Human Preadipocytes Display a Depot-Specific Susceptibility to Apoptosis

Abstract

Adipose tissue mass is determined by both the number and volume of adipose cells. Adipose cell number reflects the balance of cell acquisition and cell loss, whereas adipose cell volume represents the balance of lipolysis and lipogenesis. It is well recognized that insulin resistance, NIDDM, and other metabolic disorders are associated more strongly with increased omental adiposity than with subcutaneous adiposity. Depotrelated differences exist in adipocyte responses to lipolytic and lipogenic stimuli, in adipocyte apoptosis, and in the potential for preadipocyte replication and differentiation. In the present study, we address the question of whether there might also be a site-specific difference in the susceptibility of human preadipocytes to apoptosis. Paired samples of human omental and subcutaneous preadipocytes from 12 individuals were cultured, and apoptosis was induced by serum deprivation or treatment with tumor necrosis factor (TNF)-α for 4 h. Cells were then stained with acridine orange, and apoptotic indices were calculated as the fraction of cells showing nuclear condensation. Under both conditions, in 9 of 11 subjects, apoptotic indices were substantially greater in preadipocytes from the omental depot than in those from the subcutaneous depot, and mean apoptotic indices were more than twofold higher in omental cells (serum-free medium: P < 0.05; TNF-α: P < 0.02; paired t test). Omental preadipocytes are therefore more susceptible to two different apoptotic stimuli than subcutaneous preadipocytes, demonstrating another intrinsic site-specific difference between human adipose cells of the two depots. These results suggest that the regulation of adipose tissue distribution in humans could involve depot-specific differences in rates of preadipocyte apoptosis.