A Polymorphism in the Human Intestinal Fatty Acid Binding Protein Alters Fatty Acid Transport across Caco-2 Cells

Baier, Leslie J.; Bogardus, Clifton; Sacchettini, James C.

doi:10.1074/jbc.271.18.10892

Cited by 160 publications

(130 citation statements)

References 27 publications

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“…In an abstract, Rolf et al [54] reported a reduction of fatty acid uptake into HepG2 liver cells transfected with antisense L-FABP cDNA and a decreased L-FABP content. Furthermore the total amount of L-FABP and I-FABP in I-FABP-cDNA-transfected Caco-2 cells was not proportional to fatty acid uptake [55]. CHO cell transfectants expressing A-FABP demonstrated a 1n5-2-fold increase in the rate of [$H]oleate uptake [26].…”

Section: Discussionmentioning

confidence: 99%

Transfection of L6 myoblasts with adipocyte fatty acid-binding protein cDNA does not affect fatty acid uptake but disturbs lipid metabolism and fusion

Prinsen

Veerkamp

1998

Biochemical Journal

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We studied the involvement of fatty acid-binding protein (FABP) in growth, differentiation and fatty acid metabolism of muscle cells by lipofection of rat L6 myoblasts with rat heart (H) FABP cDNA or with rat adipocyte (A) FABP cDNA in a eukaryotic expression vector which contained a puromycin acetyltransferase cassette. Stable transfectants showed integration into the genome for all constructs and type-specific overexpression at the mRNA and protein level for the clones with H-FABP and A-FABP cDNA constructs. The rate of proliferation of myoblasts transfected with rat A-FABP cDNA was 2-fold higher compared with all other transfected cells. In addition, these myoblasts showed disturbed fusion and differentiation, as assessed by morphological examination and creatine kinase activity. Uptake rates of palmitate were equal for all clone types, in spite of different FABP INTRODUCTIONFatty acid-binding proteins (FABPs) belong to a conserved family of intracellular lipid-binding proteins with low molecular mass (14-15 kDa) [1][2][3]. Eight different FABP types have been described : heart, liver, adipose, myelin, intestinal, epidermal, brain and ileal. Many FABP cDNAs have been isolated, cloned and the proteins expressed in bacterial systems. In this way, large amounts of proteins have become available for three-dimensional analysis by crystallography and\or NMR (reviewed in [1,3]). All FABPs studied thus far contain a folding motif designated an up-and-down β-barrel [3].The main function of FABP is thought to be intracellular binding and targeting of fatty acids. FABPs may also modulate the effect of fatty acids on various metabolic enzymes and receptors and cellular processes such as signal transduction and gene expression [1,4]. The function significance of the different FABP types is not clear and may vary with the tissues and the physiological conditions. Adaptation may be related to metabolic requirements of the cell, ligand trafficking and\or modulatory functions.A relation has been observed between fatty acid-oxidation capacity and FABP content of various rat tissues and various human and rat muscles [5][6][7]. FABP content of muscle showed no change under various physiological conditions, except an increase in fast-twitch muscles on chronic electrostimulation and endurance training [7]. Heart FABP (H-FABP) content and fatty acid-oxidation capacity increase in skeletal and heart muscle during postnatal development [7,8]. Some indications of a role Abbreviations used : A-FABP, adipocyte fatty acid-binding protein ; CHO, Chinese hamster ovary ; CK, creatine kinase ; CS, citrate synthase ; D-PBS, Dulbecco's modified PBS ; H-FABP, heart fatty acid-binding protein ; I-FABP, intestinal fatty acid-binding protein ; L-FABP, liver fatty acid-binding protein ; PC, phosphatidylcholine ; PE, phosphatidylethanolamine ; RT, reverse transcriptase ; DMEM, Dulbecco's modified Eagle's medium ; SV40, simian virus 40 ; GAPDH, glyceraldehyde-3-phosphate dehydrogenase ; pac, puromycin acetyltransferase.1 To whom correspondence shou...

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Section: Discussionmentioning

confidence: 99%

Transfection of L6 myoblasts with adipocyte fatty acid-binding protein cDNA does not affect fatty acid uptake but disturbs lipid metabolism and fusion

Prinsen

Veerkamp

1998

Biochemical Journal

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“…The T54 variant of FABP2 shows increased binding affinity and intestinal uptake of long chain fatty acids, 30,31 and has previously been found to be associated with increased plasma triglyceride concentrations, 32 increased BMI and increased percent body fat. 23 Thus, an association might be expected between HTGW and FABP2.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic associations with hypertriglyceridemic waist in a Canadian aboriginal population

et al. 2005

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Objectives: To determine the prevalence of 'hypertriglyceridemic waist' (HTGW) in Oji-Cree, to examine its interaction with hepatic nuclear factor-1a (HNF1A) in association with type 2 diabetes, and to characterize its putative genetic determinants. Method: The presence or absence of HTGW was determined in 522 Oji-Cree subjects (223 males, 299 females), X18 years of age, in whom physical measurements and fasting plasma analyte concentrations were gathered, and a 75-g oral glucose tolerance test was administered, as part of a cross-sectional study. Subjects were genotyped for HNF1A codon 319, angiotensinogen (AGT) codons 174 and 235, G-protein b3-subunit (GNB3) nucleotide 825, fatty acid-binding protein (FABP2) codon 54, nucleotides À455 and À482 of the apolipoprotein (apo) C-III (APOC3) promoter, and a 5-bp insertion/deletion polymorphism within the 3 0 -untranslated region of protein phosphatase 1 regulatory subunit 3 (PPP1R3). Results: The unadjusted prevalence of HTGW in Oji-Cree adults was 20.5%, with more males affected than females (27.8 vs 15.1%, P ¼ 0.0004). Logistic regression analysis, adjusted for age and gender, showed type 2 diabetes was associated with both HNF1A G319S (odds ratio (OR) 4.85, 95% CI 2.45, 9.58) and HTGW (OR 4.96, 95% CI 2.49, 9.88). When the HNF1A mutation and HTGW were present in combination, the OR for type 2 diabetes was markedly increased (OR 43.2, 95% CI 12.4, 150). In women only, both GNB3 825C4T and FABP2 A54T genotypes were significantly associated with HTGW (OR 2.02, 95% CI 1.01, 4.05 and OR 1.95, 95% CI 1.01, 3.74, respectively). Conclusions: HTGW is prevalent in Oji-Cree, especially in men. The ORs for type 2 diabetes were similar (B5-fold) for subjects with either the presence of HTGW or the private HNF1A G319S mutation. These two independent risk factors acted synergistically to confer an even greater increased risk of type 2 diabetes.

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“…The G to A polymorphism of codon 54 of the FABP 2 gene, resulting in the substitution of threonine (Thr) for alanine (Ala) in I-FABP, has been reported as showing increased affinity of I-FABP for long-chain FA 3) and increased triglyceride secretion by Caco-2 cells 4) . Among Pima Indians, who are known to have the highest prevalence of type 2 diabetes mellitus, the Thr encoding allele (Thr54) is associated with insulin resistance and enhanced fat oxidation rates 4,5) . This polymorphism was further associated with postprandi-…”

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confidence: 99%

Thr-encoding Allele Homozygosity at Codon 54 of FABP 2 Gene May be Associated with Impaired Delta 6 Desatruase Activity and Reduced Plasma Arachidonic Acid in Obese Children

Okada

Furuhashi-Sato

Kuromori

et al. 2006

JAT

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Background: Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Impairment in the activity of delta 6 and 5 desaturases is also supposed to be a factor predisposing the development of insulin resistance syndrome. Aim: We investigated the relationship between A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty acid metabolism in obese children. Methods: Thirty-two obese children participated. During the study, the children continued their habitual diet, which was documented in a 3-day food record using household measures. Anthropometry was performed, and serum lipid and fatty acid composition in plasma were analyzed. The polymorphism of codon 54 in the FABP 2 gene was analyzed. Results: The allele frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no significant differences in age, body mass index, fasting serum glucose, insulin or serum lipoproteins among the three polymorphism groups. These were also no significant differences in the intake of energy, the percentage of energy nutrients or in the dietary lipid composition. The content of arachidonic acid (AA) in plasma was lowest in Thr/Thr54 (p 0.05). The indices of delta-6 desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54 or Ala/Ala54 (p 0.05, p 0.01, respectively). Conclusions: In obese children, Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may predispose the to development of insulin resistance.

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A Polymorphism in the Human Intestinal Fatty Acid Binding Protein Alters Fatty Acid Transport across Caco-2 Cells

Cited by 160 publications

References 27 publications

Transfection of L6 myoblasts with adipocyte fatty acid-binding protein cDNA does not affect fatty acid uptake but disturbs lipid metabolism and fusion

Transfection of L6 myoblasts with adipocyte fatty acid-binding protein cDNA does not affect fatty acid uptake but disturbs lipid metabolism and fusion

Clinical and genetic associations with hypertriglyceridemic waist in a Canadian aboriginal population

Thr-encoding Allele Homozygosity at Codon 54 of FABP 2 Gene May be Associated with Impaired Delta 6 Desatruase Activity and Reduced Plasma Arachidonic Acid in Obese Children

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