Decreased hepatic expression of the low-density lipoprotein (LDL) receptorand LDL receptor-related protein in aging rats is associated with delayed clearance of chylomicrons from the circulation

Aging in both humans and rats is associated with the development of insulin resistance and the ensuing alterations in the plasma Lipoprotein profile. In this study, young (2 months) and old (15 months) Sprague-Dawley (SD) rat s were used to investigate age-related alterations in the chylomicron clear ance pathway. Clearance from the blood of an intravenously injected bolus o f C-14-labeled cholesterol ester (CE) and H-3-labeled triacylglycerol (TAG) lymph chylomicrons was markedly delayed in the old rats (P <.05). Hepatic expression of the two principal receptors of chylomicron remnant removal, t he low-density lipoprotein (LDL) receptor and LDL receptor-related protein (LRP), was determined by ligand blotting and immunoblotting, The old rats e xpressed 43% +/- 7% of the level of LDL receptor in the young animals (P <. 05) and 45% +/- 16%. of the corresponding level of LRP (P <.05). The result s suggest that the delayed clearance of chylomicron remnants in this animal model of aging and insulin resistance is due, at least in part, to a decre ase in the hepatic expression of LDL receptor and LRP. Copyright (C) 2000 b y W.B. Saunders Company.