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Novel approaches to enhance insulin-sensitizing effects of exercise: targeting PAHSA metabolism (ETAPA)

Exercise represents an important tool in the prevention and treatment of metabolic disorders associated with obesity and aging. Metabolic effects of exercise also rely on the induction of favorable changes in adipose tissue function. Adipose tissue is a source of lipokines from the family of palmitic acid esters of hydroxyl fatty acids (PAHSA), which have anti-inflammatory and insulin-sensitizing properties. We have recently shown that 4 months of exercise training increases PAHSA levels in adipose tissue and circulation. However, the mechanisms involved in the induction of PAHSA levels in response to exercise are unknown.

The aim of the ETAPA project is to explore:

1.  the effect of obesity and age on the regulation of PAHSA release from adipose tissue in response to a single bout of exercise (in inbred mice and human volunteers);

2. the mechanisms affecting the synthesis and degradation of PAHSA and their relationship to adipose tissue health, using primary cultures of human adipocytes from lean, obese and aged individuals;

3. the relationship between the changes of adipose tissue as well as systemic PAHSA levels and metabolic effects of chronic exercise, using genetic and pharmacological approaches to decrease PAHSA degradation or increase PAHSA synthesis (mouse studies).

Supported by the Ministry of Health of the Czech Republic (project no. NU21-01-00469; 2021-2024; PI: Martin Rossmeisl, MD, PhD, IPHYS; co-PI: MSc. Lenka Rossmeislová, PhD, 3rd Faculty of Medicine, Charles University).