ADIPOSE TISSUE GROWTH AND MAINTENANCE

Because obesity is fast becoming a global health pandemic, understanding the molecular and cellular processes that regulate fat mass has acquired new importance. Characterized by an increase in adipose tissue to the point where it is associated with adverse health effects, the prevalence of obesity has nearly tripled over the past fifty years. Though for many years adipose tissue was considered to be merely a storage depot for fatty acids, it is now regarded as an important endocrine organ involved in the regulation of energy balance, glucose and lipid homeostasis, blood pressure control, reproduction, inflammation and immune response. Obesity has an enormous economic burden and it is the second leading cause of preventable death. The source of increased fat mass in obesity is currently attributed to two mechanisms: adipocyte hypertrophy, the process by which preexisting fat cells increase in size due to an accumulation of lipids, and adipocyte differentiation from fat precursor cells. Stem cells are defined by the ability to self-renew and differentiate into a variety of cell types. While some adult organs, including the intestine (Cheng and Leblond, 1974), skin (Oshima et al., 2001), blood (Spangrude et al., 1988), and parts of the brain (Doetsch et al., 1999; Reynolds and Weiss, 1992), are maintained by stem cells, others, such as the pancreas (Dor et al., 2004), are not. Though it was recently demonstrated that there is a substantial degree of cellular turnover within the human adipocyte population (Spalding et al., 2008), the source of new adipocytes during one’s lifetime has been entirely attributed to the differentiation of new adipocytes from preadipocytes and/or stem cells (Avram et al., 2007; Greenwood and Hirsch, 1974; Hausman et al., 2001; Lemonnier, 1972; Salans et al., 1971; Spalding et al., 2008; Tang et al., 2008). Adipocytes are thought to represent a terminal stage of differentiation and are widely believed to lack proliferative ability (Prins and O'Rahilly, 1997). Through four independent experimental approaches —dilution of an inducible histone 2B-green fluorescent protein (H2BGFP) through cell division, incorporation of BrdU, labeling with the cell cycle marker Ki67, and genetic lineage analysis, we aimed to investigate the adult adipose tissue maintenance and its behavior in the cell cycle.