Thr54 allele carriers of the Ala54Thr variant of FABP2 gene have associations with metabolic syndrome and hypertriglyceridemia in urban South Indians

The intestinal fatty acid-binding protein gene is proposed as a candidate gene for diabetes because the protein it codes is involved in fatty acid absorption and metabolism. This study investigates the association of the Ala54Thr variant of the intestinal fatty acid-binding protein gene on type 2 diabetes mellitus and other related metabolic traits in Asian Indians. Ala54Thr polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism in unrelated 773 type 2 diabetic and 899 normal glucose-tolerant (NGT) subjects, randomly chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in South India. The Ala54Thr polymorphism was not associated with type 2 diabetes mellitus or obesity. However, genotype-phenotype study revealed that the NGT subjects carrying the Thr54 allele had significantly higher 2-hour plasma glucose (P = .007), glycated hemoglobin (P = .004), 2-hour insulin (P = .027), and fasting low-density lipoprotein cholesterol (P = .032) levels compared with those with the Ala54 allele. Normal glucose-tolerant subjects with Ala54Thr and Thr54Thr genotypes had significantly higher fasting serum triglyceride levels (P = .003) compared with those with Ala54Ala. The subjects were stratified into those with hypertriglyceridemia (serum triglyceride levels >or=150 mg/dL) and those without. The odds ratio for hypertriglyceridemia for the individuals carrying the Ala54Thr genotype was 1.491 (95% confidence interval [CI], 1.22-1.83, P < .0001), and for those carrying the Thr54Thr genotype, it was 1.888 (95% CI, 1.34-2.67; P < .0001). Subjects were also stratified into those with metabolic syndrome (MS) and those without, according to modified Adult Treatment Panel III guidelines. The odds ratio (adjusted for age and sex) for MS for the individuals carrying the Ala54Thr genotype was 1.240 (95% CI, 1.02-1.51; P = .03), whereas for those carrying the Thr54Thr genotype, it was 1.812 (95% CI, 1.28-2.57; P = .001). Carriers of the Thr54 allele have associations with MS and hypertriglyceridemia in this urban South Indian population.     

No association found between the Ala54Thr polymorphism of FABP2 gene and obesity and obesity with dyslipidemia in Japanese schoolchildren

To investigate whether the Ala54Thr polymorphism of the fatty acid binding protein 2 gene is associated with obesity and obesity with dyslipidemia in Japanese schoolchildren, we analyzed 370 children with morbid obesity and 463 control children of normal weight. The allele frequencies did not differ significantly between the control group and the morbidly obese group. The odds ratio (95% confidence interval CI) in obesity of the The54 allele was 1.0 (0.9-1.3). There were no significant differences in obesity index and metabolic characteristics between the two groups. The odds ratio (95% CI) in dyslipidemia of the Thr54 allele was 1.1 (0.8-1.4) in the morbidly obese group. Our data suggested that Ala54Thr polymorphism of the FABP2 gene is not a major contributing factor for obesity and obesity with dyslipidemia in Japanese children.     

Adolescent obesity adversely affects blood pressure and resting heart rate.

BACKGROUND: Obesity is associated with hypertension (HT) and high resting heart rate (HR), as well as metabolic disturbances. However, little is known about how strongly these hemodynamic abnormalities are associated with the degree of obesity in adolescents. METHODS AND RESULTS: Height, body weight, resting HR, and systolic and diastolic blood pressures were measured in 20,165 male and 19,683 female high-school students. Adiposity levels were classified into 6 groups by body mass index: group 1 (<20th percentile), group 2 (20th-39.9th percentile), group 3 (40th-59.9th percentile), group 4 (60th-79.9th percentile), group 5 (80th-98.9th percentile), and group 6 (> or =99th percentile). Systolic and diastolic hypertensions were defined as > or =140 mmHg and > or =85 mmHg, respectively. Resting tachycardia was defined as the corresponding 95th percentile or greater. Resting HR and systolic and diastolic blood pressures increased with adiposity level in both sexes (p<0.0001). Both systolic HT and diastolic HT were associated with high resting HR, and the clustering of these unfavorable conditions increased with the degree of obesity. CONCLUSION: Hemodynamic abnormalities, such as HT and a high resting HR, are closely associated with adolescent obesity and are probably explained by impaired autonomic nerve function.     

Angiotensinogen gene polymorphism (Met235Thr) influences visceral obesity and insulin resistance in obese Japanese women

To investigate the relationship between angiotensinogen (AGT) Met235Thr polymorphism (M235T) and human obesity, because AGT is regarded as one of the cytokines produced from adipocytes and serum AGT concentrations are reported to be positively correlated with body mass index. One hundred and twenty obese Japanese women (age, 58.8+/-9.4 years; body mass index, 32.2+/-4.9 kg/m(2)) were enrolled. Angiotensinogen genotypes were determined with a fluorescent allele-specific DNA primer assay system. Subjects were divided into M/M, M/T, and T/T groups. Control subjects comprised 146 healthy age-matched women. Clinical characteristics and the effects of diet and exercise therapy for 6 months were compared among the 3 genotypes. The genotype frequencies of AGT M235T polymorphism were in accordance with the Hardy-Weinberg equation (obese: M/M, 6.7%; M/T, 27.5%; T/T, 65.8%; control: M/M, 6.8%; M/T, 21.2%; T/T, 71.9%). The frequency of the T allele did not differ between obese and control subjects (0.80 vs 0.83). As the number of obese women with M/M genotype was only 8, comparisons of the characteristics and outcomes of weight reduction therapy were performed only between subjects with M/T genotype and T/T genotype. In the T/T group, % body fat and waist circumference at baseline were significantly greater than in the M/T group (36.3%+/-4.8% vs 33.8%+/-4.7%, P=.0105; 107.9+/-10.9 vs 102.6+/-7.9 cm, P=.0428, respectively). Before the weight reduction therapy, significantly higher insulin and higher homeostasis model assessment (HOMA-R) were demonstrated in the T/T group than in the M/T group (9.1+/-5.5 microU/mL vs 5.9+/-4.4 microU/mL, P=.0056; 2.3+/-1.4 vs 1.6+/-1.3, P=.0252, respectively). Both systolic and diastolic blood pressure at baseline in the T/T group tended to be higher than those in the M/T group, but the differences were not significant. No genotype-dependent difference in energy expenditure or outcome of weight reduction therapy was observed with respect to AGT M235T polymorphism. After the diet and exercise therapy, the blood pressure in the T/T group tended to be higher than that in the M/T group, but the difference was not significant. We demonstrated that the T/T genotype of the AGT M235T gene polymorphism was positively related to visceral obesity and hyperinsulinemia in obese Japanese women. Blood pressure did not show genotype-specific differences before or after the treatment. Further studies of the association between obesity and this gene polymorphism should contribute to understanding and treating obesity-related diseases.     

Impact of obesity on resting metabolic rate and glucose-induced thermogenesis in non-insulin dependent diabetes mellitus.

Previous studies have shown that patients with non-insulin dependent diabetes mellitus (NIDDM) have a higher metabolic rate (RMR) and lower thermogenesis in comparison with persons with normal glucose tolerance. It is not clear whether this impairment is due to the diabetic state per se or to the association of the diabetic and obese state. The impact of obesity on RMR and glucose-induced thermogenesis (GIT) was studied in seven non-obese and 12 obese men with NIDDM; the results are compared with a group of six obese men with normal glucose tolerance. RMR was significantly higher for the obese subjects (P < 0.02) but this difference disappeared after correction for fat-free mass. Mean GIT was significantly lower (P < 0.01) in the diabetic patients, whether they were obese or non-obese. The results of this study indicate that for patients with NIDDM, the impact of obesity on both RMR and GIT is rather limited. On the other hand, a significant influence of glucose tolerance on GIT in obese patients could be demonstrated.     

Association of urine acidification with visceral obesity and the metabolic syndrome

Urine acidification is induced by metabolic acidosis which is associated with a high intake of protein-rich diet. The purpose of this study was to investigate the relationship of urine acidification with visceral obesity and the metabolic syndrome. We recruited 1,051 male subjects who underwent health examinations at the Health Care Center in Kinki Central Hospital. Subjects who were treated for hypertension, dyslipidemia, diabetes mellitus, and hyperuricemia and had the past history of chronic liver disease, chronic kidney disease and cancer, were excluded in this study. All subjects were administered to urine pH, blood and physical examinations. Lower urine pH was associated with higher serum urea nitrogen which reflects high intake of protein-rich diet, whereas it had no relation to serum creatinine. Lower urine pH was also associated with an increase in waist circumference, homeostasis model assessment-R, fasting plasma glucose, HbA1c, serum triglyceride, serum uric acid and with a decrease in high density lipoprotein cholesterol. Urine pH was not associated with mean blood pressure. Urine acidification is a characteristic of visceral obesity and the metabolic syndrome. High intake of protein-rich diet may contribute urine acidification, which is associated with various metabolic abnormalities in visceral obesity.     

Thr-encoding allele homozygosity at codon 54 of FABP 2 gene may be associated with impaired delta 6 desatruase activity and reduced plasma arachidonic acid in obese children

BACKGROUND: Alanine-for-threonine substitution at codon 54 (A54T polymorphism) in the fatty acid-binding protein 2 gene (FABP2) has been associated with hypertriglyceridemia and insulin resistance. Impairment in the activity of delta 6 and 5 desaturases is also supposed to be a factor predisposing the development of insulin resistance syndrome. AIM: We investigated the relationship between A54T polymorphism in FABP2 and the impairment of long-chain polyunsaturated fatty acid metabolism in obese children. METHODS: Thirty-two obese children participated. During the study, the children continued their habitual diet, which was documented in a 3-day food record using household measures. Anthropometry was performed, and serum lipid and fatty acid composition in plasma were analyzed. The polymorphism of codon 54 in the FABP 2 gene was analyzed. RESULTS: The allele frequency was 0.66 and 0.34 for Ala54 and Thr54, respectively. There were no significant differences in age, body mass index, fasting serum glucose, insulin or serum lipoproteins among the three polymorphism groups. These were also no significant differences in the intake of energy, the percentage of energy nutrients or in the dietary lipid composition. The content of arachidonic acid (AA) in plasma was lowest in Thr/Thr54 (p < 0.05). The indices of delta-6 desaturase (D6D) activity in Thr/Thr54 were significantly lower than in Thr/Ala54 or Ala/Ala54 (p < 0.05, p < 0.01, respectively). CONCLUSIONS: In obese children, Thr/Thr54 of the FABP 2 gene is associated with impaired activation of D6D and reduced AA content. The results in the LCPUFA profile suggest that Thr/Thr54 may predispose the to development of insulin resistance.     

Diet and exercise training effects on resting metabolic rate

The decline in resting metabolic rate (RMR) during periods of caloric restriction is a well documented phenomenon. The purpose of this study was to determine if either 30 min of daily self-selected aerobic activity (Group D) or prescribed exercise training performed every other day (Group P) for 12 weeks can prevent the decrease in RMR during caloric restriction for weight loss. Seventy-eight adult subjects (38 M, 40 F) whose weights were 15-35 percent above the upper limit for age, sex and frame were randomly assigned to three treatment groups. All three groups followed the same 1200, 1500 or 1800 kcal/d (5023, 6279, 7534 kJ) diet exchange plan. Group C (Control) followed no exercise program, while D and P exercised as described above. Maximal oxygen consumption (VO2 max, m10(2)/kg X min-1) predicted from the Bruce Test increased by 0.08 +/- 7, 9 +/- 12 and 12 +/- 9 percent in groups C, D and P, respectively. The increases for D and P were significantly higher than for C (P less than 0.01). RMR (m10(2)/kg X min-1) increased by 2 +/- 9, 4 +/- 7 and 10 +/- 9 percent in groups C, D and P respectively. The percent change for group P was significantly greater than that for groups C and D (P less than 0.05). There was a significant relationship across all subjects between the % delta in VO2 max and % delta in RMR (r = 0.307, P less than 0.01). However, the association between these two variables was stronger for females than for males.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical determinants of resting metabolic rate in geriatric outpatients

PurposeAccurate estimation of the energy requirements including resting metabolic rate (RMR) is important for optimal nutritional care, yet its clinical determinants are unknown. This study examined the associations between clinical determinants of the Comprehensive Geriatric Assessment (CGA) domains with RMR among geriatric outpatients.Materials & methodsData were retrieved from cohorts of community-dwelling older adults (n = 84, 54 female) referring to geriatrics outpatient mobility clinics in both Amsterdam, The Netherlands and Melbourne, Australia. Determinants within domains of the CGA included diseases (number, type and severity of diseases, polypharmacy), nutrition (body weight, body mass index, absolute and relative skeletal muscle mass, fat-free mass and fat mass, risk of malnutrition), physical function (handgrip strength, Short Physical Performance Battery, Timed Up & Go), cognition (Mini-Mental State Examination), psychological wellbeing (Geriatric Depression Scale) and blood pressure. RMR was objectively measured using indirect calorimetry with a canopy hood. Association between the clinical determinants with standardized RMR (country and sex-specific z-score) were analysed with linear regression adjusted for age, sex and body weight.ResultsDeterminants within the nutritional domain were associated with RMR; body weight showed the strongest association with RMR. Significant associations between determinants within the nutritional domain with RMR disappeared after further adjustment for body weight. None of the other domains were associated with RMR.ConclusionsBody weight is the strongest clinical determinant of RMR and should be taken into account when estimating RMR in geriatric care.     

Resting metabolic rate and substrate use in obesity hypertension

There is substantial evidence that obesity is a prime risk factor for the development of hypertension. Although hyperinsulinemia and an increased activity of the sympathetic nervous system have been implicated in the pathogenesis of "obesity hypertension," their effects on energy metabolism have not been studied thus far. In the present study, we therefore examined resting metabolic rate (RMR) and basal substrate oxidation in subjects with obesity and obesity-related hypertension. A total of 166 subjects were characterized for RMR and basal substrate use through indirect calorimetry. Blood pressure was measured at rest and with 24-hour ambulatory monitoring. Blood samples were collected for the measurement of plasma catecholamines, leptin, and the insulin response to an oral glucose load. In our study population, 116 subjects were defined as hypertensive and 91 were defined as obese. Hypertensive patients under beta-adrenergic blockade (n=42) had a significantly lower RMR than did patients without beta-blockade (P<0. 05) and were therefore excluded from further analyses. Univariate regression analysis revealed a significant relationship between RMR and body fat mass, as well as body fat-free mass, in both groups. Compared with obese normotensive control subjects (n=27), obese hypertensives (n=43) had a 9% higher RMR (P<0.05), higher plasma catecholamine (P<0.05) and leptin (P<0.05) levels, and an increased insulin response to oral glucose (P<0.01). Together, these findings are compatible with the idea that chronic neurogenic and metabolic adaptations related to obesity may play a role in the development of obesity hypertension in susceptible individuals.     

老年人小肠脂肪酸结合蛋白基因54位密码子多态性与血脂水平的关系

目的 调查老年人小肠脂肪酸结合蛋白(I-FABP)基因外显子2中54位点密码子A/T 单核苷酸多态性和不同基因型人群的血脂水平,探讨I-FABP基因多态性与老年人血脂水平的关系.方法 采用聚合酶链反应(PCR)、DNA限制性内切酶酶切等技术对72例汉族老年人54A/T I-FABP基因型进行分析;用全自动生化仪检测入选人群的血浆总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平.结果 基因型分组Thr54(-)组、Thr54(+)组各36例,Thr54(-)组与Thr54(+)组比较,TC为(4.50±0.73) mmol/L与(5.48±0.49)mmol/L、TG为(1.08±0.48)mmol/L与(2.02±0.53) mmol/L、LDL-C为(3.10±0.44)mmol/L与(3.50±0.66) mmol/L和HDL-C为(1.14±0.25)mmol/L与(0.96±0.23) mmol/L,差异有统计学意义(t值分别为-6.67、-7.84、-3.03、3.05,均P＜0.05).结论 I-FAB外显子2中54位点密码子A/T SNP与老年人群的血脂水平相关.     

Meta-analysis on the effect of the Ala54Thr polymorphism of the fatty acid-binding protein 2 gene on body mass index

Background and aim

The results from studies published on the association of fatty acid-binding protein 2 (FABP2) Ala54Thr polymorphism with body mass index (BMI) are conflicting. In this meta-analysis, we investigated the association of the FABP2 Ala54Thr polymorphism with BMI.

Methods and results

We searched for articles published prior to June 2009 using PubMed, HugeNavigator and China National Knowledge Internet. The languages were limited to English and Chinese. Data on BMI were collected. A pooled weighted mean difference (WMD), together with 95% confidence interval (CI), was used for this meta-analysis.A total of 27 studies with 10 974 subjects were included in this meta-analysis. The pooled effect for dominant, recessive and co-dominant model comparisons did not suggest the significant association between the FABP2 Ala54Thr polymorphism and BMI in overall populations: WMD_{fixed effects} = −0.00, 95% CI: (−0.16 to 0.15), p = 0.99, WMD_{random effects} = −0.00, 95% CI: (−0.16 to 0.15), p = 0.99, p_Q = 0.77, I² = 0%, WMD_{fixed effects} = −0.12, 95% CI: (−0.39 to 0.14), p = 0.35, WMD_{random effects} = −0.12, 95% CI: (−0.39 to 0.14), p = 0.35, p_Q = 0.47, I² = 0% and WMD_{fixed effects} = 0.07, 95% CI: (−0.11 to 0.25), p = 0.45, WMD_{random effects} = 0.07, 95% CI: (−0.11 to 0.25), p = 0.45, p_Q = 0.90, I² = 0%, respectively. The results from the comparisons of ThrThr versus AlaAla and AlaThr versus AlaAla showed no evidence that the FABP2 Ala54Thr polymorphism is significantly associated with BMI in overall populations (p > 0.05). All the results from the subgroup analyses for these genetic models comparisons were not significant (p > 0.05).

Conclusions

Our meta-analysis does not support the association between the FABP2 Ala54Thr polymorphism and BMI.     

The cross-sectional and longitudinal dependence of the resting metabolic rate on the fat-free mass

The dependence of the resting metabolic rate (RMR) on the fat-free mass (FFM) of temporarily fasted well-fed subjects has been studied by many researchers over the years. The results of 10 such studies yield an average linear dependence with a slope of 75 +/- 15 kJ/kg per day. In the work of Keys et al (The biology of human starvation. Minneapolis, MN: University of Minnesota Press, 1950) on semistarved subjects, however, the slope of the RMR dependence on the FFM was found to be 280 +/- 50 kJ/kg per day. The argument presented in this article is that the result derived for the large group of well-fed subjects is cross-sectional information, whereas that for the semistarved subjects is longitudinal data. The linear regression of the longitudinal data yields a negative offset term that when combined with the RMR vs FFM slope divides the FFM into active and inactive components, active tissue being that which interacts directly with oxygen. The linearity of the RMR vs FFM curve suggests that the elements of the active tissue mass are energetically similar regardless of their distribution in the body's organ systems. The active-inactive model implies that the longitudinal data results from the decrease in active tissue alone, whereas cross-sectional data for different individuals correspond to an admixture of both active and inactive tissue. For different individuals having the average RMR vs FFM slope of the semistarved subjects, it is calculated that a change in the FFM consists of about 27% active and 73% inactive tissue. A histogram of the individual longitudinal RMR vs FFM slopes for the 32 semistarved subjects yields an unexpected non-Gaussian distribution with a minimal value of 158 kJ/kg per day and a maximal value of 405 kJ/kg per day.