An investigation of L-carnitine treatment in the hyperlipidemic rabbit
Creators: name: James, Leighton Rolston
Publisher: name: University of British Columbia
Year: 2010

description: Cardiovascular disease, specifically coronary heart disease, remains the leading cause of morbidity and mortality among the adult population in North America and Western Europe. Hyperlipidemia ranks as one of the most important risk factors for cardiovascular disease. Thus, the need for effective therapy in the management and treatment of hyperlipidemia remains high. At present, dietary manipulations and/or drug therapy are the methods of choice in the management and treatment of hyperlipidemia. Though most of the currently used hypolipidemic drugs are very effective in reducing plasma lipids, many of these have unpleasant side-effects. The search for effective hypolipidemic agents, with relatively few side-effects, continues. One such compound presently under consideration is L-carnitine ( β-hydroxy-γ -trimethylaminobutyrate). This acid is a naturally occurring substance which has been reported to possess lipid-lowering properties. It is required for the optimum oxidation of long-chain fatty acids. In addition, it functions as a buffer for coenzyme A pools within the cell. The present study was designed to examine the hypolipidemic effect of 4 weeks of L-carnitine treatment (170 mg/kg b.w/day) in New Zealand White rabbits fed a high-fat diet. In particular, the effect of L-carnitine treatment on plasma concentrations of cholesterol, triglycerides, VLDL and HDL-cholesterol were examined. In addition, ³H-glycerol and ¹²⁵I-VLDL turnover studies were conducted in order to examine the effect of treatment on VLDL kinetics. In rabbits fed the high-fat diet, plasma total cholesterol, and triglycerides, cholesterol, apoprotein B and total protein associated with the VLDL particle increased significantly. There were no significant changes in HDL-cholesterol and plasma triglycerides. The fractional catabolic rate for VLDL-triglycerides and VLDL-apoprotein B were significantly reduced in the hyperlipidemic state. In addition, the transport rate for these two components of the VLDL particle were moderately elevated. With hyperlipidemia, plasma concentrations of free carnitine, acetylcarnitine, acylcarnitine and total carnitine were increased. Although carnitine levels were increased, the relative percentage of acetyl and acyl carnitine esters within the plasma pool were unchanged. Liver and skeletal muscle long-chain acylcarnitines were also significantly increased. On the other hand, the liver concentrations of free carnitine, short-chain acylcarnitine and total carnitine were significantly reduced. L-carnitine treatment of the hyperlipidemic rabbit produced significant reductions in plasma concentrations of total cholesterol, triglycerides, VLDL-triglycerides, VLDL-cholesterol and VLDL total protein. It had no effect on plasma HDL-cholesterol. Liver and skeletal muscle carnitine levels in the hyperlipidemic carnitine-treated animals were normalized. Although treatment significantly elevated all plasma carnitine fractions well above those seen in the hyperlipidemic untreated animals, the percentage of acetyl- and acylcarnitines remained unchanged. The fractional catabolic rate of VLDL-triglycerides returned to control values with L-carnitine treatment. Treatment had no effect on VLDL-apoprotein B kinetics. On the basis of these results, it was concluded that the reduction in plasma triglycerides in the hyperlipidemic rabbit following L-carnitine treatment was due to an increase in the catabolism of VLDL-triglycerides.