The anti-inflammatory effects of melatonin on obesity: a literature review

  • Caroline Prochnow Médica, Especialização em Nutrologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. Ribeirão Preto-SP, Brasil.
  • Liane Gonçalves Borges Médica Nutróloga, Universidade Federal de Uberlândia, Complementação Especializada em Nutrologia na USP de Ribeirão Preto e Professora do Curso de Especialização Lato Sensu Nutrologia USP
  • Vivian Marques Miguel Suen Doutora em Medicina, Clínica Médica-FMRP/USP, Docente da FMRP, Coordenadora do Curso de Especialização em Nutrologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade
  • Heitor Bernardes Pereira Delfino Doutor em Medicina, Clínica Médica-FMRP/USP, Docente do Curso de Especialização em Nutrologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brasil.
Keywords: Obesity, Inflammation, Adipose tissue, Melatonina, Oxidative stress

Abstract

multifactorial etiology responsible for generating a state of subclinical chronic inflammation. Melatonin, a hormone physiologically produced by the pineal gland, has been widely studied for its anti-inflammatory effect in several diseases. Objective: To analyze the anti-inflammatory effects of melatonin supplementation in the treatment of obesity. Materials and Methods: This narrative review was carried out through a bibliographic survey, using the digital databases Pubmed, Scielo, Lilacs, Google Scholar and CAPES Periodicals. Results: A double-blind randomized study evaluated 44 women with obesity, who were randomly divided into a group that used melatonin (n=22) and another group that used placebo (n=22). It was observed that only the group of patients who used melatonin showed a significant reduction in the serum concentrations of inflammatory markers such as TNF alpha, IL-6, hsCRP and MDA. Another randomized double-blind study analyzed 30 patients with obesity who were randomized into 2 groups, group 1 (n=15) received 10 mg of melatonin and group 2 (n=15) received placebo. With melatonin supplementation, concentrations of adiponectin omentin 1 and GPx (antioxidant enzyme) increased significantly, while levels of MDA (marker of oxidative stress) decreased significantly. Conclusion: Although clinical studies on this topic are scarce and the existing ones have a small sample number, the results so far have demonstrated the effectiveness of melatonin in counterbalancing the deleterious effects of excess adipose tissue.

References

-Arner, P.; Agné, K. “MicroRNA regulatory networks in human adipose tissue and obesity.” Nature reviews. Endocrinology. Vol. 11. Núm. 5. 2015. p. 276-88. doi:10.1038/nrendo.2015.25.

-Bouatia-Naji, N.; e colaboradores. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nature Genetics. Vol. 41. Núm. 1. 2009. p. 89-94. DOI: 10.1038/ng.277.

-Carrillo-Vico, A.; Lardone, P. J.; Álvarez-Śanchez, N.; Rodriguez-Rodriguez, A.; Guerrero, J. M. Melatonin: Buffering the immune system. International Journal of Molecular Sciences. Vol. 14. Núm. 4. 2013. p. 8638-8683. DOI: 10.3390/ijms14048638.

-Cipolla-Neto, J.; Amaral, F. G. Melatonin as a Hormone: New Physiological and Clinical Insights. Endocrine Reviews. Vol. 39. Núm. 6. 2018. p. 990-1028. DOI: 10.1210/er.2018-00084.

-Corrêa, T. A. F.; Rogero, M. M. Polyphenols regulating microRNAs and inflammation biomarkers in obesity. Nutrition. Vol. 59. 2019. p. 150-157. DOI: 10.1016/j.nut.2018.08.010.

-Cuesta, S.; Kireev, R.; García, C.; Forman, K.; Escames, G.; Vara, E.; Tresguerres, J. A. F. Beneficial effect of melatonin treatment on inflammation, apoptosis and oxidative stress on pancreas of a senescence accelerated mice model. Mechanisms of Ageing and Development. Vol. 132. Núm. 11-12. 2011. p. 573-582. DOI: 10.1016/j.mad.2011.10.005.

-Dubocovich, M. L.; Delagrange, P; Krause, D. N.; Sugden, D.; Cardinali, D. P.; Olcese, J. International union of basic and clinical pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacological Reviews. Vol. 62. Núm. 3. 2010. p. 343-380. DOI: 10.1124/pr.110.002832.

-El-Bakry, H. A.; Ismail, I. A.; Soliman, S. S. Immunosenescence-like state is accelerated by constant light exposure and counteracted by melatonin or turmeric administration through DJ-1/Nrf2 and P53/Bax pathways. Journal of Photochemistry and Photobiology B: Biology. Vol. 186. 2018. p. 69-80. DOI: 10.1016/j.jphotobiol.2018.07.003.

-Farias, T. S. M.; e colaboradores. Melatonin Supplementation Decreases Hypertrophic Obesity and Inflammation Induced by High-Fat Diet in Mice. Frontiers in Endocrinology. Vol. 10. 2019. p.1-13. DOI: 10.3389/fendo.2019.00750.

-Favero, G.; Franco, C.; Stacchiotti, A.; Rodella, L. F.; Rezzani, R. Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury. Frontiers in Physiology. Vol. 11. 2020. p. 1-11. DOI: 10.3389/fphys.2020.00103.

-Garaleut, M.; Qian, J.; Florez, J. C.; Arendt, J.; Saxena, R.; Scheer, F. A. J. L. Melatonin Effects on Glucose Metabolism: Time To Unlock the Controversy. Trends Endocrinol Metab. Vol. 31. Núm. 3. p. 192-204. 2020. doi: 10.1016/j.tem.2019.11.011.

-Gooley, J. J.; Chamberlain, K.; Smith, K. A.; Khalsa, S. B. S.; Rajaratnam, S. M. W.; Van-Reen, E.; Zeitzer, J. M.; Czeisler, C. A.; Lockley, S. W. Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans. Journal of Clinical Endocrinology and Metabolism. Vol.96. Núm.3. 2011. p.463-472. DOI: 10.1210/jc.2010-2098.

-Halpern, B.; e colaboradores. Melatonin increases brown adipose tissue volume and activity in patients with melatonin deficiency: A proof-of-concept study. Diabetes. Vol. 68. Núm. 5. 2019. p. 947-952. DOI: 10.2337/db18-0956.

-Halpern, B.; Mancini, M. C.; Halpern, A. Brown adipose tissue: What have we learned since its recent identification in human adults. Arquivos Brasileiros de Endocrinologia e Metabologia. Vol. 58. Núm. 9. 2014. p. 889-899. DOI: 10.1590/0004-2730000003492.

-Hardeland, R. Melatonin and inflammation-Story of a double-edged blade. Journal of Pineal Research. Vol. 65. Núm. 4. 2018. p.1-23. DOI: 10.1111/jpi.12525.

-Karamitri, A.; Jockers, R. Melatonin in type 2 diabetes mellitus and obesity. Nat Rev Endocrinol. Vol. 15. Núm. 2. p.105-125. 2019. doi: 10.1038/s41574-018-0130-1.

-Kawai, T.; Autieri, M. V.; Scalia, R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol. Vol. 320. Núm. 3. p.C375-C391. 2021. doi: 10.1152/ajpcell.00379.2020.

-Korkmaz, A.; Rosales-Corral, S.; Reiter, R. J. Gene regulation by melatonin linked to epigenetic phenomena. Gene. Vol. 503. Núm. 1. 2012. p.1-11. DOI: 10.1016/j.gene.2012.04.040.

-Liu, Z.; Gan, L, Xu, Y.; Luo, D.; Ren, Q.; Wu, S.; Sun, C. Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue. J Pineal Res. Vol. 63. Núm. 1. 2017. doi: 10.1111/jpi.12414.

-Lumeng, C. N.; Alan, R. S. “Inflammatory links between obesity and metabolic disease.” The Journal of clinical investigation. Vol. 121. Núm. 6. 2011. 2111-7. doi:10.1172/JCI57132

-Manna, P.; Jain, S. K. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies. Metabolic Syndrome and Related Disorders. Vol. 13. Núm. 10. 2015. p. 423-444. DOI: 10.1089/met.2015.0095.

-Mesri-Alamdari, N.; Mahdavi, R.; Roshanravan, N.; Lotfi-Yaghin, N.; Ostadrahimi, A. R.; Faramarzi, E. A double-blind, placebo-controlled trial related to the effects of melatonin on oxidative stress and inflammatory parameters of obese women. Horm Metab Res. Vol. 47. Núm. 7. p.504-8. 2015. doi: 10.1055/s-0034-1384587.

-Negi, G.; Kumar, A.; Sharma, S. S. Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: Effects on NF-κB and Nrf2 cascades. Journal of Pineal Research. Vol. 50. Núm. 2. 2011. p. 124-131. DOI: 10.1111/j.1600-079X.2010.00821.x.

-Nicoletti, C. F.; Delfino, H. B. P.; Ferreira, F. C.; Pinhel, M. A. S.; Nonino, C. B. Role of eating disorders-related polymorphisms in obesity pathophysiology. Rev Endocr Metab Disord. Vol. 20. Núm. 1. p.115-125. 2019. doi: 10.1007/s11154-019-09489-w.

-Nilson, E. A. F.; Santin-Andrade, R. C.; Brito, D. A.; Oliveira; M. L. Costs attributable to obesity, hypertension, and diabetes in the Unified Health System, Brazil, 2018. Revista Panamericana de Salud Publica. Vol. 44. 2020. p. 1-7. DOI: 10.26633/RPSP.2020.32.

-Nonino, C. B.; Barato, M.; Ferreira, F. C.; Delfino, H. B. P.; Noronha, N. Y.; Nicoletti, C. F.; Junior, W. S.; Welendorf, C. R.; Souza, D. R. S.; Ferreira-Julio, M. A.; Watanabe, L. M.; Pinhel M. A. S. DRD2 and BDNF polymorphisms are associated with binge eating disorder in patients with weight regain after bariatric surgery. Eat Weight Disord. Sep 3. 2021. doi: 10.1007/s40519-021-01290-6.

-Papagiannidou, E.; Skene, D. J.; Ioannides, C. Potential drug interactions with melatonin. Physiology and Behavior. Vol. 131. 2014. p. 17-24. DOI: 10.1016/j.physbeh.2014.04.016.

-Quarta, C.; Sánchez-Garrido, M. A.; Tschöp, M. H.; Clemmensen, C. Renaissance of leptin for obesity therapy. Diabetologia. Vol. 59. Núm. 5. p.920-7. 2016. doi: 10.1007/s00125-016-3906-7.

-Reiter, R. J.; Tan, D. X.; Kim, S. J.; Cruz, M. H. C. Delivery of pineal melatonin to the brain and SCN: role of canaliculi, cerebrospinal fluid, tanycytes and Virchow-Robin perivascular spaces. Brain Structure and Function. Vol. 219. Núm. 6. 2014. p.1873-1887. DOI: 10.1007/s00429-014-0719-7.

-Roopin, M.; Levy, O. Temporal and histological evaluation of melatonin patterns in a “basal” metazoan. Journal of Pineal Research. Vol. 53. Núm. 3. 2012. p.259-269. DOI: 10.1111/j.1600-079X.2012.00994.x.

-Scholtens, R. M.; Van-Munster, B. C.; Van-Kempen, M. F.; De-Rooij, S. E. J. A. Physiological melatonin levels in healthy older people: A systematic review. Journal of Psychosomatic Research. Vol. 86. 2016. p. 20-27. DOI: 10.1016/j.jpsychores.2016.05.005.

-Stolarczyk, E. Adipose tissue inflammation in obesity: a metabolic or immune response? Current Opinion in Pharmacology. Vol. 37. 2017. p. 35-40. DOI: 10.1016/j.coph.2017.08.006.

-Szewczyk-Golec, K.; Rajewski, P.; Gackowski, M.; Mila-Kierzenkowska, C.; Wesolowski, R.; Sutkowy, P.; Pawlowska, M.; Wozniak, A. Melatonin Supplementation Lowers Oxidative Stress and Regulates Adipokines in Obese Patients on a Calorie-Restricted Diet. Oxidative Medicine and Cellular Longevity. Vol. 2017. 2017. DOI: 10.1155/2017/8494107.

-Tan, D. X.; Manchester, L. C.; Qin, L.; Reiter, R. J. Melatonin: A mitochondrial targeting molecule involving mitochondrial protection and dynamics. International Journal of Molecular Sciences. Vol. 17. Núm. 12. 2016. DOI: 10.3390/ijms17122124.

-Vigitel. Brasil. Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico. Estimativas sobre frequência e distribuição sociodemográfica de fatores de risco e proteção para doenças crônicas nas capitais dos 26 estados brasileiros e no Distrito Federal em 2019. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Análise em Saúde e Vigilância de Doenças não transmissíveis. 2019.

-Ying, W.; Fu, W.; Lee, Y. S.; Olefsky, J. M. The role of macrophages in obesity-associated islet inflammation and β-cell abnormalities. Nat Rev Endocrinol. Vol. 16. Núm. 2. p.81-90. 2020. doi: 10.1038/s41574-019-0286-3.

Published
2022-11-17
How to Cite
Prochnow, C., Borges, L. G., Suen, V. M. M., & Delfino, H. B. P. (2022). The anti-inflammatory effects of melatonin on obesity: a literature review. Brazilian Journal of Obesity, Nutrition and Weight Loss, 16(101), 409-418. Retrieved from https://www.rbone.com.br/index.php/rbone/article/view/2000
Issue
Vol. 16 No. 101 (2022)
Section
Scientific Articles - Review

Copyright (c) 2022 Caroline Prochnow, Liane Gonçalves Borges, Vivian Marques Miguel Suen, Heitor Bernardes Pereira Delfino

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