Pharmacologic action of l-carnitine on hypertriglyceridemia in obese Zucker rats

Linda J. Brady, Catherine M. Knoeber, Charles L. Hoppel, Charles W. Leathers, Douglas McFarland, Paul S. Brady

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13 Scopus citations

Abstract

Administration of pharmacologic amounts of l-carnitine was studied in the hypertriglyceridemic Zucker rat. When administered subcutaneously, doses from 250 to 2,000 mg/kg/d significantly decreased plasma triglycerides in obese rats over eight to 12 weeks, with no effect on plasma triglycerides in lean rats. Oral doses at the same high levels were not effective in decreasing plasma triglycerides. Triglyceride secretion rate was reduced from 367 μg/min to 168 μg/min in treated obese rats. Concurrently, liver lipid was increased twofold in obese treated rats, and the livers of these rats showed significant fatty infiltration. The mechanism of action of carnitine in decreasing plasma triglycerides appeared to be via decreased secretion of triglycerides by the liver of obese rats. There was no effect of l-carnitine in lean or obese rats on the following variables: carnitine palmitoyltransferase-A kinetics or malonyl CoA inhibition, mitochondrial or peroxisomal oxidative capacity, lipoprotein lipase in heart, muscle, and adipose, or fecal lipids. The effect of pharmacologic l-carnitine thus appears to be an inhibition of triglyceride synthesis and/or secretion by the liver.

Original languageEnglish (US)
Pages (from-to)555-562
Number of pages8
JournalMetabolism
Volume35
Issue number6
DOIs
StatePublished - Jun 1986

Bibliographical note

Funding Information:
From the Departments of Food Science and Human Nutrition, Animal Sciences, and Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington and VA Medical Center and Departments of Pharmacology and Medicine, Case Western Reserve University, Cleveland. Supported by the Washington State Agricultural Experiment Station (Paper No. 7197). Presented in part at the 45th annual meeting of the Federation of American Societies for Experimental Biology, held in Anaheim, Calix April 21-26. 1985. Address reprint requests to Linda J. Brady, PhD. Food Science and Human Nutrition, Washington State University, Pullman. WA 99164-2032. o 1986 by Grune & Stratton, Inc. 0026-0495/86/3506-00I5$03.00/0

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