Effect of Chronic Exercise on Human Thermogenic Adipose Tissue & Elucidation of Mechanisms

Effect of Chronic Exercise on Human Thermogenic Adipose Tissue & Elucidation of Mechanisms

Physical exercise can stimulate heat production in our bodies. This is healthy because it burns sugar and fat. Heat production is influenced, among other things, by what is known as 'brown or beige adipose tissue', which is capable of producing heat in our bodies. However, everyone reacts differently to physical exercise. In addition, different types of exercise can influence heat production. That is why the investigators want to use this study to investigate why different people show different reactions in brown and beige adipose tissue. This is important for our metabolism and our health.

The study will last approximately 6 weeks. The participants are healthy individuals who are participating in the study. The test subjects will be divided into two groups by drawing lots, so that there are equal numbers of men and women in each group.

One group will complete a 6-week endurance training programme. The other group (control) will not do any additional training and will serve as a control group. However, the accompanying examinations will be the same for both groups. By comparing the two groups, the investigators will be able to see whether training has a better effect on heat production and thus health.

As part of this study, the investigators want to investigate how 6 weeks of endurance training affects the function of brown and beige adipose tissue. To do this, the investigators will take some blood and adipose tissue samples before and after the training period.

In order to investigate the regulation of thermogenic adipose tissue by physical exercise and other stimuli without the need for biopsies, the investigators have developed a cell assay that allows to investigate the effect of sera taken before or after physical exertion, e.g. on the expression of the heat-generating UCP1 protein. Experiments using this test have shown that exercise-conditioned serum stimulates UCP1 expression on average compared to resting serum. However, the increase in UCP1 expression in athletes is more than twice as high and there are large inter-individual variations, i.e. non-responders, average responders and 'super responders'. This implies that some subjects secrete serum factors during exercise that can activate thermogenesis in adipose tissue.

It is also known that immune cells have an effect on adipose tissue and may also be involved in crosstalk. Therefore, the aim here is to investigate the reactivity of immune cells using single-cell mRNA sequencing. This analysis may provide further insight into immune responses, including in relation to obesity.

Using this methodology, the investigators now want to investigate how acute physical exercise 6-week training intervention (endurance training) influence the thermogenic adipose tissue, metabolism and energy expenditure of the participants.

The investigators have three specific objectives:

1. The investigators will analyse how serum taken before or after training affects the expression of the heat-generating UCP1 protein in human adipocytes in cell culture. The investigators will also measure oxygen consumption/energy expenditure during cold stimulation and correlate these measurements with those obtained in adipocyte cell cultures. Furthermore, the investigators will quantify mRNA expression in isolated immune cells (peripheral mononuclear cells and granulocytes).
2. The investigators will use the sera, cells and biopsy samples obtained to analyse the mechanisms of white/beige adipose tissue regulation in cooperation with the project consortium. One focus will be on miRNAs in exosomes, which have been identified as biomarkers for thermogenesis. In addition, the investigators will add thermogenic super-responder sera and non-thermogenic non-responder sera to human adipocytes in cell culture and perform a phosphoproteomics analysis. Based on this analysis, the investigators will then attempt to identify the factors that activate thermogenesis.

Inclusion Criteria:

• BMI 18-25
• male/female
• less than 3 hours/week of regular training
• must be able to perform performance analysis and endurance training by cycling
• must be able to do six weeks of training

Exclusion Criteria:

• cardiovascular, pulmonary, neoplastic, orthopaedic, metabolic, or chronic diseases
• problems that preclude performance testing or endurance testing
• pregnancy (only female)
• regular medication
• smoking
• dependency relationship with the TUM Professorship of Exercise Biology