Prof. Dr. Dominik Pesta

Energy metabolism of earth- and spaceflight-associated metabolic disorders

Since the beginning of the spaceflight era, there have been reports on the detrimental effects of prolonged stays in microgravity on human health. Important contributory factors include stress, radiation, restricted physical activity, altered light-dark cycles, and changes in atmospheric conditions. On Earth, some of these factors and are associated with the development of metabolic diseases such as obesity, insulin resistance, or type 2 diabetes and can impair physical capacity, muscle function, and bone health. Identifying key underlying mechanisms that lead to organ-specific or whole-body alterations of metabolism will enable us to derive effective, personalized countermeasures.

Our research: Our research focuses on metabolic adaptations in relation to exercise and physical training, inactivity, caloric restriction, and aging. All of these stimuli impact the entire organism, but are central for adaptations with skeletal muscle, adipose tissue, and the liver. We are interested in how these stimuli affect healthy people but also individuals with metabolic diseases, and how these adaptations specifically relate to bioenergetic changes within the mitochondria, a central hub for cellular energy homeostasis. For that purpose, we mostly use humans but also preclinical mouse models. The DLR has a unique research facility called the :envihab, which stands for "environment" and "habitat. The :envihab offers excellent opportunities for advanced human metabolic research. In the :envihab, the effects of extreme environmental conditions on humans and possible countermeasures can be simulated and researched on 3,500 square meters. One of our strengths and unique features is therefore the option to carry out strictly controlled intervention studies on site.

Our goals: Our goal is to better understand metabolic adaptation in the context of exercise and physical training, inactivity, caloric restriction, and aging and to derive optimized countermeasures that can serve as best practice models to enable a healthy lifespan on earth and in a spaceflight environment. Orbital exposure on a space station is of particular potential interest for aging research, as a sojourn in the orbit is commonly viewed as a model for accelerated aging. Despite intensive daily training, negative metabolic changes such as insulin resistance and ectopic lipid accumulation occur as undesirable and problematic side effects. We aim to assess short- and long-term effects of bed rest and various countermeasure interventions on health and metabolic parameters such as glucose metabolism, mitochondrial function and oxidative stress, liver health, and cardiovascular fitness. The results of these studies will improve our understanding of systemic and cellular energy metabolism in the context of Earth- and space-associated metabolic diseases and allow us to derive more targeted countermeasures and therapies in the spirit of precision medicine. Understanding the contributory role of these factors will enable us to derive effective countermeasures.

Our methods/techniques: In the lab, we have a good variety of gold-standard methods available to comprehensively assess the metabolic status of humans. We use the hyperinsulinemic-euglycemic clamp technique to assess tissue-specific insulin sensitivity and can estimate nutrient tolerance from mixed meal and oral glucose tolerance tests with/without biopsies of skeletal muscle and adipose tissue. Further to that, we assay mitochondrial function and oxidative stress in different tissues and we use advanced methods to assess body composition (Bodpod, DEXA, Bioimpedance Analysis) and performance parameters (muscle strength, jumping performance, muscle volume) as well as innovative in vivo methodology to assess muscle and liver energy metabolism non-invasively in a PET-MRT-Scanner. In our unique research facility called the :envihab, we can carry out advanced human metabolic research studies under strictly controlled conditions.