Melatonin Enhances Muscle Energy Efficiency, Paving the Way for 'Diabesity' Treatment

An international research initiative spearheaded by the University of Granada has uncovered that melatonin, a hormone renowned for its role in regulating sleep patterns, has the potential to restore muscle fiber composition and shield skeletal muscle from the detrimental effects of obesity and type 2 diabetes, collectively referred to as 'diabesity.'

The findings, published in the scientific journals Free Radical Biology and Medicine and Antioxidants, indicate that melatonin enhances mitochondrial function, mitigates cellular stress, and inhibits programmed cell death, suggesting a novel therapeutic approach to address this metabolic disorder.

The study, directed by Professor Ahmad Agil of the University of Granada, demonstrated that administering melatonin to obese and diabetic rodents over a 12-week period successfully encouraged the transformation of glycolytic (fast-twitch) muscle fibers into oxidative (slow-twitch) fibers, thereby improving muscle energy efficiency. This remarkable shift not only optimizes energy production but also fortifies the muscle against deterioration associated with 'diabesity.'

The collaborative effort involved researchers from the Department of Pharmacology at the University of Granada, the Federico Olóriz Institute of Neurosciences, the Granada Biosanitary Institute, the Department of Nutrition and Food Science, the Department of Histology at the University of Granada, the Center for Endocrinology, Diabetes, and Nutrition in Madrid, along with institutions from the University of Qatar and Yarmouk University in Jordan. The focus of the study on skeletal muscle is critical, as it constitutes over 50% of total body weight.

Muscle fibers are categorized into three types: slow-twitch (type I), fast-twitch (type IIb), and intermediate (type IIa). Each muscle type exhibits variable proportions of these fibers, contingent on the nature of movement performed. During brief, intense physical activity, fast-twitch fibers, which rely on glycolytic metabolism, dominate, whereas during extended, low-intensity activities, slow-twitch fibers, characterized by oxidative metabolism, are prevalent.

Melatonin effectively restored a healthier balance of these fiber types, increasing the proportion of oxidative fibers while decreasing glycolytic fibers. This reversal counteracts the adverse effects of 'diabesity,' enhancing the muscle's capacity to burn fat and generate energy. Furthermore, melatonin exhibited effects akin to those observed with prolonged aerobic exercise, particularly in terms of improving mitochondrial function and regulating calcium levels within cellular compartments, which helps alleviate cellular stress and avert programmed cell death.

Dr. Agil noted that the research revealed melatonin's ability to restore calcium homeostasis in mitochondria and the endoplasmic reticulum, which is crucial in reducing cellular damage. These results align with previous studies conducted by this research team, potentially paving the way for the development of therapeutic strategies utilizing melatonin to promote muscle health in diabetes patients. The researchers emphasize the need to advance melatonin's application in medical settings.

Obesity and type 2 diabetes rank among the most widespread metabolic diseases globally, affecting nearly 900 million and 800 million individuals, respectively. Both conditions frequently coexist, forming what is known as 'diabesity.' This syndrome not only diminishes the quality of life for affected individuals but also poses significant challenges for healthcare systems.

These findings from the University of Granada illuminate new avenues for the therapeutic application of melatonin, a compound that boasts a well-established safety profile. The lead researcher highlighted that the results reinforce the potential of melatonin in treating metabolic disorders and enhancing muscle health among patients. Maintaining a healthy and active lifestyle, coupled with adequate rest, is essential for preserving muscle integrity and mitigating the harmful effects of obesity.

The study indicates that melatonin could represent a viable and effective treatment option for 'diabesity' and its related complications. However, the researchers stress the importance of conducting clinical trials in humans to validate these findings and ascertain the optimal dosage for various cases. Demonstrating its efficacy in human subjects could yield an innovative treatment that significantly improves the lives of millions.