Short-term weight loss in overweight/obese low-income women improves plasma zinc and metabolic syndrome risk factors.

Metabolic syndrome is a group of disorders involving obesity, insulin resistance, dyslipidemia and hypertension. Obesity is the most crucial risk factor of metabolic syndrome, because it is known to precede other risk factors. Obesity is also associated with disturbances in the metabolism of the trace mineral, zinc. The overall purpose of this study was to investigate the effects of short-term weight loss on plasma zinc and metabolic syndrome risk factors. An 8-week weight loss intervention study was conducted with 90 low-income overweight/obese mothers, whose youngest child was 1-3 years old. Plasma levels of zinc, glucose, insulin, leptin, triglycerides, total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were measured and compared at weeks 0 and 8 of the weight loss program. At pre-study, plasma zinc was low in 39% and, within normal values in 46%, of obese/overweight mothers. By the end of intervention, plasma zinc rose by 22% and only 5% of the mothers continued to exhibit low plasma zinc. At post-study, the metabolic syndrome risk factors of waist circumference, HDL cholesterol, and diastolic blood pressure (p<0.05) showed significant improvements. Plasma zinc increased by a greater margin (67%) in women with low zinc, as compared to those with normal zinc (18%); weight reduction was similar in both the groups. Finally, changes in % body fat were related negatively with changes in plasma zinc (r=- 0.28, p<0.05). The circulating levels of zinc, as well as the metabolic syndrome components, showed significant improvements in overweight/obese low-income women after weight loss.

Pleiotropic effects on subclasses of HDL, adiposity, and glucose metabolism in adult Alaskan Eskimos.

The aim of this study was to analyze the heritability and the presence of pleiotropic effects on subfractions of high-density lipoproteins (HDLs) as measured by nuclear magnetic resonance (NMR), parameters for adiposity, and glucose metabolism in adult Alaskan Eskimos. The present family study included 1,214 adult Alaskan Eskimos (537 male/677 female). Body weight, height, circumferences, selected skinfolds, and blood pressure were measured in all participants. Blood samples were collected under fasting conditions for the isolation of plasma. Glucose, insulin, subclasses and size of lipoproteins, triglycerides, total, and HDL cholesterol and lipoprotein (a) were measured in plasma. HbA1c was measured in total blood. Univariate and bivariate quantitative genetic analyses were conducted between HDL subclasses and size and the anthropometric and biochemical measures using the variance decomposition approach. Variation in all the analyzed traits exhibits a significant genetic component. Heritabilities ranged between 0.18 +/- 0.11 for LDL(2) (intermediate) and 0.89 +/- 0.07 for small HDL. No common genetic effects were found on the HDL subclasses (small, intermediate, and large). Small HDL particles were genetically correlated with LDL particles and HbA1c. Negative genetic correlations were observed between intermediate and large HDL subfractions, HDL size and measures of adiposity, and LDL and parameters for glucose metabolism (HbA1, insulin). These observations confirm the presence of possible pleiotropic effects on HDL, adiposity, and cardiovascular risk factors and provide novel insight on the relationship between HDL subclasses, adiposity, and glucose regulation.

Evidence that multiple genetic variants of MC4R play a functional role in the regulation of energy expenditure and appetite in Hispanic children.

BACKGROUND: Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain. OBJECTIVE: The aim was to identify and characterize the effects of MC4R variants in Hispanic children. DESIGN: MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva la Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits. RESULTS: Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81. CONCLUSION: This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure.

A nutrition and physical activity intervention promotes weight loss and enhances diet attitudes in low-income mothers of young children.

The purpose of this study was to evaluate a nutrition and physical activity program for reducing body weight and improving nutrition attitudes in mothers of young children. A convenience sample of 114 intervention mothers and 33 comparison mothers was recruited from public health clinics and community centers. Eligibility criteria included Hispanic, African American, or white ethnicity; body mass index of at least 25 kg/m(2); low income (< 200% of the federal poverty index); and youngest child aged 1 to 4 years. For intervention participants, height, weight, percentage of body fat, waist circumference, demographics, nutrition attitudes, and dietary intake were measured at weeks 0 and 8; height, weight, percentage of body fat, and waist circumference were reassessed at 6 months. Overweight mothers in the comparison group provided anthropometric and demographic data at weeks 0 and 8. Changes in anthropometrics, attitudes, and dietary intake were evaluated in intervention mothers. Anthropometric data of intervention vs comparison group mothers were examined. Differences in anthropometrics and attitude scores between weight loss responders (> or = 2.27 kg) and nonresponders (< 2.27 kg) were assessed at week 8. Intervention participants lost weight (x = -2.7 kg; P < .001), whereas comparison mothers gained a slight amount of weight (x = 0.1 kg) by week 8. Weight loss responders had healthier eating attitudes (5.6 vs 5.2; P < .01) and fewer perceived barriers (2.4 vs 2.9; P < .05) than nonresponders postintervention. In conclusion, this dietary and physical activity curriculum is a valuable resource for weight management programs serving low-income women.

A genetic contribution to circulating cytokines and obesity in children.

Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children enrolled in VIVA LA FAMILIA Study. Cytokine phenotypes included monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta 1 (TGF-beta1), C-reactive protein (CRP), regulated upon activation, normal T-cell expressed and secreted (RANTES) and eotaxin. Obesity-related phenotypes included body mass index (BMI), fat mass (FM), truncal FM and fasting serum insulin. Heritabilities ranged from 0.33 to 0.97. Pleiotropy was observed between cytokines and obesity traits. Positive genetic correlations were seen between CRP, leptin, MCP-1 and obesity traits, and negative genetic correlations with adiponectin, ICAM-1 and TGF-beta1. Genome-wide scan of sICAM-1 mapped to chromosome 3 (LOD=3.74) between markers D3S1580 and D3S1601, which flanks the adiponectin gene (ADIPOQ). Suggestive linkage signals were found in other chromosomal regions for other cytokines. In summary, significant heritabilities for circulating cytokines, pleiotropy between cytokines and obesity traits, and linkage for sICAM-1 on chromosome 3q substantiate a genetic contribution to circulating cytokine levels in Hispanic children.

A quantitative trait locus on chromosome 13q affects fasting glucose levels in Hispanic children.

OBJECTIVE: The prevalence of childhood obesity has increased dramatically in the United States. Early presentation of type 2 diabetes has been observed in children and adolescents, especially in the Hispanic population. The genetic contribution of glucose homeostasis related to childhood obesity is poorly understood. The objective of this study was to localize quantitative trait loci influencing fasting serum glucose levels in Hispanic children participating in the Viva La Familia Study. DESIGN: Subjects were 1030 children ascertained through an overweight child from 319 Hispanic families. Fasting serum glucose levels were measured enzymatically, and genetic linkage analyses were conducted using SOLAR software. RESULTS: Fasting glucose was heritable, with a heritability of 0.62 +/- 0.08 (P < 0.01). Genome-wide scan mapped fasting serum glucose to markers D13S158-D13S173 on chromosome 13q (LOD score of 4.6). A strong positional candidate gene is insulin receptor substrate 2, regulator of glucose homeostasis and a candidate gene for obesity. This region was reported previously to be linked to obesity- and diabetes-related phenotypes. CONCLUSIONS: A quantitative trait locus on chromosome 13q contributes to the variation in fasting serum glucose levels in Hispanic children at high risk for obesity.

A chromosome 11q quantitative-trait locus influences change of blood-pressure measurements over time in Mexican Americans of the San Antonio Family Heart Study.

Although previous genome scans have searched for quantitative-trait loci (QTLs) influencing variation in blood pressure (BP), few have investigated the rate of change in BP over time as a phenotype. Here, we compare results from genomewide scans to localize QTLs for systolic, diastolic, and mean arterial BPs (SBP, DBP, and MBP, respectively) and for rates of change in systolic, diastolic, and mean arterial BPs (rSBP, rDBP, and rMBP, respectively), with use of the longitudinal data collected about Mexican Americans of the San Antonio Family Heart Study (SAFHS). Significant evidence of linkage was found for rSBP (LOD 4.15) and for rMBP (LOD 3.94) near marker D11S4464 located on chromosome 11q24.1. This same chromosome 11q region also shows suggestive linkage to SBP (LOD 2.23) and MBP (LOD 2.37) measurements collected during the second clinic visit. Suggestive evidence of linkage to chromosome 5 was also found for rMBP, to chromosome 16 for rSBP, and to chromosomes 1, 5, 6, 7, and 21 for the single-time-point BP traits collected at the first two SAFHS clinic visits. We also present results from fine mapping the chromosome 11 QTL with use of SNP-association analysis within candidate genes identified from a bioinformatic search of the region and from whole-genome transcriptional expression data collected from 1,240 SAFHS participants. Our results show that the use of longitudinal BP data to calculate the rate of change in BP over time provides more information than do the single-time measurements, since they reveal physiological trends in the subjects that a single-time measurement could never capture. Further investigation of this region is necessary for the identification of the genetic variation responsible for QTLs influencing the rate of change in BP.

Genome-wide scan for serum ghrelin detects linkage on chromosome 1p36 in Hispanic children: results from the Viva La Familia study.

This study was conducted to investigate genetic influence on serum ghrelin and its relationship with adiposity-related phenotypes in Hispanic children (n=1030) from the Viva La Familia study (VFS). Anthropometric measurements and levels of serum ghrelin were estimated and genetic analyses conducted according to standard procedures. Mean age, body mass index (BMI), and serum ghrelin were 11+/-0.13 y, 25+/-0.24 kg/m2 and 38+/-0.5 ng/mL, respectively. Significant heritabilities (p<0.001) were obtained for BMI, weight, fat mass, percent fat, waist circumference, waist-to-height ratio, and ghrelin. Bivariate analyses of ghrelin with adiposity traits showed significant negative genetic correlations (p<0.0001) with weight, BMI, fat mass, percent fat, waist circumference, and waist-to-height ratio. A genome-wide scan for ghrelin detected significant linkage on chromosome 1p36.2 between STR markers D1S2697 and D1S199 (LOD=3.2). The same region on chromosome 1 was the site of linkage for insulin (LOD=3.3), insulinlike growth factor binding protein 1 (IGFBP1) (LOD=3.4), homeostatic model assessment method (HOMA) (LOD=2.9), and C-peptide (LOD=2.0). Several family-based studies have reported linkages for obesity-related phenotypes in the region of 1p36. These results indicate the importance of this region in relation to adiposity in children from the VFS.

Low-income, overweight and obese mothers as agents of change to improve food choices, fat habits, and physical activity in their 1-to-3-year-old children.

OBJECTIVE: To examine the effects of a weight loss program for mothers on the diet and activity of mothers and their 1-3 year old children. DESIGN: Overweight and obese mothers participated in an 8-week weight loss intervention encompassing diet, physical activity, and behavioral modification. Anthropometrics, demographic, dietary, and physical activity questionnaires were administered at weeks 0 and 8; anthropometrics were re-evaluated at week 24. SUBJECTS: Mothers (N=91) of a 1-3 year old child; body mass index (BMI) >or= 25 kg/m2; non-breastfeeding; age 18-45 years; income < 200% of federal poverty index; Hispanic, African American, or white; and English-speaking were recruited from Special Supplemental Program for Women Infants and Children (WIC) and public health clinics. INTERVENTION MEASURES OF OUTCOME: Weight loss in mothers and improvements in diet (reduction in calories, fat, snacks/desserts, sweetened beverages, and increases in fruit, vegetables) and activity in mothers and children. RESULTS: Weight loss in mothers was modest (-2.7 kg, p < 0.001) and sustained at week 24 (-2.8 kg, p < 0.001), and children gained in height and weight as expected for normal growth (p < 0.001). Initial energy intakes of children exceeded Estimated Energy Requirements (123%) and were reduced to acceptable levels post-intervention (102%, p < 0.001); additional beneficial changes in children's diets were decreased total (47.7 to 39.9 g/day) and saturated fat (19.2 to 16.6 g/day), high-fat snacks/desserts (1.6 to 0.9 servings/day), added fats (81.8 to 40.9% using), sweetened beverages (0.8 to 0.4 servings/day), and fast food consumption (11.6 to 6.6% of meals), and increased home-prepared meals (63.2 to 71.6% of meals) (p < 0.01 for all). Physical activity scores improved by 7% in children (p < 0.05). Comparable changes in food choices and activity also were seen in mothers. CONCLUSION: Offering weight loss classes was a successful method of enticing low-income women to participate in an educational intervention that benefited their children. Overweight and obese mothers who modified their food choices and fat habits made comparable changes for their child.

Metabolic and behavioral predictors of weight gain in Hispanic children: the Viva la Familia Study.

BACKGROUND: Despite the high prevalence of overweight among Hispanic children in the United States, definitive predictors of weight gain have not been identified in this population. OBJECTIVE: The study objective was to test sociodemographic, metabolic, and behavioral predictors of 1-y weight gains in a large cohort of Hispanic children studied longitudinally. DESIGN: Subjects (n = 879) were siblings from 319 Hispanic families enrolled in the Viva la Familia Study. Families were required to have at least one overweight child aged 4-19 y. One-year changes in weight and body composition by dual-energy X-ray absorptiometry were measured. Data were from parental interviews, birth certificates, multiple-pass 24-h dietary recalls, 3-d accelerometry, 24-h respiration calorimetry, measurements of eating in the absence of hunger, and measurement of fasting blood biochemistry indexes by radioimmunoassay. Generalized estimating equations and principal component analysis were applied. RESULTS: Weight gain increased with age (P = 0.001), peaking at approximately 10 y of age in girls and approximately 11 y of age in boys. Mean (+/-SD) weight gain was significantly higher in overweight (7.5 +/- 3.7 kg/y) than in nonoverweight (4.4 +/- 2.4 kg/y) children and in boys than in girls. When adjusted for age, age squared, sex, and Tanner stage, the final model indicated a child's body mass index (BMI; kg/m2) status, maternal BMI, energy expenditure (total energy expenditure, basal metabolic rate, and sleeping metabolic rate), and fasting blood biochemistry indexes (total triiodothyronine, insulin, leptin, and ghrelin) as independent, positive predictors of weight gain (P = 0.01-0.001). CONCLUSION: Knowledge of the metabolic and behavioral predictors of weight gain in Hispanic children will inform prevention and treatment efforts to address this serious public health problem in the United States.

Heritability of hyperphagic eating behavior and appetite-related hormones among Hispanic children.

OBJECTIVE: Eating in the absence of hunger (EAH) may be a genetically influenced phenotype of overweight children, but evidence is limited. This research evaluated the heritability (h(2)) of EAH and its association with overweight among Hispanic children 5 to 18 years old. Genetic and environmental associations of EAH with overweight, fat mass, and key hormonal regulators of food intake were also evaluated. RESEARCH METHODS AND PROCEDURES: A family design was used to study 801 children from 300 Hispanic families. Weighed food intakes were used to measure EAH after an ad libitum dinner providing 50% of estimated energy needs. Fasting ghrelin, amylin, insulin, and leptin were measured by immunoassays. Measured heights, weights, and fat mass (using DXA) were obtained. Total energy expenditure (TEE) was measured by room respiration calorimetry. RESULTS: On average, children consumed 41% of TEE at the dinner meal, followed by an additional 19% of TEE in the absence of hunger. Overweight children consumed 6.5% more energy at dinner (p < 0.001) and 14% more energy in the absence of hunger (p < 0.001) than non-overweight children. Significant heritabilities were seen for EAH (h(2) = 0.51) and dinner intake (h(2) = 0.52) and for fasting levels of ghrelin (h(2) = 0.67), amylin (h(2) = 0.37), insulin (h(2) = 0.37), and leptin (h(2) = 0.34). Genetic correlations were seen between eating behavior and fasting hormones, suggesting common underlying genes affecting their expression. DISCUSSION: This research provides new evidence that overweight Hispanic children exhibit elevated levels of hyperphagic eating behaviors that are influenced by genetic endowment.

Bivariate linkage confirms genetic contribution to fetal origins of childhood growth and cardiovascular disease risk in Hispanic children.

Birth weight has been shown to be associated with obesity and metabolic diseases in adulthood, however, the genetic contribution is still controversial. The objective of this analysis is to explore the genetic contribution to the relationship between birth weight and later risk for obesity and metabolic diseases in Hispanic children. Subjects were 1,030 Hispanic children in the Viva La Familia Study. Phenotypes included body size, body composition, blood pressure, fasting glucose, insulin, lipids, and liver enzymes. Birth weights were obtained from Texas birth certificates. Quantitative genetic analyses were conducted using SOLAR software. Birth weight was highly heritable, as were all other phenotypes. Phenotypically, birth weight was positively correlated to childhood body size parameters. Decomposition of these phenotypic correlations into genetic and environmental components revealed significant genetic correlations, ranging from 0.30 to 0.59. Negative genetic correlations were seen between birth weight and lipids. The genome scan of birth weight mapped to a region near marker D10S537 (LOD = 2.6). The bivariate genome-wide scan of birth weight and childhood weight or total cholesterol, improved the LOD score to 3.09 and 2.85, respectively. Chromosome 10q22 harbors genes influencing both birth weight and childhood body size and cardiovascular disease risk in Hispanic children.

Heritability of determinants of the metabolic syndrome among healthy Arabs of the Oman family study.

The metabolic syndrome, as defined by the International Diabetes Federation, was investigated in five large, extended, highly consanguineous, healthy Omani Arab families of a total of 1277 individuals. Heritability (h2) of the phenotypic abnormalities that make up the syndrome and other related traits was estimated by variance decomposition method using SOLAR software. The overall prevalence of the syndrome was 23%. The prevalence of abnormalities making the syndrome in a descending order were: obligatory waist circumference, hypertension, raised fasting blood glucose, low serum high-density lipoprotein (HDL), and raised serum triglycerides (TGs). Highly significant, but widely spread, h2 values were obtained for: height (0.68), weight (0.68), BMI (0.68), serum HDL (0.63), serum leptin (0.55), percentage body fat (0.53), total serum cholesterol (0.53), fasting serum insulin (0.51), homeostasis model assessment-insulin resistance index (0.48), serum TG (0.43), waist circumference (0.40), diastolic blood pressure (0.38), and 2-hour glucose level (0.17), whereas for the metabolic syndrome itself, h2 was 0.38. The wide spread of h2 results (0.07 to 0.68) indicates that some determinants, such as weight, BMI, and HDL level, are under significant genetic influence among the Omani Arabs. Other determinants such as insulin resistance, abdominal obesity, diastolic blood pressure, and TG levels seem to be more environmentally driven.

A quantitative trait locus on chromosome 18q for physical activity and dietary intake in Hispanic children.

OBJECTIVE: Genetic components of energy homeostasis contributing to childhood obesity are poorly understood. Genome scans were performed to identify chromosomal regions contributing to physical activity and dietary intake traits in Hispanic children participating in the VIVA LA FAMILIA Study. RESEARCH METHODS AND PROCEDURES: We report linkage findings on chromosome 18 for physical activity and dietary intake in 1030 siblings from 319 Hispanic families. Measurements entailed physical activity by accelerometry, dietary intake by two 24-hour recalls, and genetic linkage analyses using SOLAR software. RESULTS: Significant heritabilities were seen for physical activity and dietary intake, ranging from 0.46 to 0.69, except for vigorous activity (h2 = 0.18). Percentage time in sedentary activity mapped to markers D18S1102-D18S64 on chromosome 18 [logarithm of the odds (LOD) score = 4.07], where melanocortin 4 receptor gene (MC4R) resides. Quantitative trait loci (QTLs) for total activity counts, percentage time in light or in moderate activity, and carbohydrate intake and percentage of energy intake from carbohydrates were detected in the same region (LOD = 2.28, 2.79, 2.2, 1.84, and 1.51, respectively). A novel loss of function mutation in MC4R (G55V) was detected in six obese relatives, but not in the rest of the cohort. Removal of these MC4R-deficient subjects from the analysis reduced the LOD score for sedentary activity to 3.94. DISCUSSION: Given its role in the regulation of food intake and energy expenditure, MC4R is a strong positional candidate gene for the QTL on chromosome 18 detected for physical activity and dietary intake in Hispanic children.

Viva la Familia Study: genetic and environmental contributions to childhood obesity and its comorbidities in the Hispanic population.

BACKGROUND: Genetic and environmental contributions to childhood obesity are poorly delineated. OBJECTIVE: The Viva la Familia Study was designed to genetically map childhood obesity and its comorbidities in the Hispanic population. The objectives of this report were to describe the study design and to summarize genetic and environmental contributions to the phenotypic variation in obesity and risk factors for metabolic diseases in Hispanic children. DESIGN: The Viva la Familia cohort consisted of 1030 children from 319 families selected based on an overweight proband between the ages of 4 and 19 y. In-depth phenotyping to characterize the overweight children and their siblings included anthropometric and body-composition traits by dual-energy X-ray absorptiometry and assessments of diet by 24-h recalls, physical activity by accelerometry, and risk factors for metabolic diseases by standard biochemical methods. Univariate quantitative genetic analysis was used to partition phenotypic variance into additive genetic and environmental components by using the computer program SOLAR. RESULTS: Sex, age, and environmental covariates explained 1-91% of the phenotypic variance. Heritabilities of anthropometric indexes ranged from 0.24 to 0.75. Heritability coefficients for the body-composition traits ranged from 0.18 to 0.35. Diet and physical activity presented heritabilities of 0.32 to 0.69. Risk factors for metabolic diseases were heritable with coefficients ranging from 0.25 to 0.73. Significant genetic correlations between obesity traits and risk factors for metabolic diseases substantiated pleiotropy between traits. CONCLUSION: The Viva la Familia Study provides evidence of a strong genetic contribution to the high prevalence of obesity and its comorbidities in Hispanic children.

Common set of genes regulates low-density lipoprotein size and obesity-related factors in Alaskan Eskimos: results from the GOCADAN study.

Increasing incidence of cardiovascular disease in traditionally low-risk Alaskan Eskimos is a cause for concern. The purpose of this study was to examine the genetic and environmental correlations of low-density lipoprotein (LDL) subfractions with obesity-related factors in Alaskan Eskimos, using data from the first 954 participants of the Genetics of Coronary Artery Disease in Alaska Natives Study. Estimates of genetic and environmental influence were calculated using a maximum likelihood variance component method implemented in SOLAR. Mean values of weight, body mass index (BMI), and waist were 73.4 +/- 0.5 kg, 27.6 +/- 0.2 kg/m2, and 88.0 +/- 0.4 cm, respectively. LDL, and its small (LDL1), medium (LDL2), and large (LDL3) subfractions, had mean values of 115.8 +/- 1.2 mg/dl, 8.3 +/- 0.4 mg/dl, 19.6 +/- 0.8 mg/dl, and 71.5 +/- 1.5 mg/dl, respectively. Bivariate analysis displayed significant genetic correlations between LDL subfractions and obesity-related factors: LDL1 with BMI (rhoG = 0.67, P < 0.05), waist (rhoG = 0.80, P < 0.001), and subscapular and tricep skinfolds (rhoG = 0.93, P < 0.005, and rhoG = 0.78, P < 0.05, respectively); LDL2 with BMI (rhoG = 0.52, P < 0.05), waist (rhoG = 0.46, P < 0.05), and tricep skinfold (rhoG = 0.60, P < 0.05); and mean LDL size with BMI (rhoG = -0.36), waist (rhoG = -0.42,), and subscapular and tricep skinfolds (rhoG = -0.44 and -0.43, respectively) (P < 0.005). These results show that a common set of genes is influencing LDL size and obesity-related factors in Alaskan Eskimos.

Nutrition knowledge is associated with greater weight loss in obese and overweight low-income mothers.

OBJECTIVE: To examine if greater nutrition knowledge vs gains in knowledge promote more successful weight loss in low-income, overweight and obese mothers with young children. DESIGN: A convenience sample of mothers and their children were measured for height and weight; mothers completed demographic and nutrition knowledge questionnaires pre- and post-intervention. SUBJECTS/SETTING: Participants (N=141) were recruited from government and public health clinics and elementary schools. Inclusion criteria for mothers were: family income <200% federal poverty level; overweight/obese; and Hispanic, African-American, or white race/ethnicity. INTERVENTION: Eight weekly weight-loss classes emphasizing diet, physical activity, and behavior modification based on Social Cognitive Theory were administered to mothers. MAIN OUTCOME MEASURES: Improvements in maternal nutrition knowledge and weight loss. STATISTICAL ANALYSES PERFORMED: Paired-samples t tests, repeated measures analysis of variance, analysis of covariance, Pearson correlations, and chi(2) statistics. RESULTS: Nutrition knowledge of mothers increased in all areas. Participants with weight loss > or =2.27 kg (responders) had greater knowledge than those who did not; however, the actual net gain was similar for those who lost and did not lose weight. Weight gainers only improved in two areas on the test, whereas weight-loss responders increased knowledge in all six. Responders appeared more cognizant of diet, weight loss, and health information. CONCLUSIONS: Weight-management programs should include a strong component of nutrition education to alleviate knowledge inequalities and promote more effective weight control. In low-income mothers, greater initial knowledge may be more predictive of weight loss than gains in knowledge during an intervention.

Quantitative genetic analysis of the metabolic syndrome in Hispanic children.

Childhood obesity is associated with a constellation of metabolic derangements including glucose intolerance, hypertension, and dyslipidemia, referred to as metabolic syndrome. The purpose of this study was to investigate genetic and environmental factors contributing to the metabolic syndrome in Hispanic children. Metabolic syndrome, defined as having three or more metabolic risk components, was determined in 1030 Hispanic children, ages 4-19 y, from 319 families enrolled in the VIVA LA FAMILIA study. Anthropometry, body composition by dual energy x-ray absorptiometry, clinical signs, and serum biochemistries were measured using standard techniques. Risk factor analysis and quantitative genetic analysis were performed. Of the overweight children, 20%, or 28% if abnormal liver function is included in the definition, presented with the metabolic syndrome. Odds ratios for the metabolic syndrome were significantly increased by body mass index z-score and fasting serum insulin; independent effects of sex, age, puberty, and body composition were not seen. Heritabilities +/- SE for waist circumference, triglycerides (TG), HDL, systolic blood pressure (SBP), glucose, and alanine aminotransferase (ALT) were highly significant. Pleiotropy (a common set of genes affecting two traits) detected between SBP and waist circumference, SBP and glucose, HDL and waist circumference, ALT and waist circumference, and TG and ALT may underlie the clustering of the components of the metabolic syndrome. Significant heritabilities and pleiotropy seen for the components of the metabolic syndrome indicate a strong genetic contribution to the metabolic syndrome in overweight Hispanic children.

Genetic variation in selenoprotein S influences inflammatory response.

Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1beta and TNF-alpha. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory cytokines. One promoter variant, -105G --> A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-alpha. To investigate further the significance of the observed associations, we genotyped -105G --> A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant association with both TNF-alpha (P = 0.0049) and IL-1beta (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation.

Pleiotropic effects of genes for insulin resistance on adiposity in baboons.

OBJECTIVE: Previous research has suggested a genetic contribution to the development of insulin resistance and obesity. We hypothesized that the same genes influencing insulin resistance might also contribute to the variation in adiposity. RESEARCH METHODS AND PROCEDURES: A total of 601 (200 male, 401 female) adult baboons (Papio hamadryas) from nine families with pedigrees ranging in size from 43 to 121 were used in this study. Plasma insulin, glucose, C-peptide, and adiponectin were analyzed, and homeostasis model assessment of insulin resistance (HOMA IR) was calculated. Fat biopsies were collected from omental fat tissue, and triglyceride concentration per gram of fat tissue was determined. Body weight and length were measured, and BMI was derived. Univariate and bivariate quantitative genetic analyses were performed using SOLAR. RESULTS: Insulin, glucose, C-peptide, and adiponectin levels, HOMA IR, triglyceride concentration of fat tissue, body weight, and BMI were all found to be significantly heritable, with heritabilities ranging from 0.15 to 0.80. Positive genetic correlations (r(G)s) were observed for HOMA IR with C-peptide (r(G) = 0.88 +/- 0.10, p = 0.01), triglyceride concentration in fat tissue (r(G) = 0.86 +/- 0.33, p = 0.02), weight (r(G) = 0.50 +/- 0.20, p = 0.03), and BMI (r(G) = 0.64 +/- 0.22, p = 0.02). DISCUSSION: These results suggest that a set of genes contributing to insulin resistance also influence general and central adiposity phenotypes. Further genetic research in a larger sample size is needed to identify the common genes that constitute the genetic basis for the development of insulin resistance and obesity.