Many diseases, including type 2 diabetes, cardiovascular disease, and multiple cancers, are strongly associated with obesity, making it one of the major health challenges worldwide. Obesity, characterized by the excessive accumulation of body fat, is typically accompanied by an increase in fat cell size (hypertrophy). We recently identified a mechanism linking fat cell hypertrophy to the secretion of pro-inflammatory factors. Contrary to long-held beliefs that mature human fat cells are post-mitotic, our research demonstrates that these cells can re-enter the cell cycle in association with obesity and hyperinsulinemia. This is accompanied by an increase in adipocyte size, nuclear size, and DNA content.
However, chronic hyperinsulinemia, both in vitro and in human studies, leads to eventual cell cycle exit, resulting in a premature senescent state, characterized by a distinct transcriptomic and secretory profile. This senescent state is associated with a pro-inflammatory environment, contributing to the negative health outcomes linked to obesity. In this context, we will discuss the causes and consequences of adipocyte cell cycle activation and its impact on obesity-related pathologies.