Title
ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglycerides (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis
Author
TNO Preventie en Gezondheid
Schaap, F.G.
Rensen, P.C.N.
Voshol, P.J.
Vrins, C.
van der Vliet, H.N.
Chamuleau, R.A.F.M.
Havekes, L.M.
Groen, A.K.
van Dijk, K.W.
Publication year
2004
Abstract
ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 x 108 plaque-forming units/mouse) dose-dependently reduced plasma very low density lipoprotein (VLDL)-TG levels. First, we evaluated whether a reduced hepatic VLDL production contributed to the TG-lowering effect. Ad-apoa5 treatment dose-dependently diminished (29-37%) the VLDL-TG production rate without affecting VLDL particle production, suggesting that apoAV impairs the lipidation of apoB. Second, Ad-apoa5 treatment dose-dependently reduced (68-88%) the postprandial hypertriglyceridemia following an intragastric fat load, suggesting that apoAV also stimulates the lipoprotein lipase (LPL)-dependent clearance of TG-rich lipoproteins. Indeed, recombinant apoAV was found to dose-dependently stimulate LPL activity up to 2.3-fold in vitro. Accordingly, intravenously injected VLDL-like TG-rich emulsions were cleared at an accelerated rate concomitant with the increased uptake of emulsion TG-derived fatty acids by skeletal muscle and white adipose tissue in Ad-apoa5-treated mice. From these data, we conclude that apoAV is a potent stimulator of LPL activity. Thus, apoAV lowers plasma TG by both reducing the hepatic VLDL-TG production rate and by enhancing the lipolytic conversion of TG-rich lipoproteins. Chemicals / CAS: Apoa5 protein, mouse; Apolipoproteins; Lipids; Lipoprotein Lipase, EC 3.1.1.34; Lipoproteins; Lipoproteins, VLDL; Recombinant Proteins; Triglycerides; very low density lipoprotein triglyceride
Subject
Biomedical Research
Data reduction
Enzymes
Gene transfer
Metabolism
Reaction kinetics
Lipolytic conversion
Lipoproteins
Biochemistry
Apolipoprotein A
Apolipoprotein a5
Triacylglycerol
Unclassified drug
Very low density lipoprotein
Animal experiment
APO5 gene
Gene
Gene transfer
Hydrolysis
Hyperlipidemia
Hypertriglyceridemia
Lipid blood level
Lipid metabolism
Lipoprotein blood level
Mouse
Nonhuman
Triacylglycerol blood level
Adenoviridae
Adipose Tissue
Animals
Apolipoproteins
Dose-Response Relationship, Drug
Gene Transfer Techniques
Hydrolysis
Kinetics
Lipids
Lipoprotein Lipase
Lipoproteins
Lipoproteins, VLDL
Liver
Male
Mice
Mice, Inbred C57BL
Muscle, Skeletal
Postprandial Period
Rats
Recombinant Proteins
Time Factors
Triglycerides
Animalia
Murinae
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DOI
https://doi.org/10.1074/jbc.m403240200
TNO identifier
237899
ISSN
0021-9258
Source
Journal of Biological Chemistry, 279 (279), 27941-27947
Document type
article