Antioxidant effects of melatonin on obese mice.

Overweight and obesity have been increasing drastically in recent years due to the growing consumption of fast food. Obese individuals exhibit reduced antioxidant defenses, which can lead to DNA damage. Thus, studies have been conducted to mitigate obesity-related complications. Animal research has used the cafeteria diet (CAF) as an obesity induction model, as it mimics human consumption of ultra-processed foods. Currently, complementary dietary strategies are being explored to prevent and/or alleviate obesity-related complications, particularly through natural compounds with anti-obesity effects. Among these, melatonin (MEL) has gained attention due to its antioxidant and anti-inflammatory properties. This study aimed to evaluate the effects of MEL supplementation on biochemical, genotoxic, and inflammatory parameters in mice fed a CAF diet. A total of 60 male Swiss mice were divided into six experimental groups (n = 10): (i) Standard Diet-fed standard chow for 21 weeks; (ii) SD + MEL-fed standard chow and supplemented with MEL for 24 weeks; (iii) CAF-fed CAF for 21 weeks; (iv) CAF + MEL-fed CAF and supplemented with MEL; (v) CAF/CAF + MEL-fed CAF for the first 17 weeks, then continued CAF while starting MEL supplementation for the last 4 weeks, totaling 17 weeks of CAF; (vi) CAF + MEL/CAF-fed CAF and supplemented with MEL for the first 17 weeks, then stopped MEL supplementation for the last 4 weeks, totaling 21 weeks. Blood samples were collected at 17 and 21 weeks to assess DNA damage, lipid profile (triglycerides, total cholesterol, and HDL), liver function (ALT and AST), inflammatory markers (TNF-α and IL-10), fasting glucose, and insulin tolerance in all six groups. At the end of the experiment, animals were euthanized, and liver, kidney, adipose tissue, and bone marrow were collected for further analyses, including the Comet Assay, Micronucleus Test, oxidative stress evaluation, and Western blot. Results showed that CAF induced an inflammatory state, characterized by increased TNF-α and decreased IL-10, along with alterations in lipid and liver profiles. Additionally, CAF led to DNA damage in multiple tissues and insulin resistance. MEL supplementation for 17 weeks reversed these changes. In the last 4 weeks of the experiment, CAF was associated with oxidative stress and damage in the liver, kidney, and bone marrow. MEL effectively attenuated these obesity-related alterations, primarily by modulating proteins involved in homologous and non-homologous DNA repair pathways. In conclusion, the findings demonstrate that MEL is a potent antioxidant and may be a promising candidate for reducing biochemical and genetic alterations associated with obesity.