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.

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.

[1]  D. Molnár,et al.  Long-chain polyunsaturated fatty acids in plasma lipids of obese children , 1996, Lipids.

[2]  U. Das.  A defect in the activity of Δ6 and Δ5 desaturases may be a factor predisposing to the development of insulin resistance syndrome , 2005 .

[3]  S. Fukuchi,et al.  Role of Fatty Acid Composition in the Development of Metabolic Disorders in Sucrose-Induced Obese Rats , 2004, Experimental biology and medicine.

[4]  R. Hegele,et al.  Postprandial lipemia in subjects with the threonine 54 variant of the fatty acid-binding protein 2 gene is dependent on the type of fat ingested. , 2004, The American journal of clinical nutrition.

[5]  D. Gašperíková,et al.  Insulin Resistance in the Hereditary Hypertriglyceridemic Rat Is Associated with an Impairment of Δ‐6 Desaturase Expression in Liver , 2002, Annals of the New York Academy of Sciences.

[6]  Manabu T. Nakamura,et al.  Metabolism and functions of highly unsaturated fatty acids: An update , 2001, Lipids.

[7]  S. O’Rahilly,et al.  Arachidonic Acid Stimulates Glucose Uptake in 3T3-L1 Adipocytes by Increasing GLUT1 and GLUT4 Levels at the Plasma Membrane , 2001, The Journal of Biological Chemistry.

[8]  M. Laakso,et al.  Postprandial responses of individual fatty acids in subjects homozygous for the threonine- or alanine-encoding allele in codon 54 of the intestinal fatty acid binding protein 2 gene. , 2001, The American journal of clinical nutrition.

[9]  E. Ravussin,et al.  Effects of an Ala54Thr polymorphism in the intestinal fatty acid-binding protein on responses to dietary fat in humans. , 2000, Journal of lipid research.

[10]  G. Vassileva,et al.  The intestinal fatty acid binding protein is not essential for dietary fat absorption in mice , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[11]  O. Aras,et al.  Codon-54 polymorphism of the fatty acid-binding protein 2 gene is associated with elevation of fasting and postprandial triglyceride in type 2 diabetes. , 2000, The Journal of clinical endocrinology and metabolism.

[12]  J. Ordovás,et al.  Genetic determinants of plasma lipid response to dietary intervention: the role of the APOA1/C3/A4 gene cluster and the APOE gene , 2000, British Journal of Nutrition.

[13]  C. Darimont,et al.  Effects of intestinal fatty acid-binding protein overexpression on fatty acid metabolism in Caco-2 cells. , 2000, Journal of lipid research.

[14]  M. Laakso,et al.  Postprandial lipemic response is modified by the polymorphism at codon 54 of the fatty acid-binding protein 2 gene. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[15]  M. Laakso,et al.  Variants in the human intestinal fatty acid binding protein 2 gene in obese subjects. , 1997, The Journal of clinical endocrinology and metabolism.

[16]  M. Laakso,et al.  Threonine allele in codon 54 of the fatty acid binding protein 2 gene does not modify the fatty acid composition of serum lipids in obese subjects , 1997, European journal of clinical investigation.

[17]  C. Bogardus,et al.  A Polymorphism in the Human Intestinal Fatty Acid Binding Protein Alters Fatty Acid Transport across Caco-2 Cells (*) , 1996, The Journal of Biological Chemistry.

[18]  C. Bogardus,et al.  An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance. , 1995, The Journal of clinical investigation.

[19]  G. Reaven,et al.  Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[20]  R. Bellù,et al.  Relationships between the fatty acid status and insulinemic indexes in obese children. , 1994, Prostaglandins, leukotrienes, and essential fatty acids.

[21]  S. Phinney,et al.  Liver fatty acid composition correlates with body fat and sex in a multigenic mouse model of obesity. , 1994, The American journal of clinical nutrition.

[22]  W. Prellwitz,et al.  The Phenomenon of a High Triglyceride Response to an Oral Lipid Load in Healthy Subjects and Its Link to the Metabolic Syndrome a , 1993, Annals of the New York Academy of Sciences.

[23]  C. Mansbach,et al.  Portal transport of long acyl chain lipids: effect of phosphatidylcholine and low infusion rates. , 1993, The American journal of physiology.

[24]  D. Chisholm,et al.  The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. , 1993, The New England journal of medicine.

[25]  J. Gordon,et al.  Developmental and structural studies of an intracellular lipid binding protein expressed in the ileal epithelium. , 1990, The Journal of biological chemistry.

[26]  P. Bennett,et al.  Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. , 1990, Diabetes/metabolism reviews.

[27]  K. Berg.  Risk factor variability and coronary heart disease. , 1990, Acta geneticae medicae et gemellologiae.

[28]  J. Gordon,et al.  THE METABOLIC SIGNIFICANCE OF MAMMALIAN FATTY-ACID­ , 1987 .

[29]  J. Gordon,et al.  The metabolic significance of mammalian fatty-acid-binding proteins: abundant proteins in search of a function. , 1987, Annual review of nutrition.

[30]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.