Regulation of lipid flux between liver and adipose tissue during transient hepatic steatosis in carnitine-depleted rats.
Rats with carnitine deficiency due to trimethylhydrazinium propionate (mildronate) administered at 80 mg/100 g body weight per day for 10 days developed liver steatosis only upon fasting. This study aimed to determine whether the transient steatosis resulted from triglyceride accumulation due to the amount of fatty acids preserved through impaired fatty acid oxidation and/or from up-regulation of lipid exchange between liver and adipose tissue. In liver, mildronate decreased the carnitine content by approximately 13-fold and, in fasted rats, lowered the palmitate oxidation rate by 50% in the perfused organ, increased 9-fold the triglyceride content, and doubled the hepatic very low density lipoprotein secretion rate. Concomitantly, triglyceridemia was 13-fold greater than in controls. Hepatic carnitine palmitoyltransferase I activity and palmitate oxidation capacities measured in vitro were increased after treatment. Gene expression of hepatic proteins involved in fatty acid oxidation, triglyceride formation, and lipid uptake were all increased and were associated with increased hepatic free fatty acid content in treated rats. In periepididymal adipose tissue, mildronate markedly increased lipoprotein lipase and hormone-sensitive lipase activities in fed and fasted rats, respectively. On refeeding, carnitine-depleted rats exhibited a rapid decrease in blood triglycerides and free fatty acids, then after approximately 2 h, a marked drop of liver triglycerides and a progressive decrease in liver free fatty acids. Data show that up-regulation of liver activities, peripheral lipolysis, and lipoprotein lipase activity were likely essential factors for excess fat deposit and release alternately occurring in liver and adipose tissue of carnitine-depleted rats during the fed/fasted transition.
Degrace
Pascal
P
UMR 866 INSERM-UB, Equipe Physiopathologie des dyslipidémies, Faculté des Sciences, 21000 Dijon, France.
Demizieux
Laurent
L
Du
Zhen-Yu
ZY
Gresti
Joseph
J
Caverot
Laurent
L
Djaouti
Louiza
L
Jourdan
Tony
T
Moindrot
Bastien
B
Guilland
Jean-Claude
JC
Hocquette
Jean-François
JF
Clouet
Pierre
P
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002331:Carnitine / Q000378:metabolism / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014304:Triolein / Q000737:chemistry
D005227:Fatty Acids; D008055:Lipids; D008077:Lipoproteins, LDL; D014304:Triolein; D008071:Lipoprotein Lipase; D002331:Carnitine