Training in metabolomics research. I. Designing the experiment, collecting and extracting samples and generating metabolomics data.

Metabolomics is perhaps the most challenging of the -omics fields, given the complexity of an organism's metabolome and the rapid rate at which it changes. When one sets out to study metabolism there are numerous dynamic variables that can influence metabolism that must be considered. Recognizing the experimental challenges confronting researchers who undertake metabolism studies, workshops like the one at University of Alabama at Birmingham have been established to offer instructional guidance. A summary of the UAB course training materials is being published as a two-part Special Feature Tutorial. In this month's Part I the authors discuss details of good experimental design and sample collection and handling. In an upcoming Part II, the authors discuss in detail the various aspects of data analysis.

Impact of weight cycling on risk of morbidity and mortality.

Unintentional weight gain is commonly observed in adult humans, often provoking intentional weight loss attempts followed by unintentional weight regain. This episodic variation in body weight over a period of time has been referred to as 'weight cycling'. Over the last two decades, weight cycling has been associated with a number of morbid health conditions and increased mortality. This article provides a comprehensive evaluation of recent weight-cycling evidence, looks to understand design differences between studies and study outcomes, assesses the need for further research on particular health outcomes, and proposes alternative methodologies that will bridge the needs and capabilities of research. Searches were conducted per PRISMA guidelines. Articles on weight cycling in the literature were initially identified using search strings in PubMed. Eligibility assessment of the remaining articles was performed independently by three reviewers to identify publications that presented direct evidence. Twenty human studies (in addition to seven animal studies) were selected and retained; 12 accounted for the intentionality of weight loss. Although weight regain following successful weight loss remains one of the most challenging aspects of body-weight regulation, evidence for an adverse effect of weight cycling appears sparse, if it exists at all.

The effect of a 3-month moderate-intensity physical activity program on body composition in overweight and obese African American college females.

SUMMARY: This study evaluated body composition outcomes following a 3-month exercise program for overweight/obese Black women. BMI decreased over the 3-month study despite an observed increase in body fat. Enhancements in bone marrow density and muscle density were also observed. Results show promising yet hypothesis-generating findings to explore in future research. INTRODUCTION: Few studies have evaluated the relationship between aerobic physical activity (PA) and body composition among young adult overweight/obese African American (AA) women. PURPOSE: The current study evaluated the effect of a 3-month moderate-intensity aerobic physical activity intervention for overweight and obese young adult women on bone, lean, and fat mass. METHODS: Participants (n = 15) were a randomly selected subset of AA female college students (M age = 21.7 years; M BMI = 33.3) enrolled in a larger PA promotion pilot study (n = 31). Study protocol required participants to engage in four 30-60-min moderate-intensity aerobic PA sessions each week. Whole body composition was measured by dual-energy X-ray absorptiometry (DXA), and peripheral quantitative computed tomography (pQCT) was used to assess additional quantitative and qualitative assessment of the radius. RESULTS: BMI decreased over the duration of the study (P = .034), reflected by a marginal decrease in body weight (P = .057). However, unexpectedly, increases in adipose tissue measures were observed, including total body fat (P = .041), percent body fat (P = .044), trunk fat (P = .031), and percent trunk fat (P = .041). No changes in DXA-measured bone outcomes were observed (i.e., bone mineral density, P = .069; bone mineral content, P = .211). Results from the pQCT assessment showed that bone marrow density increased (P = .011), but cortical density remained stable (P = .211). A marginally significant increase in muscle density (P = .053) and no changes in muscle area (P = .776) were observed. CONCLUSIONS: A 3-month moderate-intensity PA program was associated with several promising findings, including increased bone marrow and stabilization of body weight. However, the increase in adipose tissue and trend for decreased bone mineral density were unexpected and indicate the need for future studies with larger samples to further explore these outcomes.

Use of a simple liquid meal test to evaluate insulin sensitivity and beta-cell function in children.

Insulin sensitivity and ß-cell function are useful indices of metabolic disease risk but are difficult to assess in young children because of the invasive nature of commonly used methodology. A meal-based method for assessing insulin sensitivity and ß-cell function may at least partially alleviate concerns. The objectives of this study were to: (i) determine the association of insulin sensitivity assessed by liquid meal test with that determined by an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT); (ii) examine the association of insulin sensitivity derived from each test with measures of body composition, fat distribution and metabolic health (lipids, fasting insulin and glucose, and surrogate indices of insulin sensitivity); and (iii) examine the associations of indices of ß-cell function derived from each test with total and regional adiposity. Forty-seven children (7-12 years) underwent both a liquid meal test and an FSIGT. The insulin sensitivity index derived from the meal test (SI-meal) was positively associated with that from the FSIGT (SI-FSIGT; r = 0.63; P < 0.001), and inversely with all measures of insulin secretion derived from the meal test. Both SI-meal and SI-FSIGT were associated with measures of total and regional adiposity. SI-meal, but not SI-FSIGT, was associated with triglycerides and fasting insulin, after adjusting for ethnicity, gender, pubertal stage and fat mass. Basal insulin secretion measured during the meal test was positively associated with all measures of adiposity, independent of insulin sensitivity. In conclusion, a liquid meal offers a valid and sensitive means of assessing insulin sensitivity and ß-cell responsivity in young children.

Calcium homeostasis may influence resting energy expenditure with effects most apparent in early pubertal girls.

AIM: Perturbations in dietary and hormonal components of the calciotropic network may be mediated through the influence of calcium homoeostasis on resting energy expenditure (REE). We investigated the association of dietary and hormonal factors involved in the regulation of calcium homoeostasis with REE in girls. METHODS: Thirty-six girls aged 7-11 years participated. REE was assessed by indirect calorimetry, and body composition, dietary intake (calcium, vitamins D and K, phosphorus) and serum hormones (PTH, osteocalcin, 25OHD) were evaluated by DXA, 24 h recall and serum assay, respectively. RESULTS: A positive association between vitamin K and REE and an inverse association of parathyroid hormone (PTH) with REE (p = 0.05) were observed. PTH and REE were positively related in those having normal adiposity (p = 0.03) and inversely related in those with excess adiposity (p = 0.01). The association of REE with vitamin K intake was evident in lean individuals (p = 0.001), but was null in those with excess adiposity. CONCLUSION: Decreased calciotropic hormone levels along with increased related nutrient intakes were associated with greater REE, although these relationships differed according to adiposity. The physiologic response to the diet and subsequent energy partitioning needs to be considered in the context of puberty. In particular, regulation and signalling of the calciotropic network during pubertal maturation warrant investigation.

Short-term physical activity intervention decreases femoral bone marrow adipose tissue in young children: a pilot study.

Mechanical stimulation is necessary for maximization of geometrical properties of bone mineralization contributing to long-term strength. The amount of mineralization in bones has been reciprocally related to volume of bone marrow adipose tissue and this relationship is suggested to be an independent predictor of fracture. Physical activity represents an extrinsic factor that impacts both mineralization and marrow volume exerting permissive capacity of the growing skeleton to achieve its full genetic potential. Because geometry- and shape-determining processes primarily manifest during the linear growth period, the accelerated structural changes accompanying early childhood (ages 3 to 6 y) may have profound impact on lifelong bone health. The objective of this pilot study was to determine if a short-term physical activity intervention in young children would result in augmentation of geometric properties of bone. Three days per week the intervention group (n=10) participated in 30 min of moderate intensity physical activity, such as jumping, hopping and running, and stretching activities, whereas controls (n=10) underwent usual activities during the 10-week intervention period. Femoral bone marrow adipose tissue volume and total body composition were assessed by magnetic resonance imaging and dual-energy X-ray absorptiometry, respectively, at baseline and after 10 weeks. Although after 10-weeks, intergroup differences were not observed, a significant decrease in femoral marrow adipose tissue volume was observed in those participating in physical activity intervention. Our findings suggest that physical activity may improve bone quality via antagonistic effects on femoral bone marrow adipose tissue and possibly long-term agonistic effects on bone mineralization.

Genetic admixture, social-behavioural factors and body composition are associated with blood pressure differently by racial-ethnic group among children.

Cardiovascular disease has a progressively earlier age of onset, and disproportionately affects African Americans (AAs) in the United States. It has been difficult to establish the extent to which group differences are due to physiological, genetic, social or behavioural factors. In this study, we examined the association between blood pressure and these factors among a sample of 294 children, identified as AA, European American or Hispanic American. We use body composition, behavioural (diet and physical activity) and survey-based measures (socio-economic status and perceived racial discrimination), as well as genetic admixture based on 142 ancestry informative markers (AIMs) to examine associations with systolic and diastolic blood pressure. We find that associations differ by ethnic/racial group. Notably, among AAs, physical activity and perceived racial discrimination, but not African genetic admixture, are associated with blood pressure, while the association between blood pressure and body fat is nearly absent. We find an association between blood pressure and an AIM near a marker identified by a recent genome-wide association study. Our findings shed light on the differences in risk factors for elevated blood pressure among ethnic/racial groups, and the importance of including social and behavioural measures to grasp the full genetic/environmental aetiology of disparities in blood pressure.

Genetic influences in childhood obesity: recent progress and recommendations for experimental designs.

The increasing prevalence of pediatric obesity around the world has become an area of scientific interest because of public health concern. Although since early stages of the lifespan body weight might be heavily influenced by an individual's behavior, epidemiological research highlights the involvement of genetic influences contributing to variation in fat accumulation and thus body composition. Results from genome-wide association studies and candidate gene approaches have identified specific regions across the human genome influencing obesity-related phenotypes. Reviewing the scientific literature provides support to the belief that at the conceptual level scientists understand that genes and environments do not act independently, but rather synergistically, and that such interaction might be the responsible factor for differences within and among populations. However, there is still limited understanding of genetic and environmental factors influencing fat accumulation and deposition among different populations, which highlights the need for innovative experimental designs, improved body composition measures and appropriate statistical methodology.

African genetic admixture is associated with body composition and fat distribution in a cross-sectional study of children.

OBJECTIVE: Although differences in body composition parameters among African American (AA), Hispanic American (HA) and European American (EA) children are well documented, the factors underlying these differences are not completely understood. Environmental and genetic contributors have been evaluated as contributors to observed differences. This study evaluated the extent to which African or European ancestral genetic background influenced body composition and fat distribution in 301 peripubertal AA (n = 107), HA (n = 79) and EA (n = 115) children aged 7-12. DESIGN: Estimates of African admixture (AFADM) and European admixture (EUADM) were obtained for every subject using 142 ancestry informative DNA markers. Dual energy X-ray absorptiometry and computed tomography scanning were used to determine body composition and abdominal fat distribution, respectively. Multiple regression models were conducted to evaluate the contribution of admixture estimates to body composition and fat distribution. RESULTS: Greater AFADM was associated with lower fat mass (P = 0.0163), lower total abdominal adipose tissue (P = 0.0006), lower intra-abdominal adipose tissue (P = 0.0035), lower subcutaneous abdominal adipose tissue (P = 0.0115) and higher bone mineral content (BMC) (P = 0.0253), after adjusting for socio-economic status, sex, age, height, race/ethnicity and pubertal status. Greater EUADM was associated with lower lean mass (LM) (P = 0.0056). CONCLUSION: These results demonstrate that ancestral genetic background contributes to racial/ethnic differences in body composition above and beyond the effects of racial/ethnic classification and suggest a genetic contribution to total body fat accumulation, abdominal adiposity, LM and BMC.

Intrabdominal fat is related to metabolic risk factors in Hispanic Americans, African Americans and in girls.

AIM: This study aimed to test the association of individual adipose depots on cardiometabolic outcomes, whether the association varied by depot and if the associations differed by race/ethnicity or gender in early pubertal children. METHODS: Three hundred and twenty children (53% male) aged 7-12 years self-identified as African American (AA; n = 114), European American (EA; n = 120) or Hispanic American (HA; n = 86) participated. Insulin dynamics were assessed by intravenous glucose tolerance test; body composition with DXA; fat distribution with CT. RESULTS: AA had the least fat in each depot and HA had the most. Fat accumulation negatively impacted cardiometabolic outcomes independent of race/ethnicity or gender. AA and females were reproductively more mature. In AA and HA, each measure of adiposity influenced the insulin sensitivity index (S(I)), whereas intra-abdominal adipose tissue (IAAT) did not contribute to S(I) in EA. IAAT was positively associated with blood pressure in AA only. In females, adiposity adversely influenced cardiometabolic outcomes such that total fat mass, IAAT and/or SAAT was inversely associated with S(I), and positively associated with blood pressure and fasting insulin. CONCLUSION: IAAT is uniquely related to metabolic risk factors in Hispanic Americans, African Americans and girls, suggesting that either the threshold for adverse effects of IAAT is lower, or the IAAT metabolism differs in these groups.