Effect of phenoxybenzamine on development of adipose tissue in lean and obese Zucker rats.

Young male Zucker lean (Fa/-) and obese (fa/fa) rats were fed the alpha-adrenergic blocking agent phenoxybenzamine as a dietary admixture for 35 days. In lean and obese rats, phenoxybenzamine treatment decreased significantly body weight gain, food consumption, grams of carcass fat, and grams of carcass protein. Lean rats exhibited reduced fat cell size and number in retroperitoneal, epididymal, and inguinal fat depots. Obese rats treated with phenoxybenzamine exhibited significantly decreased numbers of fat cells in the retroperitoneal, epididymal, and inguinal fat depots and a small decreased cell size in the inguinal fat depot only. The levels of carcass fat and protein and fat cell number in obese and lean rats treated with phenoxybenzamine for 35 days were similar to pretreatment values in agreement with the lack of body weight gain. Although values in agreement with the lack of body weight gain. Although rats exhibited marked decreases in fat accumulation during phenoxybenzamine treatment, fat cell size and number returned to control values during the posttreatment period with a marked hyperplasia occurring particularly in the retroperitoneal fat depot of obese rats. Serum levels of insulin were suppressed and free fatty acid levels increased in obese rats during phenoxybenzamine treatment, suggesting a stimulation of the sympathoadrenal system. This study shows that despite severe restrictions in fat cell proliferation during the rapid-growth phase of the obese Zucker rat, the mechanisms for cellular proliferation and fat deposition remain intact.