Changes in dietary fatty acids modify the decreased lipolytic beta3-adrenergic response to hyperinsulinemia in adipocytes from pregnant and nonpregnant rats.

The effect of dietary olive oil and fish oil on the lipolytic dose-response of the beta3-adrenergic agonists, epinephrine, isoproterenol, BRL-37344, and CGP-12177, in adipocytes was studied in pregnant and virgin rats either untreated or under hyperinsulinemic-euglycemic conditions. Rats were fed a semisynthetic diet containing 5% of either olive oil or fish oil and studied at day 20 of treatment and/or gestation. Plasma glucose was lower and plasma insulin, triglycerides, and free fatty acids (FFAs) were higher in pregnant versus virgin rats, and the insulin sensitivity index was lower in the former. Lumbar adipose tissue phospholipid fatty acids showed a significantly higher monounsaturated fatty acid and a lower (n - 3) fatty acid content in rats fed the olive oil diet versus the fish oil diet. The lipolytic dose-response curve of either adrenergic agent was always lower in adipocytes from untreated pregnant rats versus virgin rats, and whereas the hyperinsulinemic-euglycemic clamp decreased these responses in adipocytes from virgin rats fed the olive oil diet only, adipocytes from pregnant rats always showed a decreased dose-response lipolytic curve. Thus, the lipolytic responsiveness of beta3-adrenoceptor (beta3-AR) agonists by adipocytes is impaired in cells from rats made hyperinsulinemic chronically by pregnancy or acutely by the hyperinsulinemic-euglycemic clamp, but such response to the acute condition disappears when the adipocyte phospholipid composition is modified by changes in dietary fatty acids.