Effects of β2‐Adrenergic Receptor Gene Variants on Adiposity: The HERITAGE Family Study

We investigated whether the Arg16Gly and Gln27Glu polymorphisms of the β2‐adrenergic receptor gene were associated with body‐fat and fat‐distribution phenotypes measured before and in response to a 20‐week endurance‐training program. BMI, fat mass (FAT), percentage of body fat (%FAT), sum of eight skinfolds (SF8), and abdominal fat areas assessed by computed tomography were measured in adult sedentary white and black participants of the HERITAGE Family Study. Evidence of gene‐by‐obesity interaction was found in whites for several adiposity phenotypes measured before training. Analyses performed separately in nonobese and obese subjects revealed that obese men carrying the Glu27 allele have lower fat accumulation (BMI, FAT, and %FAT) than noncarriers. Among white obese women, Gly16Gly homozygotes had a lower fat accumulation (BMI, FAT, and SF8) than Arg16Gly and Arg16Arg carriers. In response to endurance training, white women with the Arg16Arg genotype exhibited a greater reduction in BMI, FAT, and %FAT. Results observed in blacks were mostly negative. These results suggest that polymorphisms in the β2‐adrenergic receptor gene influence the amount of body fat in white obese men (Gln27Glu) and women (Arg16Gly), as well as the changes in adiposity in response to endurance training in white women (Arg16Gly).     

Intelligence Test Score and Educational Level in Relation to BMI Changes and Obesity

Objective: To investigate whether intelligence and education are related to subsequent BMI changes and development and persistence of obesity in men from young adulthood through middle‐age. Research Methods and Procedures: Subjects were selected among men (median age, 19 years; examined between 1956 and 1977) appearing at Danish draft boards: a group with juvenile‐onset obesity, including all men with a BMI of ≥31.0 kg/m²; and a nonobese group randomly selected as a 1% sample of the study population. The obese group and 50% of the nonobese group were invited to participate in follow‐up studies between 1982 and 1984 and between 1992 and 1994. Among 907 men with juvenile‐onset obesity and 883 nonobese men, age, examination region, intelligence test score, education, and BMI from baseline to first follow‐up were analyzed by multiple linear and logistic regressions analyses. Results: Education and intelligence, analyzed separately, were inversely related to BMI changes in both groups and to the development of obesity in the nonobese group. When adjusted for education, the association between intelligence score and BMI changes and development of obesity vanished, whereas the inverse relationship for education persisted only for BMI changes. Intelligence score was not associated with the persistence of obesity in the obese group, whereas inverse relationships were found for education. Discussion: Intelligence test score was inversely related to risk of BMI changes and the risk of development of obesity, perhaps with education acting as a mediator or indicator of cognitive ability. Education, but not intelligence, was inversely associated with risk of remaining obese.     

Relationships between Insulin Sensitivity and Measures of Body Fat in Asymptomatic Men and Women

Objective: To assess whether measures of body fat by DXA scanning can improve prediction of insulin sensitivity (S_I) beyond what is possible with traditional measures, such as BMI, waist circumference, and waist‐to‐hip ratio (WHR). Research Methods and Procedures: Frequently sampled intravenous glucose tolerance tests were performed in 256 asymptomatic non‐Hispanic white subjects from Rochester, MN (age 19‐60 years; 123 men and 133 women) to determine the S_I index by Bergman's minimal model technique. Height, weight, and waist and hip circumferences were measured for calculation of BMI and WHR; DXA was used to determine fat in the head, upper body, abdomen, and lower body. Linear regression was used to assess their relationships with S_I after sex stratification and adjustment for age. Results: After controlling for age, increases in traditional and DXA measures of fat were consistently associated with smaller declines in S_I among women than among men. In men, after controlling for age, all of the predictive information of S_I was provided by waist circumference (additional R² = 0.39, p < 0.001); none of the DXA measures improved the ability to predict S_I. In women, after adjustment for age, BMI, and WHR, the only DXA measure that improved the prediction of S_I was percentage head fat (additional R² = 0.03, p < 0.001). Discussion: Equivalent increases in most measures of body fat had lesser impact on S_I in women than in men. In both sexes, the predictive information provided by DXA measures is approximately equal to, but not additive to, that provided by simpler, traditional measures.     

C825T Polymorphism of the G Protein β3 Subunit Is Associated with Obesity but Not with Insulin Sensitivity

Objective: The common C825T polymorphism of the gene that encodes the G protein β₃ subunit has been shown to influence lipolysis in human adipocytes and to be associated with hypertension, body fat distribution, and obesity. In addition, it has been shown to be associated with insulin resistance in a small group of hypertensive subjects. We investigated whether this polymorphism contributed to the variability in obesity in our population from southern Germany and whether it was associated with insulin sensitivity of lipolysis and/or glucose disposal. Research Methods and Procedures: We determined percentage body fat, body fat distribution, glucose tolerance [oral glucose‐tolerance test (OGTT)], insulin sensitivity, and serum free fatty acids using data from OGTTs (N = 774) and clamp (euglycemic hyperinsulinemic clamp, N = 216) in normal and impaired glucose tolerant subjects who were genotyped for this polymorphism. Results: Compared with noncarriers of the C825T mutation, subjects with the C825T variant (prevalence ～32%) had higher percentage body fat (p = 0.02) and higher BMI (p = 0.03). No conclusive effect was seen on serum free fatty acids measured either during fasting or at the end of a 2‐hour OGTT. Insulin sensitivity determined during the OGTT and during the clamp, both adjusted for age, gender, and percentage body fat, was not different between the genotypes (p = 0.33 and p = 0.48, respectively). Discussion: We have concluded that the C825T polymorphism in the G protein β₃ subunit played an important role in the determination of obesity in this German population. However, it probably had no direct effects on insulin sensitivity of lipolysis and glucose disposal.     

Polymorphisms of the tumor necrosis factor-alpha receptor 2 gene are associated with obesity phenotypes among 405 Caucasian nuclear families

The plasma level of the tumor necrosis factor-alpha receptor 2 (TNFR2) is associated with obesity phenotypes. However, the genetic polymorphisms for such an association have rarely been explored and are generally unknown. In this study, by employing a large sample of 1,873 subjects from 405 Caucasian nuclear families, we explored the association of 12 SNPs of the TNFR2 gene and obesity-related phenotypes, including body mass index (BMI), fat mass, and percentage fat mass (PFM). The within-family quantitative transmission disequilibrium test, which is robust to sample stratification, was implemented to evaluate the association of TNFR2 gene with obesity phenotypes. Evidence of association was obtained at SNP9 (rs5746059) with fat mass (P = 0.0002), BMI (P = 0.002), and PFM (P = 0.0006). The contribution of this polymorphism to the variation of fat mass and PFM was 6.24 and 7.82%, respectively. Individuals carrying allele A at the SNP9 site had a 4.6% higher fat mass and a 2.5% increased PFM compared to noncarriers. The results remained significant even after correction for multiple testing. Evidence of association between the TNFR2 gene and obesity phenotypes are also found in 700 independent Chinese Han and 1,000 random Caucasians samples. The results suggest that the TNFR2 gene polymorphisms contribute to the variation of obesity phenotypes.     

Sex‐ and Depot‐Dependent Differences in Adipogenesis in Normal‐Weight Humans

To elucidate cellular mechanisms of sex‐related differences in fat distribution, we determined body fat distribution (dual‐energy X‐ray absorptiometry and single‐slice abdominal computed tomography (CT)), adipocyte size, adipocyte number, and proportion of early‐differentiated adipocytes (aP2⁺CD68^?) in the stromovascular fraction (SVF) in the upper and lower body of normal‐weight healthy men (n = 12) and premenopausal women (n = 20) (age: 18–49 years, BMI: 18–26 kg/m²). Women had more subcutaneous and less visceral fat than men. The proportion of early differentiated adipocytes in the subcutaneous adipose tissue SVF of women was greater than in men (P = 0.01), especially in the femoral depot, although in vitro adipogenesis, as assessed by peroxisome proliferator activated receptor‐γ (PPARγ) expression, was not increased in femoral preadipocytes cultured from women compared with men. In women, differentiation of femoral preadipocytes was less than that of abdominal subcutaneous preadipocytes (P = 0.04), and femoral subcutaneous preadipocytes tended to be more resistant to tumor necrosis factor‐α (TNFα)–induced apoptosis (P = 0.06). Thus, turnover and utilization of the preadipocyte pool may be reduced in lower vs. the upper‐body fat in women. Collectively, these data indicate that the microenvironment, rather than differences in inherent properties of preadipocytes between genders, may explain the gynoid obesity phenotype and higher percent body fat in women compared to men.     

BMI Is the Main Determinant of the Circulating Leptin in Women after Vertical Banded Gastroplasty

Objective: To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty. Research Methods and Procedures: Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls. Results: Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration. Discussion: Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti‐obesity surgery.     

Associations of Fat Distribution and Obesity with Hypertension in a Bi‐ethnic Population: The ARIC Study

Objective: To examine associations of hypertension with obesity and fat distribution among African American and white men and women. Research Methods and Procedures: The analysis sample included 15,063 African American and white men and women between the ages of 45 and 64 years who were participants in the 1987 through 1989 examination of the Atherosclerosis Risk in Communities Study (ARIC). Odds ratios and adjusted prevalences of hypertension were calculated across sexspecific quintiles of body mass index (BMI), waist‐to‐hip ratio (WHR), waist circumference, and waist‐to‐height ratio (waist/height) and adjusted for age, research center, smoking, education, physical activity, alcohol consumption, hormone replacement therapy, and menopausal status. Results: The prevalence of hypertension was higher among African Americans than whites. In the lowest quintile of BMI, 41% of African American women and 43% of African American men had hypertension compared with 14% of white women and 19% of white men. Elevated BMI, WHR, waist circumference, and waist/height were associated with increased odds of hypertension in African American and white men and women. In women, but not in men, there were significant interactions between ethnicity and the anthropometric variables studied here. The direction of the interaction indicated larger odds ratios for hypertension with increasing levels of anthropometric indices in white compared with African American women. Discussion: Obesity and abdominal fat preponderance were associated with increased prevalence of hypertension in African American and white men and women. Associations were similar among African American and white men, but obesity and fat patterning were less strongly associated with hypertension in African American than in white women.     

A Prospective Study of Adiposity and All‐Cause Mortality: The Malmö Diet and Cancer Study

Objective: This study aims to examine the association between various measures of adiposity and all‐cause mortality in Swedish middle‐aged and older men and women and, additionally, to describe the influences of age and sex on these associations. Research Methods and Procedures: A prospective analysis was performed in a cohort of 10,902 men and 16,814 women ages 45 to 73 years who participated in the Malmö Diet and Cancer Study in Sweden. Baseline examinations took place between 1991 and 1996, and 982 deaths were documented during an average follow‐up of 5.7 years. All‐cause mortality was related to the following variables measured at baseline: body mass index (BMI), percentage of body fat, lean body mass (LBM), and waist‐to‐hip ratio (WHR), with adjustment for age and selected covariates. Body composition data were derived from bioelectrical impedance analysis. Results: The association between percentage of body fat and mortality was modified by age, particularly in women. For instance, fatness was associated with excess mortality in the younger women but with reduced mortality in the older women. Weaker associations were seen for BMI than for percentage of body fat in both sexes. Placement in the top quintiles of waist‐to‐hip ratio, independent of overall body fat, was a stronger predictor of mortality in women than in men. The observed associations could not be explained by bias from early death or antecedent disease. Discussion: The findings reveal sex and age differences for the effects of adiposity and WHR on mortality and indicate the importance of considering direct measures of adiposity, as opposed to BMI, when describing obesity‐related mortality risks.     

A green tea extract high in catechins reduces body fat and cardiovascular risks in humans

Objective: The body fat reducing effect and reduction of risks for cardiovascular disease by a green tea extract (GTE) high in catechins was investigated in humans with typical lifestyles. Research Methods and Procedures: Japanese women and men with visceral fat‐type obesity were recruited for the trial. After a 2‐week diet run‐in period, a 12‐week double‐blind parallel multicenter trial was performed, in which the subjects ingested green tea containing 583 mg of catechins (catechin group) or 96 mg of catechins (control group) per day. Randomization was stratified by gender and body mass index at each medical institution. The subjects were instructed to maintain their usual dietary intake and normal physical activity. Results: Data were analyzed using per‐protocol samples of 240 subjects (catechin group; n = 123, control group; n = 117). Decreases in body weight, body mass index, body fat ratio, body fat mass, waist circumference, hip circumference, visceral fat area, and subcutaneous fat area were found to be greater in the catechin group than in the control group. A greater decrease in systolic blood pressure (SBP) was found in the catechin group compared with the control group for subjects whose initial SBP was 130 mm Hg or higher. Low‐density lipoprotein (LDL) cholesterol was also decreased to a greater extent in the catechin group. No adverse effect was found. Discussion: The continuous ingestion of a GTE high in catechins led to a reduction in body fat, SBP, and LDL cholesterol, suggesting that the ingestion of such an extract contributes to a decrease in obesity and cardiovascular disease risks.     

Comparison of Overall Obesity and Body Fat Distribution in Predicting Risk of Mortality

Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30–102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988–1994. During a 12‐year follow‐up (102,172 person‐years), 1,188 men and 925 women died. In multivariable‐adjusted analyses, waist‐to‐thigh ratio (WTR) in both sexes (P_trend <0.01 for both) and waist‐to‐hip ratio (WHR) in women (P_trend 0.001) were positively associated with mortality in middle‐aged adults (30–64 years), while BMI and waist circumference (WC) exhibited U‐ or J‐shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5–24.9 kg/m²) and obese (BMI ≥30.0 kg/m²) adults. In older adults (65–102 years), a higher BMI in both sexes (P_trend <0.05) and WC in men (P_trend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle‐aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.     

Genetic Variation and Obesity in Australian Women: A Prospective Study

Objective: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the β‐3 adrenergic receptor, tumor necrosis factor‐α, leptin, and leptin receptor (Lepr) in a cohort of Australian women. Research Methods and Procedures: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double‐energy X‐ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2‐year follow‐up. Genomic DNA was extracted and used for polymerase chain reaction‐based genotyping of all polymorphisms. Results: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass, percent body fat, and body mass index over a 2‐year period were not associated with genetic variation in the β‐3 adrenergic receptor (Trp64Arg), tumor necrosis factor‐α promoter, or leptin genes in non‐obese or obese women. Discussion: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population.     

Influence of Excess Fat on Cardiac Morphology and Function: Study in Uncomplicated Obesity

Objective: To evaluate whether or not “uncomplicated” obesity (without associated comorbidities) is really associated with cardiac abnormalities. Research Methods and Procedures: We evaluated cardiac parameters in obese subjects with long‐term obesity, normal glucose tolerance, normal blood pressure, and regular plasma lipids. We selected 75 obese patients [body mass index (BMI) >30 kg/m²], who included 58 women and 17 men (mean age, 33.7 ± 11.9 years; BMI, 37.8 ± 5.5 kg/m²) with a ≥10‐year history of excess fat, and 60 age‐matched normal‐weight controls, who included 47 women and 13 men (mean age, 32.7 ± 10.4 years; BMI, 23.1 ± 1.4 kg/m²). Each subject underwent an oral glucose tolerance test to exclude impaired glucose tolerance or diabetes mellitus, bioelectrical impedance analysis to calculate fat mass and fat‐free mass, and echocardiography. Results: Obese patients presented diastolic function impairment, hyperkinetic systole, and greater aortic root and left atrium compared with normal subjects. No statistically significant differences between obese subjects and normal subjects were found in indexed left ventricular mass (LVM/body surface area, LVM/height^2.7, and LVM/fat‐free mass_kg), and no changes in left ventricular geometry were observed. No statistically significant differences in cardiac parameters between extreme (BMI > 40 kg/m²) and mild obesity (BMI < 35 kg/m²) were observed. Discussion: In conclusion, our data showed that obesity, in the absence of glucose intolerance, hypertension, and dyslipidemia, seems to be associated only with an impairment of diastolic function and hyperkinetic systole, and not with left ventricular hypertrophy.     

The Trp64Arg Polymorphism of the β3‐Adrenergic Receptor Gene Is Not Associated with Training‐Induced Changes in Body Composition: The HERITAGE Family Study

Objective: To investigate the association between the Trp64Arg polymorphism of the β3‐adrenergic receptor gene and changes in body composition in response to endurance training. Research Methods and Procedures: Adult sedentary white and black subjects participating in the HERITAGE Family Study were measured before and after 20 weeks on endurance training for the body mass index, fat mass, percentage of body fat, fat‐free mass, sum of eight skinfolds, and subcutaneous, visceral, and total abdominal fat areas. The association between the Trp64Arg polymorphism and the response phenotypes, computed as the difference between pre‐ and post‐training values, was tested by analysis of covariance separately in men and women. The gene by race interaction term was also tested. Results: No race differences were observed for allelic and genotype frequencies. Training resulted in significant reduction of body fat in both men and women. No association of the Trp64Arg polymorphism was observed with training‐induced changes for any of the body composition phenotypes in both men and women. Discussion: These results suggest that the Trp64Arg polymorphism of the β3‐adrenergic receptor gene is not related to changes in body composition in response to exercise training.     

β3 Adrenergic Receptor Polymorphism and Obesity‐Related Phenotypes in Hypertensive Patients

Objectives: Obesity is a complex trait that is affected by both environmental and genetic risk factors. The β₃ adrenergic receptor (ADRB3) is expressed in adipose tissue and plays a role in energy metabolism. A missense mutation on codon 64 of this gene (W64R) is associated with receptor malfunction. Previous studies examining the relation between this polymorphism and obesity produced inconsistent findings. The current study assessed the association between the W64R genotype and obesity‐related phenotypes, including body weight, BMI, and serum triglycerides, cholesterol, and glucose. Research Methods and Procedures: We determined the ADRB3 W64R genotypes and fasting serum lipid and glucose concentrations for 695 hypertensive adults (336 men, 359 women) from a rural county in Anhui Province, China. Multivariate linear regression models were fit to detect associations between the genetic polymorphism and obesity‐related phenotypes. Results: The ADRB3 W64R polymorphism was significantly associated with body weight and BMI in men but not in women. After controlling for potential confounding variables, men who were homozygous for the R64 allele were 11.8 kg heavier (p < 0.001) and had a BMI that was 3.7 kg/m² greater (p = 0.001) than men who were homozygous for the W64 allele. Serum concentrations of lipids and glucose were found not associated with the genetic polymorphism. Discussion: The ADRB3 R64 allele was associated with increased body weight and BMI in men but not in women. The genetic association was not modified by triglyceride, cholesterol, blood glucose, or blood pressure levels of the subjects.     

Body Fat and Fat‐Free Mass and All‐Cause Mortality

Objective: To investigate whether the association between BMI and all‐cause mortality could be disentangled into opposite effects of body fat and fat‐free mass (FFM). Research Methods and Procedures: All‐cause mortality was studied in the Danish follow‐up study “Diet, Cancer and Health” with 27, 178 men and 29, 875 women 50 to 64 years old recruited from 1993 to 1997. By the end of year 2001, the median follow‐up was 5.8 years, and 1851 had died. Body composition was assessed by bioelectrical impedance. Cox regression models were used to estimate the relationships among body fat mass index (body fat mass divided by height squared), FFM index (FFM divided by height squared), and mortality. All analyses were adjusted for smoking habits. Results: Men and women showed similar associations. J‐shaped associations were found between body fat mass index and mortality adjusted for FFM and smoking. The mortality rate ratios in the upper part of body fat mass were 1.12 per kg/m² (95% confidence interval: 1.07, 1.18) in men and 1.06 per kg/m² (95% confidence interval: 1.02, 1.10) in women. Reversed J‐shaped associations were found between FFM index and mortality with a tendency to level off for high values of FFM. Discussion: Our findings suggest that BMI represents joint but opposite associations of body fat and FFM with mortality. Both high body fat and low FFM are independent predictors of all‐cause mortality.     

Association of Obesity,but not Diabetes or Hypertension,with Glucocorticoid Receptor N363S Variant

Objective: To determine whether the N363S variant in the glucocorticoid receptor (encoded by nuclear receptor subfamily 3, group C, member 1: NR3C1) is associated with obesity, type 2 diabetes, or hypertension. Research Methods and Procedures: This was a cross‐sectional case‐control study involving 951 Anglo‐Celtic/Northern European subjects from Sydney. This study consisted of the following: 1) an obesity clinic group, most of whom had “morbid obesity” (mean BMI for group = 43 ± 8 kg/m²; n = 152); 2) a type 2 diabetes clinic group (n = 356); 3) patients with essential hypertension who had a strong family history (n = 141); and 4) normal healthy controls (n = 302). N363S genotype, BMI, and a range of other parameters relevant to each group were measured. Results: Compared with the frequency of 0.04 in nonobese healthy subjects, the S363 allele was significantly higher in obesity clinic patients (0.17; p = 5.6 × 10^?8), subjects with diabetes who were also obese (0.09; p = 0.0045), subjects with hypertension who were also overweight (0.08; p = 0.0016), and overweight healthy subjects (0.12; p = 0.0004). Discussion: The NR3C1 N363S variant is associated with obesity and overweight in a range of patient settings but is not associated with hypertension or type 2 diabetes.     

Role of Ghrelin Polymorphisms in Obesity Based on Three Different Studies

Objective: Associations between preproghrelin DNA variants and obesity‐related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study. Research Methods and Procedures: Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction. Results: Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p = 0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the lowest FM (p < 0.001). Met72 carrier status (Met72+) was associated with lower FM (p = 0.026) and higher insulin‐like growth factor‐1 levels (p = 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p < 0.05) in SOS subjects whose BMI was ≤25 kg/m² than in those with BMI >25 kg/m² (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence of hypertension than noncarriers (23.9%). Discussion: Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.     

Secular trends of obesity and cardiovascular risk factors in a Mediterranean population

Objective: To evaluate time trends of obesity, abdominal obesity, and cardiovascular risk factors (CRFs) according to BMI and waist circumference (WC) categories in a Mediterranean population. Research Methods and Procedures: Subjects were Spanish men (n = 2383) and women (n = 2525) 25 to 74 years old, examined in 1994 to 1995 and 1999 to 2000 in two independent population‐based cross‐sectional surveys in the northeast of Spain. Lifestyle measures, CRFs, and anthropometric variables were analyzed. Results: Over the 5 years of the study, mean age‐standardized BMI increased by 1.0 units in men and by 0.8 units in women. At the same time the prevalence of obesity increased from 15.4% to 21.9% in men and from 15.4% to 21.4% in women. An upward trend was observed for WC and abdominal obesity (WC > 102 cm in men and WC > 88 cm in women) only in men. The proportion of men and women with hypercholesterolemia, diabetes, and low high‐density lipoprotein‐cholesterol plasma concentration remained stable within BMI and WC categories. The proportion of hypertension and smoking in obese men significantly increased from 1995 to 2000. Discussion: The 5‐year increase in BMI and WC is of considerable magnitude in the present population, although several CRFs remained stable within BMI and WC categories.     

Association of the mitochondrial DNA 15497G/A polymorphism with obesity in a middle-aged and elderly Japanese population

Although polymorphism of the mitochondrial DNA 15497guanine/adenine (Mt15497GA) leads to the Gly251Ser amino acid replacement on human cytochrome b, it is unknown whether functional alteration of the mitochondrion is induced by the Gly251Ser replacement. To see if an association exists between the Mt15497GA polymorphism and obesity, we examined differences in body size, body composition, and regional body fat distribution between the two genotypes in middle-aged and elderly Japanese individuals (825 women and 906 men). The Mt15497 genotype was determined with an automated colorimetric allele-specific DNA probe assay system using the polymerase chain reaction (PCR) method. The Mt15497GA polymorphism was detected in 3.5% (n=60) of all subjects: 2.8% (n=23) among women and 4.1% (n=37) among men. After adjusting for age and smoking, we found that body weight, body mass index, waist and hip circumferences, fat mass, fat-free mass, intra-abdominal fat and triglycerides were significantly greater in women with the A allele compared with the G allele (p=0.001–0.025). For men, waist to hip ratio was significantly greater (p=0.032), and waist circumference, intra-abdominal fat and triglycerides had a trend to be significantly greater (p=0.062–0.087) in subjects with the A allele compared with the G allele. These data suggest that the Mt15497 polymorphism may be associated with obesity-related variables and lipid metabolism.