The Effect of Diet-Induced Obesity and Subsequent Weight Loss on Body Composition, Glucose Clearance, Metabolite Profile and Liver Amp-Activated Protein Kinase in Mice

Obesity, currently an epidemic, is a difficult disease to combat because it is marked by both a change in body weight and an underlying dysregulation in metabolism, making consistent weight loss challenging. We sought to elucidate this metabolic dysregulation resulting from diet-induced obesity (DIO) that persists through subsequent weight loss. We hypothesized that weight gain imparts a change in “metabolic set point” persisting through subsequent weight loss and that this modification may involve a persistent change in hepatic AMP-activated protein kinase (AMPK), a key energy-sensing enzyme in the body. To test these hypotheses, we tracked metabolic perturbations through this period, measuring changes in hepatic AMPK. To further understand the role of AMPK we used AICAR, an AMPK activator, following DIO. Our findings established a more dynamic metabolic model of DIO and subsequent weight loss. We observed hepatic AMPK elevation following weight loss, but AICAR administration without similar dieting was unsuccessful in improving metabolic dysregulation. Our findings provide an approach to modeling DIO and subsequent dieting that can be built upon in future studies and hopefully contribute to more effective long-term treatments of obesity.

Comparison between weight loss of bends in a pneumatic conveyor and erosion rate obtained in a centrifugal erosion tester for the same materials

In order to find a link between results obtained from a laboratory erosion tester and tests carried out on a pneumatic conveyor, a comparison has been made between weight loss from bends on an industrial-scale pneumatic conveyor and erosion rates obtained in a small centrifugal erosion tester, for the same materials. Identical test conditions have been applied to both experiments so that comparable test results have been obtained. The erosion rate of mild steel commonly used as the wall material of conveyor pipes and pipe bends was determined individually on both test rigs. A relationship between weight loss from the bends and erosion rate determined from the tester has been developed. A discussion based on the results and their applicability to the prediction of wear in pneumatic conveyors concludes the paper.

Low-fat versus low-carbohydrate weight reduction diets:Effects on weight loss, insulin resistance, and cardiovascular risk: a randomized control trial

OBJECTIVE Low-fat hypocaloric diets reduce insulin resistance and prevent type 2 diabetes in those at risk. Low-carbohydrate, high-fat diets are advocated as an alternative, but reciprocal increases in dietary fat may have detrimental effects on insulin resistance and offset the benefits of weight reduction.

RESEARCH DESIGN AND METHODS We investigated a low-fat (20% fat, 60% carbohydrate) versus a low-carbohydrate (60% fat, 20% carbohydrate) weight reduction diet in 24 overweight/obese subjects ([mean ± SD] BMI 33.6 ± 3.7 kg/m2, aged 39 ± 10 years) in an 8-week randomized controlled trial. All food was weighed and distributed, and intake was calculated to produce a 500 kcal/day energy deficit. Insulin action was assessed by the euglycemic clamp and insulin secretion by meal tolerance test. Body composition, adipokine levels, and vascular compliance by pulse-wave analysis were also measured.

RESULTS Significant weight loss occurred in both groups (P < 0.01), with no difference between groups (P = 0.40). Peripheral glucose uptake increased, but there was no difference between groups (P = 0.28), and suppression of endogenous glucose production was also similar between groups. Meal tolerance–related insulin secretion decreased with weight loss with no difference between groups (P = 0.71). The change in overall systemic arterial stiffness was, however, significantly different between diets (P = 0.04); this reflected a significant decrease in augmentation index following the low-fat diet, compared with a nonsignificant increase within the low-carbohydrate group.

CONCLUSIONS This study demonstrates comparable effects on insulin resistance of low-fat and low-carbohydrate diets independent of macronutrient content. The difference in augmentation index may imply a negative effect of low-carbohydrate diets on vascular risk.

Gene Sets Net Correlations Analysis (GSNCA): a multivariate differential coexpression test for gene sets

Motivation: To date, Gene Set Analysis (GSA) approaches primarily focus on identifying differentially expressed gene sets (pathways). Methods for identifying differentially coexpressed pathways also exist but are mostly based on aggregated pairwise correlations, or other pairwise measures of coexpression. Instead, we propose Gene Sets Net Correlations Analysis (GSNCA), a multivariate differential coexpression test that accounts for the complete correlation structure between genes.

Results: In GSNCA, weight factors are assigned to genes in proportion to the genes' cross-correlations (intergene correlations). The problem of finding the weight vectors is formulated as an eigenvector problem with a unique solution. GSNCA tests the null hypothesis that for a gene set there is no difference in the weight vectors of the genes between two conditions. In simulation studies and the analyses of experimental data, we demonstrate that GSNCA, indeed, captures changes in the structure of genes' cross-correlations rather than differences in the averaged pairwise correlations. Thus, GSNCA infers differences in coexpression networks, however, bypassing method-dependent steps of network inference. As an additional result from GSNCA, we define hub genes as genes with the largest weights and show that these genes correspond frequently to major and specific pathway regulators, as well as to genes that are most affected by the biological difference between two conditions. In summary, GSNCA is a new approach for the analysis of differentially coexpressed pathways that also evaluates the importance of the genes in the pathways, thus providing unique information that may result in the generation of novel biological hypotheses.

Still Unequal at Birth: Birth Weight, Socioeconomic Status and Outcomes at Age 9

The prevalence of low birth weight is an important aspect of public health which has been linked to increased risk of infant death, increased cost of care, and a range of later life outcomes. Using data from a new Irish cohort study, I document the relationship between birth weight and socio-economic status. The association of maternal education with birth weight does not appear to be due to the timing of birth or complications during pregnancy, even controlling for a wide range of background characteristics. However, results do suggest intergenerational persistence in the transmission of poor early life conditions. Birth weight predicts a number of outcomes at age 9, including test scores, hospital stays and health. An advantage of the data is that I am able to control for a number of typically unmeasured variables. I determine whether parental investments (as measured by the quality of interaction with the child, parenting style, or school quality) mediate the association between birth weight and later indicators. For test scores, there is evidence of non-linearity, and boys are more adversely affected than girls. I also consider whether there are heterogeneous effects by ability using quantile regression. These results are consistent with a literature which finds that there is a causal relationship between early life conditions and later outcomes.

Validity and Test –retest Reliability of the TIVRE-Basket® Test for the Determination of Aerobic Power in Elite Male Basketball Players

The aims of this study were to 1) determine the relationship between performance on the court-based TIVRE-Basket® test and peak aerobic power determined from a criterion lab-based incremental treadmill test and 2) to examine the test-retest reliability of the TIVRE-Basket® test in elite male basketball players. To address aim 1, 36 elite male basketball players (age 25.2 + 4.7 years, weight 94.1 + 11.4 kg, height 195.83 + 9.6 cm) completed a graded treadmill exercise test and the TIVRE-Basket® within 72 hours. Mean distance recorded during the TIVRE-Basket® test was 4001.8 + 176.4m, and mean VO2 peak was 54.7 + 2.8 ml.kg.min-1, and the correlation between the two parameters was r=0.824 (P= <0.001). Linear regression analysis identified TIVRE-Basket® distance (m) as the only unique predictor of VO2 peak in a single variable plus constant model: VO2 peak = 2.595 + ((0.13* TIVRE-Basket® distance (m)). Performance on the TIVRE-Basket® test accounted for 67.8% of the variance in VO2 peak (t=8.466, P=<.001, 95% CI 0.01 - 0.016, SEE 1.61). To address aim 2, 20 male basketball players (age 26.7±4.2; height 1.94±0.92; weight 94.0±9.1) performed the TIVRE-Basket® test on two occasions. There was no significant difference in total distance covered between Trial 1 (4138.8 + 677.3m) and Trial 2 (4188.0 + 648.8m; t = 0.5798, P = 0.5688). Mean difference between trials was 49.2 + 399.5m, with an ICC of 0.85 suggesting a moderate level of reliability. Standardised TEM was 0.88%, representing a moderate degree of trial to trial error, and the CV was 6.3%. The TIVRE-Basket® test therefore represents a valid and moderately reliable court-based sport-specific test of aerobic power for use with individuals and teams of elite level male basketball players. Future research is required to ascertain its validity and reliability in other basketball populations e.g. across age groups, at different levels of competition, in females and in different forms of the game e.g. wheelchair basketball.

Weight status and gender-related differences in motor skills and in child care - based physical activity in young children.

Over the last decades, a decline in motor skills and in physical activity and an increase in obesity has been observed in children. However, there is a lack of data in young children. We tested if differences in motor skills and in physical activity according to weight or gender were already present in 2- to 4-year-old children. Fifty-eight child care centers in the French part of Switzerland were randomly selected for the Youp'là bouge study. Motor skills were assessed by an obstacle course including 5 motor skills, derived from the Zurich Neuromotor Assessment test. Physical activity was measured with accelerometers (GT1M, Actigraph, Florida, USA) using age-adapted cut-offs. Weight status was assessed using the International Obesity Task Force criteria (healthy weight vs overweight) for body mass index (BMI). Of the 529 children (49% girls, 3.4 ± 0.6 years, BMI 16.2 ± 1.2 kg/m2), 13% were overweight. There were no significant weight status-related differences in the single skills of the obstacle course, but there was a trend (p = 0.059) for a lower performance of overweight children in the overall motor skills score. No significant weight status-related differences in child care-based physical activity were observed. No gender-related differences were found in the overall motor skills score, but boys performed better than girls in 2 of the 5 motor skills (p ≤ 0.04). Total physical activity as well as time spent in moderate-vigorous and in vigorous activity during child care were 12-25% higher and sedentary activity 5% lower in boys compared to girls (all p < 0.01). At this early age, there were no significant weight status- or gender-related differences in global motor skills. However, in accordance to data in older children, child care-based physical activity was higher in boys compared to girls. These results are important to consider when establishing physical activity recommendations or targeting health promotion interventions in young children.

Increased body fat is independently and negatively related with cardiorespiratory fitness levels in children and adolescents with normal weight.

Body mass index (BMI) is related with cardiorespiratory fitness (CRF), but less is known regarding the combined relationships between BMI and body fat (BF) on CRF. Cross-sectional study included 2361 girls and 2328 boys aged 10–18 years living in the area of Lisbon, Portugal. BMI was calculated by measuring height and weight, and obesity was assessed by international criteria. BF was assessed by bioimpedance. CRF was assessed by the 20-m shuttle run and the participants were classified as normal-to-high or low-CRF level according to Fitness gram criterion-referenced standards. The prevalence of low CRF was 47 and 39% in girls and boys, respectively. The corresponding values for the prevalence of obesity were 4.8 and 5.6% (not significant) and of excess BF of 12.1 and 25.1% (P <0.001), respectively. In both sexes, BMI and BF were inversely related with CRF: r = – 0.53 and – 0.45 for BMI and % BF, respectively, in boys and the corresponding values in girls were – 0.50 and – 0.33 (all P <0.01). When compared with a participant with normal BMI and BF, the odds ratios (95% confidence interval) for low CRF were 1.94 (1.46–2.58) for a participant with normal BMI and high BF, and 6.19 (5.02–7.63) for a participant with high BMI and high BF. The prevalence of low-CRF levels is high in Portuguese youths. BF negatively influences CRF levels among children/adolescents with normal BMI.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

Propiedades psicométricas del test de competencias motoras Bruininks Oseretsky en versión corta para niños entre 4 y 7 años en Chía y Bogotá – Colombia.

Existen importantes pruebas de valoración que miden habilidades o competencias motoras en el niño; a pesar de ello Colombia carece de estudios que demuestren la validez y la confiabilidad de un test de medición que permita emitir un juicio valorativo relacionado con las competencias motoras infantiles, teniendo presente que la intervención debe basarse en la rigurosidad que exigen los procesos de valoración y evaluación del movimiento corporal. Objetivo. El presente estudio se centró en determinar las propiedades psicométricas del test de competencias motoras Bruininiks Oseretsky –BOT 2- segunda edición. Materiales y métodos. Se realizó una evaluación de pruebas diagnósticas con 24 niños aparentemente sanos de ambos géneros, entre 4 y 7 años, residentes en las ciudades de Chía y Bogotá. La evaluación fue realizada por 3 evaluadores expertos; el análisis para consistencia interna se realizó utilizando el Coeficiente Alfa de Cronbach, el análisis de reproducibilidad se estableció a través del Coeficiente de Correlación Intraclase –CCI- y para el análisis de la validez concurrente se utilizó el Coeficiente de Correlación de Pearson, considerando un alfa=0.05. Resultados. Para la totalidad de las pruebas, se encontraron altos índices de confiabilidad y validez. Conclusiones. El BOT 2 es un instrumento válido y confiable, que puede ser utilizado para la evaluación e identificación del nivel de desarrollo en que se encuentran las competencias motoras en el niño.

Survival, Pb-uptake and behaviour of three species of earthworm in Pb treated soils determined using an OECD-style toxicity test and a soil avoidance test

Mature (clitellate) Eisenia andrei Bouche (ultra epigeic), Lumbricus rubellus Hoffmeister (epigeic), and Aporrectodea caliginosa (Savigny) (endogeic) earthworms were placed in soils treated with Pb(NO3)(2) to have concentrations in the range 1000 to 10 000 mg Pb kg(-1). After 28 days LC50(-95%confidence limit) (+95%confidence limit) values were E. andrei 5824(-361)(+898) mg Pb kg(-1), L. rubellus 2867(-193)(+145) mg Pb kg(-1) and A. caliginosa 2747(-304)(+239) mg Pb kg(-1) and EC50s for weight change were E. andrei 2841(-68)(+150) Pb kg(-1), L. rubellus 1303(-201)(+204) mg Pb kg(-1) and A. caliginosa 1208(-206)(+212) Mg Pb kg(-1). At any given soil Pb concentration, Pb tissue concentrations after 28 days were the same for all three earthworm species. In a soil avoidance test there was no difference between the behaviour of the different species. The lower sensitivity to Pb exhibited by E. andrei is most likely due to physiological adaptations associated with the modes of life of the earthworms, and could have serious implications for the use of this earthworm as the species of choice in standard toxicological testing. (c) 2005 Elsevier Ltd. All rights reserved.

Intergenerational effects of birth weight on glucose tolerance and reproductive performance

Women who were themselves small-for-gestational age (SGA) are at a greater risk of adulthood diseases such as non-insulin-dependent diabetes mellitus (NIDDM), and twice at risk of having an SGA baby themselves. The aim of this study was to examine the intergenerational pig. Low (L) and normal (N) birth weight female piglets were followed throughout their first pregnancy (generation 1 (0)). After they had given birth, the growth and development of the lightest (I) and heaviest (n) female piglet from each litter were monitored until approximately 5 months of age (generation 2 (G2)). A glucose tolerance test (GTT) was conducted on G1 pig at similar to 6 months of age and again during late pregnancy; a GTT was also conducted on G2 pigs at similar to 4 months of age. G1 L offspring exhibited impaired glucose metabolism in later life compared to their G1 N sibling but in the next generation a similar scenario was only observed between I and n offspring born to G1 L mothers. Despite G1 L mothers showing greater glucose intolerance in late pregnancy and a decreased litter size, average piglet birth weight was reduced and there was also a large variation in litter weight; this suggests that they were, to some extent, prioritising their nutrient intake towards themselves rather than promoting their reproductive performance. There were numerous relationships between body shape at birth and glucose curve characteristics in later life, which can, to some extent, be used to predict neonatal outcome. In conclusion, intergenerational effects are partly seen in the pig. It is likely that some of the intergenerational influences may be masked due to the pig being a litter-bearing species.

Influence of dietary protein intake and glycemic index on the association between TCF7L2 HapA and weight gain

BACKGROUND: Genetic polymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BMI. OBJECTIVE: The objective was to investigate whether TCF7L2 HapA is associated with weight development and whether such an association is modulated by protein intake or by the glycemic index (GI). DESIGN: The investigation was based on prospective data from 5 cohort studies nested within the European Prospective Investigation into Cancer and Nutrition. Weight change was followed up for a mean (±SD) of 6.8 ± 2.5 y. TCF7L2 rs7903146 and rs10885406 were successfully genotyped in 11,069 individuals and used to derive HapA. Multiple logistic and linear regression analysis was applied to test for the main effect of HapA and its interaction with dietary protein or GI. Analyses from the cohorts were combined by random-effects meta-analysis. RESULTS: HapA was associated neither with baseline BMI (0.03 ± 0.07 BMI units per allele; P = 0.6) nor with annual weight change (8.8 ± 11.7 g/y per allele; P = 0.5). However, a previously shown positive association between intake of protein, particularly of animal origin, and subsequent weight change in this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01). We showed that weight gain becomes independent of protein intake with an increasing number of HapA alleles. Substitution of protein with either fat or carbohydrates showed the same effects. No interaction with GI was observed. CONCLUSION: TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet.

Genetic heterogeneity of within-family variance of body weight in Atlantic salmon (Salmo salar)

BACKGROUND: Canalization is defined as the stability of a genotype against minor variations in both environment and genetics. Genetic variation in degree of canalization causes heterogeneity of within-family variance. The aims of this study are twofold: (1) quantify genetic heterogeneity of (within-family) residual variance in Atlantic salmon and (2) test whether the observed heterogeneity of (within-family) residual variance can be explained by simple scaling effects. RESULTS: Analysis of body weight in Atlantic salmon using a double hierarchical generalized linear model (DHGLM) revealed substantial heterogeneity of within-family variance. The 95% prediction interval for within-family variance ranged from ~0.4 to 1.2 kg2, implying that the within-family variance of the most extreme high families is expected to be approximately three times larger than the extreme low families. For cross-sectional data, DHGLM with an animal mean sub-model resulted in severe bias, while a corresponding sire-dam model was appropriate. Heterogeneity of variance was not sensitive to Box-Cox transformations of phenotypes, which implies that heterogeneity of variance exists beyond what would be expected from simple scaling effects. CONCLUSIONS: Substantial heterogeneity of within-family variance was found for body weight in Atlantic salmon. A tendency towards higher variance with higher means (scaling effects) was observed, but heterogeneity of within-family variance existed beyond what could be explained by simple scaling effects. For cross-sectional data, using the animal mean sub-model in the DHGLM resulted in biased estimates of variance components, which differed substantially both from a standard linear mean animal model and a sire-dam DHGLM model. Although genetic differences in canalization were observed, selection for increased canalization is difficult, because there is limited individual information for the variance sub-model, especially when based on cross-sectional data. Furthermore, potential macro-environmental changes (diet, climatic region, etc.) may make genetic heterogeneity of variance a less stable trait over time and space.

Evaluation of a brief pilot nutrition and exercise intervention for the prevention of weight gain in general practice patients

Objective To pilot-test a brief written prescription recommending lifestyle changes delivered by general practitioners (GPs) to their patients.

Design The Active Nutrition Script (ANS) included five nutrition messages and personalised exercise advice for a healthy lifestyle and/or the prevention of weight gain. GPs were asked to administer 10 scripts over 4 weeks to 10 adult patients with a body mass index (BMI) of between 23 and 30 kg m− 2. Information recorded on the script consisted of patients' weight, height, waist circumference, gender and date of birth, type and frequency of physical activity prescribed, and the selected nutrition messages. GPs also recorded reasons for administering the script. Interviews recorded GPs views on using the script.

Setting General practices located across greater Melbourne.

Subjects and results Nineteen GPs (63% female) provided a median of nine scripts over 4 weeks. Scripts were administered to 145 patients (mean age: 54 ± 13.2 years, mean BMI: 31.7 ± 6.3 kg m− 2; 57% female), 52% of whom were classified as obese (BMI >30 kg m− 2). GPs cited ‘weight reduction’ as a reason for writing the script for 78% of patients. All interviewed GPs (90%, n = 17) indicated that the messages were clear and simple to deliver.

Conclusions GPs found the ANS provided clear nutrition messages that were simple to deliver. However, GPs administered the script to obese patients for weight loss rather than to prevent weight gain among the target group. This has important implications for future health promotion interventions designed for general practice.