| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Studies |
Department of Clinical Nutrition (R.S., M.U.) and Department of Medicine (S.H., M.L.), University of Kuopio, 70211 Kuopio; Eating Disorder Unit (A.R.), University Hospital of Helsinki, 00270,Helsinki, Finland
Address correspondence and requests for reprints to: Raisa Sipiläinen, M.Sc., Department of Clinical Nutrition, University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. E-mail: raisa.sipilainen{at}uku.fi
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Thr) on insulin levels and basal
metabolic rate in 170 obese subjects. The frequencies of the variants
found in exon 4 (GTA GTG) and 3'-noncoding region (GCGCA
GCACA), as well as the allele frequencies for the variable lengths of
the ATT repeat sequence in intron 2 did not differ between the obese
subjects and nonobese controls. The frequency of threonine-encoding
allele in codon 54 of the FABP2 gene did not differ between obese and
control subjects (28 vs. 29%, respectively). In the
obese group there were no differences in gender distribution, age,
weight, body mass index, lean body mass, percentage of body fat, waist
circumference, and waist-to-hip ratio among the individuals homozygous
for Ala54, heterozygous for Thr54, and
homozygous for Thr54-encoding alleles. Similarly, fasting
serum insulin, glucose, lipids and lipoprotein concentrations, basal
metabolic rate (adjusted for lean body mass and age), respiratory
quotient, and rates of glucose and lipid oxidation did not differ among
the groups. We conclude that obesity is not associated with specific
variants in the FABP2 gene. Furthermore, the codon 54 Ala to Thr
polymorphism of this gene does not influence insulin levels or basal
metabolic rate in obese Finns. |
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
ACT) of the FABP2 gene has been
related to insulin resistance in nondiabetic Pima Indians (6). However,
in Caucasian populations no association was found between the FABP2
gene locus and insulin levels (7). The FABP2 gene encodes the protein
that binds intestinal fatty acids, and it contains a high affinity
binding site for both saturated and unsaturated long-chain fatty acids,
indicating that it might have a role in the absorption and
intracellular transport of dietary long-chain fatty acids (8). In Pima
Indians the codon 54 polymorphism of the FABP2 gene has been associated
with increased lipid oxidation rate and also insulin resistance
(6). To investigate the hypothesis that defects in the FABP2 gene could be associated with obesity, we screened the whole coding region of this gene in obese nondiabetic Finns. We also investigated the frequency of the codon 54 polymorphism of the FABP2 gene and the effects of this polymorphism on insulin levels and basal metabolic rate in a large group of obese Finns.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
.
|
Altogether 40 obese women, randomly drawn from the weight reduction study, were screened for the variants of the FABP2 gene by single strand conformation polymorphism (SSCP) analysis. Their mean age was 43 ± 8 yr, body mass index (BMI) 33.9 ± 3.4 kg/m2, and fasting blood glucose 5.2 ± 0.5 mmol/L. None of them had impaired glucose tolerance or diabetes according to the criteria of the World Health Organization (11). All subjects had normal liver, kidney, and thyroid functions, and none had a history of excessive alcohol intake. The allele frequencies of the variants of the FABP2 gene were compared with 40 healthy normoglycemic subjects who were participants in our previous study investigating the relationship between insulin resistance and dyslipidemia (12). None of the control subjects had any chronic disease, any drug treatment, glucose intolerance, or hypertension.
Additional screening
Screening for the codon 54 amino acid substitution of the FABP2 gene (6) was performed in an additional sample of 130 obese subjects participating in the same weight reduction study as those 40 subjects initially screened. They fulfilled the same inclusion criteria as did the subjects participating in the initial screening, and none of them was receiving drugs known to affect basal metabolic rate (BMR) or glucose metabolism. The frequency of the codon 54 polymorphism of the FABP2 gene in obese subjects was compared with that of 82 healthy normoglycemic subjects (an additional sample of 42 subjects was studied for this polymorphism) (12).
Study protocol
Every subject in the initial screening program underwent an oral glucose tolerance test (75 g glucose) to exclude noninsulin-dependent diabetes mellitus and impaired glucose tolerance. The protocol was approved by the Ethics Committees of the University of Kuopio and the University Helsinki, and all subjects gave their informed consent.
Analytical methods
All measurements were done in the morning after an overnight fast. Weight was measured by electronic scales. BMI was calculated from the following formula: BMI = weight (kg)/height2 (m). Waist and hip circumferences were measured as described previously (10). Body composition was determined by bioelectrical impedance (RJL Systems, Detroit, MI). Basal metabolic rate (BMR) was measured by indirect calorimetry (Deltatrac, TM Datex, Helsinki, Finland) after a 12-h fast, as previously reported in detail (13). Energy production rate (cal/min) was calculated according to Ferrannini (14) and expressed as kcal/day. Urinary nitrogen was measured in 119 subjects. The adjusted BMR was calculated according to Ravussin (15). Serum insulin was analyzed by radioimmunoassay with the double antibody-PEG technique (CIS Bio International, Gif-sur-Yvette, France) and serum glucose by kinetic photometry with glucose-dehydrogenase (16). Serum lipids and lipoproteins were analyzed after ultracentrifugation (92500 xg, 18 h, 5 C) and precipitation by enzymatic methods (17, 18, 19), the CHOD-PAP method (HiCo cholesterol reagents, Boehringer Mannheim, Mannheim, Germany) for cholesterol and high-density-lipoprotein (HDL) cholesterol, and the GPO-PAP method (Boehringer Mannheim) for triglycerides.
DNA was prepared from peripheral blood leucocytes by the proteinase K-phenol-chloroform extraction method. All four exons and the intron-exon junctions of the FABP2-gene were amplified with the polymerase chain reaction (PCR) using the primers reported in a previous study (6). SSCP analysis was performed essentially according to the method of Orita et al. (20). Genomic DNA from individuals with variant single strand conformers was directly sequenced using Sequenase (US Biochemicals, Cleveland, OH) as previously described (21). Determination of the frequency of the GCT to ACT nucleotide substitution in codon 54 of the FABP2 gene was detected by PCR-RFLP (restriction fragment length polymorphism) assays as previously decribed (6).
Statistical analysis
All calculations were performed using the SPSS/WIN programs
(Version 6.0, SPSS Inc., Chicago, IL). Data are presented as means
± SD. Statistical significance among the three groups was
evaluated using the 
-squared test or ANOVA, when appropriate.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
).
Similarly, a silent substitution of GTA118GTG in exon 4 was as frequent
in obese subjects as in normal weight controls. In addition, we found a
substitution of GCGCA to GCACA in the
3'-noncoding region. The frequencies of this variant as well as the
allele frequencies for the variable lengths of the ATT repeat sequence
in intron 2 did not differ between the obese and control subjects
(Table 2).
|
). Similarly, fasting serum insulin and glucose
concentrations, serum lipids and lipoproteins, basal metabolic rate
(adjusted for lean body mass and age), respiratory quotient, and rates
of glucose and lipid oxidation did not differ among the three groups
(Table 4).
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
In a previous study on nondiabetic, obese Pima Indians (6) fasting insulin levels or rates of lipid oxidation were associated with the codon 54 polymorphism of the FABP2 gene. This could not be found in the present study on obese Finns, however, nor was this polymorphism associated with basal metabolic rate, suggesting that the codon 54 polymorphism of the FABP2 gene is not related to energy metabolism in obese Finnish subjects. In the Pima Indian population higher mean fasting plasma insulin concentrations and lower insulin sensitivity were observed only after pooling of subjects who were homozygous and heterozygous for the Thr54-encoding allele of the FABP2 gene (6). Moreover, the reported differences were of borderline statistical significance. Our analysis was not based on direct measurement of insulin sensitivity, but on fasting insulin levels only. Although fasting insulin levels correlate quite closely with insulin sensitivity determined by the euglycemic hyperinsulinemic clamp (22), our findings cannot entirely rule out the possibility that insulin resistance measured by a direct method could be associated with the presence of the Thr54 allele of the FABP2 gene.
Obesity, especially abdominal obesity and lipid abnormalities, are common features of insulin resistance syndrome. In our study, the three genotypes (Ala54 homozygotes, Thr54 heterozygotes, Thr54 homozygotes) of the FABP2 gene did not differ with respect to any clinical characteristics of insulin resistance syndrome. This finding implies that the codon 54 polymorphism of the FABP2 gene is not a significant determinant of insulin resistance syndrome in obese Finns. However, there was a tendency toward elevated concentrations of serum free fatty acids in Thr54 homozygotes; these subjects also had highly elevated very-low-density-lipid (VLDL) cholesterol and total triglyceride levels. Therefore, modest effects of the Thr54 allele on lipid levels cannot be ruled out because our study included only a small number of Thr54 homozygotes. It should also be emphasized that our findings do not exclude the possibility that the effects of the Thr54 allele of the FABP2 gene could be population specific, and that other genes close to the FABP2 gene locus may have an effect on insulin action and thereby insulin resistance, as has been suggested earlier (5, 6, 7).
Received January 23, 1997.
Revised April 23, 1997.
Accepted May 13, 1997.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  S. Morcillo, G. Rojo-Martinez, F. Cardona, M. de la Cruz Almaraz, M. de la Soledad Ruiz de Adana, I. Esteva, I. Cardona, and F. Soriguer Effect of the interaction between the fatty acid binding protein 2 gene Ala54Thr polymorphism and dietary fatty acids on peripheral insulin sensitivity: a cross-sectional study Am. J. Clinical Nutrition, October 1, 2007; 86(4): 1232 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Stan, M. Lambert, E. Delvin, G. Paradis, J. O'Loughlin, J. A. Hanley, and E. Levy Intestinal fatty acid binding protein and microsomal triglyceride transfer protein polymorphisms in French-Canadian youth J. Lipid Res., February 1, 2005; 46(2): 320 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lara-Castro, G. R. Hunter, J. C. Lovejoy, B. A. Gower, and J. R. Fernandez Association of the Intestinal Fatty Acid-Binding Protein Ala54Thr Polymorphism and Abdominal Adipose Tissue in African-American and Caucasian Women J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1196 - 1201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Dworatzek, R. A Hegele, and T. M. Wolever 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 Am. J. Clinical Nutrition, June 1, 2004; 79(6): 1110 - 1117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. Weiss, M. D. Brown, A. R. Shuldiner, and J. M. Hagberg Fatty acid binding protein-2 gene variants and insulin resistance: gene and gene-environment interaction effects Physiol Genomics, September 3, 2002; 10(3): 145 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Lewis, A. Carpentier, K. Adeli, and A. Giacca Disordered Fat Storage and Mobilization in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Endocr. Rev., April 1, 2002; 23(2): 201 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Levy, D. Menard, E. Delvin, S. Stan, G. Mitchell, M. Lambert, E. Ziv, J. C. Feoli-Fonseca, and E. Seidman The Polymorphism at Codon 54 of the FABP2 Gene Increases Fat Absorption in Human Intestinal Explants J. Biol. Chem., October 19, 2001; 276(43): 39679 - 39684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Galluzzi, L. A. Cupples, J. B. Meigs, P. W.F. Wilson, E. J. Schaefer, and J. M. Ordovas Association of the Ala54-thr Polymorphism in the Intestinal Fatty Acid-Binding Protein With 2-h Postchallenge Insulin Levels in the Framingham Offspring Study Diabetes Care, July 1, 2001; 24(7): 1161 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Pratley, L. Baier, D. A. Pan, A. D. Salbe, L. Storlien, E. Ravussin, and C. Bogardus Effects of an Ala54Thr polymorphism in the intestinal fatty acid-binding protein on responses to dietary fat in humans J. Lipid Res., December 1, 2000; 41(12): 2002 - 2008. [Abstract] [Full Text]
|
|
|
|
|
|
A. Georgopoulos, O. Aras, and M. Y. Tsai Codon-54 Polymorphism of the Fatty Acid-Binding Protein 2 Gene Is Associated with Elevation of Fasting and Postprandial Triglyceride in Type 2 Diabetes J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3155 - 3160. [Abstract] [Full Text]
|
|
|
|
|
|
M. Carlsson, M. Orho-Melander, J. Hedenbro, P. Almgren, and L. C. Groop The T 54 Allele of the Intestinal Fatty Acid-Binding Protein 2 Is Associated with a Parental History of Stroke J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2801 - 2804. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Meirhaeghe, G. Martin, M. Nemoto, S. Deeb, D. Cottel, J. Auwerx, P. Amouyel, and N. Helbecque Intronic Polymorphism in the Fatty Acid Transport Protein 1 Gene Is Associated With Increased Plasma Triglyceride Levels in a French Population Arterioscler Thromb Vasc Biol, May 1, 2000; 20(5): 1330 - 1334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Agren, R. Valve, H. Vidgren, M. Laakso, and M. Uusitupa Postprandial Lipemic Response Is Modified by the Polymorphism at Codon 54 of the Fatty Acid–Binding Protein 2 Gene Arterioscler Thromb Vasc Biol, October 1, 1998; 18(10): 1606 - 1610. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
