, Z.D., Clifton, P.G., Yueh, C.-Y., Evans, M.L., et al. (2007). Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Cell Metab. 6, 398-405. https://doi.org/10.1016/j.cmet.2007.10.008

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  44. Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice vol.3, pp.9, 2021, https://doi.org/10.1038/s42255-021-00458-9
  45. Histological and transcriptomic analysis of adipose and muscle of dairy calves supplemented with 5-hydroxytryptophan vol.11, pp.1, 2015, https://doi.org/10.1038/s41598-021-88443-w
  46. Proximate causes and ultimate effects of common antidepressants, fluoxetine and venlafaxine, on fish behavior vol.807, pp.p2, 2015, https://doi.org/10.1016/j.scitotenv.2021.150846