Focus on Muscle Metabolism: Sex Differences in Sport and Obesity
The skeletal muscles of men and women process glucose and fats in different ways. A study conducted by the University Hospital of Tübingen, the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich and the German Center for Diabetes Research (DZD) e.V. provides the first comprehensive molecular analysis of these differences. The results possibly give an explanation why metabolic diseases such as diabetes manifest differently in women and men – and why they respond differently to physical activity.
Skeletal muscles are far more than just “movement driving motors.” They play a central role in glucose metabolism and therefore also in the development of type 2 diabetes. This is due to the fact that around 85 percent of insulin-dependent glucose uptake takes place in the muscles. This means that if muscle cells react less sensitively to insulin, for example in the case of insulin resistance, glucose is less easily absorbed from the blood. This process is specifically counteracted by physical activity.
Women’s and Men’s Muscles Work Differently
The degree to which muscles work differently in women and men has long been underestimated. It is precisely this issue which has now been investigated by researchers led by Simon Dreher and Cora Weigert. They examined muscle biopsies from 25 healthy but overweight adults (16 women, 9 men) aged around 30 years. The test subjects had not taken part in regular sporting activities beforehand. Over a period of eight weeks, they completed one hour of endurance training three times a week, consisting of 30 minutes of cycling and 30 minutes of walking on the treadmill.
Muscle samples were taken before they started, after they had the first training session and at the end of the program. Using state-of-the-art molecular biological methods, including epigenome, transcriptome and proteome analyses, the team investigated sex-specific differences at various levels.
Men React with more Stress to Exercise
The result: The first training session triggered a stronger stress response at the molecular level in men, which became manifest in the increased activation of stress genes and the increase in the muscle protein myoglobin in the blood. In addition, male muscles showed a distinct pattern of what are called fast-twitch fibers, which are designed for short-term, intensive exercise and preferably use glucose as an energy source.
Women had significantly higher amounts of proteins that are responsible for the absorption and storage of fatty acids: an indication of more efficient fat utilization. After eight weeks of regular endurance training, the muscles of both sexes matched and the muscle fiber-specific differences decreased. At the same time, women and men produced more proteins that promote the utilization of glucose and fat in the mitochondria, the “power plants of the cells.”
“These adjustments indicate an overall improvement in metabolic performance, which can help to reduce the risk of type 2 diabetes,” says Weigert. “In future, our new findings might help to better predict individual diabetes risks and tailor recommendations for exercise therapies more specifically to women and men.”
What happens next? The scientists now want to investigate the role sex hormones such as estrogen and testosterone play in these differences – and how hormonal changes in old age influence the risk of metabolic diseases.
Original publication:
Dreher SI et al. „Sex differences in resting skeletal muscle and the acute and long-term response to endurance exercise in individuals with overweight and obesity“. Molecular Metabolism, 2025 , DOI: 10.1016/j.molmet.2025.102185
Scientific contact:
Prof. Dr. rer. nat. Cora Weigert
Phone.: 07071 29-85670
E-Mail: cora.weigert(at)med.uni-tuebingen.de
Founded in 1805, Tübingen University Hospital is one of the leading centers of university medicine in Germany. Being one of the 33 university hospitals in Germany, it contributes to the successful combination of high-performance medicine, research and teaching. More than 400,000 inpatients and outpatients from all over the world benefit from this combination of science and practice every year. The clinics, institutes and centers bring together specialists from a wide range of disciplines under one roof.
The experts work together on an interdisciplinary basis and offer each patient the best possible treatment based on the latest research findings. The University Hospital of Tübingen is researching for better diagnoses, therapies and chances of recovery. Many new treatment methods are being clinically tested and applied here. In addition to diabetology, research in Tübingen focuses on neurosciences, oncology, immunology, infection research and vascular medicine. Over the past 25 years, the Chair of Diabetology / Endocrinology has been a center of interdisciplinary research, particularly involving surgery, radiology and laboratory medicine.
The discovery of prediabetes subtypes was only possible thanks to interdisciplinary collaboration. The University Hospital is a reliable partner of four of the six German Centers for Health Research initiated by the federal government. www.medizin.uni-tuebingen.de
Helmholtz Munich is a top biomedical research center. Its mission is to develop solutions for a healthier society in a rapidly changing world. Interdisciplinary research teams focus on various diseases, in particular the treatment and prevention of diabetes, obesity, allergies and chronic lung diseases. www.helmholtz-munich.de
The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Munich – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of Helmholtz Munich at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. www.dzd-ev.de/en
