Effects of an Ala54Thr polymorphism in the intestinal fatty acid-binding protein on responses to dietary fat in humans.
A polymorphism in FABP2 that results in an alanine-to-threonine substitution at amino acid 54 of the intestinal fatty acid-binding protein (IFABP) is associated with insulin resistance in Pima Indians. In vitro, the threonine form (Thr54) has a higher binding affinity for long-chain fatty acids than does the alanine form (Ala54). We tested whether this polymorphism affected metabolic responses to dietary fat, in vivo. Eighteen healthy Pima Indians, half homozygous for the Thr54 form of IFABP and half homozygous for the Ala54 form, were studied. The groups were matched for sex, age, and body mass index. Plasma triglyceride, nonesterified fatty acid (NEFA), glucose, and insulin responses were measured after a mixed meal (35% of daily energy requirements, 50 g of fat) and after a high fat challenge (1362 kcal, 129 g of fat). NEFA concentrations were approximately 15% higher after the mixed meal and peaked earlier and were approximately 20% higher at 7 h in response to the high fat test meal in Thr54 homozygotes compared with Ala54 homozygotes. Insulin responses to the test meals tended to be higher in Thr54 homozygotes, but glucose and triglyceride responses were not different.The results of this study suggest that the Thr54 form of IFABP is associated with higher and prolonged NEFA responses to dietary fat in vivo. Higher NEFA concentrations may contribute to insulin resistance and hyperinsulinemia in individuals with this allele.
Pratley
R E
RE
Clinical Diabetes and Nutrition Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ 85016, USA.
Baier
L
L
Pan
D A
DA
Salbe
A D
AD
Storlien
L
L
Ravussin
E
E
Bogardus
C
C
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000409:Alanine / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009363:Neoplasm Proteins; D009765:Obesity / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011110:Polymorphism, Genetic; D013912:Threonine / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D004041:Dietary Fats; C493404:FABP2 protein, human; C107608:FABP7 protein, human; C493405:Fabp2 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D008563:Membrane Lipids; D009363:Neoplasm Proteins; D010743:Phospholipids; D025521:Tumor Suppressor Proteins; D013912:Threonine; D000409:Alanine