L-CARNITINE ADMINISTRATION AND WITHDRAWAL AFFECT PLASMA AND HEPATIC CARNITINE CONCENTRATIONS, PLASMA-LIPID AND LIPOPROTEIN COMPOSITION, AND INVITRO HEPATIC LIPOGENESIS FROM LABELED MEVALONATE AND OLEATE IN NORMAL RABBITS

Carnitine was administered to normal rabbits to investigate the possible effects of pharmacologic doses on various aspects of normal lipid and lipoprotein metabolism. Carnitine concentrations were measured in the plasma and liver of normal rabbits that received L-carnitine orally [40 mg/(kg.d)] for 21 d and after withdrawal from the carnitine supplement for 21 d. Plasma lipids, plasma lipoprotein composition and in vitro hepatic lipid biosynthesis from [2-C-14]mevalonate and [1-C-14]oleate were also measured. Threefold elevations in plasma carnitine with carnitine treatment were essentially reversed after 48 h of carnitine withdrawal, but elevated hepatic carnitine accumulation (twofold) persisted for 21 d, suggesting that the accumulated carnitine constituted a pool that is only slowly miscible with plasma. The rabbits withdrawn from L-carnitine for 21 d experienced a 35% decrease in plasma cholesterol, a 50% decrease in VLDL cholesterol, and an increase in the protein content of HDL and of intermediate density lipoprotein + LDL. Additionally, the proportion of [C-14]oleate incorporated into hepatic phospholipids increased 35% at the expense of triglyceride and the ratio of hepatic [C-14]cholesterol to [C-14]squalene derived from [C-14]mevalonate increased over twofold following carnitine withdrawal. These studies provide evidence that normal lipid homeostasis can be altered by supplemental carnitine and that the perturbations are reflected by changes in plasma lipids and lipoproteins and in the proportions of the hepatic lipids synthesized.