Depot-specific differences in the lipolytic effect of leptin on isolated white adipocytes

In the present study we hypothesized that leptin-induced lipolytic effects show depot-specific differences.

Three-month-old male lean (+/+) and obese fa/fa rats were used. Lipolysis was determined in the absence or presence of leptin (0.63, 6.25 and 62.5 nM) together with agents acting at the A1 adenosine receptor of fat cells isolated from both subcutaneous and omental depots. The glycerol released into the incubation medium was taken as the lipolytic rate index.

The highest dose of leptin produced a 57.5 +/- 7.3% and 70.3 +/- 3.8% increase in omental and subcutaneous glycerol release, respectively, compared to the basal lipolytic rate (P<0.001). The addition of the three leptin concentrations in the ligand-free state produced a significantly greater stimulation of lipolysis in subcutaneous fat cells (P=0.0331; P=0.0003 and P=0.0015, respectively) compared to omental adipocytes. Under adenosine A1 receptor agonism and antagonism the same pattern of response was observed between visceral and subcutaneous adipocytes of lean rats. Although adenosine deaminase produced near maximum lipolysis in the adipocytes of lean animals, only half of the maximum lipolytic rate (50.9 +/- 3.2%) was achieved in fat cells from fa/fa rats (P=0.0034). Leptin had no effect on the lipolytic activity of adipocytes from either localization in fa/fa rats.

It can be concluded that decreased sensitivity to the lipolytic effect of leptin in omental adipocytes compared to subcutaneous fat cells may underlie, at least in part, the association of visceral fat accumulation with increased co-morbidities.