bluuebunny/crossref_metadata_2025 huggingface dataset:
Defective Dietary Induction of Uncoupling Protein 3 in Skeletal Muscle of Obesity‐Prone Rats
Authors: Weigle David S. , Levin Barry E.
Published: April 2008

Objective: The goal of this study was to determine whether differential induction of skeletal muscle uncoupling protein 3 (UCP3) contributes to the development of diet‐induced obesity (DIO) or resistance to the development of obesity (DR) when rats are placed on a moderate fat (31%) high energy (HE) diet.

Research Methods and Procedures: Gastrocnemius muscle was obtained from Sprague‐Dawley rats that were identified as DIO‐prone (n = 5) or DR (n = 5) on the basis of urinary norepinephrine excretion while consuming a chow diet. Muscle was also obtained from animals in the top tertile of weight gain (DIOHE, n = 5) and the bottom tertile of weight gain (DRHE, n = 5) after 2 weeks on the HE diet. UCP3 and actin mRNA levels were measured in all muscle samples by Northern analysis. To distinguish the effect of dietary energy content from the effect of obesity itself, we studied additional DIO and DR animals that had been returned to a chow diet for 10 weeks after consuming a HE diet for 10 weeks.

Results: The muscle UCP3/actin mRNA ratio in animals that resisted the development of obesity during 2 weeks on the HE diet was 3‐fold higher than in the other groups (DRHE = 3.24 ± 0.83, DIOHE = 0.91 ± 0.20, DIO‐prone = 0.72 ± 0.15, DR = 0.63 ± 0.15; p = 0.002). However, there was no difference in muscle UCP3/actin mRNA ratios between DIO animals and DR animals that had been fed the HE diet for 10 weeks and then returned to either an ad libitum chow diet for 10 weeks (DIO = 13.8 ± 3.53, DR = 11.1 ± 3.43, p = NS) or to a restricted chow diet for 10 weeks (DIO = 11.0 ± 2.85, DR = 10.6 ± 2.20, p = NS) despite significantly greater body weight of the DIO animals.

Discussion: DR animals may initially resist weight gain when placed on a HE diet through a greater induction of muscle UCP3. This induction is transient and is related more closely to dietary fat content than to body fat stores. DIO animals show no initial induction of muscle UCP3, which may contribute to their increased metabolic efficiency soon after exposure to a HE diet.
Access and Use of Medical Care among Obese Persons
Authors: Fontaine Kevin R. , Bartlett Susan J.
Published: April 2008

The prevalence of obesity and severe obesity is growing rapidly, along with obesity‐related comorbidities and mortality. Given the increased health risks associated with obesity, it is vital that obese persons have adequate access to, and make consistent use of, medical care services. Assuming obese persons have access to medical care that is comparable to non‐obese persons, one would expect to observe greater use of medical services among obese persons. In this article we briefly review empirical evidence of the access to and use of medical care among obese persons. Although certain subgroups that tend to have disproportionately high prevalences of obesity (i.e., low socioeconomic status, minority groups) have reduced access to care, no studies have specifically examined whether or not obese persons have the same access to health care as do their lean counterparts. With respect to use of health care services, however, obesity has been consistently linked with greater rates of utilization and increased health care expenditures. Both the increased use and cost appear to be largely a function of treating obesity‐associated comorbidities such as diabetes and hypertension. We conclude that, although it is clear that obesity is associated with both greater use and cost of medical care, the relationship between obesity and access to medical care has not been determined.
Leptin Responses to Weight Loss in Postmenopausal Women: Relationship to Sex‐Hormone Binding Globulin and Visceral Obesity
Authors: van Rossum Elisabeth F. C. , Nicklas Barbara J. , Dennis Karen E. , Berman Dora M. , Goldberg Andrew P.
Published: April 2008

Objective: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women.

Research Methods and Procedures: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone‐binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0 ± 4.5 kg/m2; mean ± SD), women (60 ± 6 years) before and after a 6‐month hypocaloric diet (250 to 350 kcal/day deficit).

Results: Body weight decreased by 5.8 ± 3.4 kg (7.1%) and leptin levels decreased by 6.6 ± 11.9 ng/mL (14.5%) after the 6‐month treatment. Insulin levels decreased 10% (p < 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p < 0.0001), fat mass (r = 0.38, p < 0.01), subcutaneous fat area (r = 0.52, p < 0.0001), and with baseline values of SHBG (r = 0.38, p < 0.01) and baseline intra‐abdominal fat area (r = −0.27, p < 0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r2 = 0.24, p < 0.01), relative changes in body weight (cumulative r2 = 0.40, p < 0.05), and baseline intra‐abdominal fat area (cumulative r2 = 0.48, p < 0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance.

Discussion: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.
Occupational Status, Cortisol Secretory Pattern, and Visceral Obesity in Middle‐aged Men
Authors: Rosmond Roland , Björntorp Per
Published: April 2008

Objective:Despite several studies indicating that social gradients are predictive of cardiovascular mortality, the pathogenetic mechanisms remain incompletely understood.

Research Methods and Procedures:A population sample of 51‐year‐old men (N= 284) was divided into a socioeconomic gradient with manual laborers, civil servants, and university graduates. Anthropometric measurements were registered. Cortisol concentrations were measured in saliva, collected repeatedly during an ordinary working day, and a low‐dose dexamethasone suppression test was performed.

Results:Lower socioeconomic status was associated with visceral obesity and higher cortisol values in relation to perceived stress. However, total cortisol secretion over the day of study was not elevated. The regulation of cortisol secretion showed less plasticity and dexamethasone inhibition was less efficient in the men in the lower socioeconomic status group than in those with a higher socioeconomic status. These are known consequences of long term stress. Longer duration in low socioeconomic conditions seemed to worsen these phenomena.

Discussion:It was concluded that a low socioeconomic status is associated with perturbed cortisol secretion, which is elevated in relation to perceived stress. When the hypothalamic‐pituitary‐adrenal axis is subjected to prolonged increases in cortisol elicited by chronic stress, the regulation of cortisol secretion is affected, indicating neuroendocrine dysregulations. These observations may provide a means for understanding the association of socioeconomic impairments with visceral obesity and the social inequality in risk for prevalent and serious diseases.
The Activity of the Hypothalamic‐Pituitary‐Adrenal Axis and the Sympathetic Nervous System in Relation to Waist/Hip Circumference Ratio in Men
Authors: Ljung Thomas , Holm Göran , Friberg Peter , Andersson Björn , Bengtsson Bengt‐Åke , Svensson Johan , Dallman Mary , McEwen Bruce , Björntorp Per
Published: April 2008

Objective: To investigate possible differences, between generally and abdominally obese men, in activity and regulation of the hypothalamic‐pituitary‐adrenal (HPA) axis and the sympathetic nervous system.

Research Methods and Procedures: Fifty non‐diabetic, middle‐aged men were selected to obtain two groups with similar body mass index (BMI) but different waist/hip circumference ratio (WHR). Measurements were performed of the activity of the HPA axis and the sympathetic nervous system, as well as metabolic and endocrine variables.

Results: Men with a high WHR, in comparisons with men with a low WHR, had higher insulin, glucose, and triglyceride values in the basal state and higher glucose and insulin after an oral glucose tolerance test. Men with high WHR had elevated diurnal adrenocorticotropic hormone (ACTH) values but similar cortisol values, except lower cortisol values in the morning. Diurnal growth hormone concentrations showed reduced peak size. Stimulation of the HPA axis with corticotropin‐releasing hormone (CRH) and laboratory stress showed no difference in ACTH values between groups, but cortisol values were lower in men with high WHR. In comparison with men with a low WHR, men with a high WHR had elevated pulse pressure and heart rate in the basal state and after challenges by CRH and laboratory stress. They also had increased urinary excretion of catecholamine metabolites.

Discussion: These results suggest a mild dysregulation of the HPA axis, occurring with elevated WHR independent of the BMI. The results also indicate a central activation of the sympathetic nervous system, such as in the early phases of hypertension, correlating with insulin resistance.
Racial Differences in Insulin Secretion and Sensitivity in Prepubertal Children: Role of Physical Fitness and Physical Activity
Authors: Ku Ching‐Yi , Gower Barbara A. , Hunter Gary R. , Goran Michael I.
Published: April 2008

Objective: To investigate in prepubertal children whether physical fitness and/or physical activity are: 1) associated with insulin secretion and sensitivity and 2) account for racial differences in insulin secretion and sensitivity.

Research Methods and Procedures: Subjects included 34 African American and 34 white nondiabetic children aged 5 to 11 years. Data were divided into two sets according to the availability of VO2max and physical activity data. Body composition was measured by dual‐energy X‐ray absorptiometry. Subcutaneous abdominal adipose tissue and intra‐abdominal adipose tissue were examined by computed tomography. Insulin sensitivity (SI) and acute insulin response (AIR) were determined by a frequently sampled intravenous glucose tolerance test. An all‐out, progressive treadmill exercise test was used for measuring VO2max. Physical activity data were collected by questionnaire.

Results: African American children had lower SI and higher AIR than white children, after adjusting for total body fat mass. African Americans reported higher levels of physical activity (hours/wk) than whites, but had a lower VO2max. In multiple linear regression analysis, hours/wk of activity and hours/wk of vigorous activity, but not moderate activity, were independently related to SI and AIR after adjusting for race, total body fat mass or fat distribution, and total lean tissue mass. VO2max was not related to AIR, and was inversely related to SI, after adjusting for body composition. Race remained significantly associated with both SI and AIR, even after adjusting for body composition, fat distribution, and hours/wk of activity or hours/wk of vigorous activity.

Discussion: In summary, overall physical activity and, especially, vigorous activity were associated with insulin secretion and sensitivity. However, neither physical activity nor VO2max explained the racial difference in insulin secretion (higher in African Americans) and sensitivity (lower in African Americans). Thus, racial (African American to white) differences in aspects of insulin action seem to be due to factors other than body composition, fat distribution, cardiovascular fitness, and amount of physical activity.
Effects of Metformin and Vanadium on Leptin Secretion from Cultured Rat Adipocytes
Authors: Mueller Wendy M. , Stanhope Kimber L. , Gregoire Francine , Evans Joseph L. , Havel Peter J.
Published: April 2008

Objective: We have reported that glucose utilization regulates leptin expression and secretion from isolated rat adipocytes. In this study, we employed two antidiabetic agents that act to increase glucose uptake by peripheral tissues, metformin and vanadium, as pharmacological tools to examine the effects of altering glucose utilization on leptin secretion in primary cultures of rat adipocytes.

Research Methods and Procedures: Isolated adipocytes (100 μL of packed cells per well) were anchored in a defined matrix of basement membrane components (Matrigel) with media containing 5.5 mM glucose and incubated for 96 hours with metformin or vanadium. Leptin secretion, glucose utilization, and lactate production were assessed.

Results: Metformin (0.5 and 1.0 mM) increased glucose uptake in the presence of 0.16 nM insulin by 37 ± 10% (p < 0.005) and 62 ± 8% (p < 0.0001) over insulin alone, respectively. Metformin from 0.5 to 5.0 mM increased lactate production by 105 ± 43% (p < 0.025) to 202 ± 52% (p < 0.0025) and at 1.0 and 5.0 mM increased the proportional rate of glucose conversion to lactate by 78 ± 18% (p < 0.005) and 166 ± 41% (p < 0.0025), respectively. At concentrations less than 0.5 mM, metformin did not affect leptin secretion, but at 0.5 mM, the only concentration that significantly increased glucose utilization without increasing glucose conversion to lactate, leptin secretion was modestly stimulated (by 20 ± 9%; p < 0.05). Concentrations from 1.0 to 25 mM inhibited leptin secretion by 25 ± 8% (p < 0.005) to 89 ± 4% (p < 0.0001). Across metformin doses, leptin secretion was inversely related to the percentage of glucose taken up and released as lactate (r = −0.74; p < 0.0001). Vanadium (5 to 20 μM) increased glucose uptake from 20 ± 7% (p < 0.01) to 34 ± 13% (p < 0.02) and increased lactate production at 5 μM by 17 ± 8% (p < 0.025) and 10 μM by 61 ± 20% (p < 0.02) but did not alter the conversion of glucose to lactate. Vanadium (5 to 50 μM) inhibited leptin secretion by 33 ± 6% (p < 0.0025) to 61 ± 8% (p < 0.0001).

Discussion: Both metformin and vanadium increase glucose uptake and inhibit leptin secretion from cultured adipocytes. The inhibition of leptin secretion by metformin is related to an increase in the metabolism of glucose to lactate. The inhibition by vanadium most likely involves direct effects on cellular phosphatases. We hypothesize that the effect of glucose utilization to stimulate leptin production involves the metabolism of glucose to a fate other than anaerobic lactate production, possibly oxidation or lipogenesis.
Asthma and Maternal Body Mass Index Are Related to Pediatric Body Mass Index and Obesity: Results from the Third National Health and Nutrition Examination Survey
Authors: Epstein Leonard H. , Wu Yow‐Wu B. , Paluch Rocco A. , Cerny Frank J. , Dorn Joan P.
Published: April 2008

Objective: Clinical research has shown an increased prevalence of obesity in children with asthma. This study was designed to assess the relationship between asthma and pediatric body mass index (BMI) in a national database and to examine factors that may modify this relationship.

Design: The cross‐sectional relationship between asthma and pediatric BMI and obesity (BMI ≥ 85th percentile) was studied. Variables that may influence the relationship between asthma and pediatric BMI, such as race/ethnicity and television watching were included in the model for the total sample. A smaller sample of 3009 white and African American youth were studied in regression models including maternal BMI.

Study Population: A nationally representative crosssectional sample of 5154 children and adolescents of 6 to 16 years of age from the Third National Health And Nutrition Examination Survey.

Results: In the full sample, asthma and television watching were related to BMI, accounting for 3% of the variance in BMI. When maternal BMI was included in the nonHispanic sample, television watching, maternal BMI, and the interaction of maternal BMI and asthma were related to youth BMI, accounting for 15% of the variance. The standardized BMI z‐score for those youth without asthma and no maternal obesity was 0.06, which increased to 0.33 if the youth had asthma, to 0.70 if the youth did not have asthma but the mother was obese, and to 1.71 if the youth had asthma and the mother was obese. Asthma, television watching, and maternal BMI were independent predictors of youth obesity.

Conclusions: BMI and prevalence of obesity is higher in youth with asthma. Pediatric BMI, but not obesity, is also related to the interaction of asthma and maternal BMI in white and African American youth. Comorbidity of asthma and obesity may complicate treatment of either condition, and prevention of obesity should be encouraged for asthmatic children.
Enhancing Effect of Troglitazone on Porcine Adipocyte Differentiation in Primary Culture: A Comparison with Dexamethasone
Authors: Tchoukalova Yourka D. , Hausman Dorothy B. , Dean Roger G. , Hausman Gary J.
Published: April 2008

Objective: This study compares the effects of the thiazolidinedione, troglitazone (TGZ), dexamethasone (DEX), and DEX plus TGZ on preadipocyte differentiation and the expression of CCAAT/enhancer‐binding protein‐α (C/EBPα) and peroxisome proliferator‐activated receptor‐γ (PPARγ).

Research Methods and Procedures: Adipose tissue was obtained from postnatal pigs to isolate stromal‐vascular cells. First, we applied 1, 5, or 10 μM TGZ and 10% fetal bovine serum for 3 days and counted the number of recruited preadipocytes. Next, we used either 10 μM TGZ, 80 nM DEX, or DEX plus TGZ with 10% fetal bovine serum for 3 days and then switched to serum‐free medium with insulin for 6 days. On day 3 of culture, we counted preadipocytes, and on days 3 and 6 of culture, we performed immunostaining and Western blot analysis to determine the expression of C/EBPα and PPARγ proteins. On day 9 of culture, we stained for lipids with oil red‐O and measured the activity of glycerol phosphate dehydrogenase.

Results: DEX and TGZ equally enhanced recruitment of preadipocytes and late differentiation, but these effects were not additive with DEX plus TGZ treatment. However, TGZ and DEX had a differential effect on morphogenesis; DEX‐treated adipocytes were larger and organized in loose clusters, whereas TGZ‐treated cells were smaller and formed compact clusters. Both agents increased C/EBPα expression but in a temporally distinct manner. DEX was a better inducer than TGZ, and its effect was early and temporary. However, treatment with either TGZ or DEX did not change PPARγ protein expression as evaluated by a Western blotting, but immunocytochemistry showed a tendency for increased numbers of PPARγ positive cells.

Discussion: TGZ and DEX equally enhance early and late adipocyte differentiation, possibly by using some common pathways for preadipocyte recruitment. The differential effect on morphogenesis implies a potential differential effect on the expression of extracellular matrix components. C/EBPα may be the critical transcription factor involved in TGZ‐ and DEX‐induced adipogenesis.
Genetic Variation and Obesity in Australian Women: A Prospective Study
Authors: de Silva Andrea M. , Walder Ken R. , Boyko Edward J. , Whitecross Kate F. , Nicholson Geoff , Kotowicz Mark , Pasco Julie , Collier Greg R.
Published: April 2008

Objective: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the β‐3 adrenergic receptor, tumor necrosis factor‐α, leptin, and leptin receptor (Lepr) in a cohort of Australian women.

Research Methods and Procedures: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double‐energy X‐ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2‐year follow‐up. Genomic DNA was extracted and used for polymerase chain reaction‐based genotyping of all polymorphisms.

Results: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass, percent body fat, and body mass index over a 2‐year period were not associated with genetic variation in the β‐3 adrenergic receptor (Trp64Arg), tumor necrosis factor‐α promoter, or leptin genes in non‐obese or obese women.

Discussion: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population.
Value of Structured Meals for Weight Management: Risk Factors and Long‐Term Weight Maintenance
Authors: Ditschuneit Herwig H. , Flechtner‐Mors Marion
Published: April 2008

Objective: To examine changes in biomarkers of disease risk after 51 months of reduced energy intake and sustained weight loss.

Research Methods and Procedures: This study was conducted as a prospective, randomized, two‐arm, parallel intervention for 12 weeks followed by a prospective, single‐arm, 4‐year trial in a university‐based hospital clinic. One hundred patients were randomly assigned to one of two dietary interventions for 3 months. Group A was prescribed an energy‐restricted diet of 1200 to 1500 kcal/d, and group B was prescribed an isocaloric diet, whereby two of three meals were replaced with nutrient‐fortified liquid meal replacements. After 3 months, the patients were prescribed the same caloric reduction and used once‐daily replacements for the succeeding 4 years. Body weight and blood pressure were checked monthly. Biomarkers of disease risk were measured after 3, 9, 15, 27, and 51 months.

Results: During the 3‐month weight‐loss period, body weight was reduced by 1.5 ± 0.4% and 7.8 ± 0.5% (mean ± SEM) for groups A and B, respectively. After 4 years, 75% of the patients were evaluated. Total mean weight loss was 3.3 ± 0.8% and 8.4 ± 0.8% for groups A and B, respectively. Both groups of patients showed significant improvement in glucose, insulin, triacylglycerol, and systolic blood pressure. Cholesterol concentrations were reduced in patients with high initial cholesterol levels and maintenance of a 7% weight loss.

Discussion: Providing a structured meal plan with liquid meal replacements is an effective treatment for obese subjects. Long‐term maintenance of weight loss with meal replacements improves biomarkers of disease risk.
Physician Involvement in the Management of Obesity as a Primary Medical Condition
Authors: Rippe James M. , McInnis Kyle J. , Melanson Kathleen J.
Published: April 2008

As the obesity epidemic escalates, increasing numbers of patients present with serious comorbidities related to excess body weight. Obesity should be recognized and treated as a primary medical condition that is progressive, chronic, and relapsing. Effective treatment of obesity has been shown to reduce cardiovascular risk factors and comorbid conditions. Physician involvement is necessary for medical assessment, management, counseling, and coordination of multidisciplinary obesity treatment. Obese patients who receive counseling and weight management from physicians are significantly more likely to undertake weight management programs than those who do not. Obesity treatment guidelines and materials are available from various health organizations. A comprehensive weight management program must include dietary adjustments, increased physical activity, and behavioral modification. Nutritional modifications should take into account the diet's energy content, composition, and suitability for the individual patient. The physical activity component should be safe and practical, including aerobic activity, strength training, and increased daily lifestyle activities. Various behavioral strategies enable the patient to make lifestyle changes that will promote weight loss and management. Adjunct therapies may serve to support lifestyle modifications in severe or resistant cases of obesity. Models for multidisciplinary care vary depending on whether they are designed for an individual medical practice or as part of the health care services of a larger facility. Lifestyle changes for healthy weight management must be permanently incorporated into a patient's daily lifestyle to reduce obesity and its associated health risks. Such intervention is necessary if the growing epidemic of obesity is to be slowed and reversed.
Daily Oral Oleoyl‐Estrone Gavage Induces a Dose‐Dependent Loss of Fat in Wistar Rats
Authors: Del Grasa Maria Mar , Cabot Cristina , Esteve Montserrat , Yubero Pilar , Masanés Rosa Maria , Blay Maria Teresa , Vilà Ruth , López‐Martí Jesus , Fernández‐López José Antonio , Remesar Xavier , Alemany Marià
Published: April 2008

Objective: To establish whether single daily oral doses of oleoyl‐estrone result in dose‐dependent slimming effects on normal weight rats, and to determine the changes in energy parameters induced by this treatment.

Research Methods and Procedures: The effects of a daily oral gavage of oleoyl‐estrone (0, 0.2, 0.5, 1, 2, 5, 10, and 20 μmol/kg per day) in 0.2 ml of sunflower oil given over a 10‐day period were studied in groups, each of which contained six adult female Wistar rats initially weighing 190 to 230 g. A group of intact control rats receiving no gavage was included for comparison. Body weight and food intake were measured daily. Rats were killed on day 10 of treatment, and body composition (protein nitrogen, lipids, and water), liver lipids, and plasma parameters (glucose, triacylglycerols, total cholesterol, free fatty acids, 3‐hydroxybutyrate, urea, aspartate, alanine transaminases, insulin, leptin, and free and acyl‐estrone) were measured.

Results: The administration of oleoyl‐estrone resulted in a dose‐dependent loss of body fat, because of a partly maintained energy expenditure combined with decreased food intake. The differences in the energy budget were met by internal fat pools. The changes recorded did not affect the levels of the main plasma energy homeostasis indicators: unaltered glucose, triacylglycerols, free fatty acids, 3hydroxybutyrate, and urea. Protein was accrued even under conditions of severe lipid store drainage. There were no changes in transaminases. No lipid accumulation was recorded in the liver. Plasma insulin and leptin levels decreased with increased oleoyl‐estrone doses, whereas the levels of free and esterified estrone increased with treatment, although not in proportion to the dose received.

Discussion: Oral treatment with oleoyl‐estrone resulted in the specific dose‐related loss of fat reserves with little change to other metabolic parameters. These results agree with the postulated role of oleoyl‐estrone as a ponderostat signal.
Effect of Insulin and Energy Restriction on the Thermic Effect of Protein in Type 2 Diabetes Mellitus
Authors: Gougeon Réjeanne
Published: April 2008

Objective: The objective of this study was to test whether the thermic effect of oral protein is blunted in poorly controlled type 2 diabetes and is corrected by normalization of glycemia with insulin and 28 days of a very‐low‐energy diet.

Research Methods and Procedures: Resting energy expenditure (REE) and the thermic effect of 90 g of oral protein were measured, using indirect calorimetry, in nine (five women and four men) obese diabetic people [weight, 108 ± 10 kg; waist circumference, 123 ± 8 cm; body mass index, 40 ± 3 kg/m2] who were hyperglycemic on day 8 or euglycemic with insulin on day 16 of a weight‐maintaining diet and euglycemic on day 28 of a very low energy diet (VLED). Results were compared with those of seven (six women and one man) weight‐ and body mass index‐matched obese nondiabetic subjects with a waist circumference of 111 ± 6 cm. Substrates and hormonal responses were determined concurrently.

Results: Fasting glucose was normalized in the diabetic subjects with insulin from day 9 of VLED onward. Weight decreased in both groups by 9.9 ± 0.9 kg with VLED. REE was 8 ± 2% lower with insulin treatment and decreased by another 14 ± 3% with VLED in the diabetic and by 15 ± 1% in the nondiabetic subjects by week 4. After the protein meal, the thermic response was significantly (p < 0.05) less with hyperglycemia than with insulin‐induced euglycemia, as percentage above REE (15.3 ± 1.4 compared with 21.2 ± 1.5%), as percentage of the energy content of the meal (19.5 ± 1.5 compared with 25.2 ± 1.7%), as kilocalories per 405 minutes (86 ± 5 compared with 110 ± 7), and less than in nondiabetic obese controls (21.0 ± 2.2% above REE, 24.4 ± 1.7% of energy of meal). After the VLED, the thermic effect of protein was significantly higher in both groups only as percentage above REE. The initial glucagon response was greater with hyperglycemia compared with euglycemia and post‐VLED but not compared with the nondiabetic subjects. Hyperglycemia was associated with 21 ± 4% greater urinary urea nitrogen excretion and urinary glucose losses of 134 ± 50 mmol/d.

Discussion: This study shows a blunted thermic effect of protein in obese hyperglycemic type 2 diabetic subjects compared with matched nondiabetic subjects that can be corrected with insulin‐ or energy restriction‐induced euglycemia.
Opioidergic Modulation of Ventilatory Response to Sustained Hypoxia in Obese Zucker Rats
Authors: Lee Shin‐Da , Magalang Ulysses J. , Krasney John A. , Farkas Gaspar A.
Published: April 2008

Objective: To determine whether altered central and/or peripheral opioidergic mechanisms contribute to the altered ventilatory response to sustained hypoxia in obese Zucker rats.

Research Methods and Procedures: Eight lean (176 ± 8 [SEM] g) and eight obese (225 ± 12 g) Zucker rats were studied at 6 weeks of age. Pulmonary ventilation (V̇E), tidal volume (VT), and breathing frequency (f) at rest and in response to sustained (30 minutes) hypoxic (10% O2) challenges were measured on three separate occasions by the barometric method after the randomized, blinded administration of equal volumes of saline (control), naloxone methiodide (NM; 5 mg/kg, peripheral opioid antagonist), or naloxone hydrochloride (NHCl; 5 mg/kg, peripheral and central opioid antagonist).

Results: Administration of NM and NHCl in lean animals had no effect on V̇E either at rest or during 30 minutes of sustained exposure to hypoxia. Similarly, NM failed to alter V̇E in obese rats. In contrast, NHCl significantly (p < 0.05) increased V̇E and VT both at rest and during 2 to 10 minutes of hypoxic exposure in obese rats. After 20 to 30 minutes of hypoxic exposure, VT remained elevated with NHCl, but the earlier elevation of V̇E seemed to be attenuated due to a decrease in f at 20 minutes of exposure to hypoxia.

Discussion: Thus, endogenous opioids modulate both resting V̇E and the ventilatory response to sustained hypoxia in obese, but not in lean, Zucker rats by acting specifically on opioid receptors located within the central nervous system.
Metabolic and Hemodynamic Response of Adipose Tissue to Angiotensin II
Authors: Boschmann Michael , Ringel Jens , Klaus Susanne , Sharma Arya M.
Published: April 2008

Objective: Recent studies have revealed the presence of a local renin‐angiotensin system in adipose tissue. To examine the possible role of this system in adipose tissue, we performed microdialysis studies on the effect of angiotensin II (Ang II) on blood flow and metabolism in abdominal subcutaneous adipose tissue (aSAT) and femoral subcutaneous adipose tissue (fSAT) in young healthy men.

Research Methods and Procedures: Using the microdialysis technique, two different protocols were run perfusion with Ringer's solution + 50 mM ethanol with the subsequent addition of 125, 250, and 500 μg/liter Ang II (n = 8) and Ringers's solution + 50 mM ethanol with the subsequent addition of isoproterenol (1 μM) alone and in combination with 500 μg/liter Ang II (n = 6). Dialysate concentrations of ethanol, glycerol, glucose, and lactate were measured for estimating blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively.

Results: Perfusion with Ang II resulted in a dose‐dependent decrease in blood flow (fSAT > aSAT), lipolysis (fSAT > aSAT), and glucose uptake (fSAT = aSAT). Isoproterenol increased blood flow and lipolysis at both sites and those effects could be returned to baseline values by the addition of Ang II in aSAT but not fSAT.

Discussion: In conclusion, our data indicate that in addition to its well‐known vasoconstricting effect, Ang II inhibits lipolysis in adipose tissue, whereby femoral fat depots seem to be more sensitive to this effect than abdominal depots.
Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats
Authors: Stevenson Frazier T. , Wheeldon Carrie M. , Gades Matthew D. , van Goor Harry , Stern Judith S.
Published: April 2008

Objective: We sought to determine whether prevention of overeating would block the very earliest manifestations of renal injury in young obese Zucker rats (OZRs).

Research Methods and Procedures: Three groups of rats were studied, obese (fa/fa) Zucker rats and lean (Fa/Fa). Zucker controls were allowed to feed ad libitum, whereas a group of obese (fa/fa) Zucker rats was pair‐fed to the lean group. Urine albumin and serum lipids were studied weekly from 6 to 10 weeks of age. Renal pathology and renal glomerular gene expression were examined when the rats were killed at 10 weeks of age.

Results: Obese rats fed ad libitum developed significant albuminuria by 6 weeks of age, increasing at each subsequent time‐point. This increase was completely blocked by pair‐feeding. Serum triglycerides were significantly increased in obese rats fed ad libitum vs. the other groups. Urine albumin correlated significantly with both body weight and serum triglyceride level. Renal histopathology was normal in all groups. Analysis of gene expression of glomerular proteins by reverse transcriptase‐polymerase chain reaction revealed that pair‐feeding attenuated the increased expression of glomerular desmin, fibronectin, and the 92‐kDa collagenase that was seen in obeseanimals fed ad libitum.

Discussion: Prevention of overeating in young OZR normalizes albuminuria and attenuates the pathogenic alterations in glomerular gene expression seen at the initiation of renal disease in obese animals allowed to feed ad libitum. This model may be relevant for studying the early end‐organ effects of obesity.
Changes of Adiposity in Response to Vitamin A Status Correlate with Changes of PPARγ2 Expression
Authors: Ribot Joan , Felipe Francisco , Bonet M. Luisa , Palou Andreu
Published: April 2008

Objective: To gain insight into the in vivo modulation of the expression of the adipogenic transcription factors PPARγ2, C/EBPα, and ADD1/SREBP1c by retinoids and its relationship with whole‐body adiposity.

Research Methods and Procedures: Three‐week‐old mice were fed with standard chow or a vitamin A‐deficient diet for 10 weeks. During the 4 days immediately before they were killed, the animals were treated either with all‐trans retinoic acid (tRA; 100 mg/kg per day, subcutaneously) or vehicle. The specific levels of the mRNAs for the three transcription factors were analyzed in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue and in brown adipose tissue (BAT). Other parameters determined were leptin and UCP2 levels in white adipose tissue depots, total cholesterol and triglyceride serum levels, energy intake, body weight, and adiposity.

Results: Vitamin A‐deficient diet feeding led to a marked increase of adiposity and to a small increase of body weight. Hypertrophy of white adipose tissue depots correlated with enhanced PPARγ2 expression. Hypertrophy of BAT, in contrast, correlated with a decrease of PPARγ2 expression that may contribute to the known reduced thermogenic potential of BAT under conditions of vitamin A restriction. Treatment with tRA triggered a reduction of adiposity and body weight that correlated with a down‐regulation of PPARγ2 expression in all adipose tissues. The effects of tRA were more pronounced in eWAT, where C/EBPα and ADD1/SREBP1c levels were also reduced. The response to tRA was impaired in the eWAT and BAT of animals fed the vitamin A‐deficient diet.

Discussion: The results emphasize the importance of retinoids as physiological regulators of adipose tissue development and function in intact animals.
Failure of Preoperative Resting Energy Expenditure in Predicting Weight Loss after Gastroplasty
Authors: Camerini Giovanni , Adami Gian Franco , Marinari Giuseppe M. , Campostano Adelia , Ravera Giambattista , Scopinaro Nicola
Published: April 2008

Objective: To evaluate the predictive efficacy of preoperative resting energy expenditure (REE) on weight loss after vertical banded gastroplasty (VBG). When subjected to a gastric restriction procedure of similar extent, the patients with higher energy expenditure should experience a greater negative energy balance than those with lower‐energy expenditure, and thus, lose more weight, thereby making REE a reliable predictor of weight loss after VBG.

Research Methods and Procedures: This was a prospective investigation after VBG, taking into account the relationship between preoperative REE values and the results at 1‐year follow‐up in terms of weight loss and success of the procedure. The correlations were evaluated by multiple and logistic regression analysis.

Results: The weight loss and the outcome at 1 year after VBG seemed to be completely independent of preoperative energy expenditure.

Discussion: These findings suggest that, despite gastric restriction, patients may voluntarily adjust their energy intake, and that the weight outcome after VBG is influenced more by behavioral and cognitive variables than by biological or surgical factors.
Orlistat Inhibits Dietary Cholesterol Absorption
Authors: Mittendorfer Bettina , Ostlund Richard E. , Patterson Bruce W. , Klein Samuel
Published: April 2008

Objective: Orlistat decreases the absorption of dietary triglycerides by inhibiting intestinal lipases. Orlistat therapy is associated with a greater decline in plasma low‐density lipoprotein‐cholesterol concentrations than that expected from weight loss alone. Therefore, we evaluated the effect of orlistat treatment on dietary cholesterol absorption as a possible mechanism for the independent effect of orlistat on plasma cholesterol concentration.

Research Methods and Procedures: Cholesterol absorption from a standardized meal, containing 72 mg of cholesterol, was determined in 18 subjects with class II abdominal obesity (BMI, 35.0 to 39.9 kg/m2) by simultaneous administration of intravenous ([2H6] cholesterol) and oral ([2H5] cholesterol) cholesterol tracers. In protocol 1 (n = 9), cholesterol absorption was determined on two different occasions, 10 to 20 days apart, to assess the reproducibility of the tracer method. In protocol 2 (n = 9), cholesterol absorption was determined with and without orlistat therapy in a prospective, randomized, crossover design to assess the effect of orlistat on cholesterol absorption.

Results: In protocol 1, cholesterol absorption from the test meal was the same on both occasions (53 ± 5% and 51 ± 5%). In protocol 2, orlistat treatment caused a 25% reduction in cholesterol absorption, from 59 ± 6% to 44 ± 5% (p < 0.01).

Discussion: These data demonstrate that orlistat inhibits dietary cholesterol absorption, which may have beneficial effects on lipoprotein metabolism in obese subjects that are independent of weight loss itself.
Effects of the FABP2 A54T Mutation on Triglyceride Metabolism of Viscerally Obese Men
Authors: Berthier Marie‐Thérèse , Couillard Charles , Prud'homme Denis , Nadeau André , Bergeron Jean , Tremblay Angelo , Després Jean‐Pierre , Vohl Marie‐Claude
Published: April 2008

Objective: Viscerally obese individuals are frequently characterized by a proatherogenic condition. A missense mutation (A54T) in the fatty acid binding protein type 2 (FABP2) gene has been associated with insulin resistance and obesity. This study examined the effect of this mutation on lipoprotein levels in viscerally obese hyperinsulinemic condition.

Research Methods and Procedures: A total of 217 men were assigned to one of two groups based on their FABP2 A54T polymorphism.

Results: The two genotypic groups showed no difference in either physiological characteristics or lipoprotein/lipid profile, before or after statistical adjustment for age. From this initial sample, 50 men accepted to have their postprandial lipid response assessed and 10 T54/A54 heterozygotes were then individually matched for visceral adipose tissue accumulation and fasting plasma triglyceride (TG) levels with 10 A54/A54 homozygotes. High‐density lipoprotein (HDL)‐TG levels were significantly increased in the fasting state as well as 4 hours after the test meal (p = 0.04 and p = 0.0008, respectively) in men bearing the A54T mutation. In addition, the area under the curve of postprandial HDL‐TG levels was also significantly higher among T54/A54 heterozygotes than among A54/A54 homozygotes (p = 0.04). Interestingly, fasting TG concentrations in large TG‐rich lipoproteins (large‐TRL; Sf > 400) were correlated with HDL‐TG levels at 4 (r = 0.74, p = 0.01) and 8 hours (r = 0.73, p = 0.01) after the test meal in T54/A54 heterozygotes only.

Discussion: The FABP2 A54T missense mutation may contribute to the TG enrichment of HDL in the postprandial state that, in turn, may alter the risk of atherosclerotic vascular disease.
Density-functional study of structural and electronic properties of SinCn (n=1–10) clusters
Authors: Hou Jinyu , Song Bin
Published: April 2008

Density-functional theory with generalized gradient approximation for the exchange-correlation potential has been used to calculate the structural and electronic structure of SinCn (n=1–10) clusters. The geometries are found to undergo a structural change from two dimensional to three dimensional when the cluster size n equals 4. Cagelike structures are favored as the cluster size increases. A distinct segregation between the silicon and carbon atoms is observed for these clusters. It is found that the C atoms favor to form five-membered rings as the cluster size n increases. However, the growth motif for Si atoms is not observed. The SinCn clusters at n=2, 6, and 9 are found to possess relatively higher stability. On the basis of the lowest-energy geometries obtained, the size dependence of cluster properties such as binding energy, HOMO-LUMO gap, Mulliken charge, vibrational spectrum, and ionization potential has been computed and analyzed. The bonding characteristics of the clusters are discussed.
Morphological change of asymmetric oxyethylene/oxybutylene block copolymers induced by montmorillonite
Authors: Yang Yong , Xu Jun-Ting , Du Bin-Yang , Xue Liang , Fan Zhi-Qiang , Mai Shao-Min , Ryan Anthony J.
Published: April 2008

Two oxyethylene/oxybutylene block copolymers (E40B79 and E47B62), which exhibit body-centered cubic sphere (bcc) and hexagonally packed cylindrical (hex) melt morphologies in bulk, respectively, were blended with nanoclay of montmorillonite (MMT). The effects of MMT on the morphology and crystallization of E40B79 and E47B62 were studied with small-angle x-ray scattering, wide-angle x-ray diffraction, and differential scanning calorimeter. It is found that the E block in the block copolymers can intercalate into the galleries of MMT, leading to a larger layer spacing than that of neat MMT. The preferential absorption of the E block onto MMT plates induces the formation of a new lamellar structure, irrespectively of original morphology in the bulk. There is, however, coexistence of the new lamellar structure with regions retaining the melt morphology. The order-disorder transition temperature (TODT) of the block copolymer is increased by MMT for E40B79, but it remains unchanged for E47B62. Crystallinity of the block copolymers is also greatly suppressed by the addition of MMT.
On solvable boson models
Authors: Pulé Joe V. , Verbeure André F. , Zagrebnov Valentin A.
Published: April 2008

The problem of equilibrium states and∕or ground states of exactly solvable homogeneous boson models is stated and explicitly proved as a special case of the general variational problem of statistical mechanics in terms of quasifree states. We apply the result to a model of super-radiant Bose–Einstein condensation and to the pairing boson model.
The role of the density gradient on intermittent cross-field transport events in a simple magnetized toroidal plasma
Authors: Theiler C. , Diallo A. , Fasoli A. , Furno I. , Labit B. , Podestà M. , Poli F. M. , Ricci P.
Published: April 2008

Intermittent cross-field particle transport events (ITEs) are studied in the basic toroidal device TORPEX [TORoidal Plasma EXperiment, A. Fasoli et al., Phys. Plasmas 13, 055902 (2006)], with focus on the role of the density gradient. ITEs are due to the intermittent radial elongation of an interchange mode. The elongating positive wave crests can break apart and form blobs. This is not necessary, however, for plasma particles to be convected a considerable distance across the magnetic field lines. Conditionally sampled data reveal two different scenarios leading to ITEs. In the first case, the interchange mode grows radially from a slab-like density profile and leads to the ITE. A novel analysis technique reveals a monotonic dependence between the vertically averaged inverse radial density scale length and the probability for a subsequent ITE. In the second case, the mode is already observed before the start of the ITE. It does not elongate radially in a first stage, but at a later time. It is shown that this elongation is preceded by a steepening of the density profile as well.
The Hall fields and fast magnetic reconnection
Authors: Drake J. F. , Shay M. A. , Swisdak M.
Published: April 2008

The results of large-scale, particle-in-cell simulations are presented on the role of Hall electric and magnetic fields on the structure of the electron dissipation region and outflow exhaust during the collisionless magnetic reconnection of antiparallel fields. The simulations reveal that the whistler wave plays the key role in driving the electrons away from the magnetic x-line. Further downstream the electron outflow exhaust consists of a narrow super-Alfvénic jet, which remains collimated far downstream of the x-line, flanked by a pedestal whose width increases monotonically with increasing distance downstream. The open outflow exhaust, which is required for fast reconnection in large systems, is driven by the Hall electric and magnetic fields. Finally, it is the whistler that ultimately facilitates fast reconnection by diverting the electrons flowing toward the current layer into the outflow direction and thereby limiting the length of this layer. The results are contrasted with reconnection in an electron-positron plasma where the Hall fields are absent. The consequence of the expanding outflow exhaust is that, consistent with recent observations, the extended super-Alfvénic electron outflow jet carries a smaller and smaller fraction of the outflowing electrons with increasing distance downstream of the x-line. The results suggest that the structure of the electron current layer and exhaust in simulations might be sensitive to boundary conditions unless the simulation boundary along the outflow direction is sufficiently far from the x-line.