title: Circulating very-low-density lipoprotein characteristics resulting from fatty liver in an insulin resistance rat model.
abstract: The close association between nonalcoholic fatty liver and insulin resistance is now widely recognized. While the former is characterized by excessive intrahepatic triglyceride accumulation, the latter induces overproduction of very-low-density lipoprotein (VLDL) particles. It has not been well elucidated whether these apparently opposite mechanisms impact on VLDL characteristics or not. The aim of the present study was to evaluate the VLDL secretion and features resulting from insulin resistance and fatty liver in rats fed a sucrose-rich diet (SRD, i.e. addition of sucrose to drinking water during 12 weeks). No differences in calorie intake were observed in comparison to controls. Both groups showed similar weight gains throughout the treatment period. However, SRD rats showed an increased proportion of body fat as assessed by X-ray absorptiometry, increased visceral obesity, liver weight and fat accumulation in the liver (p < 0.04). Histological study revealed moderate micro- and macrovesicular steatosis. Fasting insulin, triglyceride and free fatty acid (FFA) levels increased while VLDLs decreased in SRD rats (p < 0.05). The chemical composition of VLDLs of SRD rats showed a higher percentage of triglycerides, and the VLDL triglyceride/protein ratio, an estimator of lipoprotein size, suggests that VLDL particles of SRD rats are larger than those of controls (p < 0.0005). FFA levels correlated with VLDL triglycerides (r = 0.49, p = 0.03) and liver fat content correlated with plasma triglycerides (r = 0.65), VLDL triglycerides (r = 0.55) and triglyceride/protein ratio (r = 0.52, p < 0.02). The VLDL secretion rate assay showed an increase in SRD rats (p < 0.02), confirming an overproduction despite liver fat accumulation. Our findings are consistent with an insulin resistance development model in which hepatic lipid content would constitute an important determinant of a triglyceride-rich, large-particle VLDL secretion; both features would increase its atherogenic potential.
authors.affiliation: Laboratory of Lipids and Lipoproteins, Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, INFIBIOC, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: V
authors.initials: V
authors.lastname: Zago
authors.forename: D
authors.initials: D
authors.lastname: Lucero
authors.forename: E V
authors.initials: EV
authors.lastname: Macri
authors.forename: L
authors.initials: L
authors.lastname: Cacciagiú
authors.forename: C A
authors.initials: CA
authors.lastname: Gamba
authors.forename: V
authors.initials: V
authors.lastname: Miksztowicz
authors.forename: G
authors.initials: G
authors.lastname: Berg
authors.forename: R
authors.initials: R
authors.lastname: Wikinski
authors.forename: S
authors.initials: S
authors.lastname: Friedman
authors.forename: L
authors.initials: L
authors.lastname: Schreier
mesh_terms: D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D002149:Energy Intake; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008079:Lipoproteins, VLDL / Q000097:blood*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides