There is evidence to support that low fitness and physical activity, excess body weight, and excess abdominal fatness are associated with increased health risk. Moreover, evidence exists to support that sufficient levels of physical activity can significantly improve body weight, fatness, and health risk. Physical activity has been shown to have a modest effect on body weight that is typically <3% of initial body weight, but has an additive effect when combined with dietary restriction. Moreover, physical activity has been shown to be an important behavioral factor for enhancing long-term weight loss and minimizing weight regain; however, this may require relatively high doses of physical activity that approach 300 min/week. Physical activity may concurrently reduce abdominal adiposity, and which may serve as a pathway by which there is also an improvement in health-related risk factors for various chronic diseases. There are important areas of research that require further investigation, with particular need to further examine the dose of physical activity that significantly affects these health outcomes. Moreover, there is a need for improved interventions to promote the adoption and long-term maintenance of physical activity, which can lead to improved weight control, abdominal adiposity, and chronic disease risk factors. Future research is also needed to understand the physiological/metabolic pathways and mechanisms that explain the influence of physical activity on long-term regulation of body weight.
Interleukin-1β (IL-1β) has recently been implicated as a major cytokine that is involved in the pancreatic islet inflammation of type 2 diabetes mellitus. This inflammation impairs insulin secretion by inducing beta-cell apoptosis. Recent evidence has suggested that in obesity-induced inflammation, IL-1β plays a key role in causing insulin resistance in peripheral tissues.
Design and methods:
To further investigate the pathophysiological role of IL-1β in causing insulin resistance, the inhibitory effects of IL-1β on several insulin-dependent metabolic processes in vitro has been neutralized by XOMA 052. The role IL-1β plays in insulin resistance in adipose tissue was assessed using differentiated 3T3-L1 adipocytes and several parameters involved in insulin signaling and lipid metabolism were examined.
Results and conclusion:
IL-1β inhibited insulin-induced activation of Akt phosphorylation, glucose transport, and fatty acid uptake. IL-1β also blocked insulin-mediated downregulation of suppressor of cytokine signaling-3 expression. Co-preincubation of IL-1β with XOMA 052 neutralized nearly all of these inhibitory effects in 3T3-L1 adipocytes. These studies provide evidence, therefore, that IL-1β is a key proinflammatory cytokine that is involved in inducing insulin resistance. These studies also suggest that the monoclonal antibody XOMA 052 may be a possible therapeutic to effectively neutralize cytokine-mediated insulin resistance in adipose tissue.
To evaluate whether MK-0557, a highly selective, orally administered neuropeptide Y Y5 receptor antagonist, could limit weight regain after very-low-calorie diet (VLCD)-induced weight loss.
We enrolled 502 patients 18 to 65 years of age with a BMI of 30 to 43 kg/m2. Patients were placed on a VLCD (800 kcal/d liquid diet) for 6 weeks. Patients who lost>or=6% of initial body weight (n=359) were randomized to 52 weeks of 1 mg/d MK-0557 or placebo and maintained on a hypocaloric diet (300 kcal below weight maintenance requirements).
In randomized patients, the VLCD was associated with an average weight loss of 9.1 kg. After 12 weeks of double-blind treatment, weight began to gradually increase for both placebo- and MK-0557-treated patients. The mean weight change (95% confidence interval) from baseline at the end of the VLCD to Week 52 was +3.1 (2.1, 4.0) and +1.5 (0.5, 2.4) kg for patients treated with placebo and MK-0557, respectively. The difference of 1.6 kg between the two groups was significant (p=0.014). Secondary endpoints, such as blood pressure, lipid profile, insulin, and leptin, as well as waist circumference and quality-of-life measurements, did not show significant differences between MK-0557 and placebo treatments.
Although the difference in weight regain between placebo- and MK-0557-treated patients was statistically significant, the magnitude of the effect was small and not clinically meaningful. Antagonism of the neuropeptide Y Y5 receptor is not an efficacious treatment strategy for reducing weight regain after VLCD.
To examine the combined influence of moderate-to-vigorous physical activity (MVPA) and sedentary behavior on obesity in US adults.
Design and methods:
Cross-sectional analyses were undertaken on a nationally representative sample of 5,083 adults from the April 2003 and June 2005 National Health and Nutrition Examination Survey. Self-reported TV time was divided into low, moderate, and high categories. Accelerometer-derived total sedentary and MVPA minutes divided into low, moderate, and high tertiles. The independent associations between MVPA, TV, and total sedentary time and obesity were examined using logistic regression. Participants were then cross tabulated into nine MVPA-sedentary behavior groups, and logistic regression was used to examine the combined influence of MVPA and sedentary behavior on the odds of being obese.
MVPA was consistently inversely associated with obesity, regardless of sedentary behavior [odds ratio (OR) = 1.80-4.00]. There were inconsistent positive associations between TV time and risk of obesity in men, but not between total sedentary time and risk of obesity in either men or women.
Obesity was more strongly related to MVPA than either TV time or total sedentary time in US adults. Small differences in daily MVPA (5-10 min) were associated with relatively large differences in risk of obesity.
Controversy exists regarding the optimal energy prescription to promote successful long-term behavioral management of obesity. Prescribing intake of 1,000 (vs. 1,500) kcal/day may produce larger initial weight reduction, but long-term advantage remains unclear. The effects of prescribing 1,000 versus 1,500 kcal/day on 6- and 12-month weight changes within behavioral treatment of obesity were examined.
Design and methods:
Participants were 125 obese women (mean ± SD; BMI = 37.84 ± 3.94 kg/m(2) ) randomly assigned goals of 1,000 or 1,500 kcal/day.
From months 0 to 6, participants prescribed 1,000 kcal/day lost more weight than those prescribed 1,500 kcal/day (mean ± SE = -10.03 ± 0.92g vs. -6.23 ± 0.94 kg, P = 0.045); however, from months 7 through 12, only the 1,000 kcal/day condition experienced a significant weight regain (1.51 ± 0.77 kg, P = 0.025). Baseline caloric consumption moderated the effect of treatment on regain; participants with baseline intakes ≧2,000 kcal/day who were assigned 1,000 kcal/day were significantly more susceptible to weight regain than those assigned 1,500 kcal/day (P = 0.049). At month 12, a significantly greater percentage of 1,000 kcal/day participants achieved weight reductions of 5% or more than those prescribed 1,500 kcal/day.
Encouraging obese individuals in behavioral treatment to adhere to a 1,000 kcal/day intake may increase their likelihood of achieving clinically meaningful weight losses.
Previous studies have described genetic associations of the insulin gene variable number tandem repeat (INS VNTR) variant with childhood obesity and associated phenotypes. We aimed to assess the contribution of INS VNTR genotypes to childhood obesity and variance of insulin resistance, insulin secretion, and birth weight using family-based design. Participants were either French or German whites. We used transmission disequilibrium tests (TDTs) for assessing binary traits and quantitative pedigree disequilibrium tests for assessing continuous traits. In contrast to previous findings, we did not observe any familial association with childhood obesity (T = 50%, P = 0.77) in the 1,023 families tested. In French obese children, INS VNTR did not associate with fasting insulin levels (P = 0.23) and class I allele showed only borderline association with increased insulin secretion index at 30 min (P = 0.03). INS VNTR did not associate with birth weight in obese children (P = 0.98) and TDT analyses in 350 French families with history of low birth weight (LBW) showed no association with this condition (P = 0.92). In summary, our study, the largest performed so far, does not support the previously reported associations between INS VNTR and childhood obesity, insulin resistance, or birth weight, and does not suggest any major role for this variant in modulating these traits.
Obesity is associated with elevated oxidative stress and low-grade systemic inflammation. We have demonstrated recently that 1alpha,25-(OH)(2)-D(3) promotes reactive oxygen species production in cultured adipocytes, whereas suppression of 1alpha,25-(OH)(2)-D(3) by increasing dietary calcium down-regulates diet-induced oxidative stress in aP2-agouti transgenic mice. However, whether the anti-obesity effect of dietary calcium plays a role in regulation of obesity-associated inflammation is not clear.
We investigated the role of dietary calcium in the regulation of inflammatory cytokine production in aP2-agouti transgenic mice fed low- and high-calcium obesigenic diets and in the modulation of cytokine production by 1alpha,25-(OH)(2)-D(3) in cultured murine and human adipocytes.
The high-calcium diet inhibited the expression of pro-inflammatory factors tumor necrosis factor alpha and interleukin (IL)-6 by 64% and 51%, respectively (p < 0.001), in visceral fat, stimulated the expression of the anti-inflammatory factors IL-15 and adiponectin by 52% (p = 0.001) and 54% (p = 0.025), respectively, in visceral fat, and induced a 2-fold increase in IL-15 expression in soleus muscle (p = 0.01) compared with litter mate controls on a low-calcium diet. 1alpha,25-(OH)(2)-D(3) also markedly stimulated the expression of tumor necrosis factor alpha (p < 0.001) and IL-6 (p = 0.016) in differentiated 3T3-L1 adipocytes and increased IL-6 (p = 0.004) and IL-8 (p < 0.001) production in differentiated human adipocytes. These effects were blocked by calcium channel antagonism with nifedipine.
These data demonstrate that 1alpha,25-(OH)(2)-D(3) favors inflammatory cytokine expression and inhibits anti-inflammatory cytokine expression; accordingly, suppression of 1alpha,25-(OH)(2)-D(3) by dietary calcium inhibits adipocyte-derived inflammation associated with obesity.
To investigate the ability of 1,25(OH)(2)D(3) (D) and genistein (G), alone and in combination, to inhibit adipogenesis and induce apoptosis in 3T3-L1 adipocytes.
3T3-L1 preadipocytes and mature adipocytes were incubated with various concentrations of D and G, alone and in combination, for 48 h. Viability was determined using the Cell Titer 96 Aqueous One Solution Cell Proliferation Assay. Post-confluent preadipocytes were incubated with D and G for up to 6 days during adipogenesis and lipid content was quantified by Nile Red dye; apoptosis was quantified by measurement of single-stranded DNA. Expression of adipocyte-specific proteins and VDR was analyzed by western blotting.
Combining D and G did not cause an enhanced effect on cell viability in either preadipocytes or mature adipocytes. In maturing preadipocytes, D at 0.5 nmol/l (D0.5) increased apoptosis by 47 +/- 10.25% (P < 0.05) and inhibited lipid accumulation by 28 +/- 10% (P < 0.001), while G at 25 micromol/l (G25) had no significant effect. However, D+G caused an enhanced apoptosis by 136 +/- 12.6% (P < 0.001) and enhanced inhibition of lipid accumulation by 82.46 +/- 2.95% (P < 0.001). Similarly, D0.5 alone decreased adipose-specific gene 422 (aP2) expression to 34.2 +/- 2.3% and increased VDR expression levels by 41.8 +/- 11% (P < 0.001), but G25 showed no effect. However, D0.5+G25 decreased aP2 expression to 52 +/- 4.2% (P < 0.05) and increased VDR expression levels by 131 +/- 14.5% (P < 0.0001).
These findings suggest that combining 1,25(OH)(2)D(3) with genistein results in an enhanced inhibition of lipid accumulation and induction of apoptosis in maturing 3T3-L1 preadipocytes.
To investigate any correlation between BMI and brain gray matter volume, we analyzed 1,428 healthy Japanese subjects by applying volumetric analysis and voxel-based morphometry (VBM) using brain magnetic resonance (MR) imaging, which enables a global analysis of brain structure without a priori identification of a region of interest.
We collected brain MR images from 690 men and 738 women, and their height, weight, and other clinical information. The collected images were automatically normalized into a common standard space for an objective assessment of neuroanatomical correlations in volumetric analysis and VBM with BMI.
Volumetric analysis revealed a significant negative correlation in men (P < 0.001, adjusting for age, lifetime alcohol intake, history of hypertension, and diabetes mellitus), although not in women, between BMI and the gray matter ratio, which represents the percentage of gray matter volume in the intracranial volume. VBM revealed that, in men, the regional gray matter volume of the bilateral medial temporal lobes, anterior lobe of the cerebellum, occipital lobe, frontal lobe, precuneus, and midbrain showed significant negative correlations with BMI, while those of the bilateral inferior frontal gyri, posterior lobe of the cerebellum, frontal lobes, temporal lobes, thalami, and caudate heads showed significant positive correlations with BMI.
Global loss and regional alterations in gray matter volume occur in obese male subjects, suggesting that male subjects with a high BMI are at greater risk for future declines in cognition or other brain functions.
To compare prevalence of overweight and obesity in young adult men from rural areas with those from urban areas of Sweden over three decades.
Eighty-two percent of the Swedish male population at military conscription age between 1969 and 2005 (n = 1,578,694; 18.3 +/- 0.4 years) was grouped by urban, semiurban, and rural place of residence. BMI was calculated from measured height and weight. Comparisons were made with and without adjustments for parental education, socioeconomic position (SEP), and intelligence quotient (IQ).
During the study period, the prevalence of obesity more than quintupled from 0.9-5.1%, while overweight tripled from 7.1-20.5% (P < 0.0001). An urban-rural gradient was observed within all socioeconomic and education strata. After adjustment for SEP, IQ, parental education level, and testing year, the odds ratios (ORs) were 1.28 (1.23-1.34) and 1.20 (1.18-1.22) for obesity and overweight, respectively, in a rural compared to an urban area. The corresponding ORs for semiurban place of residence were 1.16 (1.13-1.19) and 1.11 (1.10-1.12), respectively. Significant effect modification by time was seen, with evidence of an increasing gradient until the early 1990s (P < 0.001).
A strong and persisting gradient of increasing overweight and obesity from urban to rural areas was observed that could not be explained by individual or family-related factors such as IQ, parental education level, or SEP. These results indicate the presence of strong environmental or contextual obesogenic factors affecting the energy balance of people in rural areas more negatively than those in urban communities.
The objective of this study was to characterize changes in metabolic bone parameters following bariatric surgery. Seventy-three obese adult patients who underwent either gastric banding (GB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion with duodenal switch (BPD/DS) were followed prospectively for 18 months postoperatively. Changes in the calcium-vitamin D axis (25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), calcium, parathyroid hormone (PTH)), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase) and resorption (urinary N-telopeptide (NTx)), as well as bone mineral density (BMD) were assessed at 3-month intervals during this time period. Bariatric surgery resulted in significant and progressive weight loss over 18 months. With supplementation, 25OHD levels increased 65.3% (P < 0.0001) by 3 months, but leveled off and decreased <30 ng/ml by 18 months. PTH initially decreased 21.4% (P = 0.01) at 3 months, but later approached presurgery levels. 1,25(OH)(2)D increased significantly starting at month 12 (50.3% increase from baseline, P = 0.008), and was positively associated with PTH (r = 0.82, P = 0.0001). When stratified by surgery type, median PTH and 1,25(OH)(2)D levels were higher following combined restrictive and malabsorptive operations (RYGB and BPD/DS) compared to GB. Bone formation/resorption markers were increased by 3 months (P < 0.05) and remained elevated through 18 months. Radial BMD decreased 3.5% by month 18, but this change was not significant (P = 0.23). Our findings show that after transient improvement, preoperative vitamin D insufficiency and secondary hyperparathyroidism persisted following surgery despite supplementation. Postoperative secondary hyperparathyroidism was associated with increased 1,25(OH)(2)D levels and increased bone turnover markers.
Based on cross-sectional analyses, it was suggested that hip circumference divided by height(1.5) minus 18 (the body adiposity index, BAI), could directly estimate percent body fat without the need for further correction for sex or age. We compared the prediction of percent body fat, as assessed by dual-energy x-ray absorptiometry (PBF(DXA)), by BAI, BMI, and circumference (waist and hip) measurements among 1151 adults who had a total body scan by DXA and circumference measurements from 1993 through 2006. After accounting for sex, we found that PBF(DXA) was related similarly to BAI, BMI, waist circumference, and hip circumference. In general, BAI underestimated PBF(DXA) among men (2.5%) and overestimated PBF(DXA) among women (4%), but the magnitudes of these biases varied with the level of body fatness. The addition of covariates and quadratic terms for the body size measures in regression models substantially improved the prediction of PBF(DXA), but none of the models based on BAI could more accurately predict PBF(DXA) than could those based on BMI or circumferences. We conclude that the use of BAI as an indicator of adiposity is likely to produce biased estimates of percent body fat, with the errors varying by sex and level of body fatness. Although regression models that account for the non-linear association, as well as the influence of sex, age and race, can yield more accurate estimates of PBF(DXA), estimates based on BAI are not more accurate than those based on BMI, waist circumference, or hip circumference.
The safety and efficacy of IQP-PV-101, a proprietary extract of Phaseolus vulgaris, on weight management in two phases was evaluated here. The weight loss (WL) phase was conducted over 12 weeks and the weight maintenance (WM) phase took 24 weeks.
In the double-blind WL phase, subjects were randomized to receive either IQP-PV-101 or placebo. All subjects adhered to a mildly hypocaloric diet. Body weight and other body composition parameters were measured at baseline and every 4 weeks thereafter. During the single arm, open label WM trial, energy intake was ad libitum. Efficacy parameters were measured at baseline, week 12 and week 24.
At the end of the WL study, the IQP-PV-101 group lost a mean of 2.91 ± 2.63 kg in body weight compared with 0.92 ± 2.00 kg in the placebo group (P < 0.001). During the WM phase, 36 out of 49 subjects (73.5%) were able to maintain their weight, even without dietary restrictions. No serious or related adverse events were reported over the combined period of 36 weeks.
Results indicate that IQP-PV-101 is safe and effective for weight loss and maintenance.
To evaluate the association between BMI (kg/m(2)) and headaches among women.
Cross-sectional analysis of 11 datasets identified after searching for all large publicly available epidemiologic cohort study datasets containing relevant variables. Datasets included National Health Interview Survey (NHIS): 1997-2003, the first National Health Examination and Nutrition Survey, Alameda County Health Study (ACHS), Tecumseh Community Health Study (TCHS), and Women's Health Initiative (WHI). The women (220,370 in total) were aged 18 years or older and had reported their headache or migraine status.
Using nonlinear regression techniques and models adjusted for age, race, and smoking, we found that increased BMI was generally associated with increased likelihood of headache or severe headache among women. A BMI of approximately 20 was associated with the lowest risk of headache. Relative to a BMI of 20, mild obesity (BMI of 30) was associated with roughly a 35% increase in the odds for experiencing headache whereas severe obesity (BMI of 40) was associated with roughly an 80% increase in odds. Results were essentially unchanged when models were further adjusted for socioeconomic variables, alcohol consumption, and hypertension. Being diagnosed with migraine showed no association with BMI.
Among US women, a BMI of approximately 20 (about the 5th percentile) was associated with the lowest likelihood of headache. Consistently across studies, obese women had significantly increased risk for headache. By contrast, the risk for diagnosed migraine headache per se was not obviously related to BMI. The direction of causation and mechanisms of action remain to be determined.
Objective:Increased tissue activity of cortisol induced by the activation of inert cortisone to active cortisol through 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) may play a role in the metabolic syndrome. We recently found that 11beta-HSD1 in subcutaneous adipose tissue (AT) was lower in lean women compared with lean men. Estrogen suppresses hepatic and renal 11beta-HSD1 in rats; hence we investigated the in vitro effect of estrogen on human and rat AT, and the in vivo effects on rat AT 11beta-HSD1 expression.Methods and Procedures:Wistar rats were divided into four groups of eight animals. One group was sham-operated (controls) and others were ovariectomized (OVX). One OVX group was left untreated (OVX-E), another (OVX+E) received estrogen treatment, and one received a hypo-caloric diet (OVX-E+D), matching the weight gain of the control group. AT from women undergoing liposuction or surgery and from killed male and female rats were incubated with estrogen alone or in the presence of IL-1beta. Gene expressions were determined by real-time reverse transcriptase PCR.Results:Ovariectomy resulted in a 280% increase in adipose 11beta-HSD1 expression P < 0.05). 11beta-HSD1 expression in the (OVX+E)-group was significantly reduced compared with the nonsubstituted group (P < 0.05). 11beta-HSD1 expression in the (OVX-E+D)-group was reduced significantly (P < 0.05) when compared with the level of the estrogen-substituted group. No significant differences between the control group, the (OVX+E)-group, and the (OVX-E+D)-group were found. In the in vitro studies, no direct effect of estrogen on adipose 11beta-HSD1 was found.Discussion:The upregulation of 11beta-HSD1 in ovariectomized rats was most likely due to changes in body composition rather than lack of estrogen.Obesity (2008) doi:10.1038/oby.2007.141.
Food preferences (FP) predict food intake in childhood; however, the predictive power of FP may decline among girls as weight concerns (WC) and dietary restraint (DR) increase during preadolescence. To examine longitudinal change in the preference-intake (P-I) relation and assess whether this relation weakens among non-Hispanic white girls (n = 197) with a history of WC and DR from age 5 to 11. Girls' preferences for and intake (kcal) of 10 palatable snack foods were assessed biennially. Height, weight, percent body fat (%BF), WC, and DR were measured. Individual correlation coefficients were calculated per girl to capture within-person P-I correlations at each time of measurement. Overall, FP predicted girls' snack food calorie intakes between 5 and 11 years, but latent profile analysis (LPA) revealed three distinct patterns of change in P-I correlations over time: "strong/stable" P-I correlations were relatively high and became stronger with age; "increasing/later null" P-I correlations were initially weak and became stronger between 5 and 9 years, but dropped to near 0 at 11 years; "initially weak/later strong" P-I correlations were initially null and increased with age. Mixed models revealed that the "increasing/later null" group had greater increases in %BF, and higher WC, DR, and BMI percentiles from 5 to 11 years, compared to the other groups. In summary, FP predicted snack food calorie intake among most girls during childhood, but waned as a predictor of calorie intake at age 11 for a subset of girls with increasing %BF, and higher WC, DR, and BMIs.
This study describes patterns of bias in self-reported dietary recall data of girls by examining differences among girls classified as under-reporters, plausible reporters, and over-reporters on weight, dietary patterns, and psychosocial characteristics.
Participants included 176 girls at age 11 and their parents. Girls' weight and height were measured. Three 24-hour dietary recalls and responses to psychosocial measures were collected. Plausibility cut-offs for reported energy intake as a percentage of predicted energy requirements were used to divide the sample into under-reporters, plausible reporters, and over-reporters. Differences among these three groups on dietary and psychosocial variables were assessed to examine possible sources of bias in reporting.
Using a +/-1 standard deviation cut-off for energy intake plausibility, 50% of the sample was categorized as plausible reporters, 34% as under-reporters, and 16% as over-reporters. Weight status of under-reporters was significantly higher than that of plausible reporters and over-reporters. With respect to reported dietary intake, under-reporters were no different from plausible reporters on intakes of foods with higher nutrient densities and lower energy densities and were significantly lower than plausible reporters on intakes of foods with lower nutrient densities and higher energy densities. Over-reporters reported significantly higher intakes of all food groups and the majority of subgroups, relative to plausible reporters. Under-reporters had significantly higher levels of weight concern and dietary restraint than both plausible reporters and over-reporters.
Techniques to categorize plausible and implausible reporters can and should be used to provide an improved understanding of the nature of error in children's dietary intake data and account for this error in analysis and interpretation.
Reduction of cortisone to cortisol is mediated by 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), a putative key enzyme in obesity-related complications. Experimental studies suggest that adipokines, notably leptin and tumor necrosis factor-alpha (TNF-alpha), are of importance for 11betaHSD1 activity. We hypothesized that the regulation of hepatic preceptor glucocorticoid metabolism is gender-specific and associated with circulating levels of leptin and TNF-alpha receptors and/or sex hormones.
A total of 34 males and 38 women (14 premenopausal and 22 postmenopausal) underwent physical examination and fasting blood sampling. Insulin sensitivity was tested by euglycemic hyperinsulinemic clamps, and hepatic 11betaHSD1 enzyme activity was estimated by the conversion of orally-ingested cortisone to cortisol.
Hepatic 11betaHSD1 activity was negatively associated with leptin and soluble TNF (sTNF) r1 and sTNFr2 in males. These correlations remained significant after adjustment for age and insulin sensitivity, and for sTNF-alpha receptors also after adjustment of BMI and waist circumference. In contrast, 11beta reduction of cortisone was positively associated to leptin in females after adjustment for BMI and waist circumference.
Hepatic 11beta reduction shows different links to circulating adipocyte-derived hormones in males and females. This emphasizes the need for further studies on tissue-specific regulation of 11betaHSD1 in both genders.
The aim of this study was to estimate the prevalence of child overweight in a regional sample of primary school-aged children, and to examine the relationships among child overweight, psychopathology, and social functioning. A cross-sectional survey was conducted in 2004 in 100 primary schools of a large French region, with 2,341 children aged 6-11 randomly selected. Child weight and height, lifestyle variables (leisure-time physical activity (LTPA), watching television (TV), playing video games), and socioeconomic characteristics were collected in parent-administered questionnaires. Child psychopathology outcomes were assessed using child- and parent-reported instruments (Dominic Interactive (DI) and Strengths and Difficulties Questionnaire (SDQ)). Overweight and obesity were estimated according to the International Obesity Task Force (IOTF) definition. Response rates to the parent questionnaire and DI were 57.4 and 95.1%, respectively. Final sample size was 1,030 children. According to the IOTF, 17.3% of the children were overweight, of whom 3.3% were obese. In univariate analysis, correlates of overweight were low parental education, low monthly income, Disadvantaged School Areas (DSAs), self-reported generalized anxiety, parent-reported conduct disorders, emotional problems, and peer difficulties. High monthly income was less frequently associated with overweight. In multivariate analysis, parent-reported peer difficulties (odds ratio (OR) = 2.06; 95% confidence interval = 1.27-3.35) and DSAs (1.88; 1.03-3.44) were independent factors significantly associated with child overweight. There was a trend of being overweight with elevated TV times (P for trend = 0.02). The psychosocial burden of excess weight appears to be significant even in young children. Findings should be considered for preventing strategies and public health interventions. School-based overweight prevention programs should be implemented first in disadvantaged areas together with information about weight stigmatization and discrimination.
Increased tissue activity of cortisol induced by the activation of inert cortisone to active cortisol through 11-beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) may play a role in the metabolic syndrome. We recently found that 11beta-HSD1 in subcutaneous adipose tissue (AT) was lower in lean women compared with lean men. Estrogen suppresses hepatic and renal 11beta-HSD1 in rats; hence we investigated the in vitro effect of estrogen on human and rat AT, and the in vivo effects on rat AT 11beta-HSD1 expression.
Wistar rats were divided into four groups of eight animals. One group was sham-operated (controls) and others were ovariectomized (OVX). One OVX group was left untreated (OVX-E), another (OVX+E) received estrogen treatment, and one received a hypo-caloric diet (OVX-E+D), matching the weight gain of the control group. AT from women undergoing liposuction or surgery and from killed male and female rats were incubated with estrogen alone or in the presence of IL-1beta. Gene expressions were determined by real-time reverse transcriptase PCR.
Ovariectomy resulted in a 280% increase in adipose 11beta-HSD1 expression P < 0.05). 11beta-HSD1 expression in the (OVX+E)-group was significantly reduced compared with the nonsubstituted group (P < 0.05). 11beta-HSD1 expression in the (OVX-E+D)-group was reduced significantly (P < 0.05) when compared with the level of the estrogen-substituted group. No significant differences between the control group, the (OVX+E)-group, and the (OVX-E+D)-group were found. In the in vitro studies, no direct effect of estrogen on adipose 11beta-HSD1 was found.
The upregulation of 11beta-HSD1 in ovariectomized rats was most likely due to changes in body composition rather than lack of estrogen.
A previous study showed that increasing the portion sizes of all foods led to an increase in energy intake that was sustained over 2 days. The objective of the present study was to determine whether participants would compensate for excess energy intake or continue to overeat when portion sizes were increased for 11 days.
Participants in the study were 23 normal-weight and overweight participants (10 women and 13 men). All of their foods and caloric beverages were provided during two different periods of 11 consecutive days, which were separated by a 2-week interval. During one period, standard portions of all items were served; during the other, all portion sizes were increased by 50%.
The 50% increase in portion sizes resulted in a mean increase in daily energy intake of 423 +/- 27 kcal (p < 0.0001), which did not differ significantly between women and men. This increase was sustained for 11 days and did not decline significantly over time, leading to a mean cumulative increase in intake of 4636 +/- 532 kcal. A significant effect of portion size on intake was seen at all meals and in all categories of foods except fruit (as a snack) and vegetables. The effect of portion size on intake was not influenced by the body weight status of participants.
These results strengthen the evidence suggesting that increased portions contribute to the overconsumption of energy and to excess body weight.
The use of a weight-based nomogram is considered as standard care for prescribing appropriate doses of unfractionated heparin (UFH). Because of the need for multiple other medications that may affect bleeding and that clinical data have relied on similar dosing algorithms, maximum initial bolus and infusion rates have been suggested (capped initial dose). Whether these weight-based heparin nomograms properly address therapeutic dosing in obese patients remains questionable.
Design and methods:
Thirty patients treated for acute coronary syndrome and weighing ≥110 kg were retrospectively compared with 90 controls (three groups of 30 patients, weighting 50-69.9, 70-89.9, or 90-109.9 kg), all treated with UFH, July 2008 to April 2009. The primary end point was the time required to obtain a threshold activated partial thromboplastin time (aPTT).
Mean time to achieve threshold aPTT was longer for obese patients weighing ≥110 kg than for controls (31.47 vs. 12.89 hours; P < 0.0001). At 24 hours, 63% of obese patients weighing ≥110 kg had not reached threshold aPTT vs. 7% of controls (P < 0.0001). However, threshold infusion rate did not differ between weight categories (13.0 vs. 13.1 U/kg/h; P = NS) and approximated the initial infusion rate recommended by nomograms without applying the dose cap (12 U/kg/h).
Adequate anticoagulation time doubled in patients weighing ≥110 kg, suggesting that these patients were not receiving appropriate heparin doses initially to achieve threshold aPTT rapidly. Using initial infusion rate recommended by a nomogram without capping for total body weight is suggested as acceptable in this study. This approach should be further evaluated in a prospective study.
In ideopathic obesity, there is evidence that enhanced cortisol regeneration within abdominal subcutaneous adipose tissue may contribute to adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), or glucocorticoid receptor (GRalpha) levels are altered in other adipose depots remains uncertain. Our objective was to determine the association between 11betaHSD1 and GRalpha mRNA levels in four distinct adipose depots and measures of obesity and the metabolic syndrome.
Adipose tissue biopsies were collected from subcutaneous (abdominal, thigh, gluteal) and intra-abdominal (omental) adipose depots from 21 women. 11betaHSD1 and GRalpha mRNA levels were measured by real-time polymerase chain reaction. Body composition, fat distribution, fat cell size, and blood lipid, glucose, and insulin levels were measured.
11betaHSD1 mRNA was highest in abdominal subcutaneous (p < 0.001) and omental (p < 0.001) depots and was positively correlated with BMI and visceral adiposity in all depots. Omental 11betaHSD1 correlated with percent body fat (R = 0.462, p < 0.05), fat cell size (R = 0.72, p < 0.001), and plasma triglycerides (R = 0.46, p < 0.05). Conversely, GRalpha mRNA was highest in omental fat (p < 0.001). GRalpha mRNA was negatively correlated with BMI in the abdominal subcutaneous (R = -0.589, p < 0.05) and omental depots (R = -0.627, p < 0.05). Omental GRalpha mRNA was inversely associated with visceral adiposity (R = -0.507, p < 0.05), fat cell size (R = -0.52, p < 0.01), and triglycerides (R = -0.50, p < 0.05).
Obesity was associated with elevated 11betaHSD1 mRNA in all adipose compartments. GRalpha mRNA is reduced in the omental depot with obesity. The novel correlation of 11betaHSD1 with omental fat cell size, independent of obesity, suggests that intracellular cortisol regeneration is a strong predictor of hypertrophy in the omentum.
This study examined the contribution of subcutaneous adipose tissue (SAT) 11βHSD1 to obese African Americans' (AA) elevated metabolic risk, despite a protective obesity phenotype of reduced visceral adipose tissue (VAT) and hepatic fat fraction (HFF) relative to obese Hispanics with similar metabolic risk.
Design and methods:
Obese AA and Hispanic adults (N = 36(16AA); BMI 35.2 ± 0.6 kg/m(2) , 18-25y) participated, with VAT, SAT, and HFF measured by MRI, SAT gene expression measured by HT-12 microarray and insulin sensitivity (SI), disposition index (DI) by IVGTT. Multiple linear regression examined relationships/interactions of ethnicity and 11βHSD1 expression on outcomes (covariates: age, sex, total fat mass), with standardized β (stβ) reported.
SAT 11βHSD1 expression significantly associated with insulin parameters and this varied by ethnicity (Pinteraction <0.1). In AA, 11βHSD1 negatively associated with SI (stβ = -0.58, P = 0.03), DI (stβ = -0.62, P = 0.03) and positively associated with fasting insulin (stβ = 0.54, P = 0.04), with no significant relationship in Hispanics. SAT 11βHSD1 associated with HFF in the combined sample (stβ = 0.42, P = 0.008), with no difference between ethnicites (Pinteraction >0.1). After controlling for HFF, 11βHSD1 associations with metabolic risk in AA became nonsignificant.
These results suggested that in AA and not Hispanics, SAT 11βHSD1 is associated with SI and DI, and may be mediated by HFF.
Although national and state estimates of child obesity are available, data at these levels are insufficient to monitor effects of local obesity prevention initiatives. The purpose of this study was to examine regional changes in the prevalence of obesity due to statewide policies and programs among children in grades 4, 8, and 11 in Texas Health Services Regions (HSRs) between 2000-2002 and 2004-2005, and nine selected counties in 2004-2005. A cross-sectional, probability-based sample of 23,190 Texas students in grades 4, 8, and 11 were weighed and measured to obtain BMI. Obesity was >95th percentile for BMI by age/sex using Centers for Disease Control and Prevention growth charts. Child obesity prevalence significantly decreased between 2000-2002 and 2004-2005 for 4th grade students in the El Paso HSR (-7.0%, P = 0.005). A leveling off in the prevalence of obesity was noted for all other regions for grades 4, 8, and 11. County-level data supported the statistically significant decreases noted in the El Paso region. The reduction of child obesity levels observed in the El Paso area is one of the few examples of effective programs and policies based on a population-wide survey: in this region, a local foundation funded extensive regional implementation of community programs for obesity prevention, including an evidence-based elementary school-based health promotion program, adult nutrition and physical activity programs, and a radio and television advertising campaign. Results emphasize the need for sustained school, community, and policy efforts, and that these efforts can result in decreases in child obesity at the population level.
The increased prevalence of overweight and obesity in the United States during the past three decades coincides with a trend of increased sugar intake, especially fructose, leading to speculation that the two trends may be linked. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), that regulates intracellular tissue-specific glucocorticoid levels, is increased in adipose and suppressed in liver of obese humans and animals. Hexose-6-phosphate dehydrogenase (H6PDH) is colocalized with 11β-HSD1 and generates nicotinamide adenosine dinucleotide phosphate, the required cofactor for 11β-HSD1 reductase activity that converts inert glucocorticoid metabolite into active hormone. We examined the acute effects of ad lib access to 16% solutions of sucrose, fructose, or glucose and chow and water. Diets high in fructose, but not glucose or sucrose increased 11β-HSD1 mRNA within 24 h in liver and adipose by greater than two- and threefold, respectively (P ≤ 0.05). After 1 week, hepatic 11β-HSD1 mRNA and protein were suppressed by >60% in all sugar-fed groups, a phenomenon not previously reported in the absence of obesity. Sucrose- and fructose-fed rats had higher plasma triglycerides than did control or glucose-fed rats at both 24 h and 1 week (P ≤ 0.02), consistent with previously reported effects of fructose on lipid metabolism. We conclude that high-sugar diets initiate glucocorticoid dysregulation associated with obesity prior to the onset of phenotypic changes, and that high fructose diets specifically induce changes in 11β-HSD1 within 24-h exposure.
Alterations in glucocorticoid (GC) metabolism may contribute to the development of obesity and insulin resistance. We aimed to study the role of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in human adiposity, paying special attention to the association between altered GC metabolism and insulin sensitivity. In 24-h urine samples of 72 extremely obese (mean BMI 45.5 ± 1.1 kg/m2), but otherwise healthy patients urinary free cortisol (UFF), urinary free cortisone (UFE), tetrahydrocortisol (THF), 5α-tetrahydrocortisol (5α-THF), and tetrahydrocortisone (THE) were quantified by radioimmunoassay. The sum of the three major tetrahydrometabolites is an estimate for daily GC secretion, and the sum of UFF and UFE represents potentially bioactive-free-GCs. Thirty healthy lean subjects (BMI 22.3 ± 0.3 kg/m2) served as controls. In obese subjects, absolute daily GC secretion and the potentially bioactive-free-GCs were significantly (P < 0.005) higher than in lean controls (11.8 ± 0.7 vs. 8.0 ± 0.6 mg/d; and 171.8 ± 11.2 vs. 117.6 ± 9.2 μg/d, respectively). However, when these values were corrected for body surface area (BSA), significant differences were no longer detectable. While enzyme activity indices for 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) were similar in lean and obese subjects, 11β-HSD2 was markedly elevated in adiposity (3.7 ± 0.2 vs. 2.1 ± 0.1; P < 0.0001). This increase was accompanied by a significant reduction in UFF excretion corrected for BSA (16.5 ± 1.2 vs. 21.7 ± 2.0 μg/d/m2; P = 0.0222). Besides, 11β-HSD2 activity was significantly correlated with insulin sensitivity (P = 0.0262). When body size is accounted for, both adrenal GC secretion and potentially bioactive-free-GCs are indistinguishable between lean and extremely obese subjects. However in obesity, the kidney appears to intensify its supply of the direct substrate cortisone for extrarenal 11β-HSD1, which may fuel visceral adiposity and insulin resistance.
Pre-receptor amplification of glucocorticoids is, in part, determined by the isoenzymes 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1 and type 2, interconverting inert cortisone and active cortisol. Increased tissue activity of cortisol may play a part in features of the metabolic syndrome. Our objective was to compare 11beta-HSD1 gene expression in different fat depots (visceral, subcutaneous abdominal, and subcutaneous gluteal) in lean and obese men and women.
A cross-sectional study design was used for healthy patients undergoing minor abdominal surgery (lean men, 10), minor gynecological surgery (lean woman, 10), or gastric banding operations (obese men, 10; and obese women, 10). Gene expressions of 11beta-HSD1 in adipose tissue samples were determined by real-time reverse transcriptase polymerase chain reaction (RT-PCR).
Lean women had lower 11beta-HSD1 gene expression in subcutaneous adipose tissue compared with men (62% lower, p < 0.01), whereas no significant difference was found between obese men and women. 11Beta-HSD1 mRNA in human adipose tissue was higher in obese subjects compared with lean subjects in both women and men and in both subcutaneous and visceral adipose tissue. No difference in mRNA expression of 11beta-HSD1 between visceral and subcutaneous adipose tissue or between subcutaneous adipose tissue from different depots was found.
11Beta-HSD1 in adipose tissue is increased in obesity in both women and men, and may contribute to the associated metabolic syndrome. As 11beta-HSD1 expression in lean women was found to be significantly lower than in lean males, the up-regulation associated with obesity may be relatively more devastating in women than in men, and may help explain the higher relative risk of cardiovascular disease in women suffering from the metabolic syndrome.
Following menopause, body fat is redistributed from peripheral to central depots. This may be linked to the age related decrease in estrogen levels. We hypothesized that estrogen supplementation could counteract this fat redistribution through tissue-specific modulation of glucocorticoid exposure. We measured fat depot masses and the expression and activity of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in fat and liver of ovariectomized female rats treated with or without 17beta-estradiol. 11betaHSD1 converts inert cortisone, or 11-dehydrocorticosterone in rats into active cortisol and corticosterone. Estradiol-treated rats gained less weight and had significantly lower visceral adipose tissue weight than nontreated rats (P < 0.01); subcutaneous adipose weight was unaltered. In addition, 11betaHSD1 activity/expression was downregulated in liver and visceral, but not subcutaneous, fat of estradiol-treated rats (P < 0.001 for both). This downregulation altered the balance of 11betaHSD1 expression and activity between adipose tissue depots, with higher levels in subcutaneous than visceral adipose tissue of estradiol-treated animals (P < 0.05 for both), opposite the pattern in ovariectomized rats not treated with estradiol (P < 0.001 for mRNA expression). Thus, estrogen modulates fat distribution, at least in part, through effects on tissue-specific glucocorticoid metabolism, suggesting that estrogen replacement therapy could influence obesity related morbidity in postmenopausal women.
Increased mRNA and activity levels of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non-diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)].
Prospective analyses were performed in 20 subjects (two whites and 18 Pima Indians) who had baseline measurements of 11betaHSD1 mRNA and activity in whole AT (follow-up, 0.3 to 4.9 years) and in 47 Pima Indians who had baseline assessments of 11betaHSD1 mRNA in isolated adipocytes (follow-up, 0.8 to 5.3 years).
In whole AT, although 11betaHSD1 mRNA levels showed positive associations with changes in weight and HOMA-IR, 11betaHSD1 activity was associated with changes in HOMA-IR but not in body weight. 11betaHSD1 mRNA levels in isolated adipocytes were not associated with follow-up changes in any of the anthropometric or metabolic variables.
Our results indicate that increased expression of 11betaHSD1 in subcutaneous abdominal AT may contribute to risk of worsening obesity and insulin resistance. This prospective relationship does not seem to be mediated by increased 11betaHSD1 expression in adipocytes.
Data from rodents provide evidence for a causal role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) in the development of obesity and its complications. In humans, 11beta-HSD-1 is increased in subcutaneous adipose tissue (SAT) of obese patients, and higher adipose 11beta-HSD-1 was associated with features of the metabolic syndrome. To date, there is no evidence for an increased expression of 11beta-HSD-1 in human visceral adipose tissue (VAT), although VAT is the major predictor for insulin resistance and the metabolic syndrome.
11beta-HSD-1 and hexose-6-phosphate dehydrogenase (the enzyme responsible for the synthesis of nicotinamide adenine dinucleotide phosphate, the cofactor required for 11beta-HSD-1 oxoreductase activity) mRNA levels were measured using real-time quantitative reverse transcriptase-polymerase chain reaction in abdominal SAT and VAT biopsies obtained from 10 normal-weight and 12 obese women. Adiponectin mRNA was used as an internal control.
11beta-HSD-1 mRNA concentrations were significantly increased in both SAT and VAT of obese patients (720% and 450% of controls, respectively; p < 0.05) and correlated with hexose-6-phosphate dehydrogenase mRNA levels. The level of VAT 11beta-HSD-1 mRNA correlated with anthropometric parameters: BMI (r = 0.41, p = 0.05), waist circumference (r = 0.44, p = 0.04), abdominal sagittal diameter (r = 0.51, p = 0.02), and percentage fat (r = 0.51, p = 0.02).
Our results demonstrate for the first time that 11beta-HSD-1 mRNA expression is increased in VAT from obese patients. They strengthen the importance of 11beta-HSD-1 in human obesity and its associated complications and suggest the need of clinical studies with specific 11beta-HSD-1 inhibitors.
Expressions of vascular endothelial growth factor (VEGF) are increased in obese adipocytes and is secreted from obese adipose tissue through hypoxia-independent pathways. Therefore, we investigated the hypoxia-independent mechanism underlying increased expression and release of VEGF in obese adipocytes.
We compared signal transduction pathways regulating VEGF with those regulating monocyte chemoattractant protein-1 (MCP-1), which is increased in obese adipocytes, in an in vitro model of artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate, without the influence of hypoxia.
Palmitate-preloaded cells exhibited significantly enhanced oxidative stress (P < 0.01) and showed increased VEGF120 and MCP-1 release (P < 0.01, respectively), while endoplasmic reticulum (ER) stress was not induced. Increased VEGF120 release was significantly decreased with PI3K inhibitor LY294002 (P < 0.01). In addition, antioxidant N-acetyl-cysteine (NAC) markedly diminished not only VEGF120 secretion (P < 0.01) but also augmented Akt phosphorylation on Ser473 (P < 0.01). In contrast, increased MCP-1 release was suppressed with JNK inhibitor SP600125 and p38 MAPK inhibitor SB203580 (P < 0.01).
VEGF120 release from hypertrophied adipocytes can be enhanced through PI3K pathways activated by oxidative stress but not by ER stress, suggesting that VEGF120 secretion is regulated through oxidative stress-dependent pathways distinct from those involved in MCP-1 release through either JNK or p38 MAPK activation.
Changes in school nutrition and physical activity policies and environments are important to combat childhood obesity. Arkansas Act 1220 of 2003 was among the first and most comprehensive statewide legislative initiatives to combat childhood obesity through school-based change. Annual surveys of principals and superintendents have been analyzed to document substantial and important changes in school environments, policies, and practices. For example, results indicate that schools are more likely to require that healthy options be provided for student parties (4.5% in 2004, 36.9% in 2008; P <or= 0.0001) and concession stands (1.6% in 2004, 19.6% in 2008; P <or= 0.0001), ban commercial advertising by food or beverage companies (31.7% in 2005, 42.6% in 2008; P <or= 0.0001), and offer skim milk options for students in cafeterias (white milk: 26.1% in 2004, 41.0% in 2008, P <or= 0.0001; chocolate milk: 9.0% in 2004, 24.0% in 2008, P <or= 0.0001). They are less likely to have vending machines available during the lunch period (72.3% in 2004, 37.2% in 2008; P <or= 0.0001) and to include sodas in vending machines (83.8% in 2004, 73.5% in 2008; P <or= 0.0001). Other changes were noted in foods and beverages offered in the cafeteria, in classrooms, and at school events, as well as in fund-raising and physical activity practices. A significant number of school districts have modified physical education requirements for elementary schools and developed policies prohibiting the use of physical activity as a punishment. We conclude that Arkansas Act 1220 of 2003 is associated with a number of changes in school environments and policies, resulting from both statewide and local initiatives spawned by the Act.
Dopamine plays an important role in both the rewarding and conditioning effects of food. These effects involve mesolimbic, mesocortical, and nigrostriatal pathways. In humans, the most consistent finding has been reduced striatal dopamine D2/3 receptor availability. In striatum, dopamine is inactivated by reuptake via the dopamine transporter (DAT). The aim of the study was to test the hypothesis of lower DAT availability in obese healthy subjects using a selective DAT radiotracer in a sample of subjects with a wide range of BMI values.
Design and methods:
Thirty-three healthy subjects with a mean age of 48.4 ± 13.3 (range, 21-71) years and a mean BMI of 29.6 ± 7.8 kg/m2 (range, 21.0-49.5) were included in the study. We used [123I]PE2I and SPECT to measure DAT availability.
Using multiple linear regression analyses with striatal DAT as the dependent variable and BMI, age and gender as predictors was performed. We found no correlation between BMI and striatal DAT availability in striatum (P = 0.99), caudate nucleus (P = 0.61), and putamen (P = 0.30). Furthermore, we found no group difference between obese/severely obese (BMI > 30 kg/m2) and normal weight controls (BMI ≤ 25 kg/m2).
We did not find any correlation between BMI and DAT availability in healthy volunteers.
It has been recognized that obese individuals are intrinsically in a state of chronic inflammation, as indicated by positive correlations between serum levels of C-reactive protein (CRP) and various anthropometric measures of obesity. To explore the hypothesis that a gene(s) may underlie this relationship, we conducted bivariate linkage analyses of BMI and CRP in white and African-American (AA) families of the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study (FHS). Variance components linkage analysis as implemented in SOLAR was performed in 1,825 whites (840 men and 985 women) and 548 AAs (199 men and 351 women). CRP exhibited significant genetic correlations with BMI in women (0.54 +/- 0.10 for white and 0.53 +/- 0.14 for AA) and the combined samples (0.37 +/- 0.09 for white and 0.56 +/- 0.13 for AA), but not in men. We detected a maximum bivariate lod score of 3.86 on chromosome 12q24.2-24.3 at 139 cM and a suggestive linkage signal (lod = 2.19) on chromosome 19p13.1 (44 cM) in white women. Both bivariate peaks were substantially higher than their respective univariate lods at the same locus for each trait. No significant lod scores were detected in AAs. Our results indicate that chromosome 12q may harbor quantitative trait loci (QTLs) jointly regulating BMI and CRP in white women.
Socioeconomic inequalities in body weight have been demonstrated in numerous cross-sectional studies; however, little research has investigated these inequalities from a life course and longitudinal perspective. We examined the association between child- and adulthood socioeconomic position (SEP) and BMI and overweight/obesity in 1991 (baseline) and changes in BMI and the prevalence of overweight and obesity between 1991 and 2004. Data from the 1991 and 2004 waves of the longitudinal Dutch GLOBE study were used. Participants (n = 1,465) were aged 40-60 years at baseline. BMI was calculated from self-reported height and weight collected by postal questionnaire. Retrospective recall of father's occupation was used as childhood socioeconomic indicator, and adulthood SEP was measured by the occupation of the main income earner of the household. The findings showed that among women, childhood SEP exerted a greater influence on body weight than SEP in adulthood: at baseline, women from disadvantaged backgrounds in childhood had a higher BMI and were more likely to be overweight or obese, and they gained significantly more weight between baseline and follow-up. In contrast, adult SEP had a greater impact than childhood circumstances on men's body weight: those from disadvantaged households had a higher mean BMI and were more likely to be overweight or obese at baseline, and they gained significantly more weight between 1991 and 2004. The findings suggest that exposure to disadvantaged circumstances at critically important periods of the life course is associated with body weight and weight gain in adulthood. Importantly, these etiologically relevant periods differ for men and women, suggesting gender-specific pathways to socioeconomic inequalities in body weight in adulthood.
Variation in anthropometric measurements due to sexual dimorphism can be the result of genotype by sex interactions (G×S). The purpose of this study was to examine the sex-specific genetic architecture in anthropometric measurements in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Maximum likelihood-based variance components decomposition methods, implemented in SOLAR, were used for G×S analyses. Anthropometric measurements included BMI, waist circumference (WC), waist/height ratio, percent body fat (%BF), and subscapular and triceps skinfolds. Except for WC, mean values of all phenotypes were significantly different in men and women (P < 0.05). All anthropometric measures were significantly heritable (P < 0.001). In a preliminary analysis not allowing for G×S interaction, evidence of linkage was detected between markers D19S414 and D19S220 on chromosome 19 for WC (logarithm of odds (lod) = 3.5), %BF (lod = 1.7), BMI (lod = 2.4), waist/height ratio (lod = 2.5), subscapular (lod = 2.1), and triceps skinfolds (lod = 1.9). In subsequent analyses which allowed for G×S interaction, linkage was again found between these traits and the same two markers on chromosome 19 with significantly improved lod scores for: WC (lod = 4.5), %BF (lod = 3.8), BMI (lod = 3.5), waist/height ratio (lod = 3.2), subscapular (lod = 3.0), and triceps skinfolds (lod = 2.9). These results support the evidence of a G×S interaction in the expression of genetic effects resulting in sexual dimorphism in anthropometric phenotypes and identify the chromosome 19q12-13 region as important for adiposity-related traits in Alaskan Eskimos.
Adverse psychosocial exposures may partially drive the high rates of obesity among blacks. The objective of this study was to prospectively examine the relationship between perceived psychosocial stress and percent change in BMI among adult black men and women. We used data from 756 women and 416 men who were participants in the Pitt County Study, a community-based, prospective cohort study of blacks in eastern North Carolina. Participants were aged 25-50 years of age on entry into the study in 1988 and follow-up was obtained in 2001. Using multivariable linear regression, we calculated the adjusted mean percentage change in BMI over the follow-up period for each tertile of baseline measures of the Perceived Stress Scale (low, medium, and high), adjusted for potential confounders. For black women, higher levels of psychosocial stress at baseline predicted higher adjusted percentage increase in BMI over the 13-year follow-up: low stress 12.0% (95% CI 9.6-14.4), medium stress 16.3% (95% CI 13.7-18.9), and high stress 15.5% (95% CI 13.1-17.8). For black men, perceived stress was not associated with percent BMI change. These data suggest that interventions targeting obesity in black women should consider the potential impact of emotional stress on weight change.
To assess whether parental overweight status and disinhibited overeating are predictive of daughters' accelerated weight gain and disinhibited overeating.
Participants were part of a longitudinal study of girls (N = 197) and their parents. Measured height and weight were used to calculate BMI [weight (kilograms)/height (meters)(2)]. Parents' disinhibited eating behavior was assessed using the Eating Inventory. Girls' disinhibited eating was assessed using a behavioral protocol to measure eating in the absence of hunger. Girls were classified based on parental overweight at study entry into four groups: neither, mother only, father only, or both parents overweight.
Girls with both parents overweight had the most rapid increases in BMI from 5 to 13 years of age; BMI increased most slowly among the neither parent overweight group, with intermediate increases in BMI among mother only and father only overweight groups. Daughters with both parents overweight at study entry were eight times more likely to be overweight at age 13, controlling for daughters' weight at age 5. Girls with both parents overweight had higher levels of disinhibited eating across all ages than all other groups. Although girls in all parental weight status groups showed increases in disinhibited eating over time, girls with both parents overweight had larger increases in disinhibited eating over time compared with all other groups.
Girls growing up in families differing in parental overweight had divergent developmental trajectories for BMI and disinhibited overeating. Findings reveal the need to focus prevention efforts on overweight parents of young children.
The -13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene, strongly associated with lactase persistence (LP) in Europeans, is emerging as a new candidate for obesity. We aimed to analyze the association of this polymorphism with obesity-related variables and its modulation by dairy product intake in an elderly population. We studied 940 high-cardiovascular risk Spanish subjects (aged 67 ± 7 years). Dairy product consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured, and metabolic syndrome-related variables were obtained. Prevalence of genotypes was: 38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genotype was not associated with lower milk or dairy product consumption in the whole population. Only in women was dairy intake significantly lower in CC subjects. The most important association was obtained with anthropometric measurements. CC individuals had lower weight (P = 0.032), lower BMI (29.7 ± 4.2 vs. 30.6 ± 4.2 kg/m(2); P = 0.003) and lower waist circumference (101.1 ± 11.8 vs. 103.5 ± 11.5 cm; P = 0.005) than T-allele carriers. Obesity risk was also significantly higher in T-allele carriers than in CC individuals (odds ratio (OR): 1.38; 95% confidence interval (CI): 1.05-1.81; P = 0.01), and remained significant even after adjustment for sex, age, diabetes, physical activity, and energy intake. However, in subgroup analysis, these associations were found to be significant only among those consuming moderate or high lactose intakes (>8 g/day). No significant associations with lipids, glucose, or blood pressure were obtained after adjustment for BMI. In conclusion, despite not finding marked differences in dairy product consumption, this polymorphism was strongly associated with BMI and obesity and modulated by lactose intake in this Mediterranean population.
The prevalence of Class 3 obesity (BMI ≥40 kg/m(2)) has more than doubled in the past 25 years. In a 14-year prospective study from age 10 to 24 of a biracial schoolgirl cohort (293 black, 256 white), we assessed childhood correlates of Class 3 BMI at age 24. Of 42 girls with Class 3 BMI at age 24, 36 (86%) were black. By logistic regression, significant explanatory variables of Class 3 BMI at age 24 included top decile waist circumference at age 11 (odds ratio (OR) 5.7, 95% confidence interval (CI) 2.3-13.9, P = 0.0002), age 10 BMI ≥ the Center for Disease Control (CDC) 2000 top 15% (OR 7.0, 95% CI 2.5-19.3, P = 0.0002), and a three-way interaction between race, childhood insulin, and average caloric intake from age 10 to age 19 (for each unit increase, OR 1.7 95% CI 1.3-2.2, P = 0.0003). Age 10 BMI, age 11 waist circumference, and interaction of race, childhood insulin, and childhood caloric intake predict Class 3 obesity in young adulthood, facilitating childhood identification of girls at high risk for developing Class 3 obesity.
To examine the effect of reverse causality and confounding on the association of BMI with all-cause and cause-specific mortality.
Data from two large prospective studies were used. One (a community-based cohort) included 8327 women and 7017 men who resided in two Scottish towns at the time of the baseline assessment in 1972-1976; the other (an occupational cohort) included 4016 men working in the central belt of Scotland at the time of the baseline assessment in 1970-1973. Participants in both cohorts were ages 45 to 64 years at baseline; the follow-up period was 28 to 34 years.
In age-adjusted analyses that did not take account of reverse causality or smoking, there was no association between being overweight (BMI 25 to <30 kg/m(2)) and mortality, and weak to modest associations between obesity (BMI > or =30 kg/m(2)) and mortality. There was a strong association between smoking and lower BMI in women and men in both cohorts (all p < 0.0001). Among never-smokers and with the first 5 years of deaths removed, overweight was associated with an increase in all-cause mortality (relative risk ranging from 1.12 to 1.38), and obesity was associated with a doubling of risk in men in both cohorts (relative risk, 2.10 and 1.96, respectively) and a 60% increase in women (relative risk, 1.56). In both never-smokers and current smokers, being overweight or obese was associated with important increases in the risk of cardiovascular disease.
These findings demonstrate that with appropriate control for smoking and reverse causality, both overweight and obesity are associated with important increases in all-cause and cause-specific mortality, and in particular with cardiovascular disease mortality.
Previous research has examined the association between screen time and average changes in adolescent body mass index (BMI). Until now, no study has evaluated the longitudinal relationship between screen time and changes in the BMI distribution across mid to late adolescence.
Design and methods:
Participants (n = 1,336) were adolescents who were followed from age 14 to age 18 and surveyed every 6 months. Time spent watching television/videos and playing video games was self-reported (<1 h day(-1) , 1 h day(-1) , 2 h day(-1) , 3 h day(-1) , 4 h day(-1) , or 5+ h day(-1) ). BMI (kg m(-2) ) was calculated from self-reported height and weight. Longitudinal quantile regression was used to model the 10th, 25th, 50th, 75th, and 90th BMI percentiles as dependent variables. Study wave and screen time were the main predictors, and adjustment was made for gender, race, maternal education, hours of sleep, and physical activity.
Increases at all the BMI percentiles over time were observed, with the greatest increase observed at the 90th BMI percentile. Screen time was positively associated with changes in BMI at the 50th (0.17, 95% CI: 0.06, 0.27), 75th (0.31, 95% CI: 0.10, 0.52), and 90th BMI percentiles (0.56, 95% CI: 0.27, 0.82). No associations were observed between screen time and changes at the 10th and 25th BMI percentiles.
Positive associations between screen time and changes in the BMI at the upper tail of the BMI distribution were observed. Therefore, lowering screen time, especially among overweight and obese adolescents, could contribute to reducing the prevalence of adolescent obesity.
To examine the associations between poverty dynamics and the long-term risk of developing overweight or obesity.
Design and methods
Our data are a representative sample of U.S. children from the National Longitudinal Survey of Youth 1979 Child and Young Adult Survey (1986-2008). We used survival analysis to compare risk of developing overweight or obesity among 5,613 children aged 4 to 14 from never poor households, transient poor households (those that became poor only once), recurrent poor households (those that became poor more than once), and persistent poor households (those that became poor and remained poor for at least 4 consecutive years) and examined interactions by race/ethnicity, gender, and age.
Compared with children from never poor households, children from transient poor households (HR 0.79, 95% CI: 0.68, 0.92), recurrent poor households (HR: 0.73, 95% CI: 0.62, 0.87), and persistently poor households (HR: 0.62, 95% CI: 0.51, 0.74) had significantly reduced risks of becoming overweight or obese. These associations did not vary by race/ethnicity, gender, or age.
Our findings suggest that poverty experiences are associated with reduced risk of becoming overweight or obese among children 4 to 14.
Trodusquemine (MSI-1436) causes rapid and reversible weight loss in genetic models of obesity. To better predict the potential effects of trodusquemine in the clinic, we investigated the effects of trodusquemine treatment in a murine model of diet-induced obesity (DIO). Trodusquemine suppressed appetite, reduced body weight (BW) in a fat-specific manner, and improved plasma insulin and leptin levels in mice. Screening assays revealed that trodusquemine selectively inhibited protein-tyrosine phosphatase 1B (PTP1B), a key enzyme regulating insulin and leptin signaling. Trodusquemine significantly enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) beta and STAT3, direct targets of PTP1B, in HepG2 cells in vitro and/or hypothalamic tissue in vivo. These data establish trodusquemine as an effective central and peripheral PTP1B inhibitor with the potential to elicit noncachectic fat-specific weight loss and improve insulin and leptin levels.
Obesity is a heritable trait and a major risk factor for highly prevalent common diseases such as hypertension and type 2 diabetes. Previously we showed that BMI was positively correlated with African ancestry among the African Americans (AAs) in the US National Heart, Lung, and Blood Institute's Family Blood Pressure Program (FBPP). In a set of 1,344 unrelated AAs, using Individual Ancestry (IA) estimates at 284 marker locations across the genome, we now present a quantitative admixture mapping analysis of BMI. We used a set of unrelated individuals from Nigeria to represent the African ancestral population and the European American (EA) in the FBPP as the European ancestral population. The analysis was based on a common set of 284 microsatellite markers genotyped in all three groups. We considered the quantitative trait, BMI, as the response variable in a regression analysis with the marker location specific excess European ancestry as the explanatory variable. After suitably adjusting for different covariates such as sex, age, and network, we found strong evidence for a positive association with European ancestry at chromosome locations 3q29 and 5q14 and a negative association on chromosome 15q26. To our knowledge, this is the largest quantitative admixture mapping effort in terms of sample size and marker locus involvement for the trait. These results suggest that these regions may harbor genes influencing BMI in the AA population.
The metabolic syndrome represents a cluster of cardiovascular risk factors co-occurring in the same individual. The aim of this study was to identify chromosomal regions encoding genes predisposing to the metabolic syndrome using composite factors derived from maximum likelihood-based factor analysis. Genetic data were obtained from the Quebec Family Study and included 707 subjects from 264 nuclear families. Factor analyses were performed on eight metabolic syndrome-related phenotypes including waist circumference; BMI; systolic and diastolic blood pressure; and plasma insulin, glucose, triglyceride, and high-density lipoprotein-cholesterol levels. Three factors were identified and interpreted as general metabolic syndrome, blood pressure, and blood lipids, respectively. The general metabolic syndrome factor had high factor loadings (>0.4) for all phenotypes and explained 42% of the total variance, and family membership accounted for 45.6% of the factor variance. A genome-wide linkage scan performed with this first factor revealed the existence of a quantitative trait locus on chromosome 15 (86 cM) with a logarithm of odds score of 3.15. Suggestive evidence of linkage (logarithm of odds > 1.75) was also observed on chromosomes 1p, 3p, 3q, 6q, 7p, 19q, and 21q. These quantitative trait loci may harbor genes contributing to the clustering of the metabolic syndrome-related phenotypes.
In the present study, we undertook a two-step fine mapping of a 20-megabase region around a quantitative trait locus previously reported on chromosome 15q26 for abdominal subcutaneous fat (ASF) in an extended sample of 707 subjects from 202 families from the Quebec Family Study.
First, 19 microsatellites (in addition to the 7 markers initially available on 15q24-q26; total = 26) were genotyped and tested for linkage with abdominal total fat, abdominal visceral fat, and ASF assessed by computed tomography and with fat mass (FM) using variance component-based approach on age- and sex-adjusted phenotypes. Second, 16 single nucleotide polymorphisms (SNPs) were genotyped and tested for association using family-based association tests.
After the fine mapping, the peak logarithm of odds ratio (LOD) score (marker D15S1004) increased from 2.79 to 3.26 for ASF and from 3.52 to 4.48 for FM, whereas for abdominal total fat, the peak linkage (marker D15S996) decreased from 2.22 to 1.53. No evidence of linkage was found for abdominal visceral fat. Overall, for genotyped SNPs, three variants located in the putative MCTP2 gene were significantly associated with FM and the three abdominal fat phenotypes (p <or= 0.05). The major allele and genotype of rs1424695 were associated with higher adiposity values (p < 0.004). The same trend was found for the two other polymorphisms (p < 0.05). None of the other SNPs was associated with adiposity phenotypes. The linkage for FM became non-significant (LOD = 0.84) after adjustment for the MCTP2 polymorphisms, whereas the one for ASF remained unchanged.
These results suggest that the MCTP2 gene, located on chromosome 15q26, influences adiposity. Other studies will be needed to investigate the function of the MCTP2 gene and its role in obesity.