Melatonin protects skeletal muscle from damage caused by "diabesity"

An international study led by the University of Granada (UGR) has revealed that melatonin, known for its ability to regulate the sleep/wake cycle, can restore the composition of muscle fibers and protect skeletal muscle from damage caused by obesity and type 2 diabetes, known as "diabesity".

The results, published in the journals Free Radical Biology and Medicine and Antioxidants, show that this hormone improves mitochondrial function, reduces cellular stress and prevents programmed cell death, offering a new therapeutic strategy to combat this metabolic disease.

Improvement and protection of the muscles

The study, led by Ahmad Agil, professor of pharmacology at the University of Granada, showed that the administration of melatonin to obese and diabetic rodents for 12 weeks succeeded in promoting the conversion of glycolytic (fast) muscle fibers to oxidative (slow) fibers, improving the energy efficiency of the muscle. This change not only optimizes energy production, but also protects the muscle from deterioration caused by "diabesity", a condition that combines obesity and type 2 diabetes.

The work, in which scientists from the Department of Pharmacology of the University of Granada, the Federico Olóriz Institute of Neurosciences and the Granada Biosanitary Institute have participated, as well as other collaborating institutions such as the Department of Nutrition and Food Science and the Department of Histology at the University of Granada, the Center for Endocrinology, Diabetes and Nutrition in Madrid, the University of Qatar and Yarmouk University in Jordan, has focused on skeletal muscle, a key organ that accounts for more than 50% of body weight.

Muscle fibers are divided into three types: slow twitch (type I) or red fibers due to the large number of mitochondria they possess, fast twitch (type IIb) or white fibers and intermediate (type IIa). In addition, each muscle in our body has a specific variable and changing proportion of each of these fiber types, depending on the type of movement performed. During short periods of intense muscular activity, white fibers with glycolytic metabolism predominate, and during prolonged periods of low-intensity muscular activity, red fibers with oxidative metabolism predominate.

Melatonin managed to restore the healthy proportion of these fibers, increasing oxidative fibers and reducing glycolytic fibers, reversing the effects of "diabesity", which improves the muscle's ability to burn fat (reducing fat accumulation, and therefore obesity) and produce energy. In addition, melatonin showed effects similar to those of prolonged aerobic activity, especially improving mitochondrial function and regulating calcium levels in cell compartments, which reduces cellular stress and prevents programmed cell death. "We discovered that melatonin restores calcium levels in the mitochondria and the endoplasmic reticulum, which helps to reduce cell damage," says Dr. Agil.

These results are in line with those previously published over the last 15 years by this research group. Their findings could open up new perspectives for the development of therapeutic strategies based on the pharmacological administration of melatonin, aimed at improving muscle health in patients with diabetes. "Our main challenge is the application of melatonin in the field of medicine," say the authors of the paper.

Confirming the results in humans

Obesity and type 2 diabetes are two of the most prevalent metabolic diseases in the world, affecting almost 900 million and 800 million people, respectively. Both conditions are closely related and tend to coexist in what is known as "diabesity". This disorder not only reduces patients' quality of life, but also represents a challenge for healthcare systems.

The findings of the UGR open up new perspectives for the therapeutic use of melatonin, a substance with a well-established safety profile. For the head of this research, "our results reinforce the idea that melatonin could have therapeutic applications in metabolic diseases, improving the muscle health of patients". For this reason, he reminds us that maintaining a healthy, active and balanced lifestyle during the day, accompanied by proper nighttime rest, is key to preserving muscle health and preventing the negative effects of obesity.

The study, funded by the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund (ERDF), suggests that melatonin could become an accessible and effective therapy to combat "diabesity" and its complications. However, the researchers stress the need for clinical studies in humans to confirm these results and determine the optimal dose in each case.

If we can demonstrate its effectiveness in humans, we could have an innovative treatment that would improve the lives of millions of people."

Ahmad Agil, professor of pharmacology, University of Granada