W06-O-002 Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan bound lipoprotein lipase

Merkel, Martin; Loeffler, B.; Kluger, Malte A.; Fabig, Nathalie; Aydin, Birol; Geppert, Gesa; Pennacchio, L; Laatsch, Alexander; Heeren, J.

doi:10.1016/s1567-5688(05)80086-8

Cited by 99 publications

(171 citation statements)

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“…However, the exact molecular mechanism underlying the role of APOA5 in triglyceride metabolism remains unclear. The fractional catabolic rate of VLDL and chylomicron triglycerides was markedly accelerated in both human APOA5 transgenic mice and adenovirus-mediated APOA5-overexpressing mice, and was sharply decreased in APOA5-deficient mice, clearly suggesting a role for APOA5 in the hydrolysis of triglycerides [9,10,21,23]. All these studies, however, were complicated by the fact that APOC3, a well-known inhibitor of lipoprotein lipase activity, is decreased in APOA5 transgenic mouse models and increased in APOA5-deficient mice [7].…”

Section: Discussionmentioning

confidence: 99%

“…APOA5 in human plasma is present on VLDL and HDL particles [19]. However, its total plasma concentration is very low and only about 4% of VLDL particles carry an APOA5 molecule [20,21]. In contrast, all VLDL particles are carrying one or more APOC3 molecules.…”

Section: Discussionmentioning

confidence: 99%

“…All these studies, however, were complicated by the fact that APOC3, a well-known inhibitor of lipoprotein lipase activity, is decreased in APOA5 transgenic mouse models and increased in APOA5-deficient mice [7]. Using a different strategy it was suggested that APOA5 may accelerate the hydrolysis of triglyceride-rich lipoproteins by facilitating their interaction with proteoglycan-bound lipoprotein lipase [21]. However, recently human APOA5 concentration was shown not to be related to VLDL kinetic parameters in 15 healthy control subjects [24].…”

Section: Discussionmentioning

confidence: 99%

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Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

et al. 2006

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Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in patients with type 2 diabetes at baseline and during atorvastatin treatment, a lipid-lowering treatment that results in a reduction in plasma triglycerides and APOC3. Subjects, materials and methods: Plasma APOA5 concentration was measured by ELISA in 215 subjects with type 2 diabetes, who were taken from the Diabetes Atorvastatin Lipid-lowering Intervention (DALI) study, a 30-week randomised, double-blind, placebo-controlled study, and given atorvastatin 10 mg or 80 mg daily. Results: At baseline, average plasma APOA5 concentration was 25.7±15.6 μg/100 ml. Plasma APOA5 (R s =0.40), APOC3 (R s =0.72) and APOE (R s =0.45) were positively correlated with plasma triglyceride levels (all p<0.001). In multiple linear regression analysis, adjusted for age and sex, the variation in plasma triglycerides was explained mostly by APOC3 (52%) and only to a small extent by APOA5 (6%) and APOE (1%). Atorvastatin treatment decreased plasma triglycerides, APOA5, APOC3 and APOE (all p<0.0001). After treatment, APOC3 remained the major determinant of plasma triglyceride levels (59%), while the contributions of APOA5 and APOE were insignificant (2 and 3%). Conclusions/interpretation: Our findings reveal a positive association between plasma APOA5 and triglycerides in patients with type 2 diabetes. Treatment with atorvastatin decreased plasma APOA5, APOC3, APOE and triglycerides. In contrast to APOC3, APOA5 is not a major determinant of triglyceride metabolism in these patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

et al. 2006

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“…In APOA5-knockout mice, the triglycerides concentration increased fourfold (van der Vliet et al, 2001), while the serum triglyceride concentrations decreased by 50% to 70% in transgenic mice with the human APOA5 (Baroukh et al, 2004). APOA5 may enhance LPL-mediated triglyceride hydrolysis in vitro and modulate hepatic very low density lipoprotein-triglyceride synthesis to affect triglyceride levels Schaap et al, 2004;Merkel et al, 2005). Additionally, APOA5 has a unique association with cellular lipid droplets, which it may be involved in the storage or mobilization of intracellular lipids (Shu et al, 2007 and.…”

Section: Discussionmentioning

confidence: 99%

Molecular cloning, expression and polymorphism of the porcine apolipoprotein A5 gene in a Jinhua × Pietrain F2 reference population

Zhang

Jiang

Hua

et al. 2010

Animal

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As a newly described member of the apolipoprotein gene family, apolipoprotein A5 (APOA5) has been suggested to play a key role in the triglyceride metabolism in both human and mice. The aim of this study was to identify the porcine (Sus scrofa) APOA5 gene, determine its mRNA and its mutations that are associated with lipid accumulation. The porcine APOA5 cDNA was amplified by reverse transcriptase polymerase chain reaction using the information of the mouse or other mammals. It had been determined that the open reading frame of the porcine APOA5 gene consists of 1092 bp, which encodes a predicted protein composed of 363 amino acids with a similarity to bovine (80.43%) and to human (78.47%). The expression analysis indicated that the porcine APOA5 gene was expressed in hypophysis, fat and liver. Twelve single nucleotide polymorphisms (SNPs), including 4 SNPs in the 5 0 end, 1 SNP in second intron, 1 SNP in third exon and 6 SNPs in the 3 0 end, were identified in the porcine APOA5 gene and genotyped on the Jinhua 3 Pietrain F 2 reference population, it had revealed that the SNP of C1834T was significantly associated with average backfat thickness and leaf fat weight ( P , 0.01 and P , 0.05, respectively). In conclusion, this study has got basic information of the porcine APOA5 gene and provides evidence that the APOA5 gene could be a potential candidate gene for fat deposition.

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“…APOA5 gene is an important regulator of triglyceride (TG)-rich lipoprotein (TRL) metabolism [46] with two roles, (1) by assembling VLDLs [51,58]; (2) as activator of intravascular TG hydrolysis by lipoprotein lipase (LPL) [16,37].…”

Section: Apolipoprotein A5mentioning

confidence: 99%

Nutrigenomics: a case for the common soil between cardiovascular disease and cancer

Iacoviello¹,

Santimone²,

Latella³

et al. 2008

Genes Nutr

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The border between health and disease is often set by a complex equilibrium between two elements, genetics on one hand, lifestyle on the other, To know it better, means to give new weapons, often crucial, in the hands of the doctors and their patients. It also means to adjust therapies, to find out which drug is good for a patient and which prevention strategy will work better for him/her. Nutrigenomics is an approach to individualize or personalize food and nutrition, and ultimately health, by tailoring the food to the individual genotype. In this review, we present the interaction between certain genetic polymorphisms and diet and increased cardiovascular or cancer risk. It is, indeed, now clear that a large number of bioactive food components may provide risk or protection at several stages of both atherosclerosis and cancer formation processes. We are giving here few examples of gene-food interactions relevant for both the risk of cardiovascular disease and cancer, since a common soil could exist in the genesis of cardiovascular disease and of some types of cancer (mainly gastrointestinal tract and hormonedependent).

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W06-O-002 Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan bound lipoprotein lipase

Cited by 99 publications

References 0 publications

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

Molecular cloning, expression and polymorphism of the porcine apolipoprotein A5 gene in a Jinhua × Pietrain F2 reference population

Nutrigenomics: a case for the common soil between cardiovascular disease and cancer

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