Effect of dietary fat and cholesterol supplements on glucagon receptor binding and adenylate cyclase activity of rat liver plasma membrane.

We have examined the effect on rat liver glucagon receptors and adenylate cyclase activity of a high saturated fat diet (butter fat), a high n-6 polyunsaturated fat diet (corn oil), and a high n-3 polyunsaturated fat diet (menhaden fish oil) with or without additional cholesterol. The number and affinity of the glucagon receptors were unaffected by diet. The glucagon-stimulated adenylate cyclase activity from fish oil-fed animals exhibited the greatest stimulation, followed by corn oil-fed animals. Butter fat-fed and all cholesterol-supplemented groups showed a depression in stimulation. The pattern of adenylate cyclase activity with fluoride stimulation was similar to that observed with glucagon. The effect of dietary fat on forskolin stimulation was similar to glucagon and fluoride for the groups without added cholesterol. However, the cholesterol-supplemented groups did not exhibit a decreased activity. It is suggested that the effect of dietary lipid on glucagon-stimulated adenylate cyclase is not due to changes in the glucagon receptor, but rather due to changes in signal transduction, the Gs-protein or the catalytic unit.