Intestinal fatty acid binding protein and microsomal triglyceride transfer protein polymorphisms in French-Canadian youth

Stan, Simona; Lambert, Marie; Delvin, Edgard; Paradis, Gilles; O’Loughlin, Jennifer; Hanley, James A.; Lévy, Émile

doi:10.1194/jlr.m400346-jlr200

Cited by 26 publications

(20 citation statements)

References 48 publications

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“…There is evidence from several studies that the minor alleles of linked [Ledmyr et al, 2002] promoter rs1800591:G4T/rs1800804:T4C (À493G4T/ À164T4C; numbering relative to transcriptional start site) and rs3816873:T4C (Ile128Thr) polymorphisms correspond to lower LDL levels and protect against other traits of the metabolic syndrome [Bernard et al, 2000;Bjorn et al, 2000;Garcia-Garcia et al, 2005;Karpe et al, 1998;Ledmyr et al, 2002Ledmyr et al, , 2004Lundahl et al, 2006;Phillips et al, 2004;Rubin et al, 2006;St-Pierre et al, 2002;Yamada et al, 2006]. No associations or opposite associations were found in other studies [Berthier et al, 2004;Chen et al, 2003;Couture et al, 2000;Herrmann et al, 1998;Juo et al, 2000;Lundahl et al, 2002;Stan et al, 2005].…”

Section: Introductionmentioning

confidence: 98%

Functional analysis of promoter variants in the microsomal triglyceride transfer protein (MTTP) gene

et al. 2007

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The microsomal triglyceride transfer protein (MTTP) is required for the assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins from the intestine and liver. According to this function, polymorphic sites in the MTTP gene showed associations to low-density lipoprotein (LDL) cholesterol and related traits of the metabolic syndrome. Here we studied the functional impact of common MTTP promoter polymorphisms rs1800804:T>C (-164T>C), rs1800803:A>T (-400A>T), and rs1800591:G>T (-493G>T) using gene-reporter assays in intestinal Caco-2 and liver Huh-7 cells. Significant results were obtained in Huh-7 cells. The common MTTP promoter haplotype -164T/-400A/-493G showed about two-fold lower activity than the rare haplotype -164C/-400T/-493T. MTTP promoter mutant constructs -164T/-400A/-493T and -164T/-400T/-493T exhibited similar activity than the common haplotype. Activities of mutants -164C/-400A/-493G and -164C/-400A/-493T resembled the rare MTTP promoter haplotype. Electrophoretic mobility shift assays (EMSAs) revealed higher binding capacity of the transcriptional factor Sterol regulatory element binding protein1a (SREBP1a) to the -164T probe in comparison to the -164C probe. In conclusion, our study indicates that the polymorphism -164T>C mediates different activities of common MTTP promoter haplotypes via SREBP1a. This suggested that the already described SREBP-dependent modulation of MTTP expression by diet is more effective in -164T than in -164C carriers.

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Section: Introductionmentioning

confidence: 98%

Functional analysis of promoter variants in the microsomal triglyceride transfer protein (MTTP) gene

et al. 2007

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“…The MTP gene is polymorphic, with several genetic variants especially in the promoter region [14,17]. A number of studies were undertaken to demonstrate associations between this single nucleotide polymorphisms (SNP) at position -493 (G/T) in the promoter region of the MTTP and the concentration of circulating cholesterol but provided inconsistent data [6,7,14,19,38,41,49].…”

Section: Introductionmentioning

confidence: 99%

Cholesterol absorption status and fasting plasma cholesterol are modulated by the microsomal triacylglycerol transfer protein −493 G/T polymorphism and the usual diet in women

et al. 2010

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An important inter-individual variability in cholesterol absorption has been reported. It could result from polymorphisms in genes coding for proteins involved in the absorption process and in interaction with dietary intakes. To assess whether the extent of cholesterol absorption or synthesis is modified in adult women according to the -493 G/T polymorphism in the microsomal triglyceride transfer protein gene (MTP) and/or the habitual diet. Cholestanol and sitosterol, as well as desmosterol and lathosterol, surrogate markers of cholesterol absorption or synthesis, respectively, were analyzed in the fasting plasma of 69 middle-aged women under a Westerntype diet (WD) and after 3 months on a low-saturated fat, low-cholesterol/Mediterranean-type diet (LFLCD). Genotypes for MTP -493G/T polymorphism were determined. Under an usual WD, subjects homozygous for the MTP -493 T allele exhibited higher (P \ 0.05) fasting serum concentrations of cholestanol (199.0 ± 30.0 vs. 133 ± 7.4 9 10 2 mmol/mol cholesterol) and lathosterol (188.7 ± 21.8 vs. 147.6 ± 9.1 9 10 2 mmol/mol cholesterol), as well as total cholesterol (7.32 ± 0.22 vs. 6.63 ± 0.12 mmol/l) compared to G carrier subjects. After 3 months on a LFLCD, level of absorption markers decreased in TT subjects with no change in synthesis ones, leading to values comparable to those measured in G carriers. The lowering of plasma total and LDL cholesterol due to dietary change was 2.4-and 2.3-fold greater in TT women than in G carriers. The polymorphism -493G/T in MTP modulates the level of cholesterol absorption but not synthesis in women under a WD, an effect abolished under a prudent LFLCD.

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“…Findings from I-Fabp 2/2 mice (4) and the Ala54Thr human mutation (7)(8)(9) suggest that I-FABP functions physiologically as a lipid-sensing component of energy homeostasis and not as a direct part of dietary FA absorption. Vassileva et al (4) proposed that "I-FABP likely feeds information about dietary lipid status into mechanisms that universally control energy utilization, energy storage, and eventually body weight."…”

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Intestinal fatty acid binding protein regulates mitochondrion β-oxidation and cholesterol uptake

Montoudis

Seidman

Boudreau

et al. 2008

Journal of Lipid Research

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The role of intestinal fatty acid binding protein (I-FABP) in lipid metabolism remains elusive. To address this issue, normal human intestinal epithelial cells (HIEC-6) were transfected with cDNA to overexpress I-FABP and compared with cells treated with empty pQCXIP vector. I-FABP overexpression stimulated mitochondrial [U-14 C]oleate oxidation to CO 2 and acid-soluble metabolites via mechanisms including the upregulation of protein expression and the activity of carnitine palmitoyltransferase 1, a critical enzyme controlling the entry of fatty acid (FA) into mitochondria, and increased activity of 3-hydroxyacyl-CoA dehydrogenase, a mitochondrial b-oxidation enzyme. On the other hand, the gene and protein expression of the key enzymes FA synthase and acetylcoenzyme A carboxylase 2 was decreased, suggesting diminished lipogenesis. Furthermore, I-FABP overexpression caused a decline in [ 14 C]free cholesterol (CHOL) incorporation. Accordingly, a significant lessening was observed in the gene expression of Niemann Pick C1-Like 1, a mediator of CHOL uptake, along with an increase in the transcripts and protein content of ABCA1 and ABCG5/ABCG8, acting as CHOL efflux pumps. Furthermore, I-FABP overexpression resulted in increased levels of mRNA, protein mass, and activity of HMG-CoA reductase, the rate-limiting step in CHOL synthesis. Scrutiny of the nuclear receptors revealed augmented peroxisome proliferator-activated receptor a,g and reduced liver X receptor-a in HIEC-6 overexpressing I-FABP. Finally, I-FABP overexpression did not influence acylcoenzyme A oxidase 1, which catalyzes the first rate-limiting step in peroxisomal FA b-oxidation. Overall, our data suggest that I-FABP may influence mitochondrial FA oxidation and CHOL transport by regulating gene expression and interaction with nuclear

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Intestinal fatty acid binding protein and microsomal triglyceride transfer protein polymorphisms in French-Canadian youth

Cited by 26 publications

References 48 publications

Functional analysis of promoter variants in the microsomal triglyceride transfer protein (MTTP) gene

Functional analysis of promoter variants in the microsomal triglyceride transfer protein (MTTP) gene

Cholesterol absorption status and fasting plasma cholesterol are modulated by the microsomal triacylglycerol transfer protein −493 G/T polymorphism and the usual diet in women

Intestinal fatty acid binding protein regulates mitochondrion β-oxidation and cholesterol uptake

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