Improvement in blood lipid levels by dietary sn-1,3-diacylglycerol in young women with variants of lipid transporters 54T-FABP2 and -493g-MTP

In a double-blind parallel-group study, serum lipids and visceral fat/total fat ratio in young women (n=49) with variants of lipid transporters, i.e., fatty acid binding protein 2 (FABP2) and microsomal triglyceride transfer protein (MTP), were analyzed by substituting dietary triacylglycerol (TAG) with sn-1,3-diacylglycerol (DAG). All subjects, including some with the hyperlipidemia-prone genotypes Ala54Thr of FABP2 and c-493g of MTP, received DAG or TAG (20 g/day) for 8 weeks. Reductions of serum lipids from weeks 4 to 8 in FABP2-Ala54Thr heterozygotes and MTP -493g homozygotes were significantly different between the DAG and TAG groups (p<0.05, p<0.01). Visceral fat/total fat (%), as determined by computed tomography (CT), was lower in FABP2-Ala54Thr heterozygotes (p<0.05) of the DAG group. The apoCII/CIII ratio was higher in the DAG group than in the TAG group (p<0.01). Other variants of lipid metabolism, including peroxisome proliferator activated receptors (PPARs) alpha and gamma and SREBP cleavage-activating protein (SCAP), were only slightly affected by dietary DAG. CONCLUSION: improvement of serum lipid profiles and visceral fat/total fat ratio (CT) was potentiated by DAG intake in subjects with hyperlipidemia-prone genotypes (Ala54Thr heterozygotes of FABP2 and -493g homozygotes of MTP).     

Elevated plasma nonesterified fatty acids are associated with deterioration of acute insulin response in IGT but not NGT

High concentrations of nonesterified fatty acids (NEFA) are a risk factor for developing type 2 diabetes in Pima Indians. In vitro and in vivo, chronic elevation of NEFA decreases glucose-stimulated insulin secretion. We hypothesized that high fasting plasma NEFA would increase the risk of type 2 diabetes by inducing a worsening of glucose-stimulated insulin secretion in Pima Indians. To test this hypothesis, fasting plasma NEFA concentrations, body composition, insulin action (M), acute insulin response (AIR, 25-g IVGTT), and glucose tolerance (75-g OGTT) were measured in 151 Pima Indians [107 normal glucose tolerant (NGT), 44 impaired glucose tolerant (IGT)] at the initial visit. These subjects, participants in ongoing studies of the pathogenesis of obesity and type 2 diabetes, had follow-up measurements of body composition, glucose tolerance, M, and AIR. In NGT individuals, cross-sectionally, high fasting plasma NEFA concentrations at the initial visit were negatively associated with AIR after adjustment for age, sex, percent body fat, and M (P = 0.03). Longitudinally, high fasting plasma NEFA concentrations at the initial visit were not associated with change in AIR. In individuals with IGT, cross-sectionally, high fasting plasma NEFA concentrations at the initial visit were not associated with AIR. Longitudinally, high fasting plasma NEFA concentrations at the initial visit were associated with a decrease in AIR before (P < 0.0001) and after adjustment for sex, age at follow-up, time of follow-up, change in percent body fat and insulin sensitivity, and AIR at the initial visit (P = 0.0006). In conclusion, findings in people with NGT indicate that fasting plasma NEFA concentrations are not a primary etiologic factor for beta-cell failure. However, in subjects who have progressed to a state of IGT, chronically elevated NEFA seem to have a deleterious effect on insulin-secretory capacity.     

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 ≥ 30) and 30 adult normal‐weight women (BMI > 18.5 and < 25 kg/m²) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor α (TNFα) 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 = 0.08). Among obese women, higher TNFα concentrations were found when comparing the Thr54/Thr54 genotype (30.0 ± 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 ± 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 ± 7.0 pg/mL) (p < 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p < 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 TNFα.     

Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population

We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated receptor gamma (PPARgamma) locus with plasma lipids and insulin resistance-related variables, according to diabetes status, in a large and representative Asian population from Singapore consisting of 2,730 Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk and examined gene-nutrient interactions between these variants and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin. We found differential effects of these gene variants. The Pro12Ala polymorphism was more associated with plasma lipids and fasting glucose concentrations, whereas the C1431T polymorphism was related to the risk of diabetes. Carriers of the 12Ala allele had higher HDL-cholesterol than did Pro12Pro homozygotes (P < 0.05), and the effect of the 12Ala allele on fasting glucose was modified by diabetes status (P < 0.001). After controlling for confounders, carriers of the T allele had decreased risk of diabetes compared with CC homozygotes [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.58-0.93; P = 0.011]; this effect was stronger in Indians (OR 0.38, 95% CI 0.15-0.92; P = 0.032). For both polymorphisms, normal subjects carrying the less prevalent allele had higher BMI (P < 0.05). The PUFA/SFA did not modify the effect of these polymorphisms on BMI or insulin.     

Intestinal fatty acid binding protein and microsomal triglyceride transfer protein polymorphisms in French-Canadian youth

Growing evidence suggests an association between lipid abnormalities and fatty acid binding protein (FABP) and microsomal triglyceride transfer protein (MTP) gene variants. Our objectives were to determine whether Ala54Thr FABP2 and G-493T MTP polymorphisms are associated with increased risks of insulin resistance syndrome (IRS) in youth and/or modify the expression of accompanying dyslipidemia. Our study of 1,742 French-Canadians aged 9, 13, and 16 years did not provide evidence of a potential predisposition to IRS related to either FABP2 or MTP genotypes. However, we observed a heterogeneity of the FABP2 effect by IRS status on total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), and apolipoprotein B (apoB) concentrations (P for interaction=0.045, 0.018, and 0.017, respectively). Among the metabolic components of IRS, only triglyceride (TG) displayed an interaction with FABP2 polymorphism: compared with Thr/Ala and Ala/Ala, the Thr/Thr genotype was associated with a steeper increase in TC, LDL-C, and apoB parallel to TG concentrations (P <0.001). IRS did not modify the associations between the MTP polymorphism and any of the biochemical parameters. Our study suggests that the effects of FABP2 allelic variations on lipid traits are context dependent, indicating that this variant may play an important role in cardiovascular pathogenesis in the presence of IRS or hypertriglyceridemia.     

Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels

ABCG5 and ABCG8 transporters play an important role in the absorption and excretion of sterols. Missence polymorphisms (Gln604Glu in the ABCG5 and Asp19His, Tyr54Cys, Thr400Lys, and Ala632Val in the ABCG8) in these genes have been described. In 131 males and 154 females whose dietary composition markedly changed and lipid parameters decreased over an 8-year follow-up study (total cholesterol decreased from 6.21+/-1.31 mmol/l in 1988 to 5.43+/-1.06 mmol/l in 1996), these polymorphisms were investigated using PCR. Plasma lipid levels and changes in plasma lipid levels were independent of the Gln604Glu polymorphism in ABCG5 and Asp19His and the Ala632Val polymorphisms in ABCG8. The Tyr54Cys polymorphism influenced the degree of reduction in total plasma cholesterol (delta -0.49 mmol/l in Tyr54 homozygotes vs. delta +0.12 mmol/l in Cys54 homozygotes, p<0.04) and LDL-cholesterol (delta -0.57 mmol/l in Tyr54 homozygotes vs. delta +0.04 mmol/l in Cys54 homozygotes, p<0.03) levels between 1988 and 1996 in females, but not in males. Male Thr400 homozygotes exhibited a greater decrease in total cholesterol (delta -0.90 mmol/l vs. delta -0.30 mmol/l, p<0.02) and LDL-cholesterol (delta -0.62 mmol/l vs. delta -0.19 mmol/l, p<0.04) than Lys400 carriers. No such association was observed in females. We conclude that Tyr54Cys and Thr400Lys variations in the ABCG8 gene may play a role in the genetic determination of plasma cholesterol levels and could possibly influence the gender-specific response of plasma cholesterol levels after dietary changes. These polymorphisms are of potential interest as genetic variants that may influence the lipid profile.     

Influence of ALA54THR polymorphism of fatty acid-binding protein 2 on obesity and cardiovascular risk factors.

A transition of G to A at codon 54 of FABP2 results in an amino acid substitution (Ala54 to Thr54). This polymorphism was associated with some cardiovascular risk factors. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 gene on obesity anthropometric parameters and cardiovascular risk factors. A population of 226 obesity (body mass index >30) nondiabetic outpatients were analyzed. An indirect calorimetry, tetrapolar electrical bioimpedance, blood pressure, a serial assessment of nutritional intake with 3 days of written food records, and biochemical analysis (lipid profile, adipocytokines, insulin, CRP, and lipoprotein-a) were performed. The statistical analysis was performed for the combined ALA54/THR54 and THR54/THR54 as a mutant group and wild type ALA54/ALA54 as a second group. Two-hundred and twenty-six patients gave informed consent and were enrolled in the study. The mean age was 44.2+/-16 years and the mean BMI 35.1+/-5.1, with 63 males (28.3%) and 163 females (71.7%). One-hundred and thirteen patients (50%) had the genotype ALA54/ALA54 (wild group) and 113 (50%) patients had the genotype ALA54/THR54 (91 patients, 40.2%) or THR54/THR54 (22 patients, 9.8%) (mutant group). The ANOVA analysis of the three groups ( ALA54/THR54, THR54/THR54 and ALA54/ALA54) shows a higher levels of fat mass in Thr54/Thr54 group (45.6+/-14.6 kg) than Ala54/Ala54 (37.5+/-11.2 kg: p<0.05), without differences with Ala54/Thr54 group (41.2+/-13.5 kg). CRP, IL-6, and lipoprotein-a were higher in mutant group ( ALA54/THR54, THR54/THR54) than in wild group ( ALA54/ALA54). The novel finding of this study is the association of the Thr54/Ala54 and Thr54/Thr54 FABP2 phenotypes with higher levels of C reactive protein, IL6, and lipoprotein-a. Further studies are needed to explain the role of this polymorphism in different populations.     

The A54T polymorphism at the intestinal fatty acid binding protein 2 is associated with insulin resistance in glucose tolerant Caucasians

Background  

An A54T polymorphism at the fatty acid binding protein 2 (FABP2) locus was found to be associated with insulin resistance in non-diabetic Pima Indians. To see whether this association is present in other populations, we performed a cross sectional study to examine the role of this polymorphism on insulin resistance in 55 healthy and normotensive Caucasian subjects with normal glucose tolerance. Insulin sensitivity (%S) and beta cell function (%B) were assessed using the Homeostasis Model Assessment (HOMA). Their genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between the genotypes and the phenotypes was examined.     

Fasting and Postprandial Plasma Concentrations of Acylation-Stimulation Protein (ASP) in Lean and Obese Pima Indians Compared to Caucasians

WEYER, CHRISTIAN AND RICHARD E. PRATLEY. Fasting and postprandial plasma concentrations of acylation-stimulation protein (ASP) in lean and obese Pima Indians compared to Caucasians. Obes Res. Objective: ASP stimulates the clearance of free fatty acids (FFA) from the circulation and the synthesis of triglycerides (TG) in adipose tissue. We tested whether fasting and post-prandial plasma ASP concentrations are increased in Pima Indians, a population with a very high prevalence of obesity, but a remarkably low prevalence of dyslipidemia. Research Methods and Procedures: Plasma concentrations of ASP, TG, FFA, total cholesterol (CHOL), and insulin (INS) were measured in 15 Pima Indians (P) and 15 Caucasians (C) closely matched for age, sex, and body weight [7 lean and 8 obese subjects, body mass index (BMI) cut-off 30 kg/m²], before and for 4 hours after a standard mixed meal (20% of daily caloric requirements, 41% carbohydrate, 44% fat, 15% protein). Results: Fasting ASP was positively related to percent body fat (dual energy X-ray absorptiometry; r=0. 49, p<0. 01) and to TG and FFA, independently of percent body fat (partial r = 0. 42 and 0. 46, respectively, both p <0. 05). There were no differences in fasting TG, FFA, CHOL, INS, or ASP between lean C and lean P. In contrast, obese P had lower TG, lower CHOL, higher INS and, on average, 27% lower ASP compared to obese C. The ethnic difference in ASP remained after adjustment for TG, FFA, and percent body fat. ASP decreased in response to the meal in all four groups with no differences between groups. There was a significant inverse correlation between preprandial ASP and the change in FFA 60 minutes after the meal (r = ?0. 56, p<0. 001). Discussion: Pima Indians do not have higher plasma ASP concentrations than Caucasians. Whether other alterations in the ASP-pathway, such as increased sensitivity of adipocytes to ASP, contribute to the high prevalence of obesity and low prevalence of dyslipidemia in Pima Indians, remains to be elucidated.     

Effects Ala54Thr polymorphism of FABP2 on obesity index and biochemical variable in response to a aerobic exercise training

The purpose of the current study was to investigate whether or not the FABP2 gene polymorphism modulated obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers through 12-week aerobic exercise training in abdominal obesity group of Korean mid-life women. A total of 243 abdominally obese subjects of Korean mid-life women voluntarily participated in aerobic exercise training program for 12 weeks. Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR-RFLP) assay was used to assess the FABP2 genotype of the participants (117 of AA homozygotes, 100 of AT heterozygotes, 26 of TT homozygotes). Prior to the participation of the exercise training program, baseline obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers were measured. All the measurements were replicated following the 12-week aerobic exercise training program, and then the following results were found. After 12-week aerobic exercise training program, wild type (Ala54Ala) and mutant type (Ala54Thr+Thr54Thr) significantly decreased weight (P > .001), BMI (P > .001), %bf (P > .001), waist circumference (P > .001), WHR (P > .001), muscle mass (wild type p < .022; mutant type P > .001), RHR (P > .001), viseceral adipose area (wild type p < .005; mutant type P > .001), subcutaneous area (P > .001), insulin (wild type p < .005; mutant type P > .001) and significantly increased VO2max (P > .001). And wild type significantly decresed NEFA (P > .05), glucose (P > .05), OGTT 120min glucose (P > .05) and significantly increased HDLC (p > .005). Mutant type significantly decreased SBP (P > .001), DBP (P > .01), TC (P > .01), LPL (P > .05), LDL (P > .001), HOMA index (P > .01). The result of the present study represents that regular aerobic exercise training may beneficially prevent obesity index, blood pressure, blood lipids and insulin resistance markers independent of FABP Ala54Thr wild type and mutant type.     

Relation of the White Blood Cell Count to Obesity and Insulin Resistance: Effect of Race and Gender

PRATLEY, RICHARD E, CHARLTON WILSON AND CLIFTON BOGARDUS. Relation of the white blood cell count to obesity and insulin resistance: effect of race and gender. Obes Res. Recent reports suggest that the white blood cell (WBC) count is related to plasma insulin concentrations and insulin resistance in healthy individuals. The present study examines whether these relations are independent of obesity and the pattern of body fat distribution and tests whether race and gender affect these relations. WBC counts, insulin responses to a 75 gram oral glucose tolerance test (OGTT) and glucose disposal during a two-step hyperinsulinemic euglycemic clamp were measured in 300 men and women (149 Pima Indians, 100 whites, and 51 blacks) with a wide range of obesity. WBC counts were lower in blacks than Pima Indians or whites and tended to be higher in women than men. The subgroups were comparable in age and body weight, but percent body fat and plasma insulin concentrations were higher and glucose disposal during the glucose clamp was lower in Pima Indians than in blacks or whites. In the group as a whole, the WBC count correlated with obesity (body mass index and percent body fat), the waist to thigh ratio (an index of the pattern of body fat distribution), and plasma insulin concentrations and was negatively related to age and glucose disposal during the clamp. In multiple regression analyses, only age, race and obesity were significantly associated with the WBC count. When the analyses were restricted to Pima men, in whom correlations between the WBC count and the metabolic variables appeared the strongest, the WBC count remained significantly associated with plasma insulin concentrations, but not glucose disposal, after controlling for age and obesity. The results of this study indicate that age, race, and obesity are significantly associated with the WBC count in healthy individuals. Plasma insulin concentrations, but not insulin resistance per se, may also be weakly associated with the WBC count, but this may be population specific.     

A promoter polymorphism in the liver-specific fatty acid transport protein 5 is associated with features of the metabolic syndrome and steatosis

The fatty acid transport protein 5 (FATP5) is exclusively expressed in the liver and is involved in hepatic lipid and bile metabolism. We investigated whether a variation in the FATP5 promoter (rs56225452) is associated with hepatic steatosis and further features of the metabolic syndrome. A total of 716 male subjects from the Metabolic Intervention Cohort Kiel (MICK) and 103 male subjects with histologically proved nonalcoholic fatty liver disease (NAFLD) were genotyped for this FATP5 polymorphism rs56225452 and phenotyped for features of the metabolic syndrome. In the MICK cohort, ALT activities, postprandial insulin, and triglyceride concentrations were higher in subjects carrying the rare A-allele compared to GG homozygotes. Accordingly, the insulin sensitivity index determined after a mixed meal and standardized glucose load was lower in A-allele carriers. NAFLD cases carrying allele A were presented with also higher ALT activities. In NAFLD subjects, the association of BMI with the degree of steatosis and glucose concentration differed across FATP5 promoter polymorphism. The FATP5 promoter polymorphism rs56225452 is associated with higher ALT activity, insulin resistance, and dyslipidemia in the general population. The impact of the BMI on the severity of steatosis in NAFLD cases seems to depend on the FATP5 polymorphism.     

Relationship between carbohydrate-induced hypertriglyceridemia and fatty acid synthesis in lean and obese subjects

We previously reported that a eucaloric, low fat, liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers. To examine the diet sensitivity of obese subjects, 7 obese and 12 lean volunteers were given two eucaloric low fat solid food diets enriched in simple sugars for 2 weeks each in a random-order, cross-over design (10% fat, 75% carbohydrate vs. 30% fat, 55% carbohydrate, ratio of sugar to starch 60:40). The fatty acid compositions of both diets were matched to the composition of each subject's adipose tissue and fatty acid synthesis measured by the method of linoleate dilution in plasma VLDL triglyceride. In all subjects, the maximum % de novo synthesized fatty acids in VLDL triglyceride 3;-9 h after the last meal was higher on the 10% versus the 30% fat diet. There was no significant difference between the dietary effects on lean (43+/-13 vs. 12+/-13%) and obese (37+/-15 vs. 6+/-6%) subjects, despite 2-fold elevated levels of insulin and reduced glucagon levels in the obese. Similar results were obtained for de novo palmitate synthesis in VLDL triglyceride measured by mass isotopomer distribution analysis after infusion of [(13)C]acetate. On the 10% fat diet, plasma triglycerides (fasting and 24 h) were increased and correlated with fatty acid synthesis. Triglycerides were higher when fatty acid synthesis was constantly elevated rather than having diurnal variation.Thus, eucaloric, solid food diets which are very low in fat and high in simple sugars markedly stimulate fatty acid synthesis from carbohydrate, and plasma triglycerides increase in proportion to the amount of fatty acid synthesis. However, this dietary effect is not related to body mass index, insulin, or glucagon levels.     

Enhanced dietary fat clearance in postobese women

The objective of this study was to examine the postprandial response to an exogenous fat source in eight weight-stable postobese subjects (2;-3 years after gastric bypass) and eight matched control women, using a stable isotope, [13C]oleate. After a high fat breakfast meal (1,062 cal, 67% fat), [13C]oleate in triglyceride (TG)-rich lipoproteins (Sf >400 and Sf 20;-400) and nonesterified fatty acids (NEFA), and 13C in breath CO2, were monitored over 8 h. There were no differences in resting energy expenditure, thermic effect of food, carbohydrate/fat oxidation ratio, breath 13CO2 enrichment, or fecal fat content between postobese and control subjects. Postprandially, there was no difference in S(f) 20;-400 TG or NEFA, but postobese subjects had lower Sf >400 incremental area under the curve (AUC) (- 33%, P < 0.0025) and glucose [P < 0.01 by repeated measures analysis of variance (RM ANOVA)]. Postprandial 13C in Sf >400 TG returned to fasting levels 4 h earlier in postobese subjects and was lower than in control subjects at 4 and 6 h (P < 0.05 by RM ANOVA). The greatest difference was in the [13C]NEFA profiles. In control subjects [13C]NEFA increased markedly over 8 h; postobese subject [13C]NEFA remained close to fasting nonenriched values, and was strikingly lower than in control subjects (72% lower by AUC, P < 0.0001 by RM ANOVA). Finally, postobese subjects tended to have lower postprandial insulin (P < 0.01, 4 h), lower postprandial acylation-stimulating protein, and lower fasting leptin (-46%, P < 0.02). This study demonstrates clear metabolic differences in exogenous dietary fat partitioning in postobese women. These findings are compatible with an increased efficiency of dietary fat storage and suggest one possible mechanism for promotion of weight regain in postobese individuals.     

The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants

Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the A54T of the FABP2 gene plays a significant role in the assimilation of dietary fatty acids. However, reports were divergent with regard to the in vivo interaction between this polymorphism and postprandial lipemia. We therefore determined the influence of this intestinal fatty acid-binding protein polymorphism on intestinal fat transport using the human jejunal organ culture model, thus avoiding the interference of various circulating factors capable of metabolizing in vivo postprandial lipids. Analysis of DNA samples from 32 fetal intestines revealed 22 homozygotes for the wild-type Ala-54/Ala-54 genotype (0.83) and 10 heterozygotes for the polymorphic Thr-54/Ala-54 genotype (0.17). The Thr-encoding allele was associated with increased secretion of newly esterified triglycerides, augmented de novo apolipoprotein B synthesis, and elevated chylomicron output. On the other hand, no alterations were found in very low density lipoprotein and high density lipoprotein production, apolipoprotein A-I biogenesis, or microsomal triglyceride transfer protein mass and activity. Similarly, the alanine to threonine substitution at residue 54 did not result in changes in brush border hydrolytic activities (sucrase, glucoamylase, lactase, and alkaline phosphatase) or in glucose uptake or oxidation. Our data clearly document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metabolism. It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis.     

Obesity in Pima Indians: Large increases among post-World War II birth cohorts

Several studies have shown secular increases in obesity during the past 35 years, and others have reported increases in dietary fat consumption during the same period. Here we report a dramatic increase in obesity among Pima Indians born after World War II that appears to be associated with increased exposure to Western customs and diet following 1945. We examined the body mass index (BMI = weight in kilograms/height² in meters) of 1,128 male and 1,372 female Pima Indians aged 15–65 years who were born between 1901 and 1964 and were examined between 1965 and 1990. We found large increases in BMI among Pima Indian men and women in post-World War II birth cohorts (1945 and later). The parallel changes in body mass index, dietary fat, and exposure to Western culture following World War II suggest that culturally mediated changes in diet and level of physical activity associated with modern industrialized society may have led to the large increases in obesity in the Pima Indians and to smaller parallel changes observed worldwide in westernized countries. © 1993 Wiley-Liss, Inc.     

Association between FABP2 Ala54Thr polymorphisms and type 2 diabetes mellitus risk: a HuGE Review and Meta‐Analysis

Many studies have examined the association between the FABP2 (rs1799883) Ala54Thr gene polymorphism and type 2 diabetes mellitus risk (T2DM) in various populations, but their results have been inconsistent. To assess this relationship more precisely, A HuGE review and meta‐analysis were performed. The PubMed and CNKI database was searched for case‐control studies published up to April 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 13 studies, comprising 2020 T2DM cases and 2910 controls were included. Overall, for the Thr carriers (Ala/Thr and Thr/Thr) versus the wild‐type homozygotes (Ala/Ala), the pooled OR was 1.18 (95% CI = 1.04–1.34, P = 0.062 for heterogeneity), for Thr/Thr versus Ala/Ala the pooled OR was 1.17 (95% CI = 1.05–1.41 P = 0.087 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians but not Caucasians. This meta‐analysis suggests that the FABP2 (rs1799883) Ala54Thr polymorphisms are associated with increased susceptibility to T2DM risk among Asians but not Caucasians.     

Circulating Interleukin‐6 in Relation to Adiposity,Insulin Action,and Insulin Secretion

Objective: Plasma concentrations of interleukin‐6 (IL‐6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined whether circulating plasma IL‐6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes. Research Methods and Procedures: Fasting plasma IL‐6 concentrations (enzyme‐linked immunosorbent assay), body composition (DXA), insulin action (M; hyperinsulinemic euglycemic clamp), and acute insulin secretory responses to glucose (25 g intravenous glucose tolerance test) were measured in 58 Pima Indians without diabetes (24 women, 34 men). Results: Fasting plasma IL‐6 concentrations were positively correlated with percentage of body fat (r = 0.26, p = 0.049) and negatively correlated with M (r = ?0.28, p = 0.031), but were not related to acute insulin response (r = 0.13, p = 0.339). After adjusting for percentage of body fat, plasma IL‐6 was not related to M (partial r = ?0.23, p = 0.089). Discussion: Fasting plasma IL‐6 concentrations are positively related to adiposity and negatively related to insulin action in Pima Indians. The relationship between IL‐6 and insulin action seems to be mediated through adiposity.     

Similar mechanisms of fatty acid transfer from human anal rodent fatty acid-binding proteins to membranes: Liver,intestine, heart muscle,and adipose tissue FABPs

The mammalian fatty acid-binding proteins (FABPs) are thought to be important for the transport and metabolism of fatty acids in numerous cell types. The transfer of FA from different members of the FABP family to membranes has been shown to occur by two distinct mechanisms, an aqueous diffusion-based mechanism and a collisional mechanism, wherein the FABP interacts directly with membrane acceptors. Much of the work that underlies this concept comes from efforts using rodent FABPs. Given the increasing awareness of links between FABPs and several chronic diseases in humans, it was important to establish the mechanisms of FA transfer for human FABPs. In the present studies, we examined the rate and mechanism of fatty acid transfer from four pairs of human and rodent (rat or mouse, as specified) FABPs: hLFABP and rLFABP, hIFABP and rIFABP, hHFABP and rHFABP, and hAFABP and mAFABP. In the case of human IFABP, both the Ala⁵⁴ and Thr⁵⁴ forms were examined. The results show clearly that for all FABPs examined, the mechanisms of ligand transfer observed for rodent proteins hold true for their human counterparts. Moreover, it appears that the Ala to Thr substitution at residue 54 of the human IFABP does not alter the fundamental mechanism of ligand transfer to membranes, but nevertheless causes a consistent decrease in the rate of transfer.