Failure of insulin to stimulate lipogenesis and triacylglycerol secretion in perfused livers from rats adapted to dietary fish oil.

Livers from male rats fed a standard commercial diet supplemented with 8% (w/w) marine fish or safflower oils were perfused for 70 min with undiluted blood in the presence and absence of insulin. Lipogenesis, as measured by the incorporation of 3H2O into liver and perfusate fatty acids, was inhibited by the feeding of fish oil. Net triacylglycerol secretion was also depressed by this dietary treatment. Infusion of insulin stimulated triacylglycerol secretion and the incorporation of newly synthesised fatty acids into liver and perfusate lipids with dietary safflower oil but not with fish oil. Hepatic cholesterol synthesis was also depressed by feeding fish oil. Net ketogenesis was raised by feeding fish oil and was depressed by insulin with both safflower and fish oil. Blood glucose was raised in the fish oil group but with both dietary oils the hormone exerted a significant hypoglycaemic effect. The data are discussed with respect to the observations that in vivo dietary fish oil (but not safflower oil) opposes the hypertriglyceridaemia arising from the hepatic overproduction of very-low-density lipoproteins.