Histone Acetylation Retards the Adipogenic Differentiation of Human Umbilical Cord - Mesenchymal Stem Cells: A Clue for Anti-obesity Approach?

Obesity represents a significant health and lifestyle issue worldwide. White and brown adipocytes, which originate from resident mesenchymal stem cells (MSCs), are critically involved in the process of adipogenesis.

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) were utilized to investigate epigenetic modifications associated with adipogenic differentiation. Briefly, histone acetylation and/or methylation pattern of hUCMSCs were evaluated with histone deacetylase inhibitor Trichostatin A (TSA) for cell viability, death rate, and adipogenic commitment.

Inhibition of histone deacetylation was accompanied by a reduction of the global methylation pattern compared to the baseline levels in untreated cells. These changes decreased cell viability at 36 hrs, while reciprocally increasing the rate of cell death from 24 hrs. Most importantly, TSA-treated cells demonstrated diminished adipogenic differentiation compared to normal cells post-induction.

Epigenetic remodeling triggered by inhibition of histone deacetylase led to reduced DNA methylation. The increased cytotoxicity, impairing cell survival due to alteration in chromatin state, reduced adipogenic differentiation potential in TSA-treated cells, promoting disruption of normal lineage commitment pathways.

Taken together, the results show a possible anti-obesity effect of histone deacetylation inhibitors (HDCAs) in MSCs, resulting in depletion and restriction of their adipogenic differentiation.