Deposition of epigenetic marks on lysine 27 of histone 3 (H3K27) in mesenchymal stem cells derived from human adipose tissue with obesity.

Abstract

Obesity, recognized by the World Health Organization as a global epidemic, is associated with various comorbidities, including cardiovascular diseases and type 2 diabetes (T2D). White adipose tissue (WAT), composed mainly of mature adipocytes, plays a central role in regulating the organism's energy homeostasis. Adipose-derived stromal cells (ASCs) or mesenchymal stem cells derived from WAT exhibit marked plasticity and differentiation capacity, exerting a significant influence on the metabolic dynamics and functionality of WAT. They actively participate in the renewal and adaptive response of this tissue to changes in energy demands, influencing tissue expansion in response to variations in caloric intake, as seen in obesity. The precise regulation of the balance between the differentiation of these cells into adipocytes and their proliferation capacity is essential for WAT homeostasis, especially in limiting hypertrophic obesity-the exacerbation of the size of mature adipocytes (which play a critical/central role in the pathogenesis of obesity). This study aims to investigate how obesity-related plasma markers correlate with changes in ASCs, particularly regarding the acetylation and methylation of lysine 27 on histone 3 (H3K27). The central hypothesis is that obesity alters the distribution of these epigenetic marks in ASCs, impacting their proliferation and differentiation. The experimental strategies involve collecting blood and adipose tissue samples from patients with a body mass index (BMI) greater and less than 25. The samples will be processed for the analysis of plasma markers of chronic inflammation and biochemical profiles. Isolated ASCs will be cultured in vitro, and their proliferation and differentiation potential will be evaluated using colorimetric assays and growth curves. Molecular analysis will include techniques such as western blotting and real-time PCR to investigate the expression of epigenetic markers, such as H3K27ac and H3K27me3. By understanding the molecular mechanisms that connect obesity to significant epigenetic changes in ASCs, this study may provide valuable insights into the biological processes underlying obesity and its complications. Additionally, this knowledge may be relevant in disease contexts for assessing/deciding on the therapeutic use of mesenchymal stem cells in individuals with obesity.