Physical activity and fat-free mass during growth and in later life.

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass. OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age. METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical activity level (PAL = TEE/REE), and calculation of FFM from isotope dilution. RESULTS: PAL was a main determinant of body composition at all ages. Models with age, fat mass (FM), and PAL explained 76% and 85% of the variation in FFM in females and males < 18 y old, and 32% and 47% of the variation in FFM in females and males ≥ 18 y old, respectively. In participants < 18 y old, mean FM-adjusted FFM was 1.7 kg (95% CI: 0.1, 3.2 kg) and 3.4 kg (95% CI: 1.0, 5.6 kg) higher in a very active participant with PAL = 2.0 than in a sedentary participant with PAL = 1.5, for females and males, respectively. At age 18 y, height and FM-adjusted FFM was 3.6 kg (95% CI: 2.8, 4.4 kg) and 4.4 kg (95% CI: 3.2, 5.7 kg) higher, and at age 80 y 0.7 kg (95% CI: -0.2, 1.7 kg) and 1.0 kg (95% CI: -0.1, 2.1 kg) higher, in a participant with PAL = 2.0 than in a participant with PAL = 1.5, for females and males, respectively. CONCLUSIONS: If these associations are causal, they suggest physical activity is a major determinant of body composition as reflected in peak FFM, and that a physically active lifestyle can only partly protect against loss of FFM in aging adults.

Asprosin is a centrally acting orexigenic hormone.

Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood-brain barrier and directly activates orexigenic AgRP+ neurons via a cAMP-dependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin. Furthermore, we found that obese humans and mice had pathologically elevated concentrations of circulating asprosin, and neutralization of asprosin in the blood with a monoclonal antibody reduced appetite and body weight in obese mice, in addition to improving their glycemic profile. Thus, in addition to performing a glucogenic function, asprosin is a centrally acting orexigenic hormone that is a potential therapeutic target in the treatment of both obesity and diabetes.

Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.

Energetic adaptations persist after bariatric surgery in severely obese adolescents.

OBJECTIVE: Energetic adaptations induced by bariatric surgery have not been studied in adolescents or for extended periods postsurgery. Energetic, metabolic, and neuroendocrine responses to Roux-en-Y gastric bypass (RYGB) surgery were investigated in extremely obese adolescents. METHODS: At baseline and at 1.5, 6, and 12 months post-baseline, 24-h room calorimetry, body composition, and fasting blood biochemistries were measured in 11 obese adolescents relative to five matched controls. RESULTS: In the RYGB group, mean weight loss was 44 ± 19 kg at 12 months. Total energy expenditure (TEE), activity EE, basal metabolic rate (BMR), sleep EE, and walking EE significantly declined by 1.5 months (P = 0.001) and remained suppressed at 6 and 12 months. Adjusted for age, sex, fat-free mass, and fat mass, EE was still lower than baseline (P = 0.001). Decreases in serum insulin, leptin, and triiodothyronine (T3), gut hormones, and urinary norepinephrine (NE) paralleled the decline in EE. Adjusted changes in TEE, BMR, and/or sleep EE were associated with decreases in insulin, homeostatic model assessment, leptin, thyroid stimulating hormone, total T3, peptide YY3-36, glucagon-like peptide-2, and urinary NE and epinephrine (P = 0.001-0.05). CONCLUSIONS: Energetic adaptations in response to RYGB-induced weight loss are associated with changes in insulin, adipokines, thyroid hormones, gut hormones, and sympathetic nervous system activity and persists 12 months postsurgery.

Longitudinal effects of parental, child and neighborhood factors on moderate-vigorous physical activity and sedentary time in Latino children.

BACKGROUND: Moderate-vigorous physical activity (%MVPA) confers beneficial effects on child musculoskeletal health, cardiovascular fitness, and psychosocial well-being; in contrast, sedentary time (%SED) is emerging as a risk factor for health. This study aimed to identify parental, child and neighborhood factors influencing longitudinal assessments of body mass index (BMI) and activity patterns among Latino children, and to estimate lagged and cross-lagged effects between child BMI, %MVPA and %SED. METHODS: A longitudinal design with assessments at baseline, 1 and 2 years follow-up (FU) was used to evaluate the effects of maternal and paternal factors (BMI, age, education level, acculturation, household income and household size), child factors (gender, age, BMI, pubertal status) and neighborhood factors (disorder, victimization) on child BMI, %MVPA and %SED, expressed as a percent of awake time, in 282 Latino children ages 8-10 y and their parents. This study was restricted to families with a mother and biological father or father figure in the child's life. RESULTS: Across time, total daily accelerometer counts (p = 0.04) and steps decreased (p = 0.0001), %SED increased (p = 0.0001), and %MVPA decreased (p = 0.02). Moderate lagged effects or tracking was seen for %MVPA and %SED (p = 0.001). %MVPA varied by gender (5.5% higher in boys than girls, p = 0.0001); child age (-0.4% per year, p = 0.03), and child BMI in boys only (-0.22%, p = 0.0002). Negative effects of paternal age, maternal education and maternal changes in BMI on %MVPA also were seen. %SED increased with child age (2.5% higher per year, p = 0.0001). Positive effects of paternal acculturation, maternal change in BMI, paternal age, and negative effects of household size on %SED were observed. A cross-lagged positive effect of BMI at FU1 on %SED at FU2 was observed for boys and girls (p = 0.03). Neighborhood disorder and victimization were not significant predictors of child BMI, %MVPA or %SED. CONCLUSION: The major child determinants of physical activity (age, gender and BMI) and minor parental influences (maternal BMI and education, paternal age and acculturation) should be considered in designing interventions to promote %MVPA and reduce %SED among Latino children as they approach adolescence.

Cross-sectional time series and multivariate adaptive regression splines models using accelerometry and heart rate predict energy expenditure of preschoolers.

Prediction equations of energy expenditure (EE) using accelerometers and miniaturized heart rate (HR) monitors have been developed in older children and adults but not in preschool-aged children. Because the relationships between accelerometer counts (ACs), HR, and EE are confounded by growth and maturation, age-specific EE prediction equations are required. We used advanced technology (fast-response room calorimetry, Actiheart and Actigraph accelerometers, and miniaturized HR monitors) and sophisticated mathematical modeling [cross-sectional time series (CSTS) and multivariate adaptive regression splines (MARS)] to develop models for the prediction of minute-by-minute EE in 69 preschool-aged children. CSTS and MARS models were developed by using participant characteristics (gender, age, weight, height), Actiheart (HR+AC_x) or ActiGraph parameters (AC_x, AC_y, AC_z, steps, posture) [x, y, and z represent the directional axes of the accelerometers], and their significant 1- and 2-min lag and lead values, and significant interactions. Relative to EE measured by calorimetry, mean percentage errors predicting awake EE (-1.1 ± 8.7%, 0.3 ± 6.9%, and -0.2 ± 6.9%) with CSTS models were slightly higher than with MARS models (-0.7 ± 6.0%, 0.3 ± 4.8%, and -0.6 ± 4.6%) for Actiheart, ActiGraph, and ActiGraph+HR devices, respectively. Predicted awake EE values were within ±10% for 81-87% of individuals for CSTS models and for 91-98% of individuals for MARS models. Concordance correlation coefficients were 0.936, 0.931, and 0.943 for CSTS EE models and 0.946, 0.948, and 0.940 for MARS EE models for Actiheart, ActiGraph, and ActiGraph+HR devices, respectively. CSTS and MARS models should prove useful in capturing the complex dynamics of EE and movement that are characteristic of preschool-aged children.

Genome-wide association replicates the association of Duffy antigen receptor for chemokines (DARC) polymorphisms with serum monocyte chemoattractant protein-1 (MCP-1) levels in Hispanic children.

Obesity is associated with a chronic low inflammatory state characterized by elevated levels of chemokines. Monocyte chemoattractant protein-1 (MCP-1) is a member of the cysteine-cysteine (CC) chemokine family and is increased in obesity. The purpose of this study was to identify loci regulating serum MCP-1 in obese Hispanic children from the Viva La Familia Study. A genome-wide association (GWA) analysis was performed in 815 children, ages 4-19 years, using genotypes assayed with the Illumina HumanOmni1-Quad v1.0 BeadChips. All analyses were performed in SOLAR using a linear regression-based test under an additive model of allelic effect, while accounting for the relatedness of family members via a kinship variance component. The strongest association for MCP-1 levels was found with a non-synonymous single nucleotide polymorphism (SNP), rs12075, resulting in an amino acid substitution (Asp42Gly) in the Duffy antigen receptor for chemokines (DARC) gene product (minor allele frequency=43.6%, p=1.3 × 10(-21)) on chromosome 1. Four other DARC SNPs were also significantly associated with MCP-1 levels (p<10(-16)-10(-6)). The Asp42Gly variant was associated with higher levels of MCP-1 and accounted for approximately 10% of its variability. In addition, MCP-1 levels were significantly associated with SNPs in chemokine receptor 3 (CCR3) and caspase recruitment domain family, member 9 (CARD9). In summary, the association of the DARC Asp42Gly variant with MCP-1 levels replicates previous GWA results substantiating a potential role for DARC in the regulation of pro-inflammatory cytokines.

A mammalian monothiol glutaredoxin, Grx3, is critical for cell cycle progression during embryogenesis.

Glutaredoxins (Grxs) have been shown to be critical in maintaining redox homeostasis in living cells. Recently, an emerging subgroup of Grxs with one cysteine residue in the putative active motif (monothiol Grxs) has been identified. However, the biological and physiological functions of this group of proteins have not been well characterized. Here, we characterize a mammalian monothiol Grx (Grx3, also termed TXNL2/PICOT) with high similarity to yeast ScGrx3/ScGrx4. In yeast expression assays, mammalian Grx3s were localized to the nuclei and able to rescue growth defects of grx3grx4 cells. Furthermore, Grx3 inhibited iron accumulation in yeast grx3gxr4 cells and suppressed the sensitivity of mutant cells to exogenous oxidants. In mice, Grx3 mRNA was ubiquitously expressed in developing embryos, adult tissues and organs, and was induced during oxidative stress. Mouse embryos absent of Grx3 grew smaller with morphological defects and eventually died at 12.5 days of gestation. Analysis in mouse embryonic fibroblasts revealed that Grx3(-/-) cells had impaired growth and cell cycle progression at the G(2) /M phase, whereas the DNA replication during the S phase was not affected by Grx3 deletion. Furthermore, Grx3-knockdown HeLa cells displayed a significant delay in mitotic exit and had a higher percentage of binucleated cells. Therefore, our findings suggest that the mammalian Grx3 has conserved functions in protecting cells against oxidative stress and deletion of Grx3 in mice causes early embryonic lethality which could be due to defective cell cycle progression during late mitosis.

BOUNCE: a community-based mother-daughter healthy lifestyle intervention for low-income Latino families.

The primary purpose of this study was to assess the efficacy of a family-based exploratory community study titled BOUNCE (Behavior Opportunities Uniting Nutrition, Counseling, and Exercise) to increase physical fitness and activity in low-income Latino mothers and daughters. The BOUNCE study consisted of a 12-week exercise (e.g., Latin dance), nutrition education, and counseling intervention. The design included a two-arm parallel group assignment to an experimental group (EG; included 26 mother-daughter dyads) and comparison group (CG; included 20 mother-daughter dyads). Pre- and postintervention 20-Meter Endurance Shuttle Run Test and accelerometry were used to measure children's aerobic capacity and physical activity, respectively. For the mothers, the Rockport Walk test and Non-Exercise Physical Activity Rating test were employed to assess aerobic fitness and physical activity. Anthropometric, demographic, and dietary assessments were also collected pre- and postintervention. Differences in outcome measures between groups were tested using repeated measures analysis of covariance. The BOUNCE intervention had a significant effect on EG Latino daughters' aerobic capacity (P = 0.044). Although not statistically significant, EG daughters reported a higher reduction of high fat food and sweetened beverages and an increase in fruit and vegetable consumption compared to CG daughters. Similarly, EG mothers reported more strategies to increase fruit/vegetable consumption and reduce fat intake compared to CG mothers. No changes in physical activity or BMI were observed between EG and CG mother-daughter dyads.

BOUNCE: an exploratory healthy lifestyle summer intervention for girls.

OBJECTIVES: To assess the efficacy of the BOUNCE parent-daughter intervention in promoting selected physical fitness measures and activity. METHODS: Thirty-seven Latino and African American parent-daughter pairs participated. The intervention entailed physical activities, nutrition classes, and self-esteem activities. Child's height, weight, waist circumference, body fat %, blood pressure, physical fitness, and activity were assessed pre- and postintervention. RESULTS: A repeated-measures ANOVA yielded significant results [F(4,26) = 793.003, P < 0.001]. Post hoc analyses demonstrated significant (P < 0.05) changes in BMI, waist circumference, physical fitness, and activity. CONCLUSIONS: The BOUNCE intervention was effective in promoting fitness and activity in minority girls.

Impact of infant feeding practices on childhood obesity.

Childhood obesity is a complex disease influenced by genetic and environmental factors and their interactions. The current surge in childhood obesity in the United States is attributable to an interaction between a genetic predisposition toward obesity and a permissive environment. Several recent systematic reviews and meta-analyses have been published on the association between breast-feeding and childhood obesity. In these analyses, adjustment for confounding factors attenuated or nullified the protective effect of breast-feeding on later obesity. The Viva La Familia Study was designed to identify genetic and environmental factors affecting obesity and its comorbidities in 1030 Hispanic children from 319 families. Odds ratios for potential risk factors associated with childhood overweight were computed using binary logistic regression for panel data. Early infant-feeding practices were not significant. Salient independent risk factors for childhood obesity in this cohort of Hispanic children were age, birth weight, maternal obesity, paternal obesity, number of children in the family, and the percentage of awake time spent in sedentary activity. Breast-feeding may have a small protective effect against childhood obesity, although residual confounding may exist. Human milk is exquisitely fitted for optimal infant growth and development and may uniquely modulate neuroendocrine and immunologic pathways involved in the regulation of body weight. Nevertheless, other genetic and environmental determinants such as socioeconomic status, parental obesity, smoking, birth weight, and rapid infancy weight gain far supersede infant-feeding practices as risk factors for childhood obesity.

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.

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.

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.

Chronicle of the Institute of Medicine physical activity recommendation: how a physical activity recommendation came to be among dietary recommendations.

Under a contract from the US Department of Health and Human Services, a multidisciplinary expert panel was appointed to review "the scientific literature regarding macronutrients and energy and develop estimates of daily intake that are compatible with good nutrition throughout the life span and that may decrease the risk of chronic disease." Within the overall context of the charge, the panel sought to quantify rates and components of daily energy expenditure in healthy adults with body mass indexes (in kg/m(2)) of 18.5-25, in growing children (in the 5th-85th percentiles of weight-for-length), and in pregnant and lactating women. The recommendation for adults became the daily energy intake necessary to cover total daily energy expenditure (TEE). For special cases, dietary macronutrients and energy to support child growth and pregnancy and lactation by women were considered. TEE was based on the results of doubly labeled water studies, and the TEE results were presented in units of physical activity level (PAL = TEE/BEE) and DeltaPAL, where BEE is the basal rate of energy expenditure extrapolated to 24 h. Most adults (66%) maintaining a BMI in the healthful range had PAL values >1.6, or the equivalent of > or =60 min of physical activity of moderate intensity each day. Hence, on the basis of the doubly labeled water data and the results of epidemiologic studies, the physical activity recommendation for adults was judged to be 60 min/d. The recommendation for children was for a minimum of 60 min/d. In conclusion, dietary and physical activity recommendations for healthful living are inextricably intertwined. Adequate physical activity provides protection against chronic diseases and helps to balance energy expenditure and intake.