Pathogenesis of carbohydrate-induced hypertriglyceridemia using HepG2 cells as a model system.
This study compares the effects of glucose and fatty acid on hepatic lipid synthesis and apolipoprotein (apo) B secretion. To do so, varying concentrations of either glucose or oleic acid were added to the medium in which HepG2 cells were being incubated. Intracellular triacylglycerol and cholesteryl ester synthesis and secretion were measured by addition of radioisotopic tracers and by determination of mass, whereas apo B concentration in the medium was measured by a specific enzyme-linked immunosorbent assay. The data indicate that increasing concentrations of glucose in the medium resulted in increased synthesis of triacylglycerol within the cell and increased secretion of triacylglycerol into the medium. Apo B secretion into the medium, however, did not change, and intracellular synthesis and secretion of cholesteryl ester did not change as well. By contrast, addition of oleic acid to the medium resulted in increased synthesis and secretion of both cholesteryl ester and triacylglycerol, and this was associated with increased secretion of apo B into the medium. Thus, a carbohydrate load resulted in secretion of normal numbers of triacylglycerol-enriched apo B particles by this hepatocyte cell line, whereas a fatty acid load led to the secretion of increased numbers of apo B particles, which were essentially normal in composition.
Cianflone
K
K
Royal Victoria Hospital, McGill Unit for the Prevention of Cardiovascular Disease, McGill University, Montreal, Canada.
Dahan
S
S
Monge
J C
JC
Sniderman
A D
AD
D001055:Apolipoproteins B / Q000378:metabolism; D002241:Carbohydrates / Q000494:pharmacology*; D002460:Cell Line; D002788:Cholesterol Esters / Q000096:biosynthesis / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D015228:Hypertriglyceridemia / Q000139:chemically induced*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D014280:Triglycerides / Q000096:biosynthesis* / Q000378:metabolism
D001055:Apolipoproteins B; D002241:Carbohydrates; D002788:Cholesterol Esters; D009829:Oleic Acids; D014280:Triglycerides; D019301:Oleic Acid; D005947:Glucose