Activatin' Human Adipose Progenitors in Obesity

Abstract

Obesity relates to the abnormal accumulation of body fat and is associated with a number of morbidities including diabetes, dyslipidemia, cardiovascular disease, and cancer. Great strides have been made in our understanding of the molecular basis for these associations, and a number of hypotheses have been put forward. One seemingly counterintuitive hypothesis is the “adipose tissue expandability hypothesis,” which suggests that the relative accumulation of adipose mass per se may not be directly causative in obesity-related metabolic abnormalities; instead, adipose tissue function and plasticity are the key determinants. Although adipose tissue is arguably the most plastic organ in our bodies, it cannot expand indefinitely—particularly in the face of years of chronic fuel surplus. Furthermore, when such a limit is reached, this would inevitably set a limit on the body's capacity to safely store neutral triglycerides. Consequently, with continued nutritional overload, excess fat is deposited in ectopic sites, in tissues not specialized to store large amounts of triglycerides. The result is lipotoxicity and metabolic dysregulation of peripheral tissues (1). Similar metabolic consequences may also be predicted when one considers impaired adipose tissue function (dysregulated adipose metabolism and endocrinology) or indeed when there is a paucity of adipose tissue. Recent evidence points to substantial adipose tissue remodeling, particularly in cases associated with metabolic dysregulation. Obese dysfunctional adipose tissue is characterized by adipocyte hypertrophy, increased angiogenesis, immune infiltration, increased extracellular matrix deposition/fibrosis, and chronic inflammation. In contrast, growth of healthy adipose tissue mass is determined by a complex coordination of adipocyte hypertrophy, adipocyte hyperplasia, adipocyte death, and angiogenesis. Furthermore, all these events appear to be orchestrated in a cell-type, context-dependent, and temporal manner. Indeed, in weight stable individuals, adipocyte turnover is thought to be balanced by the acquisition of new adipocytes from adult adipose tissue progenitors (mesenchymal stem cells and preadipocytes) via adipogenesis …