Italian Society of Obesity XII National Congress

Introduction: Excess White Adipose Tissue (WAT) deposition in obesity is characterized by low-grade chronic inflammation; as such, WAT is one of the organs mostly affected by senescence, a cellular process characterized by cell-cycle arrest and metabolic alterations.Although cell senescence (CS) is a physiological processes, chronic or excessive CS is harmful for organisms and is a key driver of aging.Senescent cells remain viable and release inflammatory cytokines which spread systemic tissue damage, thus contributing to the multi-organ dysfunction of obesity, of which cardiovascular disease is the most common.Reducing CS could therefore represent a valuable therapeutic tool toward obesity-associated diseases.We have previously shown that essential amino acids (EAAs), by increasing mitochondrial biogenesis (MB), have a positive outcome on obesity and diabetes, counteract doxorubicininduced cardiotoxicity, and also extend lifespan in mice 345 .Here, we investigated whether the anti-obesity and cardioprotective effects of EAAs are associated with reduced CS.Methods: C57BL/6N mice were fed with chow (CD), a high-fat diet (HFD-60% fat), or a HFD in which the protein content was substituted with a mixture of EAAs (HFD-EAA) for 10 weeks; afterwards, markers of CS and MB were analysed in epididymal WAT (eWAT).Furthermore, doxorubicin-treated HL-1 cardiomyocytes were used as in an in vitro model of cardiotoxicity-induced senescence.Results: After 10 weeks, body weight (BW) and glucose intolerance of HFD-fed animals increased (+ 35% and + 56% vs CD, respectively); however, HFD-EAA diet prevented the increase in BW and improved glucose homeostasis of HFD-fed mice (-25%, -22% vs HFD).This was associated with an increase in the expression of CS markers and β-gal staining in eWAT of HFD mice, which were both blunted by HFD-EAA diet.Furthermore, in vitro supplementation of an EAA mixture with an equivalent formulation of HFD-EAA diet also increased MB and oxygen consumption and normalized the doxorubicin-induced increase in CS markers and β-gal staining in HL-1.Conclusion: Our data suggest that EAAs mitigate CS in obesity and cardiotoxicity.This nutritional strategy may therefore represent a promising approach for combating CS and improving outcomes in obesity and age-related diseases.