Early hypothalamic FTO overexpression in response to maternal obesity--potential contribution to postweaning hyperphagia

Background

Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO.

Methods

Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured.

Results

At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding.

Significance

Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human data. No effect of maternal obesity was observed on FTO in adulthood.     

Selective Leptin Insensitivity and Alterations in Female-Reproductive Patterns Linked to Hyperleptinemia during Infancy

The dramatic increase in the prevalence of childhood obesity worldwide makes the investigation of its early developmental stages and effective prevention strategies an urgent issue. CCK₁ deficient OLETF rats are a model of obesity previously used to study the early phases of this disorder. Here, we exposed wild type (LETO) females to an early obesogenic environment and genetically obese OLETF females to a lean postnatal environment, to assess long term alterations in leptin sensitivity, predisposition to diet induced obesity and adult female health. We found that genetically lean females reared by obese mothers presented early postnatal hyperleptemia, selectively reduced response to leptin and sensitivity to diet induced obesity when exposed to a high palatable diet as adults. The estrous cycle structure and intake profile were permanently disrupted, despite presenting normal adiposity/body weight/food intake. Genetically obese females reared by lean dams showed normalized early levels of leptin and reduced body weight, food intake and body fat at adulthood; normalized estrous cycle structure and food intake across the cycle, improved hormonal profile and peripheral leptin sensitivity and a remarkable progress in self-control when exposed to a high fat/palatable diet. Altogether, it appears that the early postnatal environment plays a critical role in determining later life coping with metabolic challenges and has an additive effect on the genetic predisposition that makes OLETF females morbidly obese as adults. This work also links, for the first time, alterations in the leptin system during early development to later life abnormalities related to female reproduction and health.     

Hypothalamic Neuroendocrine Circuitry is Programmed by Maternal Obesity: Interaction with Postnatal Nutritional Environment

Objective

Early life nutrition is critical for the development of hypothalamic neurons involved in energy homeostasis. We previously showed that intrauterine and early postnatal overnutrition programmed hypothalamic neurons expressing the appetite stimulator neuropeptide Y (NPY) and suppressor proopiomelanocortin (POMC) in offspring at weaning. However, the long-term effects of such programming and its interactions with post-weaning high-fat-diet (HFD) consumption are unclear.

Research Design and Methods

Female Sprague Dawley rats were exposed to chow or HFD for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1, litters were adjusted to 3/litter to induce postnatal overnutrition (vs. 12 in control). At postnatal day 20, half of the rats from each maternal group were weaned onto chow or HFD for 15 weeks. Hypothalamic appetite regulators, and fuel (glucose and lipid) metabolic markers were measured.

Results

Offspring from obese dams gained more weight than those from lean dams independent of post-weaning diet. Maternal obesity interacted with post-weaning HFD consumption to cause greater levels of hyperphagia, adiposity, hyperlipidemia, and glucose intolerance in offspring. This was linked to increased hypothalamic NPY signaling and leptin resistance in adult offspring. Litter size reduction had a detrimental impact on insulin and adiponectin, while hypothalamic NPY and POMC mRNA expression were suppressed in the face of normal energy intake and weight gain.

Conclusions

Maternal obesity, postnatal litter size reduction and post-weaning HFD consumption caused obesity via different neuroendocrine mechanims. There were strong additive effects of maternal obesity and post-weaning HFD consumption to increase the metabolic disorders in offspring.     

Prenatal Polycyclic Aromatic Hydrocarbon,Adiposity, Peroxisome Proliferator-Activated Receptor (PPAR) γ Methylation in Offspring,Grand-Offspring Mice

Rationale

Greater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH) have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear.

Objectives

We hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected.

Materials and Methods

Pregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND) 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding proteins (C/EBP) α, cyclooxygenase (Cox)-2, fatty acid synthase (FAS) and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue.

Findings

Offspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice.

Conclusions

Greater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny.     

Long-term obesity levels in female OLETF rats following time-specific post-weaning food restriction

Obesity and the metabolic syndrome represent serious health threats affecting increasing numbers of individuals, with females being more affected than males and with growing incidence among children and adolescents. In the present study, we used the OLETF rat model of early-onset obesity to examine the influence of different timing of food restriction on long-term obesity levels in females. Food restriction took place at different time windows: from weaning until postnatal day (PND) 45 (early); from weaning until PND90 (chronic); or from PND45 until PND70 (late). Follow-up continued until PND90. During and after the termination of the diet-restriction period, we focused on peripheral adiposity-related measures such as fat pad weight (brown, retroperitoneal and inguinal); inguinal adipocyte size and number; and leptin, oxytocin and glucose levels. We also examined body weight, feeding efficiency, spontaneous intake after release from diet-restriction, and plasma creatinine levels and estrous cycle characteristics as a result of the chronic diet. The results suggest that while food restriction produced significant weight and adiposity loss, OLETF females presented poor weight loss retention after the early and late short-term diets. The estrous cycle structure and time of first estrous of the OLETF rats were normalized by chronic food restriction. Females responded to early food restriction in a different manner than males did in previous studies, further emphasizing the importance of sex-appropriate approaches in the investigation and treatment of the pathologies related to obesity and the metabolic syndrome.     

Long-term obesity levels in female OLETF rats following time-specific post-weaning food restriction

Obesity and the metabolic syndrome represent serious health threats affecting increasing numbers of individuals, with females being more affected than males and with growing incidence among children and adolescents. In the present study, we used the OLETF rat model of early-onset obesity to examine the influence of different timing of food restriction on long-term obesity levels in females. Food restriction took place at different time windows: from weaning until postnatal day (PND) 45 (early); from weaning until PND90 (chronic); or from PND45 until PND70 (late). Follow-up continued until PND90. During and after the termination of the diet-restriction period, we focused on peripheral adiposity-related measures such as fat pad weight (brown, retroperitoneal and inguinal); inguinal adipocyte size and number; and leptin, oxytocin and glucose levels. We also examined body weight, feeding efficiency, spontaneous intake after release from diet-restriction, and plasma creatinine levels and estrous cycle characteristics as a result of the chronic diet. The results suggest that while food restriction produced significant weight and adiposity loss, OLETF females presented poor weight loss retention after the early and late short-term diets. The estrous cycle structure and time of first estrous of the OLETF rats were normalized by chronic food restriction. Females responded to early food restriction in a different manner than males did in previous studies, further emphasizing the importance of sex-appropriate approaches in the investigation and treatment of the pathologies related to obesity and the metabolic syndrome.     

Relationship of Adipocyte Size with Adiposity and Metabolic Risk Factors in Asian Indians

Background

Enlargement of adipocyte is associated with their dysfunction and alterations in metabolic functions.

Objectives

We evaluated the association of adipocyte size of subcutaneous and omental adipose tissue with body composition and cardiovascular risk factors in Asian Indians.

Methodology

Eighty (40 males and 40 females) non-diabetic adult subjects undergoing elective abdominal surgery were included. Pre-surgery evaluation included anthropometric measurements, % body fat by bioimpedance, abdominal fat area at L_2–3 level (computed tomography) and biochemical investigations (fasting blood glucose and insulin, lipids and hsCRP). During surgery, about 5 grams each of omental and subcutaneous adipose tissue was obtained for adipocyte size determination.

Results

Females had higher BMI, % body fat, skinfold thickness, total and subcutaneous abdominal fat area as compared to males. Overweight was present in 42.5% and 67.5%, and abdominal obesity in 5% and 52.5% males and females, respectively. Subcutaneous adipocyte size was significantly higher than omental adipocyte size. Omental adipocyte size correlated more strongly than subcutaneous adipocyte size with measures of adiposity (BMI, waist circumference, %BF), total and subcutaneous abdominal fat area and biochemical measures (fasting glucose, total cholesterol, triglycerides and HOMA-IR), the correlations being stronger in females. The correlation of adipocyte size with metabolic parameters was attenuated after adjusting for measures of adiposity.

Conclusion

Omental adipocyte size, though smaller than the subcutaneous adipocyte size, was more closely related to measures of adiposity and metabolic parameters. However, the relationship was not independent of measures of adiposity.     

Loss of Magel2, a Candidate Gene for Features of Prader-Willi Syndrome,Impairs Reproductive Function in Mice

Background

MAGEL2 is one of several genes typically inactivated in the developmental obesity disorder Prader-Willi syndrome (PWS). The physiological consequences of loss of MAGEL2, but without the concurrent loss of other PWS genes, are not well understood. Gene-targeted mutation of Magel2 in mice disrupts circadian rhythm and metabolism causing reduced total activity, reduced weight gain before weaning, and increased adiposity after weaning.

Principal Findings

We now show that loss of Magel2 in mice causes reduced fertility in both males and females through extended breeding intervals and early reproductive decline and termination. Female Magel2-null mice display extended and irregular estrous cycles, while males show decreased testosterone levels, and reduced olfactory preference for female odors.

Conclusions

Our results suggest that loss of MAGEL2 contributes to the reproductive deficits seen in people with PWS, and further highlights the role of normal circadian rhythm in the maintenance of fertility.     

Maternal cigarette smoke exposure contributes to glucose intolerance and decreased brain insulin action in mice offspring independent of maternal diet

Background

Maternal smoking leads to intrauterine undernutrition and is associated with low birthweight and higher risk of offspring obesity. Intrauterine smoke exposure (SE) may alter neuroendocrine mediators regulating energy homeostasis as chemicals in cigarette smoke can reach the fetus. Maternal high-fat diet (HFD) consumption causes fetal overnutrition; however, combined effects of HFD and SE are unknown. Thus we investigated the impact of combined maternal HFD and SE on adiposity and energy metabolism in offspring.

Method

Female Balb/c mice had SE (2 cigarettes/day, 5 days/week) or were sham exposed for 5 weeks before mating. Half of each group was fed HFD (33% fat) versus chow as control. The same treatment continued throughout gestation and lactation. Female offspring were fed chow after weaning and sacrificed at 12 weeks.

Results

Birthweights were similar across maternal groups. Faster growth was evident in pups from SE and/or HFD dams before weaning. At 12 weeks, offspring from HFD-fed dams were significantly heavier than those from chow-fed dams (chow-sham 17.6±0.3 g; chow-SE 17.8±0.2 g; HFD-sham 18.7±0.3 g; HFD-SE 18.8±0.4 g, P<0.05 maternal diet effect); fat mass was significantly greater in offspring from chow+SE, HFD+SE and HFD+sham dams. Both maternal HFD and SE affected brain lactate transport. Glucose intolerance and impaired brain response to insulin were observed in SE offspring, and this was aggravated by maternal HFD consumption.

Conclusion

While maternal HFD led to increased body weight in offspring, maternal SE independently programmed adverse health outcomes in offspring. A smoke free environment and healthy diet during pregnancy is desirable to optimize offspring health.     

Different anthropometric adiposity measures and their association with cardiovascular disease risk factors: a meta-analysis

Objectives

To investigate which anthropometric adiposity measure has the strongest association with cardiovascular disease (CVD) risk factors in Caucasian men and women without a history of CVD.

Design

Systematic review and meta-analysis.

Methods

We searched databases for studies reporting correlations between anthropometric adiposity measures and CVD risk factors in Caucasian subjects without a history of CVD. Body mass index (BMI), waist circumference, waist-to-hip ratio, waist-to-height ratio and body fat percentage were considered the anthropometric adiposity measures. Primary CVD risk factors were: systolic blood pressure, diastolic blood pressure, high density lipoprotein (HDL) cholesterol, triglycerides and fasting glucose. Two independent reviewers performed abstract, full text and data selection.

Results

Twenty articles were included describing 21,618 males and 24,139 females. Waist circumference had the strongest correlation with all CVD risk factors for both men and women, except for HDL and LDL in men. When comparing BMI with waist circumference, the latter showed significantly better correlations to CVD risk factors, except for diastolic blood pressure in women and HDL and total cholesterol in men.

Conclusions

We recommend the use of waist circumference in clinical and research studies above other anthropometric adiposity measures, especially compared with BMI, when evaluating CVD risk factors.     

Association of a Body Mass Index Genetic Risk Score with Growth throughout Childhood and Adolescence

Background

While the number of established genetic variants associated with adult body mass index (BMI) is growing, the relationships between these variants and growth during childhood are yet to be fully characterised. We examined the association between validated adult BMI associated single nucleotide polymorphisms (SNPs) and growth trajectories across childhood. We investigated the timing of onset of the genetic effect and whether it was sex specific.

Methods

Children from the ALSPAC and Raine birth cohorts were used for analysis (n = 9,328). Genotype data from 32 adult BMI associated SNPs were investigated individually and as an allelic score. Linear mixed effects models with smoothing splines were used for longitudinal modelling of the growth parameters and measures of adiposity peak and rebound were derived.

Results

The allelic score was associated with BMI growth throughout childhood, explaining 0.58% of the total variance in BMI in females and 0.44% in males. The allelic score was associated with higher BMI at the adiposity peak (females  =  0.0163 kg/m² per allele, males  =  0.0123 kg/m² per allele) and earlier age (-0.0362 years per allele in males and females) and higher BMI (0.0332 kg/m² per allele in females and 0.0364 kg/m² per allele in males) at the adiposity rebound. No gene:sex interactions were detected for BMI growth.

Conclusions

This study suggests that known adult genetic determinants of BMI have observable effects on growth from early childhood, and is consistent with the hypothesis that genetic determinants of adult susceptibility to obesity act from early childhood and develop over the life course.     

Reduction in Adiposity, β-Cell Function,Insulin Sensitivity,and Cardiovascular Risk Factors: A Prospective Study among Japanese with Obesity

Background

A reduction in adiposity may be associated with an improvement in insulin sensitivity and β-cell function as well as cardiovascular disease (CVD) risk factors; however, few studies have investigated these associations in a longitudinal setting.

Methods

To investigate these associations over a 1-year period, we conducted an observational analysis of 196 Japanese subjects with obesity in the Saku Control Obesity Program. We investigated the relations between changes in adiposity (body mass index [BMI], waist circumference, subcutaneous fat area [SFAT], and visceral fat area [VFAT]) and changes in HbA1c, fasting plasma glucose (FPG), insulin sensitivity index (ISI), the homeostasis model assessment β cell function (HOMA-β), lipids, and blood pressure.

Results

All adiposity changes were positively associated with HbA1c and FPG changes. Reductions in BMI and VFAT were associated with HOMA-β reduction. Reductions in all adiposity measures were associated with an improvement in the ISI. Changes in most adiposity measures were positively associated with changes in blood pressure and lipid levels, except for LDL.

Conclusion

The present findings provide additional supportive evidence indicating that a reduction in adiposity may lead to an improvement in insulin sensitivity and the reduction of CVD risk factors in obese individuals.     

Serum fetuin A and chemerin levels correlate with hepatic steatosis and regional adiposity in maintenance hemodialysis patients

Background

A deficiency of fetuin A is linked to cardiovascular calcification and mortality in dialysis patients. But, high levels of fetuin A and chemerin correlate with hepatic steatosis and regional adiposity in general population. The association between hepatic steatosis and fetuin A/chemerin levels in hemodialysis (HD) remains unclear.

Methods

We performed a cross-sectional, observational study; 216 prevalent HD patients from a single center were enrolled. Baseline serum fetuin A, chemerin levels, conicity index and anthropometric parameters were checked. Presence of hepatic steatosis was qualified by liver ultrasound and quantified by the hepato-renal index (HRI); central obesity defined by waist circumference (WC). ROC analyses and multivariate logistic regression analyses for prediction of hepatic steatosis and central obesity on the basis of fetuin A/chemerin levels, anthropometric parameters, and other relevant covariates were performed.

Results

Data from 103 women and 113 men (mean age 60±12 years) were analyzed. Eighty subjects had hepatic steatosis and their HRIs were significantly higher than those without hepatic steatosis (P<0.001). Serum fetuin A levels were positively associated with HRIs (P<0.001) and chemerin levels (P<0.001). Fetuin A, chemerin and WC were predictors for hepatic steatosis and central obesity by ROC curve. In multivariate logistic regression analysis, fetuin A and WC independently predicted hepatic steatosis defined by HRIs. And chemerin predicted central obesity and regional adiposity after covariate adjustments (all P<0.05).

Conclusions

Serum fetuin A levels were higher in prevalent HD patients with hepatic steatosis, and positively correlated with chemerin levels. Chemerin levels predicted central obesity as well as regional adiposity in the HD patients.     

Postnatal Depression among Rural Women in South India: Do Socio-Demographic,Obstetric and Pregnancy Outcome Have a Role to Play?

Introduction

Postnatal depression (PND) is one of the most common psychopathology and is considered as a serious public health issue because of its devastating effects on mother, family, and infant or the child.

Objective

To elicit socio-demographic, obstetric and pregnancy outcome predictors of Postnatal Depression (PND) among rural postnatal women in Karnataka state, India.

Design

Hospital based analytical cross sectional study

Setting

A rural tertiary care hospital of Mandya District, Karnataka state, India.

Sample

PND prevalence based estimated sample of 102 women who came for postnatal follow up from 4th to 10th week of lactation.

Method

Study participants were interviewed using validated kannada version of Edinburgh Postnatal Depression Scale (EPDS). Cut-off score of ≥13 was used as high risk of PND. The percentage of women at risk of PND was estimated, and differences according to socio-demographic, obstetric and pregnancy outcome were described. Logistic regression was applied to identify the independent predictors of PND risk.

Main Outcome Measures

Prevalence, Odds ratio (OR) and adjusted (adj) OR of PND

Results

Prevalence of PND was 31.4% (95% CI 22.7–41.4%). PND showed significant (P<0.05) association with joint family, working women, non-farmer husbands, poverty, female baby and pregnancy complications or known medical illness. In binomial logistic regression poverty (adjOR: 11.95, 95% CI:1.36–105), birth of female baby (adjOR: 3.6, 95% CI:1.26–10.23) and pregnancy complications or known medical illness (adjOR: 17.4, 95% CI:2.5–121.2) remained as independent predictors of PND.

Conclusion

Risk of PND among rural postnatal women was high (31.4%). Birth of female baby, poverty and complications in pregnancy or known medical illness could predict the high risk of PND. PND screening should be an integral part of postnatal care. Capacity building of grass root level workers and feasibility trials for screening PND by them are needed.     

Central Obesity and Albuminuria: Both Cross-Sectional and Longitudinal Studies in Chinese

Background

Albuminuria is recognized as a marker of vascular dysfunction. Central obesity increases the risk of cardiovascular disease. Little is known about the association between albuminuria and central obesity in Chinese. We aimed to assess the association between central obesity and prevalence and incidence of albuminuria in a middle-aged population-based cohort study.

Methods

This is a cross-sectional and longitudinal cohort study. A total of 2350 subjects aged ≥40 years were recruited in 2004 in Taiwan for cross-sectional analysis. Longitudinal analysis included 1432 baseline normoalbuminuria subjects with a mean 2.8 years follow-up, 67 of whom exhibited incident albuminuria. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g creatinine. Multiple logistic regression analyses were used to evaluate the relationship between central obesity and prevalence and incidence of albuminuria after adjustment for age, gender, body mass index, blood pressure, renal function, glucose, high sensitivity c-reactive protein, smoking, betel nut chewing, alcohol drinking, and physical activity.

Results

At baseline, albuminuria is significantly associated with central obesity. The adjusted odds ratio of having albuminuria among subjects with central obesity was 1.73(95% confidence interval (CI): 1.04–2.85), compared to the subjects without central obesity. In multivariable models, participants with central obesity at baseline had a 112% increase in risk of incident albuminuria (adjusted incidence rate ratio (95% CI): 2.12(1.01–4.44)) compared with participants with non-central obesity.

Conclusions

Abdominal adiposity was independently associated with increased prevalence and incidence of albuminuria in Chinese. The mechanisms linking adiposity and albuminuria need to be addressed.     

Short-Term Overfeeding Increases Circulating Adiponectin Independent of Obesity Status

Background

Adiponectin is an adipose tissue derived hormone which strengthens insulin sensitivity. However, there is little data available regarding the influence of a positive energy challenge (PEC) on circulating adiponectin and the role of obesity status on this response.

Objective

The purpose of this study was to investigate how circulating adiponectin will respond to a short-term PEC and whether or not this response will differ among normal-weight(NW), overweight(OW) and obese(OB).

Design

We examined adiponectin among 64 young men (19-29 yr) before and after a 7-day overfeeding (70% above normal energy requirements). The relationship between adiponectin and obesity related phenotypes including; weight, percent body fat (%BF), percent trunk fat (%TF), percent android fat (%AF), body mass index (BMI), total cholesterol, HDLc, LDLc, glucose, insulin, homeostatic model assessment insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were analyzed before and after overfeeding.

Results

Analysis of variance (ANOVA) and partial correlations were used to compute the effect of overfeeding on adiponectin and its association with adiposity measurements, respectively. Circulating Adiponectin levels significantly increased after the 7-day overfeeding in all three adiposity groups. Moreover, adiponectin at baseline was not significantly different among NW, OW and OB subjects defined by either %BF or BMI. Baseline adiponectin was negatively correlated with weight and BMI for the entire cohort and %TF, glucose, insulin and HOMA-IR in OB. However, after controlling for insulin resistance the correlation of adiponectin with weight, BMI and %TF were nullified.

Conclusion

Our study provides evidence that the protective response of adiponectin is preserved during a PEC regardless of adiposity. Baseline adiponectin level is not directly associated with obesity status and weight gain in response to short-term overfeeding. However, the significant increase of adiponectin in response to overfeeding indicates the physiological potential for adiponectin to attenuate insulin resistance during the development of obesity.     

Transformation of adrenal medullary chromaffin cells increases asthmatic susceptibility in pups from allergen-sensitized rats

Background

Studies have shown that epinephrine release is impaired in patients with asthma. The pregnancy of female rats (dams) with asthma promotes in their pups the differentiation of adrenal medulla chromaffin cells (AMCCs) into sympathetic neurons, mediated by nerve growth factor, which leads to a reduction in epinephrine secretion. However, the relatedness between the alteration of AMCCs and increased asthma susceptibility in such offspring has not been established.

Methods

In this study, we observed the effects of allergization via ovalbumin on rat pups born of asthmatic dams.

Results

Compared to the offspring of untreated controls, bronchial hyperreactivity and airway inflammation were more severe in the pups from sensitized (asthmatic) dams. In pups exposed to nerve growth factor (NGF) in utero these effects were aggravated further, but the effects were blocked in pups whose dams had been treated with anti-NGF. Furthermore, alterations in AMCC phenotype corresponded to the degree of bronchial hyperreactivity and lung lesions of the different treatment groups. Such AMCC alterations included degranulation of chromaffin granules, reduction of epinephrine and phenylethanolamine-n-methyl transferase, and elevation of NGF and peripherin levels.

Conclusions

Our results present evidence that asthma during the pregnancy of rat dams promotes asthma susceptibility in their offspring, and that the transformation of AMCCs to neurons induced by NGF plays an important role in this process.     

Comparisons of Measured and Self-Reported Anthropometric Variables and Blood Pressure in a Sample of Hong Kong Female Nurses

Objectives

To assess the validity of self-reported weight, height, body mass index (BMI), waist circumference and blood pressure compared with standardized clinical measurements and to determine the classification accuracy in overweight/obesity and central adiposity.

Methods

This pilot study was integrated into a life-course study entitled “Hong Kong Women''s Health Study” among 1,253 female nurses in Hong Kong who were aged 35 years to 65 years. Data were collected from self-administered questionnaires that were mailed to the respondents. Of these participants, we obtained the standard body measurements of 144 (11.5%) at our research center. We then compared the self-reported anthropometric variables and blood pressure with the measured data to assess validity based on the level of misreporting, percentage of agreement, consistency, sensitivity and specificity.

Results

The self-reported and measured values were highly correlated in terms of anthropometry and blood pressure (correlation coefficients ranged from 0.72 to 0.96). Height was overestimated at an average of 0.42 cm, and waist circumference was underestimated at 2.33 cm (both P<0.05), while no significant differences were observed from weight, blood pressure and BMI (all P>0.05). The proportions of overweight, obesity, and central adiposity by self-reported data did not vary greatly from the measured data (all P>0.05). The self-reporting resulted in correct classifications of BMI, waist circumference, and systolic blood pressure in 85%, 78%, and 87% of women, with corresponding Kappa index values of 0.79, 0.55, and 0.82, respectively. Sensitivity and specificity were 84.6% and 95.7%, respectively, with respect to overweight/obesity detection, whereas those for central adiposity detection were 70.6% and 83.8%, respectively.

Conclusion

In a sample of female Hong Kong nurses, the self-reported measures of height, weight, BMI, waist circumference and blood pressure were generally valid. Furthermore, the classification accuracies of overweight/obesity and central adiposity were acceptable.     

Serum Acylated Ghrelin Concentrations in Response to Short-Term Overfeeding in Normal Weight,Overweight, and Obese Men

Background

Ghrelin, an orexigenic gut hormone secreted primarily from the stomach, is involved in energy homeostasis. However, little data is available regarding its response to energy surplus and the development of human obesity.

Objective

The present study investigated the response of circulating acylated ghrelin to a 7-day positive energy challenge.

Design

A total of 68 healthy young men were overfed 70% more calories than required, for 1-week. Subjects were classified based on percent body fat (measured by dual-energy X-ray absorptiometry) as normal weight, overweight, and obese. Serum acylated ghrelin concentration was measured before and after the positive energy challenge. Additionally, the relationship between acylated ghrelin and obesity-related phenotypes including weight, body mass index, percent body fat, cholesterol, HDL-c, LDL-c, glucose, insulin and homeostasis model assessment of insulin resistance and β-cell function at baseline and change due to overfeeding, were assessed.

Results

Contrary to our expectations, serum acylated ghrelin was significantly increased in response to overfeeding and the increase was independent of obesity status. There was no significant difference in fasting acylated ghrelin between normal weight, overweight, and obese men at baseline. Acylated ghrelin was negatively correlated with weight and BMI for normal weight and with BMI in overweight men. Also ghrelin was correlated with change in weight and BMI in overweight (negative relationship) and obese (positive relationship) groups.

Conclusion

Our results showed that circulating acylated ghrelin was increased after a 7-day positive energy challenge regardless of adiposity status. However, acylated ghrelin was correlated with change in weight and BMI in opposing directions, in overweight and obese subjects respectively, thus dependent on obesity status.