FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid oxidation after a high-fat meal in sedentary nondiabetic men and women.
BACKGROUND
A common functional missense mutation [Ala54Thr of the fatty acid-binding protein 2 gene (FABP2)] has previously been studied for associations with glucoregulation, postprandial lipemia, and lipid oxidation rates. However, most of those studies have not accounted for the interactive and potentially confounding effects of habitual physical activity and diet.


OBJECTIVE
We tested the hypothesis that, in sedentary nondiabetic subjects following a low-fat diet, Thr54 FABP2 carriers have lower glucoregulatory function, greater postprandial lipemia, and greater lipid oxidation rates than do their Ala54 FABP2-homozygous counterparts.


METHODS
Men and women (n = 122) aged 50-75 y who were following a low-fat diet were genotyped and underwent oral-glucose-tolerance tests. A subgroup (n = 36) also underwent postprandial lipemia tests with lipid oxidation rate measurements.


RESULTS
Thr54 carriers were less likely to have normal glucose tolerance (P = 0.05) and had higher fasting glucose concentrations (P = 0.003) than did Ala54 homozygotes. In Thr54 carriers, the insulin sensitivity index was lower (P = 0.02), and the fasting insulin and the oral-glucose-tolerance test insulin area under the curve were higher (P = 0.05 and 0.03, respectively) than in Ala54 homozygotes. FABP2 genotype was not associated with fasting or postprandial lipemia test triacylglycerol or free fatty acids (P > or = 0.22 for all), but postprandial lipid oxidation rates were higher (P = 0.01), which suggests that fat absorption is higher in Thr54 carriers than in Ala54 homozygotes.


CONCLUSIONS
In sedentary nondiabetic persons following a low-fat diet, FABP2 Thr54 carriers have lower glucose tolerance and lower insulin action than do Ala54-homozygous persons. Furthermore, FABP Thr54 carriers have higher lipid oxidation rates, which may be the mechanism of glucoregulatory dysfunction.
Weiss
Edward P
EP
Department of Kinesiology, University of Maryland, College Park, MD, USA. eweiss4@slu.edu
Brandauer
Josef
J
Kulaputana
Onanong
O
Ghiu
Ioana A
IA
Wohn
Christopher R
CR
Phares
Dana A
DA
Shuldiner
Alan R
AR
Hagberg
James M
JM
D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D018752:Diet, Fat-Restricted; D004041:Dietary Fats / Q000008:administration & dosage*; D015444:Exercise / Q000502:physiology; D050556:Fatty Acid-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010349:Patient Compliance; D019518:Postprandial Period
D001786:Blood Glucose; D004041:Dietary Fats; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins