Partial characterization of the fructose-induced defect in very-low-density lipoprotein triglyceride metabolism.
Very-low-density lipoprotein triglyceride (VLDL-TG) catabolism was studied in rats receiving either fructose or glucose as a 10% drinking solution. Consumption of either of the hexoses for 16 hours significantly elevated postheparin plasma (PHP) lipoprotein lipase (LPL) activity compared with normal control animals. Prolonged feeding of the carbohydrates for 14 days abolished the higher LPL activities, which were similar to control levels. PHP hepatic lipase (HL) activity was significantly reduced in carbohydrate-fed rats compared with control animals despite the duration of feeding. The kinetic parameters Km and Vmax cannot be obtained with lipoproteins and so the first-order rate constant (k1) of triglyceride hydrolysis was used to assess the effectiveness of VLDL-TG as substrates for endothelial lipases. VLDL-TG from fructose and VLDL-TG from glucose donors was lipolyzed with PHP LPL and HL from normal rats. The k1 (fraction of VLDL-TG lipolyzed) of VLDL-TG was found to be lower when donors had been fed fructose compared with VLDL that had come from glucose-fed donors. Rates of VLDL-TG removal from fructose and glucose donors were determined simultaneously in perfused livers of normal control, fructose-fed, and glucose-fed animals. Livers of fructose-fed animals cleared VLDL-TG at a slower rate than livers from glucose-fed or control rats. VLDL-TG from fructose-fed rats was cleared less effectively than VLDL-TG from glucose-fed rats in livers of both control and glucose-fed animals. We conclude that an impairment in the ability of fructose-fed rats to hydrolyze VLDL-TG, and of their livers to remove VLDL-TG, may in part explain fructose-induced hypertriglyceridemia.
Mamo
J C
JC
Department of Medicine, Toronto General Hospital, Ontario, Canada.
Hirano
T
T
James
L
L
Szeto
L
L
Steiner
G
G
D000818:Animals; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D008049:Lipase / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000097:blood; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism*
D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D005632:Fructose; D006493:Heparin; D008049:Lipase; D008071:Lipoprotein Lipase; D005947:Glucose