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FGF21 effects on adipose tissue metabolism and their importance for treatment of metabolic syndrome (concluded project)

Fibroblast growth factor 21 (FGF21) treatment lowers body weight and increases insulin sensitivity in rodents. However, a mechanism of its action is still unclear. 

FGF21 is reported to affect metabolism of adipose tissue, especially lipolysis. In rodent model, administration of FGF21 led to an increase in energy expenditure. On the other hand, whether FGF21 directly increases basal energy expenditure regardless of ambient temperature (thermogenic effect) or whether it only affects the process of regulation of body temperature (pyretic effect) is still unresolved question that is important for the translation of preclinical data into human medicine. By using unique techniques such as i) indirect calorimetry with variable ambient temperature setting, and ii) assessment of metabolic turnover by 2H labelling, this project enables a detailed characterization of the effects of FGF21 on energy expenditure and metabolism of brown and white adipose tissue and clarify the role of adipose tissue in antiobesogenic and antidiabetic effects of FGF21.

The specific aims of the project were as follows:

  1. to test whether FGF21 exerts any pyretic effects;
  2. to find out whether FGF21 has an effect on lipolysis and lipogenesis in white adipose tissue;
  3. to identify the primary target organ of FGF21 action; and
  4. to compare FGF21’s effects in vivo and in cell culture of adipocytes. 

Main publication output of the research team at IPHYS (Zouhar et al. 2021. Mol Metab)

The project was funded by junior grant of Czech Science Foundation (19-05356Y, 2019-2021, PI: Petr Zouhar)