Effect of chronic glucagon administration on lipoprotein composition in normally fed, fasted and cholesterol-fed rats

Male adult Wistar rats received daily (at 9 a.m. and 5 p.m.) 10 micrograms of zinc-protamine glucagon by subcutaneous injection for 8 days. Plasma cholesterol levels were decreased by 36% in fed rats, 33% in cholesterol-fed rats and by 55% in fasted rats. Lipoproteins were separated into 22 fractions by ultracentrifugation using a density gradient. Glucagon administration decreased the cholesterol content in all lipoproteins except low density lipoprotein (LDL1) (1.006-1.040) and very low density lipoprotein (VLDL) from cholesterol-fed rats. The main decrease (-57 to -81%) was observed in 1.050-1.100 g/mL lipoproteins (LDL2 and HDL2), which contained a large amount of apo E, while HDL3 cholesterol was not affected. Triacylglycerol levels were decreased only in chylomicrons and VLDL (-70%) of fed and cholesterol-fed rats, while plasma and lipoprotein triacylglycerol levels were not changed in fasted rats treated with glucagon. In normally fed rats glucagon administration increased by 42% the fractional catabolic rate of [125I]HDL2 while the absolute catabolic rate appeared to be unchanged. Glucagon seems to be a potent hypolipidemic agent affecting mainly the apo E-rich lipoproteins. Its chronic administration limits lipoprotein accumulation which occurs upon cholesterol feeding.