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Apoprotein A-V: An important regulator of triglyceride metabolism

  • SSIEM Symposium 2007
  • Published:
Journal of Inherited Metabolic Disease

Summary

Apolipoprotein A-V (apoA-V) was discovered in 2001 both by comparative sequencing and as a liver regeneration protein. The gene is a located at the APOA1/C3/A4/A5 gene cluster on chromosome 11q23, a locus well known for playing a major role in regulating plasma cholesterol and triglyceride (TG) levels. ApoA-V is produced in the liver and has very low plasma concentrations (0.1–0.4 μg/ml). Mice lacking apoA-V have 4-fold increased TG levels, whereas apoA-V overexpression leads to 40% plasma TG reduction. Based on metabolic studies in vivo, apoA-V enhances the catabolism of TG rich lipoproteins rather than affecting their intestinal or hepatic production. By activating proteoglycans-bound lipoprotein lipase (LPL), apoA-V can accelerate TG hydrolysis from VLDL and chylomicrons independent from other apoproteins. Several variants at the APOA5 gene locus have been detected in humans. Some single nucleotide polymorphisms (SNPs) are associated with significantly higher plasma TG levels in patients (e.g., −1131T > C, S19W, G185C). In addition, these SNPs may affect fibrate response and obesity. However, data for a possible association of APOA5 variants with coronary heart disease are not consistent. Severe structural mutations (Q139X, Q148X, IVS3 + 3G > C) predispose to familial hypertriglyceridaemia and late-onset chylomicronaemia. Thus, despite its low plasma concentration, apoA-V is a major regulator of plasma TG metabolism in humans. However, the precise mechanism of its function is not yet clear.

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Abbreviations

APOA5 :

human apoA-V gene

apoa5 :

mouse apoA-V gene

apoA-V:

apolipoprotein A-V

BMI:

body mass index

HDL:

high-density lipoprotein

LPL:

lipoprotein lipase

SNP:

single-nucleotide polymorphism

TG:

triglyceride

VLDL:

very low-density lipoprotein

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Acknowledgement

This work was supported by LiDia (Lipids and Diabetes).

Author information

Authors and Affiliations

  1. III. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    M. Kluger

  2. Department of Biochemistry and Molecular Biology II: Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    J. Heeren

  3. Department of Internal Medicine 1 (Gastroenterology, Endocrinology, Diabetes and Metabolic Disease), Asklepios Klinik St. Georg, Lohmuehlenstr. 5, 20099, Hamburg, Germany

    M. Merkel

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  1. M. Kluger
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  2. J. Heeren
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  3. M. Merkel
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Corresponding author

Correspondence to M. Merkel.

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Communicating editor: Robert Steiner

Competing interests: None declared

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Kluger, M., Heeren, J. & Merkel, M. Apoprotein A-V: An important regulator of triglyceride metabolism. J Inherit Metab Dis 31, 281–288 (2008). https://doi.org/10.1007/s10545-008-0863-4

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