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Background: Recent studies showed that eating behaviors such as disinhibition, emotional and external eating, and snacking mediate genetic susceptibility to obesity. It remains unknown if diet quality and intake of specific food groups also mediate the genetic susceptibility to obesity.Objective: This study aimed to assess if diet quality and intakes of specific food groups mediate the association between a polygenic risk score (PRS) for BMI and BMI and waist circumference (WC). We hypothesized that poor diet quality, high intakes of energy-dense food groups, and low intakes of nutrient-dense food groups mediate the genetic susceptibility to obesity.Methods: This cross-sectional study included 750 participants (56.3% women, aged 41.5 ± 14.9 y, BMI 27.8 ± 7.5 kg/m2) from the Quebec Family Study. A PRSBMI based on >500,000 genetic variants was calculated using LDpred2. Dietary intakes were assessed with a 3-d food record from which a diet quality score (i.e. Nutrient Rich Food Index 6.3) and food groups were derived. Mediation analyses were conducted using a regression-based and bootstrapping approach.Results: The PRSBMI explained 25.7% and 19.8% of the variance in BMI and WC, respectively. The association between PRSBMI and BMI was partly mediated by poor diet quality (β = 0.33 ± 0.12; 95% CI: 0.13, 0.60), high intakes of fat and high-fat foods (β = 0.46 ± 0.16; 95% CI: 0.19, 0.79) and sugar-sweetened beverages (β = 0.25 ± 0.14; 95% CI: 0.05, 0.60), and low intakes of vegetables (β = 0.15 ± 0.08; 95% CI: 0.03, 0.32), fruits (β = 0.37 ± 0.12; 95% CI: 0.17, 0.64), and dairy products (β = 0.17 ± 0.09; 95% CI: 0.02, 0.37). The same trends were observed for WC.Conclusions: The genetic susceptibility to obesity was partly mediated by poor diet quality and intakes of specific food groups. These results suggest that improvement in diet quality may reduce obesity risk among individuals with high genetic susceptibility and emphasize the need to intervene on diet quality among these individuals. [ABSTRACT FROM AUTHOR]

Background Data on the relationship between protein intake and the risk of type 2 diabetes are conflicting. Objective We studied prospective associations between the intake of total, plant-based, and animal protein and the risk of pre-diabetes and diabetes in 4 population-based studies included in the PREVIEW project. Methods Analyses were conducted with the use of data from 3 European cohorts and 1 Canadian cohort, including 78,851 participants. Protein intake was assessed through the use of harmonized data from food-frequency questionnaires or 3-d dietary records. Cohort-specific incidence ratios (IRs) were estimated for pre-diabetes and diabetes, adjusting for general characteristics, lifestyle and dietary factors, disease history, and body mass index (BMI) and waist circumference; results were pooled based on a random-effects meta-analysis. Results Higher total protein intake (g · kg–1 · d–1) was associated with lower incidences of pre-diabetes and diabetes (pooled IRs: 0.84; 95% CI: 0.82, 0.87 and 0.49; 95% CI: 0.28, 0.83, respectively); plant-based protein intake was the main determinant (pooled IRs: 0.83; 95% CI: 0.81, 0.86 and 0.53; 95% CI: 0.36, 0.76, respectively). Substituting 2 energy percentage (E%) protein at the expense of carbohydrates revealed increased risks of pre-diabetes and diabetes (pooled IRs: 1.04; 95% CI: 1.01, 1.07 and 1.09; 95% CI: 1.01, 1.18, respectively). Except for the associations between intakes of total protein and plant-based protein (g · kg–1 · d–1) and diabetes, all other associations became nonsignificant after adjustment for BMI and waist circumference. Conclusions Higher protein intake (g · kg–1 · d–1) was associated with a lower risk of pre-diabetes and diabetes. Associations were substantially attenuated after adjustments for BMI and waist circumference, which demonstrates a crucial role for adiposity and may account for previous conflicting findings. This study was registered at ISRCTN as ISRCTN31174892. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWASs) have identified several genes associated with obesity. The mechanisms through which these genes affect body weight are not fully characterized. Recent studies suggest that eating behavior (EB) traits could be involved, but only a few EB traits were investigated. Objective: This study aimed to investigate whether genetic susceptibility to obesity is mediated by EB traits (cognitive restraint, disinhibition, hunger) and their subscales. We hypothesized that EB traits, and their subscales, partly mediate this association. Design: Adult individuals (n = 768) who participated in the Quebec Family Study were included in this cross-sectional study. A genetic risk score (GRS) of obesity was calculated based on the 97 genetic variants recently identified in a GWAS meta-analysis of body mass index (BMI). EB traits and their subscales were assessed with the use of the Three-Factor Eating Questionnaire. Regression analyses with age and sex as covariates were used to investigate the associations between GRS, EB traits, BMI, and WC and whether the association between GRS and obesity is mediated by EB traits, which represents the indirect effect of GRS on obesity. Results: The GRS of obesity was positively associated with BMI (β = 0.19 ± 0.04, P < 0.0001) and WC (β = 0.46 ± 0.10, P < 0.0001). Regression analyses also revealed that the association between GRS of obesity and BMI was partly mediated by disinhibition and susceptibility to hunger (βindirect = 0.09 ± 0.03, P = 0.0007, and βindirect = 0.04 ± 0.02, P = 0.02, respectively). Habitual and situational susceptibility to disinhibition (βindirect = 0.08 ± 0.03, P = 0.002 and βindirect = 0.05 ± 0.02, P = 0.003, respectively) as well as internal and external locus of hunger (βindirect = 0.03 ± 0.02, P = 0.03 for both) were also found to mediate the association between GRS of obesity and BMI. The same trends were observed with WC. Conclusions: The results of this study indicate that the genetic susceptibility to obesity is partly mediated through undesirable EB traits, which suggests that they could be targeted in obesity treatment and prevention. [ABSTRACT FROM AUTHOR]

Objective Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated ( ENHO ) gene linked to metabolic control and vascular function. Methods Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico , in cultured human cells, and in animal models. Results In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis of hepatic Enho expression in male mice suggests control by the biological clock. Expression is rhythmic, peaking during maximal food consumption in the dark correlating with transcriptional activation by RORα/γ. The nadir in the light phase coincides with the rest phase and repression by Rev-erb. Plasma adropin concentrations in nonhuman primates (rhesus monkeys) also exhibit peaks coinciding with feeding times (07:00 h, 15:00 h). The ROR inverse agonists SR1001 and the 7-oxygenated sterols 7-β-hydroxysterol and 7-ketocholesterol, or the Rev-erb agonist SR9009, suppress ENHO expression in cultured human HepG2 cells. Consumption of high-cholesterol diets suppress expression of the adropin transcript in mouse liver. However, adropin over expression does not prevent hypercholesterolemia resulting from a high cholesterol diet and/or LDL receptor mutations. Conclusions In humans, associations between plasma adropin concentrations and LDL-C suggest a link with hepatic lipid metabolism. Mouse studies suggest that the relationship between adropin and cholesterol metabolism is unidirectional, and predominantly involves suppression of adropin expression by cholesterol and 7-oxygenated sterols. Sensing of fatty acids, cholesterol and oxysterols by the RORα/γ ligand-binding domain suggests a plausible functional link between adropin expression and cellular lipid metabolism. Furthermore, the nuclear receptors RORα/γ and Rev-erb may couple adropin synthesis with circadian rhythms in carbohydrate and lipid metabolism. [ABSTRACT FROM AUTHOR]

The beneficial effects of physical activity (PA) are well documented, yet the mechanisms by which PA prevents disease and improves health outcomes are poorly understood. To identify major gaps in knowledge and potential strategies for catalyzing progress in the field, the NIH convened a workshop in late October 2014 entitled “Understanding the Cellular and Molecular Mechanisms of Physical Activity-Induced Health Benefits.” Presentations and discussions emphasized the challenges imposed by the integrative and intermittent nature of PA, the tremendous discovery potential of applying “-omics” technologies to understand interorgan crosstalk and biological networking systems during PA, and the need to establish an infrastructure of clinical trial sites with sufficient expertise to incorporate mechanistic outcome measures into adequately sized human PA trials. Identification of the mechanisms that underlie the link between PA and improved health holds extraordinary promise for discovery of novel therapeutic targets and development of personalized exercise medicine. [ABSTRACT FROM AUTHOR]

Regular exercise and a physically active lifestyle have favorable effects on health. Several issues related to this theme are addressed in this report. A comment on the requirements of personalized exercise medicine and in-depth biological profiling along with the opportunities that they offer is presented. This is followed by a brief overview of the evidence for the contributions of genetic differences to the ability to benefit from regular exercise. Subsequently, studies showing that mutations in TP53 influence exercise capacity in mice and humans are succinctly described. The evidence for effects of exercise on endothelial function in health and disease also is covered. Finally, changes in cardiac and skeletal muscle in response to exercise and their implications for patients with cardiac disease are summarized. Innovative research strategies are needed to define the molecular mechanisms involved in adaptation to exercise and to translate them into useful clinical and public health applications. [ABSTRACT FROM AUTHOR]

Background: Clinical weight loss in individuals typically stabilizes at 6 mo. However, validated models of dynamic energy balance have consistently shown weight plateaus between 1 and 2 y. The cause for this discrepancy is unclear. Objective: We developed 2 mathematical models on the basis of the first law of thermodynamics to investigate plausible explanations for reaching an early weight plateau at 6 mo. Design: The first model was an energy-expenditure adaptation model and was applied to determine the degree of metabolic adaptation required to generate this plateau. The second model was an intermittent lack-of-adherence model formulated by using a randomly fluctuating energy intake term accounting for intermittent noncompliance in dietary intake to reach this plateau. To set model variables, validate models, and compare free-living weight-loss patterns to in-residence supervised programs, we applied the following 4 different studies: The US NHANES 1999-2004, Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CAL ERIE) weight-loss study, the Bouchard Twin overfeeding study, and the Minnesota Starvation Experiment. Results: The metabolic adaptation model increased final weight but did not affect the predicted plateau time point. The intermittent lack-of-adherence model generated oscillating weight graphs that have been frequently observed in weight-loss studies. The model showed that a 6-mo weight-loss plateau can be attained despite what can be considered as high diet adherence. The model was programmed as a downloadable application. Conclusions: An intermittent lack of diet adherence, not metabolic adaptation, is a major contributor to the frequently observed early weight-loss plateau. The new weight-loss prediction software, which incorporates an intermittent lack of adherence, can be used to guide and inform patients on realistic levels of adherence on the basis of patient lifestyle. [ABSTRACT FROM AUTHOR]

Summary: The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to exercise. Muscle PGC-1α transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1α-mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolomic approach to examine metabolites secreted from myocytes with forced expression of PGC-1α, and identified β-aminoisobutyric acid (BAIBA) as a small molecule myokine. BAIBA increases the expression of brown adipocyte-specific genes in white adipocytes and β-oxidation in hepatocytes both in vitro and in vivo through a PPARα-mediated mechanism, induces a brown adipose-like phenotype in human pluripotent stem cells, and improves glucose homeostasis in mice. In humans, plasma BAIBA concentrations are increased with exercise and inversely associated with metabolic risk factors. BAIBA may thus contribute to exercise-induced protection from metabolic diseases. [Copyright &y& Elsevier]

Background: Visceral adipose tissue (VAT) has been identified as a harmful fat depot, and sex and race differences in VAT have been reported in white and African Americans. Objectives: We determined the clinical utility of VAT in the identification of individuals at elevated cardiometabolic risk in white and African American adults and compared the clinical utility with measures obtained by using dual-energy X-ray absorptiometry (DXA) and anthropometric measures. Design: The sample included 429 white women, 311 African American women, 406 white men, and 100 African American men who were 18-74 y of age. VAT was measured by using computed tomography, fat mass (FM) and percentage of body fat were measured by using DXA, and waist circumference (WC) and BMI were assessed. Receiver operating characteristic curves were used to compare the utility of measures in the identification of participants in the upper quintile of a continuous score derived from principal components analysis of fasting glucose, HDL cholesterol, triglycerides, and blood pressure. Results: The clinical utility of measures varied across sex-by-race groups. In the overall sample, the areas under the curve were significantly higher for VAT and WC in comparison with the other indicators. Identified VAT thresholds were higher in white men (140 cm² and women (141 cm² than in African American men (82 cm and women (97 cm²). Conclusions: VAT and WC showed greater clinical utility than did other obesity measures. Because of the complexity of measuring VAT, the use of WC is recommended for the identification of adults with elevated cardiometabolic risk factors. The Pennington Center Longitudinal Study was registered at clinicaltrials.gov as NCT00959270. [ABSTRACT FROM AUTHOR]

Background: The assessment of fat mass and fat-free mass in relation to the symptom-limited maximal exercise duration (Maxdur) of a treadmill test allows for insight into the association of body composition with treadmill performance potential. Objective: We investigated the complex associations between fat mass and fat-free mass and Maxdur in a population setting. Design: The Maxdur of a graded exercise treadmill test and body composition by dual-energy X-ray absorptiometry were estimated in 2413 black and white men and women aged 38-50 y from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. Results: The mean Maxdur was ≈7.5 s shorter per kilogram of fat mass in both men and women and independent of fat-free mass, height, race, television watching, physical activity, systolic blood pressure, lung function, and education. Fat mass modified the association of fat-free mass with the Maxdur (2-way interaction P < 0.001), and the interaction was stronger in women than in men. In men in the lowest fat-mass quartile, the Maxdur was 1.3 s longer per kilogram of fat-free mass and was 0.5 s shorter per kilogram of fat-free mass in the highest fat-mass quartile. In contrast, in women with the least fat mass, the Maxdur was 2.7 s longer per kilogram of fat-free mass and was 2.8 s shorter per kilogram of fat-free mass in the highest fat-mass quartile. Conclusions: The Maxdur was negatively related to fat mass. Fat-free mass in obese people contributed little to the treadmill performance potential as assessed by the Maxdur, although the contribution of fat-free mass was positive in thinner people. [ABSTRACT FROM AUTHOR]

Abstract: As visceral adipose tissue (AT) accumulation and inflammatory markers are known to increase with age, we examined whether this age-related change in regional AT distribution could contribute to the increase in the concentration of some inflammatory markers found with age. Two hundred eight healthy men aged 18.6 to 72.2 years and covering a wide range of adiposity values (body mass index, 18.5-39.3 kg/m2) were studied. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor–α (TNF-α) levels were measured by enzyme-linked immunosorbent assay. Anthropometric characteristics such as height, weight, and waist girth were measured; and body mass index was calculated. Cross-sectional areas of abdominal AT were obtained at L4-L5 by computed tomography. Fasting blood samples were collected to determine a complete lipoprotein lipid profile, and a 75-g oral glucose tolerance test was performed. Overall, visceral AT accumulation was positively correlated with age (r = 0.51, P < .0001) as well as with plasma CRP (r = 0.39, P < .0001), IL-6 (r = 0.32, P < .0001), and TNF-α (r = 0.14, P < .05) levels. A significant positive relationship was also observed between age and CRP (r = 0.36, P < .0001), IL-6 (r = 0.39, P < .0001), or TNF-α (r = 0.15, P < .05) concentrations. As middle-aged men were characterized by higher CRP (1.32 [25th percentile, 0.71; 75th percentile, 2.71] vs 0.66 [0.36, 1.62] mg/L, P < .0001) and IL-6 (1.60 [1.09, 2.28] vs 1.12 [0.77, 1.60] pg/mL, P < .0001) levels as well as by a greater amount of visceral AT (P < .0001) than young men, we have individually matched 43 young men (age, 28.6 ± 5.82 years) with 43 middle-aged men (age, 57.6 ± 5.15 years) on the basis of their visceral AT. Matching for visceral AT eliminated the difference between middle-aged men and younger adult men in inflammatory markers. These results suggest that the age-related variation in CRP and IL-6 is largely explained by differences in visceral AT. [Copyright &y& Elsevier]

Abstract: Ghrelin is a hormone that is involved in the regulation of food intake. Neuronal, endocrine, and genetic factors have been shown to regulate plasma ghrelin levels; but the determinants of fasting ghrelin concentrations are not yet fully understood. The main aim was to explore the roles of adiposity and genetic differences in determining fasting plasma total ghrelin levels. We measured total ghrelin levels in a population of 23 monozygotic twin pairs discordant for obesity. In addition, 2 variants of ghrelin gene, namely, Arg51Gln and Leu72Met, were genotyped in 3 populations of monozygotic twin pairs: 23 obesity-discordant, 43 lean-concordant, and 46 obesity-concordant twin pairs. In discordant twins, lean co-twins had higher fasting plasma total ghrelin levels (950 pg/mL, SD = 328 pg/mL) than obese twins (720 pg/mL, SD = 143 pg/mL; P = .003). Arg51Gln-polymorphism of the ghrelin gene was equally distributed between the twin groups. However, there were significant differences in genotype frequencies at the Leu72Met polymorphism between the discordant and obese-concordant groups (P = .003) and between the discordant and lean-concordant groups (P = .011), but not between the 2 concordant groups. In the discordant group, there were fewer Met carriers (4%) than among the obese (17%) or the lean-concordant groups (15%). Plasma total ghrelin levels are affected by acquired obesity independent of genetic background. The Leu72 allele is particularly common among monozygotic twins discordant for obesity, suggesting that this ghrelin allele is more permissive in the regulation of energy balance. The ghrelin gene may thus play a role in the regulation of variability of body weight, such that Leu72 allele carriers are more prone to weight variability in response to environmental factors. [Copyright &y& Elsevier]

Background: Genes influencing resting metabolic rate (RMR) and respiratory quotient (RQ) represent candidate genes for obesity, type 2 diabetes, and the metabolic syndrome because of the involvement of these traits in energy balance and substrate oxidation. Objective: We conducted a genome-wide scan for quantitative trait loci (QTL) contributing to the variability in RMR and RQ. Design: Regression-based and variance components-based genome-wide autosomal scans on RMR and RQ phenotypes, obtained from indirect calorimetry, were performed in 169 families ascertained via an obese proband or from the general population. Results: We found evidence for linkage to RMR on chromosomes 3q26.1 (lod = 2.74), 1q21.2 (2.44), and 22q12.3 (1.33). QTL influencing RQ were found on chromosomes 12q13 (1.65) and 14q22 (1.83) when the analyses were performed in all families. Considerable locus heterogeneity within this population was suggested because most of the families were unlinked to any one quantitative trait locus. Significant associations between traits and linked microsatellites were detected within the linked, informative subsets. Conclusions: We found several new QTL for energy metabolism, but the QTL on 1q may be a replication of the one reported in Pima Indians. All 3RMRlinkages overlapped regions previously linked to the metabolic syndrome or its components, and the significant association between RMR and the metabolic syndrome in the present cohort reinforces this relation. We conclude that considerable locus heterogeneity exists even within populations, which should be taken into account when considering candidate gene studies of energy metabolism phenotypes and other complex traits. [ABSTRACT FROM AUTHOR]

Background: The Agouti-related protein (AGRP), an appetite modulator, induces hyperphagia when administered intracerebroven-tricularly or when overexpressed in transgenic mice. Exogenous administration of AGRP in rodents predisposes to high fat and high sugar intakes. Objective: The objective was to examine the potential associations of 2 ethnic-specific polymorphisms in the AGRP gene (Ala67Thr in whites and -38C>T in blacks) in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study. Design: We examined the effect of the 2 polymorphisms in the AGRP gene on self-reported macronutrient intakes in 478 white and 272 black participants in the HERITAGE Family Study. Results: Both AGRP polymorphisms showed a significant association with energy intake. In whites, a smaller proportion of total energy was derived from fat by the Ala67Thr heterozygotes (x ± SEM: 29.4 ± 0.7%) than by the Ala67Ala homozygotes (31.5 ± 0.5%; P = 0.009), mainly because of a lower intake of saturated (P = 0.06) and monoun-saturated (P = 0.01) fats by the Ala67Thr heterozygotes. The percentage of energy from carbohydrates was 2.6% greater in the Ala67Thr heterozygotes (55.1 ± 1.1%) than in the Ala67Ala homozygotes (52.5 ± 0.6%; P = 0.03). In blacks, protein intake was associated with the -38C>T promoter polymorphism. T/T homozygotes had a significantly lower protein intake than did the C-allele carriers (C/ C : 16.8 ± 0.4%; C/T: 17.2 ± 0.2%; T/T: 15.4 ± 0.7%; P = 0.04). No significant differences in total energy and alcohol intakes existed between genotype groups in blacks or whites. Conclusions: The present study suggests that 2 ethnic-specific AGRP variants, previously shown to be associated with leanness in the HERITAGE Family Study, are also associated with macronutrient intake. [ABSTRACT FROM AUTHOR]

Abstract: Plasma dehydroepiandrosterone sulfate (DHEA-S) and testosterone levels both decline with age in healthy men. Features of the metabolic syndrome also show age-related deteriorations. We examined the relative contribution of age and declining androgen levels to features of the metabolic syndrome in men. In a sample of 130 nonsmoking men from the Quebec Family Study, we tested the hypothesis that age-related decreases in DHEA-S and testosterone levels would explain most of the variance in alterations of the metabolic profile associated with aging. As expected, we found that plasma DHEA-S and testosterone levels were negatively associated with age. Significant negative correlations were found between androgen levels and adiposity measures, body fat distribution, and metabolic risk variables. Statistical control for age eliminated correlations with DHEA-S, whereas age-adjusted associations between testosterone and most adiposity and metabolic variables remained significant. The percentage frequency of men characterized by 3 or more features of the metabolic syndrome increased with decreasing testosterone (8.9%-44.2%, χ 2 = 15.89, P < .0005 ) and DHEA-S levels (8.9%-41.5%, χ 2 = 13.02, P < .005). Logistic regression analyses showed that men in the upper tertile of testosterone levels had a lower risk of being characterized by 3 or more features of the metabolic syndrome (odds ratio = 0.24, P < .04) independent of age, whereas tertiles of DHEA-S levels were not related to the metabolic syndrome independent of age. In conclusion, results suggest that age per se is an important correlate of the associations between DHEA-S and metabolic variables, whereas the association of plasma testosterone levels to features of the metabolic syndrome appears to be independent of age. [Copyright &y& Elsevier]

Background: Obesity is frequently associated with eating disorders, and evidence indicates that both conditions are influenced by genetic factors. However, little is known about the genes influencing eating behaviors. Objective: The objective was to identify genes associated with eating behaviors. Design: Three eating behaviors were assessed in 660 adults from the Québec Family Study with the use of the Three-Factor Eating Questionnaire. A genome-wide scan was conducted with a total of 471 genetic markers spanning the 22 autosomes to identify quantitative trait loci for eating behaviors. Body composition and macronutrient and energy intakes were also measured. Results: Four quantitative trait loci were identified for disinhibition and susceptibility to hunger. Of these, the best evidence of linkage was found between a locus on chromosome 15q24-q25 and disinhibition (P < 0.0058) and susceptibility to hunger (P < 0.0001). After fine-mapping, the peak linkage was found between markers D15S206 and D15S201 surrounding the neuromedin β(NMB) gene. Amissense mutation (p.P73T) located within the NMB gene showed significant associations with eating behaviors and obesity phenotypes. The T73T homozygotes were 2 times as likely to exhibit high levels of disinhibition (odds ratio: 1.8; 95% CI: 1.07, 2.89; P0.03) and susceptibility to hunger (odds ratio: 1.9; 95% CI: 1.15, 3.06; P = 0.01) as were the P73 allele carriers. Six-year follow-up data showed that the amount of body fat gain over time in T73T subjects was >2 times that than in P73P homozygotes (3.6 compared with 1.5 kg; P < 0.05). Conclusion: The results suggest that NMB is a very strong candidate gene of eating behaviors and predisposition to obesity. [ABSTRACT FROM AUTHOR]

Background: Dietary patterns play an important role in the control of body weight. Objective: The aim of this study was to verify whether changes in some dietary patterns over a 6-y follow-up period would be associated with weight changes. Design: A sample of 248 volunteers of the Québec Family Study were measured twice (visit 1: 1989-1994; visit 2: 1995-2000). Body weight, percentage body fat, subcutaneous skinfold thicknesses, and waist circumference measurements as well as 3-d dietary and physical activity records were obtained at each visit. At visit 2, all participants filled out a food-based questionnaire examining changes in the consumption of 10 food categories. To further investigate the relation between changes in food-group consumption and bodyweight changes, a total of 51 food subcategories were identified from dietary records. Results: A self-reported decrease in the consumption of food in the fat group or an increase in consumption in the fruit group from the food-based questionnaire predicted a lower increase in body weight and adiposity indicators over time. A more detailed examination of the change in food groups between diet records revealed that increases in the consumption of whole fruit as well as skimmed milk and partly skimmed milk were the 2 food patterns that negatively correlated with the changes of each body weight-related indicator. Conclusions: These results show that changes in the consumption of some specific food groups are associated with body-weight changes. Such specific eating patterns could help to improve obesity treatment and prevention. [ABSTRACT FROM AUTHOR]

Calcium (Ca(2+)) intake may play a role in the regulation of body weight. Increased Ca(2+) intake has been associated with lower body weight, BMI, and adiposity measures in cross-sectional studies. We examined the association between Ca(2+) intake, derived from the Willett FFQ, and overall and abdominal adiposity in Black and White men and women of the HERITAGE Family Study. BMI, the percentage of body fat (%FAT), the sum of 8 skinfold thicknesses, computerized tomography total abdominal fat (TAF), abdominal visceral (AVF) and abdominal subcutaneous (ASF) fat, and waist circumference were measured in 362 men (109 Blacks, 253 Whites) and 462 women (201 Blacks, 261 Whites). Subjects were divided into tertiles of energy-adjusted Ca(2+) intake. Adiposity measures across tertiles were compared by ANOVA and also regressed against the energy-adjusted Ca(2+) intake to test for a linear trend. The strongest inverse associations appeared in Black men and White women. Black men in the high Ca(2+) intake group were leaner than those in the low Ca(2+) intake group: BMI 23.4 +/- 0.9 vs. 26.7 +/- 1.1 kg/m(2) (P = 0.01); for all other adiposity measures, P < 0.05. In White women, regression analyses showed significant inverse associations between Ca(2+) intake and BMI (P = 0.02), %FAT (P = 0.001), TAF (P = 0.006), AVF (P = 0.03), and ASF (P = 0.01). The percentage of fat of White men in the highest Ca(2+) intake group was significantly lower than in the lowest Ca(2+) group (P = 0.04). No significant associations were found in Black women. Low Ca(2+) intake may be associated with higher adiposity, particularly in men and White women. [ABSTRACT FROM AUTHOR]

Background: A poor diet is a risk factor for chronic diseases such as obesity, cardiovascular disease, hypertension, and some cancers. Twin and family studies suggest that genetic factors potentially influence energy and nutrient intakes. Objective: We sought to identify genomic regions harboring genes affecting total energy, carbohydrate, protein, and fat intakes. Design: We performed a genomic scan in 347 white sibling pairs and 99 black sibling pairs. Dietary energy and nutrient intakes were assessed by using Willett's food-frequency questionnaire. Singlepoint and multipoint Haseman-Elston regression techniques were used to test for linkage. These subjects were part of the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study, a multicenter project undertaken by 5 laboratories. Results: In the whites, the strongest evidence of linkage appeared for dietary energy and nutrient intakes on chromosomes 1p21.2 (P=0.0002) and 20q13.13 (P=0.00007), and that for fat intake appeared on chromosome 12q14.1 (P = 0.0013). The linkage evidence on chromosomes 1 and 20 related to total energy intake rather than to the intake of specific macronutrients. In the blacks, promising linkages for macronutrient intakes occurred on chromosomes 12q23-q24.21, 1q32.1, and 7q11.1. Several potential candidate genes are encoded in and around the linkage regions on chromosomes 1p21.2, 12q14.1, and 20q13.13. Conclusions: These are the first reported human quantitative trait loci for dietary energy and macronutrient intakes. Further study may refine these quantitative trait loci to identify potential candidate genes for energy and specific macronutrient intakes that would be amenable to more detailed molecular studies. [ABSTRACT FROM AUTHOR]

: PurposeTo examine the association between estimated daily energy expenditure and blood lipids in a sample of adolescents.: MethodsThe sample consisted of 415 males and 356 females aged 10–19 years, mainly French Canadian, recruited from the greater Quebec City area through the media as part of Phase I of the Quebec Family Study. Estimates of daily energy expenditure (DEE) were obtained with a 3-day physical activity record. Blood lipids were measured by standard procedures. The sample was stratified into three activity groups (least active, less than 25th percentile of DEE; moderately active, 25–74th percentile of DEE; and most active, 75th percentile or greater of DEE), and also by clinical cutpoints for blood lipids. Analysis of covariance, controlling for age and fatness, was conducted to compare blood lipids within gender across activity groups. Logistic regression analysis, controlling for age and fatness, was used to estimate the relative risk of being classified with an undesirable level of a blood lipid parameter on the basis of the DEE.: ResultsTotal cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were not significantly different across activity groups in males or females. High-density lipoprotein cholesterol (HDL-C) was significantly different across activity groups in males (p < .05) and females (p < .05), but the pattern of variation was different between genders. In males, the TC/HDL-C and LDL-C/HDL-C ratios decreased between the moderately active and most active groups (p < .05). Significant differences remained when subcutaneous fatness was considered as a covariate. The results from logistic regression analysis indicated that the odds ratios for low HDL-C levels was significant only in low DEE girls (odds ratio 2.83) compared with high DEE girls.: ConclusionsThe results suggest that increased energy expenditure and physical activity are associated with higher levels of HDL-C in adolescents of both sexes. [Copyright &y& Elsevier]

Background: Recent data suggest that variations in calcium intake may influence lipid metabolism and body composition. Objective: The association between daily calcium intake and body composition and plasma lipoprotein-lipid concentrations was studied cross-sectionally in adults from phase 2 of the Québec Family Study. Design: Adults aged 20-65 y (235 men, 235 women) were studied. Subjects who consumed vitamin or mineral supplements were excluded. Subjects were divided into 3 groups on the basis of their daily calcium intake: groups A (<600 mg), B (600-1000 mg), and C (>1000 mg). Results: Daily calcium intake was negatively correlated with plasma LDL cholesterol, total cholesterol, and total:HDL cholesterol in women and men after adjustment for variations in body fat mass and waist circumference (P < 0.05). In women, a significantly greater ratio of total to HDL cholesterol (P < 0.05) was observed in group A than in group C after correction for body fat mass and waist circumference. In women, body weight, percentage body fat, fat mass, body mass index, waist circumference, and total abdominal adipose tissue area measured by computed tomography were significantly greater (P < 0.05) in group A than in groups B and C, even after adjustments for confounding variables. Comparable trends were observed in men, but not after adjustment for the same covariates. Conclusion: A low daily calcium intake is associated with greater adiposity, particularly in women. In both sexes, a high calcium intake is associated with a plasma lipoprotein-lipid profile predictive of a lower risk of coronary heart disease risk compared with a low calcium intake. [ABSTRACT FROM AUTHOR]

Background: A high waist-to-hip ratio is associated with unfavorable cardiovascular disease risk factors. This could be due to either a relatively large waist or a small hip girth. Objective: We sought to define the separate contributions of waist girth, hip girth, and body mass index (BMI) to measures of body composition, fat distribution, and cardiovascular disease risk factors. Design: Three-hundred thirteen men and 382 women living in the greater Quebec City area were involved in this cross-sectional study. Percentage body fat, anthropometric measurements, and abdominal fat distribution were obtained and BMI (in kg/m2) and waist-to-hip ratio were calculated. Serum blood lipids were determined from blood samples collected after subjects had fasted overnight Results: A large waist circumference in men and women (adjusted for age, BMI, and hip circumference) was associated significantly with low HDL-cholesterol concentrations (P < 0.05) and high fasting triacylglycerol, insulin, and glucose concentrations (P < 0.01). In women alone, a large waist circumference was also associated with high LDL-cholesterol concentrations and blood pressure. A narrow hip circumference (adjusted for age, BMI, and waist circumference) was associated with low HDL-cholesterol and high glucose concentrations in men (P < 0.05) and high triacylglycerol and insulin concentrations in men and women (P < 0.05). Waist and hip girths showed different relations to body fat, fat-free mass, and visceral fat accumulation. Conclusions: Waist and hip circumferences measure different aspects of body composition and fat distribution and have independent and often opposite effects on cardiovascular disease risk factors. A narrow waist and large hips may both protect against cardiovascular disease. These specific effects of each girth measure are poorly captured in the waist-to-hip ratio. [ABSTRACT FROM AUTHOR]

A considerable amount of research on the genetics of obesity has been reported in the past few years. Despite evidence that genetic factors play a significant role in the etiology of this nutritional disease and the increasing number of obesity genes identified, relatively little is known about the role of genes in the response of obesity phenotypes to alterations in energy balance or diet composition. This is especially true for dietary fat, which is known to be associated with obesity at the population level. The aim of this review was to summarize the evidence currently available about the role of gene-nutrient interactions in human obesity. Evidence from both genetic epidemiology and molecular epidemiology studies suggests that genetic factors are involved in determining the susceptibility to gaining or losing fat in response to diet or the risk of developing some of the comorbidities generally observed in obese individuals. Recent evidence suggests that quantitative trait loci identified from animal models of diet-induced obesity could influence body fat in humans. Despite the limited number of studies, the evidence on gene-diet interactions in obesity is convincing. More research is needed to identify the genes responsible for these interaction effects, and the use of animal models of diet-induced obesity represents a promising approach. Finally, data on children are needed to allow assessment of the tracking of nutrient intake between childhood and adulthood. In addition, gene-diet interactions in children need to be investigated to determine whether the genes involved are the same as those found in adults. [ABSTRACT FROM AUTHOR]

Examines the genetic heritability of obesity. Identification of obesity genes; Reference to several studies on genetic obesity.

Discusses the genetic influences on human obesity. Heterogeneity of response to changes in energy balance conditions; Comparison of the between-pair and within-pair heterogeneities; Role of genetic variation to energy balance conditions.

This study investigated the effects of overfeeding on the body composition and fat morphology characteristics of 6 pairs of male monozygotic twins. Each participant was submitted to a 22-day overfeeding period, supplemented by an additional 1000 kcal/day. Significant changes were observed in body composition and fat morphology as shown by increases in body weight, fat mass, sum of 9 skinfolds, and fat cell diameter. Significant within-pair resemblance for absolute changes was observed for body weight, percent body fat, fat mass, sum of skinfolds, trunk skinfolds, and extremity skinfolds, suggesting a role for the genotype in determining the sensitivity of the response to an energy surplus. Significant within-pair resemblance was noted for the biceps, triceps, and thigh with less resemblance noted in the subscapular, abdomen, suprailiac, calf, axillary, and chest sites, suggesting a variation in genotype dependency for subcutaneous fat The results suggest that changes in body fat following short-term overfeeding appear to have a genetic basis. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the effects of endurance exercise training on the resting metabolic rate (RMR) of the human body. Objective of the study; Discussion on the effects of RMR; Percentage of RMR that is accountable of a normally active person per day; Reference to the HERITAGE Family Study; Method used in the study; Results from the study.

The associations between the amount of abdominal adipose tissue (AT) measured by computed tomography (CT) or estimated with predictive equations and the amount of total body fat were compared in samples of 89 men and 75 women. After correction for total body fat mass, men had significantly higher values of visceral AT volume (P < 0.0001) and also higher abdominal visceral AT areas, measured by CT or estimated by predictive equations than women (P < 0.0001). In addition, an increase in total fat mass was associated with a significantly greater increase in visceral AT volume in men than in women (P < 0.0001). In conclusion, these results suggest that the greater health hazards associated with excess fatness in men than in women may be explained by the fact that premenopausal women can accumulate more body fat than men of the same age before reaching the amounts of visceral AT found in men. [ABSTRACT FROM AUTHOR]

The effect of overfeeding on energy expenditure was investigated in 23 young men subjected to a 353-MJ energy intake surplus over 100 d. The major part of this excess (222 MJ was stored as body energy. The increase in energy cost of weight maintenance amounted to 52 MJ and was proportional to body weight gain. When it was added to the obligatory cost of fat and fat-free mass gains, the overall increase in energy expenditure amounted to a mean of 100 MJ. Four months after overfeeding, subjects had lost 82%, feeding gain in body weight, fat mass, and fat-free mass, respectively. We conclude that 1) in response to overfeeding, two-thirds of the excess energy intake is stored as body energy; 2) overfeeding induces an increase in energy cost of weight maintenance proportional to body weight gain, and 3) preoverfeeding energy balance tends to be restored when nonobese individuals return to their normal daily-life habits. [ABSTRACT FROM AUTHOR]

This report deals with the association between the constituents of lean body mass (LBM) and resting metabolic rate (RMR) before and after a 100-d overfeeding period. Computed-tomography (CT) scans of 22 young adult males at nine different body levels were used to estimate adipose tissue mass (ATMCT), LBMCT, skeletal-muscle mass (SMMCT), and non-muscular LBMCT (NM-LBMCT). Before overfeeding, all body constituents, except ATMCT, were significantly correlated with RMR. Only body mass changes were significantly correlated with RMR changes. Comparison of these results with those of several studies in the literature reveals that the relationship between RMR and fat-free mass is highly influenced by the size of the SD for the latter variable. In stepwise-multiple-regression analysis, only SMMCT could be used to predict RMR. It was concluded that SMMCT and ATMCT, increased during overfeeding and that the best correlates of RMR remain LBMCT, SMMCT, and body mass. [ABSTRACT FROM AUTHOR]

Associations of body mass index (BMI), absolute fat mass, percent body fat, and regional fat distribution with concentrations of fasting blood glucose and blood pressure were examined cross-sectionally in 1551 men and women aged 15-79 y from two study centers. Measurements included height, weight, multiple skinfold thicknesses, body density by underwater weighing, and waist and hip girths. Three principal findings emerged: 7) Absolute overall body mass and fat mass were stronger predictors of blood pressure and blood glucose than were relative fat mass, after age, height, and current cigarette-smoking status were adjusted for; 2) when diastolic blood pressure and serum glucose were used as the external validity criteria, densitometry was not a "gold standard" for body composition associated with risk for increased blood pressure and serum glucose ; and 3) BMI was as good a predictor of blood pressure and glucose as was any other measure of body fat in nearly all analyses. [ABSTRACT FROM AUTHOR]

Three studies were performed to assess the effects of a high-fat diet and exercise-induced changes in fat oxidation on energy intake in humans. In the first study the short-term effect of a high-fat diet on spontaneous energy intake was investigated. The second study evaluated the long-term effect of a high-fat diet on adiposity and the third study evaluated the effect of exercise-induced changes in fat oxidation on short-term regulation of energy intake when subjects were consuming a high-fat diet. The results of these studies indicate that a high-fat diet induces a short-term hyperphagia, a high percentage of lipids in the usual diet is associated with a higher adiposity, and exercise may attenuate or amplify the high-fat, diet-induced hyperphagia, depending on the magnitude of the exercise-induced increase in fat oxidation. [ABSTRACT FROM AUTHOR]

Total energy intake and intakes of carbohydrate, fat, and protein as well as the percentage of energy derived from these nutrients were calculated from a 3-d dietary record in 1597 subjects living in 375 families of French descent. Familial correlations were computed in pairs of biological relatives and relatives by adoption and used in the path-analysis BETA model to determine the contribution of genetic and nongenetic factors in the familial resemblance observed in energy intake. No significant genetic effect was found for intake of any nutrient tested (h² ≤ 11%) and cultural inheritance was found to be more important than genetic inheritance. Nontransmitted environmental factors, including home environmental effects, were found to account for more than 50% of the variation observed in the energy-intake components. These results suggest that the average genetic influence on nutrient intake is negligible and that nongenetic effects associated mainly with home environmental effects are the major affecters of energy intake. [ABSTRACT FROM AUTHOR]

Abstract: The Arg16Gly single nucleotide polymorphism of the human β 2-adrenoceptor (ADRB2) gene was evaluated in a case-control study that included 313 white male elite endurance athletes and 297 white male sedentary controls (SCs) recruited in a multicenter project from North America, Finland, and Germany. The groups were matched by country of origin. The elite endurance athletes were required to have a maximum oxygen uptake ≥75 mL·kg−1·min−1 (mean [SD], 79.0 [3.5]), whereas SC subjects had to be sedentary with a measured maximum oxygen uptake ≤50 mL·kg−1·min−1 (40.1 [7.0]). Polymerase chain reaction technique was used to amplify the single nucleotide polymorphism–containing region in codon 16 of the ADRB2 gene. ADRB2 genotypes were in Hardy-Weinberg equilibrium in both groups. Genotypes did not differ between countries or sports of the athletes. The χ 2 analysis for the genotype distribution showed a significant difference between the 2 cohorts (P = .030), suggesting a positive association between the tested Arg16Gly polymorphism and endurance performance. Comparing carriers vs non-carriers for the 2 alleles, an excess of Gly allele carriers was seen in the SC group (P = .009), indicating an unfavorable effect of the Gly allele with respect to the performance status. In conclusion, we found suggestive evidence that the Arg16Gly polymorphism in the gene encoding for the β 2-adrenergic receptor may associate with endurance performance status in white men. [Copyright &y& Elsevier]

The article discusses a meeting on the role of fat distribution during growth and its relationship to health held in Quebec City, Quebec on June 9-11, 1987.

Long-term exposure to antipsychotics like haloperidol can increase sensitivity to dopamine agonist stimulation. This could contribute to treatment failure and increase relapse to psychosis. Chronic antipsychotic treatment elevates neurotensin levels in the nucleus accumbens (NAc), where the neuropeptide modulates dopamine function by signalling through NTS1 receptors. We hypothesized that increasing neurotensin activity in the NAc attenuates the expression of antipsychotic-induced dopamine supersensitivity, which is indicated by a potentiated psychomotor response to amphetamine. Rats received either continuous (CONT-HAL; achieved via subcutaneous osmotic minipump) or intermittent (INT-HAL; achieved via daily subcutaneous injection) haloperidol treatment for 16–17 days. Three to 5 days later, we injected neurotensin into the NAc and measured amphetamine-induced locomotion. Only CONT-HAL rats showed potentiated amphetamine-induced locomotion, indicating dopamine supersensitivity. Compared to intra-NAc saline, intra-NAc neurotensin suppressed amphetamine-induced locomotion in CONT-HAL rats, but not in INT-HAL or control rats. In a new cohort of CONT-HAL and INT-HAL rats, we measured striatal levels of proneurotensin mRNA and NTS1 receptors. The two treatments led to overlapping but also distinct neurochemical profiles. Neither treatment altered NTS1 receptor levels in the NAc, but both increased proneurotensin mRNA levels in the NAc core. In the caudate-putamen, only INT-HAL increased NTS1 receptor levels, while only CONT-HAL increased proneurotensin mRNA expression. Thus, antipsychotic-induced dopamine supersensitivity enhances the ability of neurotensin in the NAc to regulate dopamine-mediated behaviours, and this likely does not involve changes in local levels of NTS1 receptors or proneurotensin mRNA. We conclude that increasing neurotensin activity could be considered to attenuate antipsychotic-induced dopamine supersensitivity. [ABSTRACT FROM AUTHOR]