National Institute for Research of Metabolic and Cardiovascular Diseases (CarDia)

LX22NPO5104

We are part of a research project that brings together several leading scientific centers. This collaboration combines experimental, preclinical, translational, and clinical research on the cardiovascular system with selected aspects of metabolic research.

CarDia

The role of Adipose tissue and muscle crosstalk in regulation of METabolic flexibility: exploration of novel predictors of the lifestyle Intervention Success in obese (AMETIS)

Czech Health Research Council project NU23-01-00509

Our position: PI

The incidence of obesity and related diseases such as type 2 diabetes, cardiovascular disease, liver steatosis and cancer is increasing worldwide. The need for innovative early intervention approaches for patients with obesity is therefore pressing. One of the core yet understudied pathophysiological mechanisms underlying metabolic dysregulation in obesity is metabolic inflexibility, characterized by the inability to efficiently adapt metabolism to substrate demand or availability. However, an accurate yet simple analysis of metabolic flexibility is lacking, and clinically relevant marker of metabolic flexibility which could readily identify at risk patients with high specificity and sensitivity is needed. Therefore, the main aim of this study is to identify surrogate markers of metabolic flexibility, with the capacity to predict the success of complex lifestyle intervention in patients with obesity. We hypothesize that these markers will be factors responsible for paracrine and endocrine communication between skeletal muscle and adipose tissue in the context of metabolic flexibility. Therefore, samples of (i) vastus lateralis muscle, (ii) adjacent intramuscular adipose tissue, and (iii) subcutaneous adipose tissue will be collected from individuals with well-characterized metabolic flexibility (glucose ingestion/feeding: Oral glucose tolerance test, euglycemic hyperinsulinemic clamp; exercise test: VO2max, low intensity cycling) and characterized by state-of-the-art transcriptomic, proteomic and metabolomic methods. The mechanism of action of regulated molecular markers of metabolic flexibility derived from these studies will be tested using the primary cultures of human muscle cells and adipocytes. Clinical relevance of the identified markers of metabolic flexibility will be validated in the large and complex dataset generated in previous cross-sectional and intervention (exercise and/or dietary) studies.

Colaborators: biomedical Research Center of the Slovak Academy of Sciences, Faculty Hospital Kralovske Vinohrady