Showing papers in "Obesity in 2010"

Microbiota and SCFA in Lean and Overweight Healthy Subjects

Abstract: Obesity has recently been linked to the composition of human microbiota and the production of short chain fatty acids (SCFAs). However, these findings rely on experimental studies carried out using rather small and defined groups of volunteers or model animals. Our aim was to evaluate differences within the human intestinal microbiota and fecal SCFA concentration of lean and obese subjects. A total of 98 subjects volunteered to take part in this study. The BMI in kg/m(2) of 30 volunteers was within the lean range, 35 were overweight and 33 were obese. The fecal microbiota was characterized by real-time PCR analyses. With the primers used herein we were able to cover 82.3% (interquartile range of 68.3-91.4%) of the total microbiota detectable with a universal primer. In addition, the concentration of SCFA was evaluated. The total amount of SCFA was higher in the obese subject group (P = 0.024) than in the lean subject group. The proportion of individual SCFA changed in favor of propionate in overweight (P = 0.019) and obese subjects (P = 0.028). The most abundant bacterial groups in faeces of lean and obese subjects belonged to the phyla Firmicutes and Bacteroidetes. The ratio of Firmicutes to Bacteroidetes changed in favor of the Bacteroidetes in overweight (P = 0.001) and obese subjects (P = 0.005). Our results are in line with previous reports suggesting that SCFA metabolism might play a considerable role in obesity. However, our results contradict previous reports with regard to the contribution of various bacterial groups to the development of obesity and this issue remains controversial.

Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity.

Abstract: Dysregulation of fatty acid oxidation (FAO) is recognized as important in the pathophysiology of obesity and insulin resistance (IR). However, demonstrating FAO defects in vivo in humans has entailed complex and invasive methodologies. Recently, the identification of genetic blocks in FAO has been vastly simplified by using tandem mass spectrometry (MS/MS) of dried bloodspots to specify acylcarnitine (AcylCN) alterations characteristic for each disorder. This technology has recently been applied to examine FAO alterations in human and animal models of obesity and type 2 diabetes mellitus (T2DM). This study focused on characterizing AcylCN profiles in human plasma from individuals with obesity and T2DM during fasting and insulin-stimulated conditions. Following an overnight fast, plasma was obtained from lean (n = 12), obese nondiabetic (n = 14), and T2DM (n = 10) participants and analyzed for AcylCN using MS/MS. Plasma samples were also obtained at the end of a 4-h insulin-stimulated euglycemic clamp. In obesity and T2DM, long-chain AcylCNs were similarly significantly increased in the fasted state; free-CN levels were also elevated. Additionally, T2DM subjects of comparable BMI had increased short- and medium-chain AcylCNs, both saturated and hydroxy, as well as increased C(4)-dicarboxylcarnitine (C(4)DC-CN) that correlated with an index of poor glycemic control (HbA(1c); r = 0.74; P < 0.0001). Insulin infusion reduced all species of plasma AcylCN but this reduction was blunted in T2DM. Plasma long-chain AcylCN species are increased in obesity and T2DM, suggesting that more fatty acids can enter mitochondria. In T2DM, many shorter species accumulate, suggesting that they have a generalized complex oxidation defect.

Mediators of weight loss and weight loss maintenance in middle-aged women.

Abstract: Long-term behavioral self-regulation is the hallmark of successful weight control. We tested mediators of weight loss and weight loss maintenance in middle-aged women who participated in a randomized controlled 12-month weight management intervention. Overweight and obese women (N = 225, BMI = 31.3 ± 4.1 kg/m2) were randomly assigned to a control or a 1-year group intervention designed to promote autonomous self-regulation of body weight. Key exercise, eating behavior, and body image variables were assessed before and after the program, and tested as mediators of weight loss (12 months, 86% retention) and weight loss maintenance (24 months, 81% retention). Multiple mediation was employed and an intention-to-treat analysis conducted. Treatment effects were observed for all putative mediators (Effect size: 0.32–0.79, P < 0.01 vs. controls). Weight change was −7.3 ± 5.9% (12-month) and −5.5 ± 5.0% (24-month) in the intervention group and −1.7 ± 5.0% and −2.2 ± 7.5% in controls. Change in most psychosocial variables was associated with 12-month weight change, but only flexible cognitive restraint (P < 0.01), disinhibition (P < 0.05), exercise self-efficacy (P < 0.001), exercise intrinsic motivation (P < 0.01), and body dissatisfaction (P < 0.05) predicted 24-month weight change. Lower emotional eating, increased flexible cognitive restraint, and fewer exercise barriers mediated 12-month weight loss (R2 = 0.31, P < 0.001; effect ratio: 0.37), but only flexible restraint and exercise self-efficacy mediated 24-month weight loss (R2 = 0.17, P < 0.001; effect ratio: 0.89). This is the first study to evaluate self-regulation mediators of weight loss and 2-year weight loss maintenance, in a large sample of overweight women. Results show that lowering emotional eating and adopting a flexible dietary restraint pattern are critical for sustained weight loss. For long-term success, interventions must also be effective in promoting exercise intrinsic motivation and self-efficacy.

Interventions to prevent obesity in 0-5 year olds: an updated systematic review of the literature.

Abstract: The small number and recency of the early childhood obesity-prevention literature identified in a previous review of interventions to prevent obesity, promote healthy eating, physical activity, and/or reduce sedentary behaviors in 0-5 year olds suggests this is a new and developing research area. The current review was conducted to provide an update of the rapidly emerging evidence in this area and to assess the quality of studies reported. Ten electronic databases were searched to identify literature published from January 1995 to August 2008. Inclusion criteria: interventions reporting child anthropometric, diet, physical activity, or sedentary behavior outcomes and focusing on children aged 0-5 years of age. Exclusion criteria: focusing on breastfeeding, eating disorders, obesity treatment, malnutrition, or school-based interventions. Two reviewers independently extracted data and assessed study quality. Twenty-three studies met all criteria. Most were conducted in preschool/childcare (n = 9) or home settings (n = 8). Approximately half targeted socioeconomically disadvantaged children (n = 12) and three quarters were published from 2003 onward (n = 17). The interventions varied widely although most were multifaceted in their approach. While study design and quality varied most studies reported their interventions were feasible and acceptable, although impact on behaviors that contribute to obesity were not achieved by all. Early childhood obesity-prevention interventions represent a rapidly growing research area. Current evidence suggests that behaviors that contribute to obesity can be positively impacted in a range of settings and provides important insights into the most effective strategies for promoting healthy weight from early childhood.

Abdominal Subcutaneous and Visceral Adipose Tissue and Insulin Resistance in the Framingham Heart Study

Abstract: Insulin resistance is associated with central obesity and an increased risk of cardiovascular disease. Our objective is to examine the association between abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) and insulin resistance, to determine which fat depot is a stronger correlate of insulin resistance, and to assess whether there was an interaction between SAT, VAT, and age, sex, or BMI. Participants without diabetes from the Framingham Heart Study (FHS), who underwent multidetector computed tomography to assess SAT and VAT (n = 3,093; 48% women; mean age 50.4 years; mean BMI 27.6 kg/m2), were evaluated. Insulin resistance was measured using the homeostasis model and defined as HOMAIR ≥75th percentile. Logistic regression models, adjusted for age, sex, smoking, alcohol, menopausal status, and hormone replacement therapy use, were used to assess the association between fat measures and insulin resistance. The odds ratio (OR) for insulin resistance per standard deviation increase in SAT was 2.5 (95% confidence interval (CI): 2.2–2.7; P < 0.0001), whereas the OR for insulin resistance per standard deviation increase in VAT was 3.5 (95% CI: 3.1–3.9; P < 0.0001). Overall, VAT was a stronger correlate of insulin resistance than SAT (P < 0.0001 for SAT vs. VAT comparison). After adjustment for BMI, the OR of insulin resistance for VAT was 2.2 (95% CI: 1.9–2.5; P < 0.0001). We observed an interaction between VAT and BMI for insulin (P interaction = 0.0004), proinsulin (P interaction = 0.003), and HOMAIR (P interaction = 0.003), where VAT had a stronger association in obese individuals. In conclusion, SAT and VAT are both correlates of insulin resistance; however, VAT is a stronger correlate of insulin resistance than SAT.

Sex differences in high-fat diet-induced obesity, metabolic alterations and learning, and synaptic plasticity deficits in mice.

Abstract: Obesity is a potential risk factor for cognitive deficits in the elder humans. Using a high-fat diet (HFD)–induced obese mouse model, we investigated the impacts of HFD on obesity, metabolic and stress hormones, learning performance, and hippocampal synaptic plasticity. Both male and female C57BL/6J mice fed with HFD (3 weeks to 9–12 months) gained significantly more weights than the sex-specific control groups. Compared with the obese female mice, the obese males had similar energy intake but developed more weight gains. The obese male mice developed hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia, but not hypertriglyceridemia. The obese females had less hyperinsulinemia and hypercholesterolemia than the obese males, and no hyperglycemia and hypertriglyceridemia. In the contextual fear conditioning and step-down passive avoidance tasks, the obese male, but not female, mice showed poorer learning performance than their normal counterparts. These learning deficits were not due to sensorimotor impairment as verified by the open-field and hot-plate tests. Although, basal synaptic transmission characteristics (input–output transfer and paired-pulse facilitation (PPF) ratio) were not significantly different between normal and HFD groups, the magnitudes of synaptic plasticity (long-term potentiation (LTP) and long-term depression (LTD)) were lower at the Schaffer collateral-CA1 synapses of the hippocampal slices isolated from the obese male, but not female, mice, as compared with their sex-specific controls. Our results suggest that male mice are more vulnerable than the females to the impacts of HFD on weight gains, metabolic alterations and deficits of learning, and hippocampal synaptic plasticity.

Randomized controlled trial of the MEND program: a family-based community intervention for childhood obesity.

Abstract: The aim of this study was to evaluate the effectiveness of the Mind, Exercise, Nutrition, Do it (MEND) Program, a multicomponent community-based childhood obesity intervention (www.mendcentral.org). One hundred and sixteen obese children (BMI ≥ 98th percentile, UK 1990 reference data) were randomly assigned to intervention or waiting list control (6-month delayed intervention). Parents and children attended eighteen 2-h group educational and physical activity sessions held twice weekly in sports centers and schools, followed by a 12-week free family swimming pass. Waist circumference, BMI, body composition, physical activity level, sedentary activities, cardiovascular fitness, and self-esteem were assessed at baseline and at 6 months. Children were followed up 12 months from baseline (0 and 6 months postintervention for the control and intervention group, respectively). Participants in the intervention group had a reduced waist circumference z-score (−0.37; P < 0.0001) and BMI z-score (−0.24; P < 0.0001) at 6 months when compared to the controls. Significant between-group differences were also observed in cardiovascular fitness, physical activity, sedentary behaviors, and self-esteem. Mean attendance for the MEND Program was 86%. At 12 months, children in the intervention group had reduced their waist and BMI z-scores by 0.47 (P < 0.0001) and 0.23 (P < 0.0001), respectively, and benefits in cardiovascular fitness, physical activity levels, and self-esteem were sustained. High-attendance rates suggest that families found this intensive community-based intervention acceptable. Further larger controlled trials are currently underway to confirm the promising findings of this initial trial.

Longitudinal trends in obesity in the United States from adolescence to the third decade of life.

Abstract: No longitudinal analyses using national data have evaluated the increase in obesity from adolescence into early adulthood. We examined obesity incidence, persistence, and reversal in a nationally representative cohort of US teens followed into their early 30s, using measured height and weight data, in individuals enrolled in wave II (1996; 12-21 years), wave III (2001; 17-26 years), and wave IV (2008 early release data; 24-32 years) of the National Longitudinal Study of Adolescent Health (N = 8,675). Obesity was defined as a BMI >or=95th percentile of the 2000 Centers for Disease Control/National Center for Health Statistics growth charts or >or=30 kg/m(2) for individuals or=30 kg/m(2) in individuals >or=20 years. In 1996, 13.3% of adolescents were obese. By 2008, obesity prevalence increased to 36.1%, and was highest among non-Hispanic black females (54.8%). Ninety percent of the obese adolescents remained obese in 2008. While annual obesity incidence did not decline in the total sample across the two study intervals (2.3% per year 1996-2001 vs. 2.2% per year 2001-2008), rates among white females declined (2.7 to 1.9% per year) and were highest among non-Hispanic black and Hispanic females (3.8 and 2.7% per year, 1996-2001 vs. 3.0 and 2.6% per year, 2002-2008, respectively). Obesity prevalence doubled from adolescence to the early 20s, and doubled again from the early to late 20s or early 30s, with strong tracking from adolescence into adulthood. This trend is likely to continue owing to high rates of pediatric obesity. Effective preventive and treatment efforts are critically needed.

Environmental Endocrine Disruptors Promote Adipogenesis in the 3T3-L1 Cell Line through Glucocorticoid Receptor Activation

Abstract: The burgeoning obesity and diabetes epidemics threaten health worldwide, yet the molecular mechanisms underlying these phenomena are incompletely understood. Recently, attention has focused on the potential contributions of environmental pollutants that act as endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases. Because glucocorticoid signaling is central to adipocyte differentiation, the ability of EDCs to stimulate the glucocorticoid receptor (GR) and drive adipogenesis was assessed in the 3T3-L1 cell line. Various EDCs were screened for glucocorticoid-like activity using a luciferase reporter construct, and four (bisphenol A (BPA), dicyclohexyl phthalate (DCHP), endrin, and tolylfluanid (TF)) were shown to significantly stimulate GR without significant activation of the peroxisome proliferator-activated receptor-γ. 3T3-L1 preadipocytes were then treated with EDCs and a weak differentiation cocktail containing dehydrocorticosterone (DHC) in place of the synthetic dexamethasone. The capacity of these compounds to promote adipogenesis was assessed by quantitative oil red O staining and immunoblotting for adipocyte-specific proteins. The four EDCs increased lipid accumulation in the differentiating adipocytes and also upregulated the expression of adipocytic proteins. Interestingly, proadipogenic effects were observed at picomolar concentrations for several of the EDCs. Because there was no detectable adipogenesis when the preadipocytes were treated with compounds alone, the EDCs are likely promoting adipocyte differentiation by synergizing with agents present in the differentiation cocktail. Thus, EDCs are able to promote adipogenesis through the activation of the GR, further implicating these compounds in the rising rates of obesity and diabetes.

Subcutaneous and Visceral Adipose Tissue Gene Expression of Serum Adipokines That Predict Type 2 Diabetes

Abstract: Type 2 diabetes mellitus (T2D) is predicted by central obesity and circulating adipokines regulating inflammation. We hypothesized that visceral adipose tissue (VAT) in T2D expresses greater levels of proinflammatory molecules. Paired samples of subcutaneous (SAT) and VAT were excised at elective surgery (n = 16, 6 with T2D, n = 8 age- and gender- matched controls). Metabolic parameters were measured in the fasted state: body composition by dual-energy X-ray absorptiometry and insulin action by hyperinsulinemic-euglycemic clamp. Adipose tissue mRNA gene expression was measured by quantitative reverse transcriptase-PCR. Subjects with T2D had higher VAT expression of molecules regulating inflammation (tumor necrosis factor-alpha (TNFalpha), macrophage inflammatory protein (MIP), interleukin-8 (IL-8)). Fasting glucose related to VAT expression of TNFalpha, MIP, serum amyloid A (SAA), IL-1alpha, IL-1beta, IL-8, and IL-8 receptor. Abdominal fat mass was related to VAT expression of MIP, SAA, cAMP response element-binding protein (CREBP), IL-1beta, and IL-8. Insulin action related inversely to VAT complement C3 expression only. There were depot-specific differences in expression of serum T2D predictors: VAT expressed higher levels of complement C3; SAT expressed higher levels of retinol-binding protein-4 (RBP4), adiponectin, and leptin. In summary, VAT in T2D expresses higher levels of adipokines involved in inflammation. VAT expression of these molecules is related to fasting glucose and insulin action. Increased production of these proinflammatory molecules by VAT may explain the links observed between visceral obesity, insulin resistance, and diabetes risk.

Neural mechanisms associated with food motivation in obese and healthy weight adults.

Abstract: One out of three adults in the United States is clinically obese. Excess food intake is associated with food motivation, which has been found to be higher in obese compared to healthy weight (HW) individuals. Little is known, however, regarding the neural mechanisms associated with food motivation in obese compared to HW adults. The current study used functional magnetic resonance imaging (fMRI) to examine changes in the hemodynamic response in obese and HW adults while they viewed food and nonfood images in premeal and postmeal states. During the premeal condition, obese participants showed increased activation, compared to HW participants, in anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC). Moreover, in the obese group, self-report measures of disinhibition were negatively correlated with premeal ACC activations and self-report measures of hunger were positively correlated with premeal MPFC activations. During the postmeal condition, obese participants also showed greater activation than HW participants in the MPFC. These results indicate that brain function associated with food motivation differs in obese and HW adults and may have implications for understanding brain mechanisms contributing to overeating and obesity, and variability in response to diet interventions.

Dietary Capsaicin Reduces Obesity‐induced Insulin Resistance and Hepatic Steatosis in Obese Mice Fed a High‐fat Diet

Abstract: Obesity-induced inflammation contributes to the development of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease. In this study, we investigated whether dietary capsaicin can reduce obesity-induced inflammation and metabolic disorders such as insulin resistance and hepatic steatosis. Male C57BL/6 obese mice fed a high-fat diet for 10 weeks received a supplement of 0.015% capsaicin for a further 10 weeks and were compared with unsupplemented controls. Glucose intolerance was estimated by glucose tolerance tests. Transcripts of adipocytokine genes and the corresponding proteins were measured by reverse transcription-PCR and enzyme-linked immunosorbent assay, and macrophage numbers were determined by flow cytometric analysis. Transient receptor potential vanilloid type-1 (TRPV-1), peroxisome proliferator-activated receptor (PPAR)-alpha, and PPARgamma coactivator-1alpha (PGC-1alpha) mRNAs were also measured by RT-PCR, and PPARalpha luciferase assays were performed. Dietary capsaicin lowered fasting glucose, insulin, leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Levels of tumor necrosis factor-alpha (TNFalpha), monocyte chemoattractant protein-1 (MCP-1), and interleukin (IL)-6 mRNAs and proteins in adipose tissue and liver decreased markedly, as did macrophage infiltration, hepatic triglycerides, and TRPV-1 expression in adipose tissue. At the same time, the mRNA/protein of adiponectin in the adipose tissue and PPARalpha/PGC-1alpha mRNA in the liver increased. Moreover, luciferase assays revealed that capsaicin is capable of binding PPARalpha. Our data suggest that dietary capsaicin may reduce obesity-induced glucose intolerance by not only suppressing inflammatory responses but also enhancing fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. The effects of capsaicin in adipose tissue and liver are related to its dual action on PPARalpha and TRPV-1 expression/activation.

T‐Cell Recruitment and Th1 Polarization in Adipose Tissue During Diet‐Induced Obesity in C57BL/6 Mice

Abstract: The role of adaptive immunity in obesity-associated adipose tissue (AT) inflammation and insulin resistance (IR) is controversial. We employed flow cytometry and quantitative PCR to assess T-cell recruitment and activation in epididymal AT (eAT) of C57BL/6 mice during 4-22 weeks of a high-fat diet (HFD (60% energy)). By week 6, eAT mass and stromal vascular cell (SVC) number increased threefold in mice fed HFD, coincident with onset of IR. We observed no increase in the proportion of CD3(+) SVCs or in gene expression of CD3, interferon-γ (IFN-γ), or regulated upon activation, normal T-cell expressed and secreted (RANTES) during the first 16 weeks of HFD. In contrast, CD11c(+) macrophages (MΦ) were enriched sixfold by week 8 (P < 0.01). SVC enrichment for T cells (predominantly CD4(+) and CD8(+)) and elevated IFN-γ and RANTES gene expression were detected by 20-22 weeks of HFD (P < 0.01), coincident with the resolution of eAT remodeling. HFD-induced T-cell priming earlier in the obesity time course is suggested by (i) elevated (fivefold) interleukin-12 (IL-12)p40 gene expression in eAT by week 12 (P ≤ 0.01) and (ii) greater IFN-γ secretion from phorbol myristate acetate (PMA)/ionophore-stimulated eAT explants at week 6 (onefold, P = 0.08) and week 12 (fivefold, P < 0.001). In conclusion, T-cell enrichment and IFN-γ gene induction occur subsequent to AT macrophage (ATMΦ) recruitment, onset of IR and resolution of eAT remodeling. However, enhanced priming for IFN-γ production suggests the contribution of CD4(+) and/or CD8(+) effectors to cell-mediated immune responses promoting HFD-induced AT inflammation and IR.

A 12-Week Aerobic Exercise Program Reduces Hepatic Fat Accumulation and Insulin Resistance in Obese, Hispanic Adolescents

Abstract: The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized that a 12-week controlled aerobic exercise program without weight loss reduces visceral, hepatic, and intramyocellular fat content and decreases insulin resistance in sedentary Hispanic adolescents. Twenty-nine postpubertal (Tanner stage IV and V), Hispanic adolescents, 15 obese (7 boys, 8 girls; 15.6 +/- 0.4 years; 33.7 +/- 1.1 kg/m(2); 38.3 +/- 1.5% body fat) and 14 lean (10 boys, 4 girls; 15.1 +/- 0.3 years; 20.6 +/- 0.8 kg/m(2); 18.9 +/- 1.5% body fat), completed a 12-week aerobic exercise program (4 x 30 min/week at > or =70% of peak oxygen consumption (VO(2)peak)). Measurements of cardiovascular fitness, visceral, hepatic, and intramyocellular fat content (magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS)), and insulin resistance were obtained at baseline and postexercise. In both groups, fitness increased (obese: 13 +/- 2%, lean: 16 +/- 4%; both P < 0.01). In obese participants, intramyocellular fat remained unchanged, whereas hepatic fat content decreased from 8.9 +/- 3.2 to 5.6 +/- 1.8%; P < 0.05 and visceral fat content from 54.7 +/- 6.0 to 49.6 +/- 5.5 cm(2); P < 0.05. Insulin resistance decreased indicated by decreased fasting insulin (21.8 +/- 2.7 to 18.2 +/- 2.4 microU/ml; P < 0.01) and homeostasis model assessment of insulin resistance (HOMA(IR)) (4.9 +/- 0.7 to 4.1 +/- 0.6; P < 0.01). The decrease in visceral fat correlated with the decrease in fasting insulin (R(2) = 0.40; P < 0.05). No significant changes were observed in any parameter in lean participants except a small increase in lean body mass (LBM). Thus, a controlled aerobic exercise program, without weight loss, reduced hepatic and visceral fat accumulation, and decreased insulin resistance in obese adolescents.

Body fat distribution and inflammation among obese older adults with and without metabolic syndrome

Abstract: The protective mechanisms by which some obese individuals escape the detrimental metabolic consequences of obesity are not understood. This study examined differences in body fat distribution and adipocytokines in obese older persons with and without metabolic syndrome. Additionally, we examined whether adipocytokines mediate the association between body fat distribution and metabolic syndrome. Data were from 729 obese men and women (BMI ≥ 30 kg/m(2)), aged 70-79 participating in the Health, Aging and Body Composition (Health ABC) study. Thirty-one percent of these obese men and women did not have metabolic syndrome. Obese persons with metabolic syndrome had significantly more abdominal visceral fat (men: P = 0.04; women: P < 0.01) and less thigh subcutaneous fat (men: P = 0.09; women: P < 0.01) than those without metabolic syndrome. Additionally, those with metabolic syndrome had significantly higher levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1) than individuals without metabolic syndrome. Per standard deviation higher in visceral fat, the likelihood of metabolic syndrome significantly increased in women (odds ratio (OR): 2.16, 95% confidence interval (CI): 1.59-2.94). In contrast, the likelihood of metabolic syndrome decreased in both men (OR: 0.56, 95% CI: 0.39-0.80) and women (OR: 0.49, 95% CI: 0.34-0.69) with each standard deviation higher in thigh subcutaneous fat. These associations were partly mediated by adipocytokines; the association between thigh subcutaneous fat and metabolic syndrome was no longer significant in men. In summary, metabolically healthy obese older persons had a more favorable fat distribution, characterized by lower visceral fat and greater thigh subcutaneous fat and a more favorable inflammatory profile compared to their metabolically unhealthy obese counterparts.

Implications of the Foresight Obesity System Map for Solutions to Childhood Obesity

Abstract: 1Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada; 2National Obesity Observatory, Oxford, England. Correspondence: Diane T. Finegood (Finegood@sfu.ca) Shifting the paradigm Our understanding of the causal factors that contribute to the obesity epidemic has evolved over time. Although some still describe the problem as “people eat too much and move too little,” this articulation has not brought us closer to understanding what to do to reverse current trends. Various conceptual models have framed the problem of obesity in different ways. Bray suggested an epidemiological model which illustrates agents such as food, viruses, and toxins acting on a host to produce disease, and a homeostatic model where fat acts on the brain (controller) which in turn feeds back to act on the fat (controlled system) (1). He described the interpretation of these models as “genetic background loads the gun, but the environment pulls the trigger” and suggested they imply the need for a simple FLOURIDE (For Lowering Universal Obesity Rates Implement ideas that Don’t demand Effort) solution. The International Obesity Task Force expanded on the concept of environmental agents by introducing its “causal web” (2). In the causal web, environmental factors are illustrated as “black boxes” such as school food and activity, public transport and urbanization. These factors are organized in columns according to their proximity to the individual, i.e., factors associated with work/school/home, community/locality, national/ regional, and international levels. Distal contextual factors such as globalization of markets, and media and culture are shown to act on more proximal factors which in turn act on energy expenditure and food intake. The connections are simple one way arrows and biological factors are not included. The causal web helps to illustrate the diversity of factors affecting individuals and suggests that we will need to implement many ideas that “don’t demand effort” on the part of the individual. Although the causal web suggests the challenge of addressing obesity is complicated, it does not explicitly illustrate the problem as “complex”. Absent from the causal web is consideration of the feedback loops which are a hallmark of complex adaptive systems. More recently the Foresight Programme of the UK Government Office for Science published an obesity system map, developed through a multistakeholder process (3). This qualitative, conceptual model has 108 variables, some of which are measureable (e.g., the ambient temperature of the indoor environment), and other variables that are more difficult to quantify (e.g., desire to differentiate food offerings). The relationships between the variables are illustrated with >300 solid or dashed lines to indicate positive and negative influences. All the variables are interconnected, some with large numbers of inputs and others with large numbers of outputs. The connections give rise to feedback loops with as few as two variables (e.g., a affects b which in turn affects a) or involving as many as 16 variables. At the core of the map is “energy balance” (energy intake vs. energy expenditure). The core (also referred to as the engine) is surrounded by variables that directly or indirectly influence energy balance. These variables are clustered in seven themes ranging from Food Production to Physiology. Apart from the physiological cluster, most of the variables can be considered on an individual, family, group, or societal scale. For example, the “level of physical activity” can be considered for a particular individual or as an average for the whole population. The Foresight obesity project articulated the ambitious goal of defining the obesity system as “the sum of all the relevant factors and their interdependencies that determine the condition of obesity for an individual or a group of people” (3). Although the notion that the process could give rise to a map of “all” relevant factors was perhaps over ambitious, the map effectively illustrates the complexity of obesity by highlighting the interdependencies among variables as diverse as the pressure on the food industry to cater for acquired tastes and conscious control of an individual’s accumulation of energy. The map is dominated by its illustration of the connections and feedback loops between variables. Although the map cannot be considered comprehensive, its construction engaged a broad range of stakeholders, including scientists, the private sector and government departments in a dialogue about how to tackle this wicked problem (4). The dialogue helped to forge multisector, multidisciplinary relationships that support future government decision making based on evidence (4). An enduring value of the map is its use as a heuristic. It illustrates the complex multifactoral nature of the systems that give rise to obesity and it can be used to stimulate an even broader discussion among relevant actors ranging from multiple government departments to school age children (5,6). In this way the map helps the development of a more sophisticated and integrated policy approach. The Foresight program on obesity gave rise to the work of organizations such as the English National Obesity Observatory (NOO) (http://www. Implications of the Foresight Obesity System Map for Solutions to Childhood Obesity

BMI and mortality: results from a national longitudinal study of Canadian adults.

Abstract: Although a clear risk of mortality is associated with obesity, the risk of mortality associated with overweight is equivocal. The objective of this study is to estimate the relationship between BMI and all-cause mortality in a nationally representative sample of Canadian adults. A sample of 11,326 respondents aged ≥25 in the 1994/1995 National Population Health Survey (Canada) was studied using Cox proportional hazards models. A significant increased risk of mortality over the 12 years of follow-up was observed for underweight (BMI 35; RR = 1.36, P 0.05). Our results are similar to those from other recent studies, confirming that underweight and obesity class II+ are clear risk factors for mortality, and showing that when compared to the acceptable BMI category, overweight appears to be protective against mortality. Obesity class I was not associated with an increased risk of mortality.

From "overweight" to "about right": evidence of a generational shift in body weight norms.

Abstract: In this article, we describe differences in the self-perception of weight status in the United States between the two most recent National Health and Nutrition Examination Survey (NHANES) periods (1988-1994 and 1999-2004), and test the hypothesis that secular increases in adult mean BMI, adult obesity, and childhood obesity contributed to changes over time in weight perceptions. We find that the probability of self-classifying as overweight is significantly lower on average in the more recent survey, for both women and men, controlling for objective weight status and other factors. Among women, the decline in the tendency to self-classify as overweight is concentrated in the 17-35 age range, and is more pronounced among women with normal BMI than those with overweight BMI. Among men, the shift away from feeling overweight is roughly equal across age groups. Overweight men exhibit a sharper decline in feeling overweight than normal weight men. Despite the declines in feeling overweight between surveys, weight misperception did not increase significantly for men and decreased by a sizable margin among women. We interpret the findings as evidence of a generational shift in social norms related to body weight. As a result, people may be less likely to desire weight loss than previously, limiting the effectiveness of public health campaigns aimed at weight reduction. On the other hand, there may be health benefits associated with improved body image.

Reducing Anti-Fat Prejudice in Preservice Health Students: A Randomized Trial

Abstract: Anti-fat sentiment is increasing, is prevalent in health professionals, and has health and social consequences. There is no evidence for effective obesity prejudice reduction techniques in health professionals. The present experiment sought to reduce implicit and explicit anti-fat prejudice in preservice health students. Health promotion/public health bachelor degree program students (n = 159) were randomized to one of three tutorial conditions. One condition presented an obesity curriculum on the controllable reasons for obesity (i.e., diet/exercise). A prejudice reduction condition presented evidence on the uncontrollable reasons for obesity (i.e., genes/environment); whereas a neutral (control) curriculum focused on alcohol use in young people. Measures of implicit and explicit anti-fat prejudice, beliefs about obese people, and dieting, were taken at baseline and postintervention. Repeated measures analyses showed decreases in two forms of implicit anti-fat prejudice (decreases of 27 and 12%) in the genes/environment condition relative to other conditions. The diet/exercise condition showed a 27% increase in one measure of implicit anti-fat prejudice. Reductions in explicit anti-fat prejudice were also seen in the genes/environment condition (P = 0.006). No significant changes in beliefs about obese people or dieting control beliefs were found across conditions. The present results show that anti-fat prejudice can be reduced or exacerbated depending on the causal information provided about obesity. The present results have implications for the training of health professionals, especially given their widespread negativity toward overweight and obesity.

Measuring Weight Self‐stigma: The Weight Self‐stigma Questionnaire

Abstract: Stigma associated with being overweight or obese is widespread. Given that weight loss is difficult to achieve and maintain, researchers have been calling for interventions that reduce the impact of weight stigma on life functioning. Sound measures that are sensitive to change are needed to help guide and inform intervention studies. This study presents the weight self-stigma questionnaire (WSSQ). The WSSQ has 12 items and is designed for use only with populations of overweight or obese persons. Two samples of participants—one treatment seeking, one nontreatment seeking—were used for validation (N = 169). Results indicate that the WSSQ has good reliability and validity, and contains two distinct subscales—self-devaluation and fear of enacted stigma. The WSSQ could be useful for identifying individuals who may benefit from a stigma reduction intervention and may also help evaluate programs designed to reduce stigma.

Prevalence of Obesity Among Children With Chronic Conditions

Abstract: New evidence suggests that children with chronic conditions may be predisposed to overweight and obesity. This study provides prevalence estimate of obesity for children and adolescents with select chronic conditions. We analyzed reported height and weight and the corresponding BMI from 46,707 subjects aged 10-17 years collected by the National Survey of Children's Health (NSCH-2003). Our main outcome measure was the prevalence of obesity (defined as >/=95th percentile of the sex-specific BMI for age growth charts), adjusted for underlying demographic and socioeconomic factors. We found that the prevalence of obesity among children 10-17 years of age without a chronic condition was 12.2% (95% confidence interval (CI) 11.5-13.0); the prevalence of obesity for children with asthma was 19.7% (19.5-19.9); with a hearing/vision condition was 18.4% (18.2-18.5); with learning disability was 19.3% (19.2-19.4); with autism was 23.4% (23.2-23.6); and with attention-deficit/hyperactivity disorder was 18.9% (18.7-19.0). Our findings suggest that children 10-17 years of age with select chronic conditions were at increased risk for obesity compared to their counterparts without a chronic condition.

Comparison of fat-water MRI and single-voxel MRS in the assessment of hepatic and pancreatic fat fractions in humans.

Abstract: The ability to accurately and noninvasively quantify fatty infiltration in organs such as the liver and the pancreas remains a critical component in understanding the link between obesity and its comorbidities such as type 2 diabetes and fatty liver disease. Single-voxel (1H) proton magnetic resonance spectroscopy (MRS) has long been regarded as the gold-standard noninvasive technique for such measurements. Recent advances in three-dimensional fat–water magnetic resonance imaging (MRI) methods have led to the development of rapid, robust, and quantitative approaches that can accurately characterize the proportion of fat and water content in underlying tissues across the full imaging volume, and hence entire organs of interest. One such technique is called IDEAL (Iterative Decomposition with Echo Asymmetry and Least squares estimation). This article prospectively compares three-dimensional (3D) IDEAL-MRI and single-voxel MRS in the assessment of hepatic (HFF) and pancreatic fat fraction (PFF) in 16 healthy subjects. MRS acquisitions took 3–4 min to complete whereas IDEAL acquisitions were completed in 20-s breath-holds. In the liver, there was a strong correlation (slope = 0.90, r2 = 0.95, P < 0.001) between IDEAL and MRS-based fat fractions. In the pancreas, a poorer agreement between IDEAL and MRS was observed (slope = 0.32, r2 = 0.51, P < 0.02). The discrepancy of PFF is likely explained by MRS signal contamination from surrounding visceral fat, presumably during respiratory motion. We conclude that IDEAL is equally accurate in characterizing hepatic fat content as MRS, and is potentially better suited for fat quantification in smaller organs such as the pancreas.

Web-based weight loss in primary care: a randomized controlled trial.

Abstract: Evidence is lacking regarding effective and sustainable weight loss approaches for use in the primary care setting. We conducted a 12-week randomized controlled trial to evaluate the short-term efficacy of a web-based weight loss intervention among 101 primary care patients with obesity and hypertension. Patients had access to a comprehensive website that used a moderate-intensity weight loss approach designed specifically for web-based implementation. Patients also participated in four (two in-person and two telephonic) counseling sessions with a health coach. Intent-to-treat analysis showed greater weight loss at 3 months (−2.56 kg; 95% CI −3.60, −1.53) among intervention participants (−2.28 ± 3.21 kg), relative to usual care (0.28 ± 1.87 kg). Similar findings were observed among intervention completers (−3.05 kg; 95% CI −4.24, −1.85). High rates of participant retention (84%) and website utilization were observed, with the greatest weight loss found among those with a high frequency of website logins (quartile 4 vs. 1: −4.16 kg; 95% CI −1.47, −6.84). The intervention's approach promoted moderate weight loss at 12 weeks, though greater weight loss was observed among those with higher levels of website utilization. Efficacious web-based weight loss interventions can be successfully offered in the primary care setting.

The Chronic Effects of Whey Proteins on Blood Pressure, Vascular Function, and Inflammatory Markers in Overweight Individuals

Abstract: Limited evidence suggests that dairy whey protein may be the major dairy component that is responsible for health benefits currently associated with increased dairy consumption. Whey proteins may reduce blood pressure and improve cardiovascular health. This study evaluated the effects of whey protein supplementation on blood pressure, vascular function and inflammatory markers compared to casein and glucose (control) supplementation in overweight/obese individuals. The subjects were randomized to either whey protein, casein or glucose supplementation for 12 weeks according to a parallel design. In all, 70 men and women with a mean (+/-s.e.m.) BMI (kg/m(2)) of 31.3 +/- 0.8 completed the study. Systolic blood pressure (SBP) decreased significantly at week 6 compared to baseline in the whey and casein groups, (P = 0.028 and P = 0.020, respectively) and at week 12 (P = 0.020, and P = 0.017, respectively). Diastolic blood pressure (DBP) decreased significantly compared to baseline in the whey and casein groups (P = 0.038 and P = 0.042, respectively) at week 12. DBP decreased significantly in the whey and casein groups (P = 0.025, P = 0.038, respectively) at week 12 compared to the control group. Augmentation index (AI) was significantly lower from baseline at 12 weeks (P = 0.021) in the whey group. AI decreased significantly in the whey group at 12 weeks compared to control (P = 0.006) and casein (P = 0.006). There were no significant changes in inflammatory markers within or between groups. This study demonstrated that supplementation with whey protein improves blood pressure and vascular function in overweight and obese individuals.

Selective alterations within executive functions in adolescents with excess weight.

Abstract: Increasing evidence underscores overlapping neurobiological pathways to addiction and obesity. In both conditions, reward processing of preferred stimuli is enhanced, whereas the executive control system that would normally regulate reward-driven responses is altered. This abnormal interaction can be greater in adolescence, a period characterized by relative immaturity of executive control systems coupled with the relative maturity of reward processing systems. The aim of this study is to explore neuropsychological performance of adolescents with excess weight (n = 27, BMI range 24-51 kg/m 2 ) vs. normal-weight adolescents (n = 34, BMI range 17-24 kg/m 2 ) on a comprehensive battery of executive functioning tests, including measures of working memory (letter-number sequencing), reasoning (similarities), planning (zoo map), response inhibition (five-digit test (FDT)-interference and Stroop), flexibility (FDT-switching and trail-making test (TMT)), self-regulation (revised-strategy application test (R-SAT)), and decision-making (Iowa gambling task (IGT)). We also aimed to explore personality traits of impulsivity and sensitivity to reward. Independent sample t- and Z Kolmogorov-Smirnov tests showed significant differences between groups on indexes of inhibition, flexibility, and decision-making (excess-weight participants performed poorer than controls), but not on tests of working memory, planning, and reasoning, nor on personality measures. Moreover, regression models showed a significant association between BMI and flexibility performance. These results are indicative of selective alterations of particular components of executive functions in overweight adolescents.

Testosterone and visceral fat in midlife women: the Study of Women's Health Across the Nation (SWAN) fat patterning study.

Abstract: Visceral fat (VF) increases with the menopause and is an independent predictor of the metabolic syndrome, diabetes, and cardiovascular disease (CVD) in women. Little is known about how hormonal changes during the menopausal transition are related to the increase in VF. We aimed to determine the relationship between bioavailable testosterone and VF in middle-aged women at various stages of the menopausal transition and whether this relationship is independent of age and other CVD risk factors. The Study of Women's Health Across the Nation (SWAN) is a longitudinal, community-based study. This report uses baseline data from a population-based longitudinal ancillary study at the Chicago site to examine the cross-sectional relationship between testosterone and computed tomography (CT)-assessed VF in women at different stages of the menopausal transition. Included are 359 women (47.2% black), aged 42-60 years, who were randomly selected from a complete community census in which a 72% participation rate was achieved. In multivariate models, bioavailable testosterone was associated with VF independent of age, race, percent total body fat, and other cardiovascular risk factors. Bioavailable testosterone was a stronger predictor than estradiol and was interchangeable in its strength of association with sex hormone-binding globulin (SHBG). As bioavailable testosterone was associated with VF even after adjusting for insulin resistance, this suggests that it plays an important role in regional fat distribution. Our findings may have direct implications in explaining the effect of menopause-related testosterone predominance on VF accumulation and subsequent cardiovascular risk.

Maladaptive eating patterns, quality of life, and weight outcomes following gastric bypass: results of an Internet survey.

Abstract: Bariatric surgery is the most effective treatment for severe obesity. However, evidence suggests that maladaptive eating behaviors such as binge eating, grazing, and a loss of control when eating may impact postsurgical weight outcomes. The current study sought to characterize the weight outcomes, eating patterns, and perceived health-related quality of life of individuals 3–10 years following gastric bypass (GBP) surgery and to assess the relationships between eating behaviors, weight outcomes, and quality of life. Eligible participants (N = 497) completed an Internet survey of their eating behaviors, health-related quality of life, and weight history. Participants self-reported a mean maximum postsurgical loss of 81% of their excess weight and maintained a mean weight loss of 70% 3–10 years following surgery (mean 4.2 years). Eighty-seven percent reported weight regain ranging from 1 to 124 lb (mean 22.6 lb). Frequency of binge eating, a loss of control when eating, and grazing were all significantly correlated with greater weight regain (binge eating r = 0.24, P = 0.006; loss of control r = 0.36, P < 0.01; grazing r = 0.39, P < 0.001) and lesser excess weight loss (EWL) (binge eating r = −0.21, P = 0.013; loss of control r = −0.41, P < 0.001; grazing r = −0.27, P < 0.001). Poorer health-related quality of life was associated with binge eating disorder (BED) (t[463] = 9.7, P < 0.001) and grazing two or more times per week (t[361] = 9.0, P < 0.001). These findings suggest that eating disturbances and a loss of control when eating are significant following GBP and are risk factors for diminished weight outcomes.

Water consumption increases weight loss during a hypocaloric diet intervention in middle-aged and older adults.

Abstract: Water consumption acutely reduces meal energy intake (EI) among middle-aged and older adults. Our objectives were to determine if premeal water consumption facilitates weight loss among overweight/obese middle-aged and older adults, and to determine if the ability of premeal water consumption to reduce meal EI is sustained after a 12-week period of increased water consumption. Adults (n = 48; 55-75 years, BMI 25-40 kg/m(2)) were assigned to one of two groups: (i) hypocaloric diet + 500 ml water prior to each daily meal (water group), or (ii) hypocaloric diet alone (nonwater group). At baseline and week 12, each participant underwent two ad libitum test meals: (i) no preload (NP), and (ii) 500 ml water preload (WP). Meal EI was assessed at each test meal and body weight was assessed weekly for 12 weeks. Weight loss was ~2 kg greater in the water group than in the nonwater group, and the water group (beta = -0.87, P < 0.001) showed a 44% greater decline in weight over the 12 weeks than the nonwater group (beta = -0.60, P < 0.001). Test meal EI was lower in the WP than NP condition at baseline, but not at week 12 (baseline: WP 498 +/- 25 kcal, NP 541 +/- 27 kcal, P = 0.009; 12-week: WP 480 +/- 25 kcal, NP 506 +/- 25 kcal, P = 0.069). Thus, when combined with a hypocaloric diet, consuming 500 ml water prior to each main meal leads to greater weight loss than a hypocaloric diet alone in middle-aged and older adults. This may be due in part to an acute reduction in meal EI following water ingestion.

Sex differences in regional body fat distribution from pre- to postpuberty.

Abstract: Few large studies have evaluated the emergence of sexual dimorphism in fat distribution with appropriate adjustment for total body composition. The objective of this study was to determine the timing and magnitude of sex differences in regional adiposity from early childhood to young adulthood. Regional fat distribution was measured using dual-energy X-ray absorptiometry (trunk and extremity fat using automatic default regions and waist and hip fat using manual analysis) in 1,009 predominantly white participants aged 5–29 years. Subjects were divided into pre (Tanner stage 1), early (Tanner stages 2–3), late (Tanner stages 4–5), and post (males ≥20 years and females ≥18 years) pubertal groups. Sexual dimorphism in trunk fat (adjusted for extremity fat) was not apparent until late puberty, when females exhibited 17% less (P < 0.001) trunk fat than males. By contrast, sex differences in waist fat (adjusted for hip fat) were apparent at each stage of puberty, the effect being magnified with age, with prepubertal girls having 5% less (P = 0.027) and adult women having 48% less (P < 0.0001) waist fat than males. Girls had considerably more peripheral fat whether measured as extremity or hip fat at each stage. Sex differences in regional adiposity were significantly greater in young adults than in late adolescence. Exclusion of overweight participants did not materially affect the estimates. Sexual dimorphism in fat patterning is apparent even prepubertally with girls having less waist and more hip fat than boys. The magnitude of the sex difference is amplified with maturation, and particularly from late puberty to early adulthood.

Pre- to postoperative physical activity changes in bariatric surgery patients: self report vs. objective measures.

Abstract: Bariatric surgery patients report significant pre- to postoperative increases in physical activity (PA). However, it is unclear whether objective measures would corroborate these changes. The present study compared self-reported and accelerometer-based estimates of changes in moderate-to-vigorous intensity PA (MVPA) from pre- (pre-op) to 6 months postsurgery (post-op). Twenty bariatric surgery (65% laparoscopic-adjustable gastric banding, 35% gastric bypass) patients (46.2 ± 9.8 years, 88% female, pre-op BMI = 50.8 ± 9.7 kg/m2) wore RT3 accelerometers as an objective measure of MVPA and completed the Paffenbarger Physical Activity Questionnaire (PPAQ) as a subjective measure before and 6 months after bariatric surgery. Time (min/week) spent in MVPA was calculated for the PPAQ and RT3 (≥1-min and ≥10-min bouts) at pre-op and post-op. Self-reported MVPA increased fivefold from pre-op to post-op (44.6 ± 80.8 to 212.3 ± 212.4 min/week; P < 0.005). By contrast, the RT3 showed nonsignificant decreases in MVPA for both ≥1-min (186.0 ± 169.0 to 151.2 ± 118.3 min/week) and ≥10-min (41.3 ± 109.3 to 39.8 ± 71.3 min/ week) bouts. At pre-op, the percentage of participants who accumulated ≥150-min/week of MVPA in bouts ≥10-min according to the PPAQ and RT3 was identical (10%). However, at post-op, 55% of participants reported compliance with the recommendation compared to 5% based on RT3 measurement (P = 0.002). Objectively-measured changes in MVPA from pre-op to 6 months post-op appear to be much smaller than self-reported changes. Further research involving larger samples is needed to confirm these findings and to determine whether self-report and objective PA measures are differentially associated with surgical weight loss outcomes.