bluuebunny/crossref_metadata_2025 huggingface dataset:
Leptin Response to Glucocorticoid Occurs at Physiological Doses and Is Abolished by Fasting
Authors: Dagogo‐Jack Samuel , Umamaheswaran Indira , Askari Hasan , Tykodi Gunjan
Published: April 2008

Objective: To examine the effects of graded doses of hydrocortisone (HC) on leptin secretion, and determine the effect of fasting.

Research Methods and Procedures: This was a randomized, placebo‐controlled, crossover study, with a 1‐week “washout” period between interventions. Eight healthy subjects [age = 36 ± 2.3 years (±SE), body mass index = 31.5 ± 1.6 kg/m2] completed the dose‐response study in which an intravenous infusion of saline (placebo) or HC (30 or 100 mg) was administered for 24 hours. Four healthy subjects (age = 35.2 ± 3.0 years, body mass index = 27.1 ± 2.1 kg/m2) completed the fasting study, which entailed continuous infusion of saline, HC (300 mg/24 hours) in the fed state, or HC (300 mg/24 hours) with total caloric deprivation for 24 hours. Blood sampling was performed every 1 to 2 hours for measurement of leptin, cortisol, insulin, and glucose levels.

Results: Peak hyperleptinemia occurred after 16 hours of HC infusion; peak/baseline leptin levels were 129% (placebo), 140% (30 mg of HC for 24 hours, p = 0.05), and 185% (100 mg of HC for 24 hours, p < 0.01). During infusion of HC (300 mg/24 hours or placebo), the peak/baseline plasma leptin levels were 16.1 ± 5.8/12.8 ± 5.9 ng/mL (placebo with food, 126%), 14.6 ± 6.0/12.5 ± 6.5 ng/mL (HC fasting, 117%), and 32.5 ± 12.5/12.0 ± 8.4 ng/mL (HC with food, 271%, p < 0.001).

Discussion: Leptin secretory responses occur at physiological doses of HC, are obliterated by fasting, and thus may be of metabolic significance.
Overweight Children's Barriers to and Support for Physical Activity
Authors: Zabinski Marion F. , Saelens Brian E. , Stein Richard I. , Hayden‐Wade Helen A. , Wilfley Denise E.
Published: April 2008

Objective: As the epidemic of overweight increases among youth, research needs to examine factors that may influence children's participation in weight‐related health behaviors. This study examined overweight children's perceived barriers to and support for physical activity compared with nonoverweight children.

Research Methods and Procedures: Barriers to and support for physical activity were examined among 84 overweight children attending a summer fitness camp or a university‐based weight loss clinic. Barriers and support levels were then compared with those of 80 nonoverweight children of a similar age range.

Results: Body‐related barriers were the most predominant barrier type among overweight youth, especially among overweight girls. Overweight children, particularly girls, reported significantly higher body‐related, resource, and social barriers to physical activity compared with nonoverweight children and lower levels of adult support for physical activity.

Discussion: Overweight children may be particularly vulnerable to body‐related barriers to physical activity, and reducing such barriers may serve as physical activity intervention points most relevant for overweight youth. Future interventions may also benefit from enhancing support for physical activity from adults and peers.
Ethnicity, Insurance Type, and Follow‐up in a Pediatric Weight Management Program
Authors: Tershakovec Andrew M. , Kuppler Kerri
Published: April 2008

Objective: To assess the characteristics of children and adolescents who drop out of a clinical weight management program.

Research Methods and Procedures: A retrospective survey of children and adolescents attending a pediatric weight management program [n = 518; mean ± SEM: age 10.4 ± 0.2 years, BMI z‐score 4.9 ± 0.1, 62% female, 41% African American and 57% white] was undertaken. Characteristics of children (age, relative weight, gender, and ethnicity) who dropped out of the program were compared with characteristics of those who continued beyond the initial assessment as a function of type of insurance.

Results: The children who dropped out of the program after the initial assessment differed by ethnicity from those who continued in the program: 63% of white children returned for more than one visit, whereas only 35% of the African‐American children continued in the program. Indemnity insurance coverage was associated with more clinic visits, as compared with managed care insurance. The association between insurance type and clinic visit number was of borderline significance (p = 0.06), when ethnic group was added to this analysis.

Discussion: Ethnicity is associated with attendance in a Pediatric Weight Management Program. Given the epidemic of obesity in children and adolescents, issues related to program compliance must be assessed to improve overall outcome. This is especially important given the high rate of obesity among African Americans and the low rate of ongoing attendance observed among African Americans in the Weight Management Program.
Increased Adiposity in Female Rhesus Monkeys Exposed to Androgen Excess During Early Gestation
Authors: Eisner Joel R. , Dumesic Daniel A. , Kemnitz Joseph W. , Colman Ricki J. , Abbott David H.
Published: April 2008

Objective: The aim of this study was to investigate the effects of early‐gestational androgen excess on adult body fat distribution in female rhesus monkeys.

Research Methods and Procedures: Six midreproductive‐aged, adult female rhesus monkeys that were exposed to androgen excess started during the first one‐third of gestation were pair‐matched to control females by age, body weight, and body mass index. Body composition was determined using somatometrics, DXA, and computed tomography.

Results: Total abdominal and intra‐abdominal fat depots are increased in adult female rhesus monkeys exposed to prenatal androgen excess.

Discussion: Early gestational androgen excess in female rhesus monkeys causes a preferential accumulation of total abdominal and intra‐abdominal fat during adulthood. Fat accumulation in these regions is independent of total body adiposity, occurring throughout the spectrum of body mass index in these animals. This study establishes alterations in abdominal adiposity as another consequence of prenatal androgen excess in female rhesus monkeys that may contribute to the impaired insulin secretion observed in these animals during adulthood.
Prescribed “Breaks” as a Means to Disrupt Weight Control Efforts
Authors: Wing Rena R. , Jeffery Robert W.
Published: April 2008

Objective: Research on long‐term maintenance of weight loss is hampered by the fact that relapse typically does not occur until after 6 months. We sought to determine whether relapses could be induced earlier by intentionally interrupting the momentum of weight loss during a treatment program and thus provide a model for weight maintenance research.

Research Methods and Procedures: Subjects (N = 142) were recruited at two centers and randomly assigned to a control group, a long break group (LB), or a short break group (SB). The control group received a standard behavioral weight loss program with 14 weekly sessions; the LB and SB groups received the same. However, the LB group took a 6‐week break after lesson 7, and the SB group took a 2‐week break after lessons 3, 6, and 9. Participants were instructed to stop all weight loss efforts during breaks.

Results: Participants seemed to take breaks as prescribed, with interruptions in self‐monitoring, dietary adherence, and self‐weighing (but not in exercise). However, participants quickly resumed these behaviors after the break. Breaks produced a slowing of weight loss or slight regain, but weight losses during the breaks were not significantly different from the control group. Importantly, overall weight losses (0 to 5 months or 0 to 11 months) did not differ between conditions.

Discussion: This study was not successful in developing a method to experimentally produce weight loss relapses. However, the finding that prescribed breaks do not have adverse effects may have clinical application.
The Human Obesity Gene Map: The 2002 Update
Authors: Chagnon Yvon C. , Rankinen Tuomo , Snyder Eric E. , Weisnagel S. John , Pérusse Louis , Bouchard Claude
Published: April 2008

This is the ninth update of the human obesity gene map, incorporating published results through October 2002 and continuing the previous format. Evidence from single‐gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) from human genome‐wide scans and various animal crossbreeding experiments, and association and linkage studies with candidate genes and other markers is reviewed. For the first time, transgenic and knockout murine models exhibiting obesity as a phenotype are incorporated (N = 38). As of October 2002, 33 Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and the causal genes or strong candidates have been identified for 23 of these syndromes. QTLs reported from animal models currently number 168; there are 68 human QTLs for obesity phenotypes from genome‐wide scans. Additionally, significant linkage peaks with candidate genes have been identified in targeted studies. Seven genomic regions harbor QTLs replicated among two to five studies. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 222 studies reporting positive associations with 71 candidate genes. Fifteen such candidate genes are supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. More than 300 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. The electronic version of the map with links to useful sites can be found at http:obesitygene.pbrc.edu.
Medium‐Chain Triglycerides Increase Energy Expenditure and Decrease Adiposity in Overweight Men
Authors: St‐Onge Marie‐Pierre , Ross Robert , Parsons William D. , Jones Peter J.H.
Published: April 2008

Objective: The objectives of this study were to compare the effects of diets rich in medium‐chain triglycerides (MCTs) or long‐chain triglycerides (LCTs) on body composition, energy expenditure, substrate oxidation, subjective appetite, and ad libitum energy intake in overweight men.

Research Methods and Procedures: Twenty‐four healthy, overweight men with body mass indexes between 25 and 31 kg/m2 consumed diets rich in MCT or LCT for 28 days each in a crossover randomized controlled trial. At baseline and after 4 weeks of each dietary intervention, energy expenditure was measured using indirect calorimetry, and body composition was analyzed using magnetic resonance imaging.

Results: Upper body adipose tissue (AT) decreased to a greater extent (p < 0.05) with functional oil (FctO) compared with olive oil (OL) consumption (−0.67 ± 0.26 kg and −0.02 ± 0.19 kg, respectively). There was a trend toward greater loss of whole‐body subcutaneous AT volume (p = 0.087) with FctO compared with OL consumption. Average energy expenditure was 0.04 ± 0.02 kcal/min greater (p < 0.05) on day 2 and 0.03 ± 0.02 kcal/min (not significant) on day 28 with FctO compared with OL consumption. Similarly, average fat oxidation was greater (p = 0.052) with FctO compared with OL intake on day 2 but not day 28.

Discussion: Consumption of a diet rich in MCTs results in greater loss of AT compared with LCTs, perhaps due to increased energy expenditure and fat oxidation observed with MCT intake. Thus, MCTs may be considered as agents that aid in the prevention of obesity or potentially stimulate weight loss.
Enhanced Erythrocyte Adhesiveness/Aggregation in Obesity Corresponds to Low‐Grade Inflammation
Authors: Samocha‐Bonet Dorit , Lichtenberg Dov , Tomer Aaron , Deutsch Varda , Mardi Tamar , Goldin Yelena , Abu‐Abeid Subchi , Shenkerman Galina , Patshornik Hana , Shapira Itzhak , Berliner Shlomo
Published: April 2008

Objective: Previous studies have suggested that obesity enhances the inflammatory response, producing macromolecules involved in the induction and/or maintenance of increased erythrocyte aggregation. The objectives of this study were to evaluate the correlation between inflammation markers, erythrocyte adhesiveness/aggregation, and the degree of obesity and to assess phosphatidylserine expression on erythrocyte surface membrane of obese vs. nonobese individuals.

Research Methods and Procedures: Erythrocyte adhesiveness/aggregation in the peripheral venous blood was evaluated by using a new biomarker, phosphatidylserine expression was assessed by means of flow cytometry, and markers of inflammation were measured in 65 subjects: 30 obese [body mass index (BMI) = 41 ± 7.7 kg/m2] and 35 nonobese (BMI = 24 ± 2.7 kg/m2) individuals. Pearson correlations and Student's t test were performed.

Results: A highly significant difference was noted in the degree of erythrocyte adhesiveness/aggregation and markers of inflammation between the study groups. BMI correlated with erythrocyte adhesiveness/aggregation (r = 0.42, p = 0.001), erythrocyte sedimentation rate (r = 0.42, p = 0.001), high‐sensitive C‐reactive protein (r = 0.55, p < 10−4), fibrinogen (r = 0.37, p = 0.004), and white blood cell count (r = 0.45, p < 10−4). The degree of erythrocyte adhesiveness/aggregation correlated with erythrocyte sedimentation rate (r = 0.5, p < 10−4), high‐sensitive C‐reactive protein (r = 0.56, p < 10−4), fibrinogen (r = 0.54, p < 10−4), and white blood cell count (r = 0.32, p = 0.01).

Discussion: Our results suggest that obesity‐related erythrocyte adhesiveness/aggregation is probably mediated through increased concentrations of adhesive macromolecules in the circulation and not necessarily through hyperlipidemia or phosphatidylserine exposure on erythrocyte's membrane.
Physical Fitness and Physical Activity in Obese and Nonobese Flemish Youth
Authors: Deforche Benedicte , Lefevre Johan , De Bourdeaudhuij Ilse , Hills Andrew P. , Duquet William , Bouckaert Jacques
Published: April 2008

Objective: To assess different aspects of physical fitness and physical activity in obese and nonobese Flemish youth.

Research Methods and Procedures: A random sample of 3214 Flemish schoolchildren was selected and divided into an “obese” and “nonobese” group based on body mass index and sum of skinfolds. Physical fitness was assessed by the European physical fitness test battery. Physical activity was estimated by a modified version of the Baecke Questionnaire.

Results: Obese subjects had inferior performances on all tests requiring propulsion or lifting of the body mass (standing‐broad jump, sit‐ups, bent‐arm hang, speed shuttle run, and endurance shuttle run) compared with their nonobese counterparts (p < 0.001). In contrast, the obese subjects showed greater strength on handgrip (p < 0.001). Both groups had similar levels of leisure‐time physical activity; however, nonobese boys had a higher sport index than their obese counterparts (p < 0.05).

Discussion: Results of this study show that obese subjects had poorer performances on weight‐bearing tasks, but did not have lower scores on all fitness components. To encourage adherence to physical activity in obese youth, it is important that activities are tailored to their capabilities. Results suggest that weight‐bearing activities should be limited at the start of an intervention with obese participants and alternative activities that rely more on static strength used.
Anthropometric Cutoff Points for Predicting Chronic Diseases in the Mexican National Health Survey 2000
Authors: Sánchez‐Castillo Claudia P. , Velázquez‐Monroy Oscar , Berber Arturo , Lara‐Esqueda Agustín , Tapia‐Conyer Roberto , James W. Philip T. ,   Encuesta Nacional de Salud (ENSA) 2000 Working Group
Published: April 2008

Objective: To determine optimum anthropometric cutoffs for predicting the likelihood ratios of type 2 diabetes mellitus (DM) and hypertension (HT) in Mexicans.

Research Methods and Procedures: Data from a randomly selected, nationally representative health survey (2000) with 11, 730 men [37.4 (± 12.9) years] and 26, 647 women [37.3(± 12.9) years] were assessed for values of body mass index (BMI) and waist circumference (WC) for predicting DM or HT by receiver operating characteristic curve analyses. Likelihood ratios for DM and HT were calculated, and BMIs or WCs for public‐health screening were developed. Subanalyses included regional data.

Results: Likelihood ratios of DM and HT increased from BMI values of 22 to 24 kg/m2 in both sexes and with WC values of 75 to 80 cm in men and 70 to 80 cm in women. The best BMI cutoffs for predicting DM were 26.3 to 27.4 kg/m2 in men and 27.7 to 28.9 kg/m2 in women, with similar values for HT, i.e., 26.2 to 27.0 kg/m2 and 27.7 to 28.5 kg/m2, for men and women, respectively; WC cutoffs for DM were 93 to 98 cm in men and 94 to 99 cm in women, and cutoffs for HT were 92 to 96 cm and 93 to 96 cm for men and women, respectively. The WC cutoffs had higher sensitivity and specificity than those of BMI.

Discussion: The risk for DM and HT starts at lower levels of BMI and WC than those suggested by WHO. WC is a better discriminator than BMI measures for use in public health.
Subdivision of the Subcutaneous Adipose Tissue Compartment and Lipid‐Lipoprotein Levels in Women
Authors: Deschênes Daniel , Couture Patrick , Dupont Pierre , Tchernof André
Published: April 2008

Objective: The aim of this study was to compare the relative importance of computed tomography‐measured abdominal fat compartment areas, including adipose tissue located posterior to the subcutaneous Fascia, in predicting plasma lipid‐lipoprotein alterations.

Research Methods and Procedures: Areas of visceral as well as subcutaneous deep and superficial abdominal adipose tissue were measured by computed tomography in a sample of 66 healthy women, ages 37 to 60 years, for whom a detailed lipid‐lipoprotein profile was available.

Results: Strong significant associations were observed between visceral adipose tissue area and most variables of the lipid‐lipoprotein profile (r = −0.25, p < 0.05 to 0.62, p < 0.0001). Measures of hepatic lipoprotein synthesis such as very‐low‐density lipoprotein‐triglyceride and cholesterol content as well as total and very‐low‐density lipoprotein‐apolipoprotein B levels were also strongly associated with visceral adipose tissue area (r = 0.57, 0.57, 0.61, and 0.62, respectively, p < 0.0001). Significant associations were found between these variables and the deep subcutaneous adipose tissue area or DXA‐measured total body fat mass. However, the correlation coefficients were of lower magnitude compared to those with visceral adipose tissue area. Multivariate regression analyses demonstrated that visceral adipose tissue area was the strongest predictor of lipid‐lipoprotein profile variables (7% to 48% explained variance, 0.02 ≥ p ≤ 0.0001).

Discussion: Although previous studies have generated controversial data as to which abdominal adipose tissue compartment was more closely associated with insulin resistance, our results suggest that visceral adipose tissue area is a stronger correlate of other obesity‐related outcomes such as lipid‐lipoprotein alterations.
Systemic Inflammation, Adipose Tissue Tumor Necrosis Factor, and Leptin Expression
Authors: Bulló Monica , García‐Lorda Pilar , Megias Isabel , Salas‐Salvadó Jordi
Published: April 2008

Objectives: To explore the links between tumor necrosis factor α (TNFα) and leptin adipose tissue expression and low‐grade systemic inflammation and to determine the relationship between inflammation and the degree of adiposity, the presence of type 2 diabetes, and other cardiovascular risk factors.

Research Methods and Procedures: Ninety‐one women (BMI 19 to 65 kg/m2) were divided into tertiles of CRP. Insulin resistance was calculated using the HOMA method. Albumin, fibrinogen, C‐reactive protein (CRP), interleukin‐6, sTNFR1, sTNFR2, and leptin levels were measured in serum and plasma samples. TNFα and leptin expression were measured by reverse transcription‐polymerase chain reaction in abdominal subcutaneous adipose tissue samples.

Results: CRP was positively related to BMI and upper distribution of adiposity. TNFα and leptin adipose tissue expression were higher in the upper tertile of CRP. Also, peripheral levels of both soluble TNFRs and leptin were higher in patients with the greatest inflammation degree. Diabetes, dislipidemia, and hypertension were most prevalent in patients in the upper CRP tertile. Inflammatory markers of diabetic women were significantly different from those of nondiabetic women, even after adjusting for differences in body fat. BMI, type 2 diabetes, and adipose TNFα mRNA levels were significant predictors of serum CRP levels (r2= 0.28,p< 0.001).

Discussion: These results are in agreement with the hypothesis that the synthesis of adipose tissue TNFα and leptin could induce the production of interleukin‐6, CRP, and other acute‐phase reactants, thus contributing to the maintenance of chronic low‐grade inflammation state involved in the progression of obesity and its associated comorbidities.
Plasma Leptin, Fatty Acids, and Tumor Necrosis Factor‐Receptor and Insulin Resistance in Children
Authors: Chu Nain‐Feng , Chang Jin‐Biou , Shieh Shih‐Ming
Published: April 2008

Objective: To evaluate the effect of plasma leptin, nonsterified fatty acids (NEFAs), and tumor necrosis factor‐receptor 1 (TNFR1) on plasma insulin and insulin‐resistance status in children.

Research Methods and Procedures: One thousand thirty‐two children (521 boys and 511 girls) were included in this study. We measured plasma insulin and leptin levels by radioimmunoassay, plasma NEFA levels by enzymatic acyl‐coenzyme A synthase—acyl‐coenzyme A oxidase spectrophotometric methods, and TNFR1 levels by enzyme‐linked immunosorbent assay. We calculated insulin resistance index (IRI) using homeostasis model assessment and calculated insulin‐resistance syndrome summary score (IRS) by adding the quartile ranks from the distribution of systolic blood pressure (BP), serum triglyceride, high‐density lipoprotein‐cholesterol (inverse), and insulin levels.

Results: Overweight children had higher BP, plasma leptin, and insulin levels and higher IRI and IRS than normal‐weight children. Plasma leptin and TNFR1 were positively correlated with insulin levels, IRI, and IRS. The correlation coefficients of leptin and TNFR1 in IRI were 0.53 and 0.12, respectively, for boys and 0.25 and 0.18, respectively, for girls. In multivariate regression analyses, TNFR1 was positively associated with insulin level and IRI in girls; NEFA was positively associated only with IRS. Plasma leptin levels were significantly positively associated with insulin levels, IRI, and IRS, even after adjusting for BMI and other potential confounders.

Discussion: Overweight children had higher BP, plasma insulin, and leptin levels and adverse insulin‐resistance status than normal‐weight children. Plasma leptin levels, rather than NEFA and TNFR1, may play a significant role in the development of hyperinsulinemia and insulin resistance in children.
The CYP19 Gene and Associations with Androgens and Abdominal Obesity in Premenopausal Women
Authors: Baghaei Fariba , Rosmond Roland , Westberg Lars , Hellstrand Monica , Eriksson Elias , Holm Göran , Björntorp Per
Published: April 2008

Objective: Elevated androgens in women are associated with type 2 diabetes and are dependent on the conversion to estrogens by aromatase cytochrome P450. Polymorphisms of a tetranucleotide repeat [TTTA]n in the fourth intron of the CYP19 gene are associated with endocrine‐dependent diseases and were examined in relation to hormone levels and disease risk factors in premenopausal women.

Research Methods and Procedures: A population sample of women born in 1956 (n = 270) were genotyped for this polymorphism and the results set in relation to steroid hormones, including saliva cortisol, anthropometric variables, estimates of insulin, glucose and lipid metabolism, and blood pressure.

Results: Seven tetranucleotide repeat [TTTA]n alleles were detected with allelic sizes of 168 to 195 bp, with a TCT deletion/insertion (168/171 bp) upstream of this microsatellite. Smoking was associated with elevated androgens (p = 0.005 to 0.019). Using the median (average stretch, 177.5 bp) as a dividing line, nonsmoking women with the shorter microsatellite had higher free testosterone (p = 0.018) and lower sex hormone binding globulin (p = 0.033). These differences were pronounced with the 168‐bp allele. Such women were also characterized by a less‐substantial decrease of morning cortisols (“unwinding”; p = 0.035) and central obesity (abdominal sagittal diameter, p = 0.049) and had waist/hip circumference ratios of borderline significance (p = 0.064).

Discussion: The results indicate that, in premenopausal women, a short microsatellite in the fourth intron of the CYP19 gene, caused by a TCT deletion upstream the [TTTA]n tract, is associated with elevated androgens, perturbed regulation of the hypothalamic‐pituitary‐adrenal axis, and abdominal obesity.
mRNA Levels of the Insulin‐Signaling Molecule SORBS1 in the Adipose Depots of Nondiabetic Women
Authors: Yang Wei‐Shiung , Lee Wei‐Jei , Huang Kuo‐Chin , Lee Kuan‐Ching , Chao Chia‐Ling , Chen Chi‐Ling , Tai Tong‐Yuan , Chuang Lee‐Ming
Published: April 2008

Objectives: The SORBS1 gene has been shown to be an important adaptor protein in the insulin‐signaling pathway in many molecular and cellular biology studies. However, its roles in humans either in health or disease are rarely explored. In this report, we measured the SORBS1 mRNA levels in human adipose tissues.

Research Methods and Procedures: Adipose tissues of both the abdominal subcutaneous and omental depots were obtained from 62 nondiabetic women. The relative SORBS1 mRNA levels were quantified using real‐time polymerase chain reaction.

Results: The relative SORBS1 mRNA levels from these two depots significantly correlated with each other (γ = 0.85, p = 0.0000). The relative SORBS1 mRNA levels in the omental depots were lower than those in the subcutaneous depots (p = 0.053 by two‐tailed test, p = 0.026 by one‐tailed paired Student's t test). The mean SORBS1 expression level in the omental depots was ∼70% that in the subcutaneous depots. Moreover, the relative SORBS1 mRNA levels in the omental depots were significantly related to BMI using either correlation analysis (γ = −0.41, p = 0.0008) or multivariate linear regression analysis (β = −0.20 ± 0.09, p = 0.031) with adjustment for age, plasma glucose, serum insulin, triglyceride, and total cholesterol levels.

Discussion: Our preliminary results indicate the depot‐specific differential expression of SORBS1 in relation to BMI. Further investigation of the functional significance of this phenomenon in human obesity is warranted.
Effects of Sibutramine on Binge Eating, Hunger, and Fullness in a Laboratory Human Feeding Paradigm
Authors: Mitchell James E. , Gosnell Blake A. , Roerig James L. , de Zwaan Martina , Wonderlich Stephen A. , Crosby Ross D. , Burgard Melissa A. , Wambach Beth N.
Published: April 2008

Objective: The purpose of this study was to evaluate the effects of sibutramine vs. placebo on binge‐eating behavior, hunger, and satiety in patients who had problems with binge eating.

Research Methods and Procedures: Seven adult subjects who had problems with binge eating (mean age, 42 years) were randomly assigned to receive alternating sibutramine and placebo in a double‐blind placebo‐controlled crossover study. This involved two 4‐week dosing periods separated by a 2‐week washout.

Results: Subjects lost weight on sibutramine but not on placebo. There was a significant difference in the number of kilocalories consumed between the sibutramine and placebo conditions, with a significant reduction of intake during binge‐eating episodes on sibutramine.

Discussion: Sibutramine suppresses intake during binge‐eating episodes. This effect is demonstrable in a human feeding laboratory paradigm.
Obesity Prevention in Preschool Native‐American Children: A Pilot Study Using Home Visiting
Authors: Harvey‐Berino Jean , Rourke Janine
Published: April 2008

Objective: To determine whether maternal participation in an obesity prevention plus parenting support (OPPS) intervention would reduce the prevalence of obesity in high‐risk Native‐American children when compared with a parenting support (PS)‐only intervention.

Research Methods and Procedures: Forty‐three mother/child pairs were recruited to participate. Mothers were 26.5 ± 5 years old with a mean BMI of 29.9 ± 3 kg/m2. Children (23 males) were 22 ± 8 months old with mean weight‐for‐height z (WHZ) scores of 0.73 ± 1.4. Mothers were randomly assigned to a 16‐week OPPS intervention or PS alone. The intervention was delivered one‐on‐one in homes by an indigenous peer educator. Baseline and week 16 assessments included weight and height (WHZ score and weight‐for‐height percentile for children), dietary intake (3‐day food records), physical activity (measured by accelerometers), parental feeding style (Child Feeding Questionnaire), and maternal outcome expectations, self‐efficacy, and intention to change diet and exercise behaviors.

Results: Changes in WHZ scores showed a trend toward significance, with WHZ scores decreasing in the PS condition and increasing among the OPPS group (−0.27 ± 1.1 vs. 0.31 ± 1.1, p = 0.06). Children in the OPPS condition also significantly decreased energy intake (−316 ± 835 kcal/d vs. 197 ± 608 kcal/d, p < 0.05). Scores on the restriction subscale of the Child Feeding Questionnaire decreased significantly in the OPPS condition (−0.22± 0.42 vs. 0.08± 0.63, p < 0.05), indicating that mothers in the OPPS group were engaging in less restrictive child feeding practices over time.

Discussion: A home‐visiting program focused on changing lifestyle behaviors and improving parenting skills showed promise for obesity prevention in high‐risk Native‐American children.
Effects of β2‐Adrenergic Receptor Gene Variants on Adiposity: The HERITAGE Family Study
Authors: Garenc Christophe , Pérusse Louis , Chagnon Yvon C. , Rankinen Tuomo , Gagnon Jacques , Borecki Ingrid B. , Leon Arthur S. , Skinner James S. , Wilmore Jack H. , Rao D.C. , Bouchard Claude
Published: April 2008

We investigated whether the Arg16Gly and Gln27Glu polymorphisms of the β2‐adrenergic receptor gene were associated with body‐fat and fat‐distribution phenotypes measured before and in response to a 20‐week endurance‐training program. BMI, fat mass (FAT), percentage of body fat (%FAT), sum of eight skinfolds (SF8), and abdominal fat areas assessed by computed tomography were measured in adult sedentary white and black participants of the HERITAGE Family Study. Evidence of gene‐by‐obesity interaction was found in whites for several adiposity phenotypes measured before training. Analyses performed separately in nonobese and obese subjects revealed that obese men carrying the Glu27 allele have lower fat accumulation (BMI, FAT, and %FAT) than noncarriers. Among white obese women, Gly16Gly homozygotes had a lower fat accumulation (BMI, FAT, and SF8) than Arg16Gly and Arg16Arg carriers. In response to endurance training, white women with the Arg16Arg genotype exhibited a greater reduction in BMI, FAT, and %FAT. Results observed in blacks were mostly negative. These results suggest that polymorphisms in the β2‐adrenergic receptor gene influence the amount of body fat in white obese men (Gln27Glu) and women (Arg16Gly), as well as the changes in adiposity in response to endurance training in white women (Arg16Gly).
Sequence Variants of the POMC Gene and Their Associations with Body Composition in Children
Authors: Feng Ningping , Adler‐Wailes Diane , Elberg Jane , Chin Jeff Y. , Fallon Erica , Carr Alison , Frazer Teresa , Yanovski Jack A.
Published: April 2008

We investigated POMC sequence variants in 242 overweight and nonoverweight African‐American and white children and examined the associations between body composition and POMC polymorphisms. Three novel polymorphisms and two previously identified sequence variants were found: A7301G, A7429G, and C8246T were all in untranslated regions. A 9‐bp (AGC AGC GGC) duplication/insertion was found between positions 7677 and 7678, and one normal‐weight African‐American girl had a 45‐bp triple duplication/insertion at this location. Compared with whites, African‐American children were significantly more likely to have polymorphisms A7301G, A7429G, and the 9‐bp insertion. However, there were no significant associations between any of the polymorphisms and body composition. Five African‐American subjects who were homozygous for A7429G had a trend (p = 0.08) for a greater BMI‐SD score (5.3 ± 5.3 kg/m2) compared with wild‐type children (BMI‐SD score, 2.4 ± 3.2 kg/m2) or heterozygotes (BMI‐SD score, 2.7 ± 3.7 kg/m2). However, there were no differences in BMI‐SD score for A7429G when African American subjects were studied separately and both gender and height were taken into account. The contribution of the POMC gene variants we studied to pediatric‐onset obesity seems to be limited.
Sympathovagal Balance, Nighttime Blood Pressure, and QT Intervals in Normotensive Obese Women
Authors: Esposito Katherine , Marfella Raffaele , Gualdiero Pasquale , Carusone Caterina , Pontillo Alessandro , Giugliano Giovanni , Nicoletti Gianfranco , Giugliano Dario
Published: April 2008

Objective: We describe associations among the heart‐rate‐corrected QT (QTc) interval, QTc dispersion (QTc‐d), circadian BP variation, and autonomic function in obese normotensive women and the effect of sustained weight loss.

Research Methods and Procedures: In 71 obese (BMI = 37.14 ± 2.6 kg/m2) women, 25 to 44 years of age, circadian BP variations (24‐hour ambulatory BP monitoring), autonomic function (power spectral analysis of RR interval oscillations), and cardiac repolarization times (QTc‐d and QTc interval) were recorded at baseline and after 1 year of a multidisciplinary program of weight reduction.

Results: Compared with nonobese age‐matched women (n = 28, BMI = 23 ± 2.0 kg/m2), obese women had higher values of QTc‐d (p < 0.05) and QTc (p < 0.05), an altered sympathovagal balance (ratio of low‐frequency/high‐frequency power, p < 0.01), and a blunted nocturnal drop in BP (p < 0.01). In obese women, QTc‐d and the QTc interval correlated with diastolic nighttime BP (p < 0.01) and sympathovagal balance (p < 0.01). Waist‐to‐hip ratio, free fatty acids, and plasma insulin levels correlated with QT intervals and reduced nocturnal drops in both systolic and diastolic BP and sympathovagal balance (p < 0.01). After 1 year, obese women lost at least 10% of their original weight, which was associated with decrements of QTc‐d (p < 0.02), the QTc interval (p < 0.05), nighttime BP (p < 0.01), and sympathovagal balance (p < 0.02).

Discussion: Sustained weight loss is a safe method to ameliorate diastolic nighttime BP drop and sympathetic overactivity, which may reduce the cardiovascular risk in obese women.
Sex Hormones and Sexual Function in Obese Men Losing Weight
Authors: Kaukua Jarmo , Pekkarinen Tuula , Sane Timo , Mustajoki Pertti
Published: April 2008

Objective: To study the impact of a weight‐loss program on sex hormones and sexual function among 38 middle‐aged obese men (BMI ≥35 kg/m2).

Research Methods and Procedures: A randomized controlled clinical trial was conducted. The treatment group (n = 19) participated in a 4‐month weight‐loss program including 10 weeks on a very‐low‐energy diet (VLED) and 17 behavior modification visits. There was no intervention in the control group (n = 19). Both groups were followed for 8 months, i.e., 22 weeks after the active weight loss in the treatment group. The outcome measures (weight, sex hormones, sexual function, leptin, and metabolic variables) were obtained at baseline and at three time‐points during follow‐up.

Results: The mean weight loss in the treatment group was 21 kg at the end of the 10‐week VLED. At the end of follow‐up, the maintained weight loss was 17 kg of baseline weight. The control group was weight stable throughout the study. In the treatment group, increases in sex hormone‐binding globulin, testosterone, and high‐density lipoprotein‐cholesterol, as well as decreases in insulin and leptin, were maintained until the end of follow‐up, although with VLED, the level of several hormones and metabolic variables improved transiently during the rapid weight loss. There were no significant changes in the questionnaire scores on sexual function in either group.

Discussion: We conclude that obese men lose weight and increase their serum testosterone level on a weight‐loss program with VLED and behavior modification. However, they do not change their sexual function scores.
The direct recovery of recombinant hepatitis B core antigen from disruptate derived from continuous‐flow bead milling
Authors: Ho Chin Woi , Tan Wen Siang , Kamaruddin Suryani , Ling Tau Chuan , Tey Beng Ti
Published: April 2008

HBcAg (hepatitis B core antigen) is a nanoplex bioproduct that has a great potential in the development of therapeutic drugs and vaccines. In the present study, a continuous‐flow bead milling for the disruption of Escherichia coli was optimized and a direct recovery protocol to isolate the recombinant HBcAg from the unclarified E. coli disruptate was developed. The optimal condition for continuous‐flow bead milling for the release of HBcAg from E. coli was achieved at a feed flow rate of 15 litres/h, biomass concentration of 10% [ww/v (wet weight/vol.)] and impeller tip speed of 14 m/s. The sucrose‐density‐gradient analysis showed that the particulate form of the HBcAg released by this optimal condition is still preserved. In the direct purification of HBcAg from the unclarified disruptate, the AE‐EBAC (anion‐exchange expanded‐bed adsorption chromatography) technique was employed. A 54% adsorption and 50.7% recovery of HBcAg were achieved in this direct recovery process. The purity of HBcAg recovered was 49.8%, which corresponds to a purification factor of 2.0. ELISA showed that the HBcAg recovered is functionally active.
The extent of co‐metabolism of glucose and galactose by Lactococcus lactis changes with the expression of the lacSZ operon from Streptococcus thermophilus
Authors: Solem Christian , Koebmann Brian , Jensen Peter R.
Published: April 2008

The lactose transporter and β‐galactosidase from Streptococcus thermophilus, encoded by the lacSZ operon, were introduced into the lactose‐negative strain Lactococcus lactis MG1363 and the expression of the lacSZ operon was modulated by substitution of the native promoter with randomized synthetic promoters. A series of strains with various expression levels of lacSZ were examined for their fermentation of lactose. Strains with a high expression level were found to metabolize lactose in a similar manner to S. thermophilus, i.e. the galactose moiety of lactose was excreted to the growth medium and only glucose was metabolized in glycolysis. Interestingly, strains with low expression of the operon showed a mixed acid metabolism and co‐metabolism of galactose and glucose. The lactose flux increased gradually with increasing expression of the lacSZ operon until an optimum was observed at intermediate β‐galactosidase activities of 2000–3000 Miller units. At higher expression levels, the flux decreased. These strains had a glycolytic flux comparable with those of reference strains with the standard lactococcal PTSlac (lactose phosphotransferase transport system) lactose transporter, which indicates that lactose transport is not rate‐limiting for glycolysis in Lactococcus. Finally, an additional ATP drain was introduced into the fastest growing strain, CS2004, to test whether the ATP demand controlled glycolysis under these conditions, but in fact no increase in glycolytic flux was observed.
Activation of p53 stimulates proteasome‐dependent truncation of eIF4E‐binding protein 1 (4E‐BP1)
Authors: Constantinou Constantina , Elia Androulla , Clemens Michael J.
Published: April 2008

Background information. The translational inhibitor protein 4E‐BP1 [eIF4E (eukaryotic initiation factor 4E)‐binding protein 1] regulates the availability of polypeptide chain initiation factor eIF4E for protein synthesis. Initiation factor eIF4E binds the 5′ cap structure present on all cellular mRNAs. Its ability to associate with initiation factors eIF4G and eIF4A, forming the eIF4F complex, brings the mRNA to the 43S complex during the initiation of translation. Binding of eIF4E to eIF4G is inhibited in a competitive manner by 4E‐BP1. Phosphorylation of 4E‐BP1 decreases the affinity of this protein for eIF4E, thus favouring the binding of eIF4G and enhancing translation. We have previously shown that induction or activation of the tumour suppressor protein p53 rapidly leads to 4E‐BP1 dephosphorylation, resulting in sequestration of eIF4E, decreased formation of the eIF4F complex and inhibition of protein synthesis.

Results. We now report that activation of p53 also results in modification of 4E‐BP1 to a truncated form. Unlike full‐length 4E‐BP1, which is reversibly phosphorylated at multiple sites, the truncated protein is almost completely unphosphorylated. Moreover, the latter interacts with eIF4E in preference to full‐length 4E‐BP1. Inhibitor studies indicate that the p53‐induced cleavage of 4E‐BP1 is mediated by the proteasome and is blocked by conditions that inhibit the dephosphorylation of full‐length 4E‐BP1. Measurements of the turnover of 4E‐BP1 indicate that the truncated form is much more stable than the full‐length protein.

Conclusions. The results suggest a model in which proteasome activity gives rise to a stable, hypophosphorylated and truncated form of 4E‐BP1, which may exert a long‐term inhibitory effect on the availability of eIF4E, thus contributing to the inhibition of protein synthesis and the growth‐inhibitory and pro‐apoptotic effects of p53.
Development and evaluation of realistic microbioassays in freely suspended droplets on a chip
Authors: Rastogi Vinayak , Velev Orlin D.
Published: April 2008

A novel technique for biomolecular detection in microliter droplets floating on the surface of high density oil is presented. Each droplet was captured and manipulated dielectrophoretically and was used as a site for a microscopic bioassay based on agglutination of antibody-conjugated particles. The results were read out by the pattern of unagglomerated gold nanoparticles collected on the droplet surface. Two formats of bioassays, namely gold only agglutination and gold and latex agglutination, were investigated experimentally by varying analyte concentration, particle size and concentration, number of antigen binding sites per particle, time for incubation, and rate of particle collection on the droplet surface. The microbioassays performance was also evaluated with ricin antibodies and compared to the ricin assays in field use. It is estimated that the droplet based assays require 100× smaller sample volume and are ten times more sensitive, though they require longer times to complete. The experiments were interpreted by modeling the kinetics of particle agglutination and mass transfer processes inside the droplets. The incubation time and antigen concentration values calculated by the model correlate well with the experimental results. The results could allow for development of efficient immunoassays on a chip requiring even smaller sample volumes.
Quantum trajectories in complex space: One-dimensional stationary scattering problems
Authors: Chou Chia-Chun , Wyatt Robert E.
Published: April 2008

One-dimensional time-independent scattering problems are investigated in the framework of the quantum Hamilton–Jacobi formalism. The equation for the local approximate quantum trajectories near the stagnation point of the quantum momentum function is derived, and the first derivative of the quantum momentum function is related to the local structure of quantum trajectories. Exact complex quantum trajectories are determined for two examples by numerically integrating the equations of motion. For the soft potential step, some particles penetrate into the nonclassical region, and then turn back to the reflection region. For the barrier scattering problem, quantum trajectories may spiral into the attractors or from the repellers in the barrier region. Although the classical potentials extended to complex space show different pole structures for each problem, the quantum potentials present the same second-order pole structure in the reflection region. This paper not only analyzes complex quantum trajectories and the total potentials for these examples but also demonstrates general properties and similar structures of the complex quantum trajectories and the quantum potentials for one-dimensional time-independent scattering problems.
Relativistic diffusions: A unifying approach
Authors: Chevalier C. , Debbasch F.
Published: April 2008

A new, wide class of relativistic stochastic processes is introduced. All relativistic processes considered so far in the literature are members of this class. For each process, the stochastic equations of motion are obtained in an arbitrary Lorentz frame. The associated Kolmogorov equation is also derived for the first time, in both (3+1)- and manifestly covariant forms.
Nonideal unilateral constraints in impulsive mechanics: A geometric approach
Authors: Pasquero Stefano
Published: April 2008

We use the differential geometric framework of the first jet bundle of the classical space-time bundle to study the impulsive behavior of a mechanical system with a finite number of degrees of freedom subject to nonideal unilateral constraints. We show that this framework allows deeper insights on the concepts of nonideal constitutive characterization and of coefficient of restitution of the constraints. We study the relations among Newton, Poisson, and Stronge definitions of coefficient of restitution: we reveal the inconsistency of the criticisms based on the energy balance of the impact for the Newton definition; we show the equivalence of the three definitions in the nonideal smooth case; we prove the equivalence of Newton and Poisson ones and the insufficiency of the Stronge one in the nonideal rough case. We analyze the relation between coefficient of restitution and Coulomb’s friction coefficient in the rough case. We present also several physically meaningful examples.
Efficient computation of transient solutions of the chemical master equation based on uniformization and quasi-Monte Carlo
Authors: Hellander Andreas
Published: April 2008

A quasi-Monte Carlo method for the simulation of discrete time Markov chains is applied to the simulation of biochemical reaction networks. The continuous process is formulated as a discrete chain subordinate to a Poisson process using the method of uniformization. It is shown that a substantial reduction of the number of trajectories that is required for an accurate estimation of the probability density functions (PDFs) can be achieved with this technique. The method is applied to the simulation of two model problems. Although the technique employed here does not address the typical stiffness of biochemical reaction networks, it is useful when computing the PDF by replication. The method can also be used in conjuncture with hybrid methods that reduce the stiffness.