Epigenetic reprogramming of H3K4me3 in adipose-derived stem cells by HFS diet consumption leads to a disturbed transcriptomic profile in adipocytes.

Abstract

Adipose tissue metabolism is actively involved in the regulation of energy balance. Adipose-derived stem cells (ASCs) play a critical role in maintaining adipose tissue function through their differentiation into mature adipocytes. This study aimed to investigate the impact of an obesogenic environment on the epigenetic landscape of ASCs and its impact on adipocyte differentiation and its metabolic consequences. Our results showed that ASCs from rats on a high-fat sucrose (HFS) diet displayed reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes compared to the control (C) group. Mitochondrial analysis revealed heightened activity in undifferentiated ASC-HFS, but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 profile in ASCs on genes related to adipogenesis, mitochondrial function, inflammation, and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations, confirming upregulation of genes associated with inflammatory and immunomodulatory pathways. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. Overall, the HFS diet induced significant epigenetic and transcriptomic changes in ASCs, impairing differentiation and causing dysfunctional adipocyte formation.