Ontogeny and dietary modulation of 3-hydroxy-3-methylglutaryl-CoA reductase activities in neonatal pigs

The development of hepatic and ileal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase was studied in three types of young pigs (crossbred, obese, and lean pigs). Pigs were fed one of two diets: a high-fat (coconut oil), high-cholesterol (1.0%; designated HC) diet or a high-fat, no-cholesterol (designated NC) diet from postpartum d 3 to d 13, 25, and 42 (crossbred only). There were four pigs per age per diet group (except for obese pigs). Liver and ileal mucosal microsomal reductase activities were determined by the conversion of [14C]HMG-CoA to mevalonic acid followed by lactonization of the product. The samples were analyzed by thin layer chromatography and liquid scintillation spectrometry. Hepatic reductase activity (1 unit of specific activity = 1 pmol.min-1.mg protein-1) was 20 units on d 3 in all groups. By d 13, the activity was 40 to 46 units in all groups of pigs fed HC and approximately 50 to 80 units in pigs fed NC. Reductase activity then decreased at d 25 to 18 to 40 units in pigs fed NC and to 14 units in pigs fed HC. The d 42 reductase values (crossbred only) were approximately 14 units for pigs fed both HC and NC diets. Intestinal reductase activity was not affected (P 0.1) by either age or diet. The data suggest that dietary cholesterol suppressed hepatic reductase activity in young pigs (d 13 and 25) from divergent genetic backgrounds. The data also suggest that the stage of development is a dominant factor in regulating porcine hepatic HMG-CoA reductase activity, which was considerably increased at d 13, even in pigs fed HC diets. The relatively modest increase in plasma cholesterol, even in pigs fed cholesterol during the suckling period, provides evidence that both dietary and endogenously synthesized cholesterol are probably used predominantly for tissue building in very young pigs (d 13)