Fatty acid binding

Objective: To assess the association between the Ala54Thr genetic polymorphism of the fatty acid-binding protein 2 (FABP2) gene with insulin resistance and obesity. Research Methods and Procedures: According to a sampling scheme based on BMI, 33 adult obese women (BMI Ն 30) and 30 adult normal-weight women (BMI Ͼ 18.5 and Ͻ 25 kg/m 2 ) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor ␣ (TNF␣) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. Results: The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p ϭ 0.08). Among obese women, higher TNF␣ concentrations were found when comparing the Thr54/Thr54 genotype (30.0 Ϯ 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 Ϯ 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 Ϯ 7.0 pg/mL) (p Ͻ 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p Ͻ 0.05). Discussion: Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF␣.

Intestinal FABP2 A54T polymorphism: association with insulin resistance and obesity in women. Objective: To assess the association between the Ala54Thr genetic polymorphism of the fatty acid-binding protein 2 (FABP2) gene with insulin resistance and obesity. Research Methods and Procedures: According to a sampling scheme based on BMI, 33 adult obese women (BMI Ն 30) and 30 adult normal-weight women (BMI Ͼ 18.5 and Ͻ 25 kg/m 2) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor ␣ (TNF␣) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. Results: The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p ϭ 0.08). Among obese women, higher TNF␣ concentrations were found when comparing the Thr54/Thr54 genotype (30.0 Ϯ 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 Ϯ 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 Ϯ 7.0 pg/mL) (p Ͻ 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p Ͻ 0.05). Discussion: Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF␣.

Intestinal FABP2 A54T polymorphism: association with insulin resistance and obesity in women. Objective: To assess the association between the Ala54Thr genetic polymorphism of the fatty acid-binding protein 2 (FABP2) gene with insulin resistance and obesity. Research Methods and Procedures: According to a sampling scheme based on BMI, 33 adult obese women (BMI Ն 30) and 30 adult normal-weight women (BMI Ͼ 18.5 and Ͻ 25 kg/m 2) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor ␣ (TNF␣) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. Results: The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p ϭ 0.08). Among obese women, higher TNF␣ concentrations were found when comparing the Thr54/Thr54 genotype (30.0 Ϯ 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 Ϯ 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 Ϯ 7.0 pg/mL) (p Ͻ 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p Ͻ 0.05). Discussion: Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF␣.

Formation of complexes between bovine-lactoglobulins (BLG) and long-chain fatty acids (FAs), effect of complex formation on protein stability, and effects of pH and ionic strength on both complex formation and protein stability were investigated as a function of pH and ionic strength by electrophoretic techniques and NMR spectroscopy. The stability of BLG against unfolding is sharply affected by the pH of the medium: both A and B BLG variants are maximally stabilized against urea denaturation at acidic pH and against SDS denaturation at alkaline pH. The complexes of BLGB with oleic (OA) and palmitic acid (PA) appear more stable than the apoprotein at neutral pH whereas no differential behavior is observed in acidic and alkaline media. PA forms with BLG more stable complexes than OA. The difference between the denaturant concentration able to bring about protein unfolding in the holo versus the apo forms is larger for urea than for SDS treatment. This evidence disfavors the hypothesis of strong hydrophobic interactions being involved in complex formation. Conversely, a significant contribution to FA binding by ionic interactions is demonstrated by the effect of pH and of chloride ion concentration on the stoichiometry of FA‚BLG complexes. At neutral pH in a low ionic strength buffer, one molecule of FA is bound per BLG monomer; this ratio decreases to ca. 0.5 per monomer in the presence of 200 mM NaCl. The polar heads of bound FA appear to be solvent accessible, and carboxyl resonances exhibit an NMR titration curve with an apparent pK a of 4.7(1).-Lactoglobulin (BLG) 1 is the most abundant protein in the whey of bovine milk (1-3). At room temperature and under physiological conditions, this small protein (ca. 18 kDa) exists as a dimer, but it exhibits complex association equilibria, shifting between monomer, dimer, tetramer, octamer, and monomer again upon lowering the pH of the solution from 8 to 3.5 (4-6). Many genetic variants of bovine BLG are known. The two most common, A (BLGA) and B (BLGB), differ in two amino acids: Asp64 and Val118 in BLGA are substituted by Gly64 and Ala118 in BLGB (7).

Intestinal FABP2 A54T polymorphism: association with insulin resistance and obesity in women. Objective: To assess the association between the Ala54Thr genetic polymorphism of the fatty acid-binding protein 2 (FABP2) gene with insulin resistance and obesity. Research Methods and Procedures: According to a sampling scheme based on BMI, 33 adult obese women (BMI Ն 30) and 30 adult normal-weight women (BMI Ͼ 18.5 and Ͻ 25 kg/m 2) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor ␣ (TNF␣) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. Results: The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p ϭ 0.08). Among obese women, higher TNF␣ concentrations were found when comparing the Thr54/Thr54 genotype (30.0 Ϯ 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 Ϯ 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 Ϯ 7.0 pg/mL) (p Ͻ 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p Ͻ 0.05). Discussion: Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF␣.

Formation of complexes between bovine-lactoglobulins (BLG) and long-chain fatty acids (FAs), effect of complex formation on protein stability, and effects of pH and ionic strength on both complex formation and protein stability were investigated as a function of pH and ionic strength by electrophoretic techniques and NMR spectroscopy. The stability of BLG against unfolding is sharply affected by the pH of the medium: both A and B BLG variants are maximally stabilized against urea denaturation at acidic pH and against SDS denaturation at alkaline pH. The complexes of BLGB with oleic (OA) and palmitic acid (PA) appear more stable than the apoprotein at neutral pH whereas no differential behavior is observed in acidic and alkaline media. PA forms with BLG more stable complexes than OA. The difference between the denaturant concentration able to bring about protein unfolding in the holo versus the apo forms is larger for urea than for SDS treatment. This evidence disfavors the hypothesis of strong hydrophobic interactions being involved in complex formation. Conversely, a significant contribution to FA binding by ionic interactions is demonstrated by the effect of pH and of chloride ion concentration on the stoichiometry of FA‚BLG complexes. At neutral pH in a low ionic strength buffer, one molecule of FA is bound per BLG monomer; this ratio decreases to ca. 0.5 per monomer in the presence of 200 mM NaCl. The polar heads of bound FA appear to be solvent accessible, and carboxyl resonances exhibit an NMR titration curve with an apparent pK a of 4.7(1).-Lactoglobulin (BLG) 1 is the most abundant protein in the whey of bovine milk (1-3). At room temperature and under physiological conditions, this small protein (ca. 18 kDa) exists as a dimer, but it exhibits complex association equilibria, shifting between monomer, dimer, tetramer, octamer, and monomer again upon lowering the pH of the solution from 8 to 3.5 (4-6). Many genetic variants of bovine BLG are known. The two most common, A (BLGA) and B (BLGB), differ in two amino acids: Asp64 and Val118 in BLGA are substituted by Gly64 and Ala118 in BLGB (7).