Apoprotein A-V: An important regulator of triglyceride metabolism
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Apoprotein A-V: An important regulator of triglyceride metabolism. / Kluger, Malte Andreas; Heeren, Jörg; Merkel, Martin.
In: J INHERIT METAB DIS, Vol. 31, No. 2, 01.04.2008, p. 281-8.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Apoprotein A-V: An important regulator of triglyceride metabolism
AU - Kluger, Malte Andreas
AU - Heeren, Jörg
AU - Merkel, Martin
PY - 2008/4/1
Y1 - 2008/4/1
N2 - 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 mug/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.
AB - 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 mug/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.
KW - Animals
KW - Apolipoproteins
KW - Apolipoproteins A
KW - Disease Models, Animal
KW - Genetic Predisposition to Disease
KW - Humans
KW - Lipid Metabolism, Inborn Errors
KW - Lipolysis
KW - Liver
KW - Mice
KW - Mutation
KW - Phenotype
KW - Triglycerides
U2 - 10.1007/s10545-008-0863-4
DO - 10.1007/s10545-008-0863-4
M3 - SCORING: Journal article
C2 - 18415697
VL - 31
SP - 281
EP - 288
JO - J INHERIT METAB DIS
JF - J INHERIT METAB DIS
SN - 0141-8955
IS - 2
ER -