Melatonin Ameliorates Autophagy Impairment in a Metabolic Syndrome Model

Metabolic syndrome is a global health problem in adults and its prevalence among children and adolescents is rising. It is strongly linked to a lifestyle with high-caloric food, which causes obesity and lipid metabolism anomalies. Molecular damage due to excessive oxidative stress plays a major role during the development of metabolic syndrome complications. Among the different hormones, melatonin presents strong antioxidant properties, and it is used to treat metabolic diseases. However, there is not a consensus about its use as a metabolic syndrome treatment. The aim of this study was to identify melatonin effects in a metabolic syndrome model. Golden hamsters were fed with 60% fructose-enriched food to induce metabolic syndrome and were compared to hamsters fed with regular chow diet. Both groups were also treated with melatonin. Fructose-fed hamsters showed altered blood lipid levels (increased cholesterol and LDL) and phenotypes restored with the melatonin treatment. The Harderian gland (HG), which is an ideal model to study autophagy modulation through oxidative stress, was the organ that was most affected by a fructose diet. Redox balance was altered in fructose-fed HG, inducing autophagic activation. However, since LC3-II was not increased, the impairment must be in the last steps of autophagy. Lipophagy HG markers were also disturbed, contributing to the dyslipidemia. Melatonin treatment improved possible oxidative homeostasis through autophagic induction. All these results point to melatonin as a possible treatment of the metabolic syndrome.This work was supported by Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia, and Innovación y Universidades, Spain (FISS-18-PI17/02009); and Newcastle University, United Kingdom (C0120R3166, C0245R4032, and BH182173). M.G.-M. has a postdoctoral fellowship from the Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia, and Innovación y Universidades. Financial support from the University of Oviedo, Spain, is also acknowledge