Obesity has emerged as one of the major challenges facing contemporary healthcare systems: its prevalence has increased exponentially over the past thirty years, and in 2016 the World Health Organization estimated that more than 1.9 billion people worldwide were overweight, of whom more than 650 million were living with obesity. This condition, characterized by an excess accumulation of fat mass resulting from an imbalance between energy intake and expenditure, is a key risk factor for numerous comorbidities, including diabetes, cardiovascular disease, hypertension, dyslipidemias, and certain cancers. While some forms arise from monogenic alterations, common obesity results from the complex interplay of multiple factors, which has fueled growing interest in understanding the remodeling of adipose tissue induced by an obesogenic environment.
This literature review takes stock of the transcriptional and epigenetic mechanisms that govern this remodeling at the level of the adipocyte. The authors recall the organization of mammalian adipose tissue, which is composed mainly of white adipose tissue and brown adipose tissue. Each comprises heterogeneous cell populations distributed between mature adipocytes—which account for 20% to 30% of total cells—and the stromal vascular fraction, which includes mesenchymal stem cells, preadipocytes, fibroblasts, endothelial cells, vascular progenitors, and immune cells. White adipose tissue, whose adipocytes contain a single lipid vacuole, ensures the storage and release of free fatty acids and functions as an active endocrine organ communicating with other metabolic organs through the secretion of adipokines. Its regional distribution, whether visceral or subcutaneous, is of particular importance in predicting the complications associated with obesity.
The authors summarize the advances made in identifying the signaling pathways and transcriptional networks that orchestrate the changes in adipocyte gene expression associated with different phenotypes. Drawing on recent progress in epigenomics, they emphasize that various environmental signals can reprogram adipocyte fate and function through epigenetic mechanisms, primarily via alterations in DNA methylation and histone modifications. A central focus of this analysis is the role of transcription factors and chromatin-modifying coregulatory complexes, identified as the key regulatory components that coordinate both the transcriptional and epigenetic alterations induced by signaling.
By bringing together these two levels of regulation, the authors propose an integrated reading of the mechanisms that trigger adipogenesis and adipose tissue remodeling in response to energy excess. They note that these alterations, and their influence on the development and progression of obesity, likely vary from one individual to another, so that their study could contribute to the development of future personalized therapeutic strategies.