P843 - ENHANCING NUTRITIONAL KETOSIS WITH MELATONIN: A PRECLINICAL APPROACH TO MANAGING OBESITY-RELATED METABOLIC DYSFUNCTIONS

P843

ENHANCING NUTRITIONAL KETOSIS WITH MELATONIN: A PRECLINICAL APPROACH TO MANAGING OBESITY-RELATED METABOLIC DYSFUNCTIONS

C. M. Dragoi^1,*, A. C. Nicolae ¹, I. B. Dumitrescu¹

¹Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila“, Bucharest, Romania

Rationale: Obesity is associated with chronic metabolic dysfunctions, including dysregulated lipid metabolism and impaired tissue morphology. This study investigates whether melatonin supplementation can enhance the metabolic benefits of intermittent fasting-induced nutritional ketosis.

Methods: An experimental study was conducted using an obese murine model divided into four groups: lean control; obese control; obese mice subjected to a 20/4 intermittent fasting regimen (ketosis without treatment); and obese mice subjected to intermittent fasting combined with melatonin supplementation. Histological analyses were performed on different tissues to assess morphological improvements. Biochemical markers were measured using standard assays. 

Results: Obese control mice exhibited significantly higher blood glucose, cholesterol, and triglyceride levels compared to lean controls. Intermittent fasting alone reduced these biochemical markers, and the addition of melatonin further enhanced the reduction. Histological analysis revealed marked improvements in tissue morphology in the brain, liver, and kidney of the melatonin-treated fasting group. Notably, the ketosis plus melatonin group showed a significant increase in serum lipid levels, which is attributed to the mobilization of lipid stores under the intermittent 20/4 fasting regimen and subsequent beta-oxidation in hepatocyte mitochondria.

Conclusion: Melatonin supplementation in conjunction with intermittent fasting-induced nutritional ketosis significantly improves tissue morphology and normalizes key biochemical parameters in obese mice. The observed increase in serum lipids likely reflects a beneficial metabolic adaptation related to enhanced lipid mobilization and oxidation, supporting the potential clinical application of melatonin as an adjunctive therapy in the early management of obesity-related metabolic dysfunction.

Disclosure of Interest: None declared