Structural changes in rat colon under obesity conditions and its correction by morning and evening injection of melatonin

I. Vareniuk, N. Shevchuk, N. Roslova, M. Dzerzhynsky
Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv


The effect of morning and evening administrations of melatonin on structural and functional changes in the large intestine of rats with obesity under conditions of the spring-autumn photoperiod (12L:12D) was studied in this work. The obesity was caused with a high-calorie diet for 6 weeks. After that, the morning or evening melatonin administrations were given to normal and obese animals at a dose of 30 mg/kg for 7 weeks. After 13 weeks, two specimens of the colon 1 cm each were taken at a distance of 3 cm from the anus; fixed in 10% formalin and in Carnua solution; paraffin sections of the large intestine were made; stained them with hematoxylin-eosin, alcian blue-carmine, or toluidine blue. Microscopic and morphometric analysis of these sections was performed. It has been shown, that obesity cause hyperactivation of the colonic mucosa, reduction of colonocytes, hypertrophy of goblet cells and overaccumulation of granules in mast cells. Morning administration of melatonin to obese animals normalizes the colonic mucosa, decreases the reduction of colonocytes, but causes the hypotrophy of goblet cells. Evening administration of melatonin significantly decreases the reduction of colonocytes, but does not eliminate other changes caused by obesity. The administration of melatonin (both morning and evening) to animals without obesity causes an activation of the mucosa, hypertrophy of goblet cells, reduction of colonocytes, and does not change the state of mast cells. Consequently, it cannot make a clear conclusion about the possibility of correction of all structural-functional changes in the large intestine during obesity by melatonin. Although, the morning administration of melatonin had some normalizing effects on the colon and it was more effective than evening administration.


melatonin, obesity, large intestine

Full Text:



Cardinali D, Cano P, Jimenez-Ortega V, Esquifino A. Neuroendocrinol melatonin and the metabolic syndrome: physiopathologic and therapeutical implications. Neuroendocrinology. 2011;93(3):131-142.

Cardinali DP, Hardeland R. Inflammaging, metabolic syndrome and melatonin: a call for treatment studies. Neuroendocrinology. 2017;104(4):382-397.

de Farias Tda S, de Oliveira AC, Andreotti S, do Amaral FG, Chimin P, de Proenca AR, Leal FL, Sertie RA, Campana AB, Lopes AB, de Souza AH, Cipolla-Neto J, Lima FB. Pinealectomy interferes with the circadian clock genes expression in white adipose tissue. J Pineal Res. 2015;58(3):251-61.

Delagrange P, Atkinson J, Boutin JA, Casteilla L, Lesieur D, Misslin R, Pellissier S, Penicaud L, Renard P. Therapeutic perspectives for melatonin agonists and antagonists. Journal of neuroendocrinology. 2003;15(4):442-448.

Jimenez-Aranda A, Fernandez-Vazquez G, Campos D, Tassi M, Velasco-Perez L, Tan DX, Reiter RJ, Agil A. Melatonin induces browning of inguinal white adipose tissue in Zucker diabetic fatty rats. J Pineal Res. 2013;55(4):416-423.

Konturek PC, Brzozowski T, Konturek SJ. Gut clock: implication of circadian rhythms in the gastrointestinal tract. J Physiol Pharmacol. 2011;62(2):139-150.

Lee CJ, Sears CL, Maruthur N. Gut microbiome and its role in obesity and insulin resistance. Ann N Y Acad Sci. 2019; May 14. [Epub ahead of print]

Liu J, Clough SJ, Hutchinson AJ, Adamah-Biassi EB, PopovskaGorevski M, Dubocovich M L. MT1 and MT2 melatonin receptors: a therapeutic perspective. Annual review of pharmacology and toxicology. 2016;56:361-383.

McNabney SM, Henagan TM. Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer, obesity and insulin resistance. Nutrients. 2017;9(12):E1348.

Nduhirabandi F, Toit E, Lochner A. Melatonin and the metabolic syndrome: a tool for effective therapy in obesity-associated abnormalities. Acta Physiol (Oxf). 2012;205(2):209-223.

Prado N, Ferd L, Manucha W. Anti-inflammatory effects of melatonin in obesity and hypertension. Curr Hypertens Rep. 2018;20(3):1-15.

Reiter R, Manchester L, Fuentes-Broto L, Tan D. Cardiac hypertrophy and remodeling: pathophysiological consequences and protective effects of melatonin. J Hypertens. 2010;28(2):7-12.

Reiter R, Tan D, Korkmaz A, Mac S. Obesity and metabolic syndrome: association with chronodisruption, sleep deprivation, and melatonin suppression. Ann Med. 2012;44(1):564-577.

Ryu V, Zarebidaki E, Albers HE, Xue B, Bartness TJ. Short photoperiod reverses obesity in Siberian hamsters via sympathetically induced lipolysis and Browning in adipose tissue. Physiol Behav. 2018;190:11-20.

Saad MJ, Santos A, Prada PO. Linking gut microbiota and inflammation to obesity and insulin resistance. Physiology (Bethesda). 2016;31(4):283-293.

Szewczyk‐Golec K, Wozniak A, Reiter RJ. Inter‐relationships of the chronobiotic, melatonin, with leptin and adiponectin: implications for obesity. Journal of pineal research. 2015;59(3):277-291.

The official data of the WHO Bulletin published in May 2017. Available from:

Torres-Farfan C, Valenzuela F, Mondaca M. Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland. J Physiol. 2008;586(2):4017-4027.

Xu P, Wang J, Hong F, Wang S, Jin X, Xue T, Jia L, Zhai Y. Melatonin prevents obesity through modulation of gut microbiota in mice. J Pineal Res. 2017;62(4):E12399.

Received: 01.10.2019

Revised: 01.11.2019

Singed for press: 01.11.2019



  • There are currently no refbacks.

Лицензия Creative Commons
This journal is available according to the Creative Commons License «Attribution» («Атрибуція») 4.0 Global (CC-BY).