L-carnitine treatment in the hyperlipidemic rabbit.
A study was designed to examine the hypolipidemic effect of L-carnitine treatment (4 weeks, 170 mg/kg/d) in rabbits fed a high fat diet (5% corn oil/0.5% cholesterol, w/w). Eight weeks of exposure to the high fat diet significantly increased plasma total cholesterol and triglycerides. VLDL associated triglycerides, cholesterol, apo-B, and total protein were also significantly increased with the diet. There was no change in HDL-cholesterol levels. Plasma concentration of carnitine (free, acyl, and total) all increased significantly with the high fat diet. The content of free, short-chain, and total carnitine were decreased in the liver whereas the content of long-chain acylcarnitines was increased. The diet generated a significant steatosis within the livers of these animals. Four weeks of treatment of L-carnitine reduced the extent of the liver steatosis and significantly decreased plasma total cholesterol, triglycerides, VLDL associated triglycerides, cholesterol, and total protein. HDL-cholesterol levels were unaffected by the treatment. All plasma fractions of carnitine (free, acetyl, acyl, and total) were significantly increased above those levels seen after 8 weeks of the high fat diet alone. The content of liver carnitine and its esters was normalized following treatment. The high fat diet decreased liver HMG-CoA reductase activity and increased the activities of 7-alpha-hydroxylase and acylcholesterol acyltransferase (ACAT). L-Carnitine treatment blunted the magnitude of the diet induced increase in 7 alpha-hydroxylase activity, yet overall the activity still remained elevated relative to controls. ACAT activity increased (1.5 times) with the high fat diet and increased further (4.5 times) following carnitine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Seccombe
D W
DW
Department of Pathology, Shaughnessy Hospital, Vancouver, British Columbia, Canada.
James
L
L
Hahn
P
P
Jones
E
E
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002331:Carnitine / Q000627:therapeutic use* / Q000633:toxicity; D004041:Dietary Fats / Q000008:administration & dosage; D005234:Fatty Liver / Q000139:chemically induced; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use* / Q000633:toxicity; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000201:enzymology; D008297:Male; D011817:Rabbits
D004041:Dietary Fats; D000960:Hypolipidemic Agents; D008055:Lipids; D002331:Carnitine