Epigenetic imprinting of H3K4me3 in adipose-derived stem cells by HFS diet consumption leads to a disturbed transcriptomic profile in adipocytes [RNA-seq]
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. The aim of this study was to investigate the effect 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 mice fed a high-fat sucrose (HFS) diet exhibited reduced adipogenic capacity, increased fat accumulation, and formed larger adipocytes than those from the control group (C). The results showed that ASCs from mice fed the HFS diet had reduced adipogenic capacity. Mitochondrial analysis showed increased mitochondrial activity in undifferentiated ASC-HFS, but decreased respiratory and glycolytic capacity in mature adipocytes. The HFS diet significantly altered the H3K4me3 acetylation profile of ASCs in genes related to adipogenesis, mitochondrial function, inflammatory response and immunomodulation. After differentiation, adipocytes retained H3K4me3 alterations in genes related to inflammatory response and immunomodulation. RNA-seq confirmed the upregulation of genes associated with inflammatory and immunomodulatory pathways in adipocytes. This study demonstrates that HFS diet induces profound epigenetic and transcriptomic changes in ASCs, leading to impaired differentiation and dysfunctional adipocyte formation. Overall design: To investigate whether the development of obesity is associated with epigenetic modifications in adipocyte precursors, potentially leading to the generation of functionally altered adipocytes, we conducted a study in Wistar rats fed either a control (C) diet or a high-fat sucrose (HFS) diet for 6 months Adipocyte precursors (ASCs) from both goups were isolated and differentiated into adipocytes (Ad). RNA-seq and ChIP-seq (H3K4me3) assays were conducted Comparative gene expression profiling analysis of RNA-seq data for ASC-HFS vs ASC-C, and AD-HFS vs C group were performed