Endocrine Abstracts

Many metabolic diseases, including type 2 diabetes, strongly associate with obesity, making obesity one of the major health challenges facing the world today. Obesity is usually accompanied by an increase in fat cell size. As fat cells enlarge, they begin to secrete factors which promote adipose tissue inflammation and dysfunction. We recently describe a mechanism connecting an increase in fat cell size (hypertrophy) with the secretion of pro-inflammatory factors: We show that despite long being considered post-mitotic, mature human fat cells can activate a cell cycle program in association with obesity and hyperinsulinemia, with a concomitant increase in adipocyte cell size, nuclear size and DNA content. Chronic hyperinsulinemia in vitro or in humans, however, is associated with subsequent cell cycle exit, leading to a premature senescent transcriptomic and secretory profile. Premature senescence is rapidly becoming recognized as an important mediator of stress-induced tissue dysfunction, with much hope held for strategies that improve tissue function by selectively eliminating senescent cells. The identification and function of senescent adipocytes in human adipose tissue will be discussed.