Basal Endothelial Nitric Oxide Release Is Preserved in Overweight and Obese Adults

Objective: Impaired basal nitric oxide release is associated with a number of cardiovascular disorders including hypertension, arterial spasm, and myocardial infarction. We determined whether basal endothelial nitric oxide release is reduced in otherwise healthy overweight and obese adult humans. Research Methods and Procedures: Seventy sedentary adults were studied: 32 normal weight (BMI <25 kg/m²), 24 overweight (BMI ≥ 25 < 30 kg/m²), and 14 obese (BMI ≥ 30 kg/m²). Forearm blood flow (FBF) responses to intra‐arterial infusions of N^g‐monomethyl‐l ‐arginine (5 mg/min), a nitric oxide synthase inhibitor, were used as an index of basal nitric oxide release. Results: N^g‐monomethyl‐l ‐arginine elicited significant reductions in FBF in the normal weight (from 4.1 ± 0.2 to 2.7 ± 0.2 mL/100 mL tissue/min), overweight (4.1 ± 0.1 to 2.8 ± 0.2 mL/100 mL tissue/min), and obese (3.9 ± 0.3 to 2.7 ± 0.2 mL/100 mL tissue/min) subjects. Importantly, the magnitude of reduction in FBF (～30%) was similar among the groups. Discussion: These results indicate that the capacity of the endothelium to release nitric oxide under basal conditions is not compromised in overweight and obese adults.     

Regular Aerobic Exercise,Without Weight Loss,Improves Endothelium‐dependent Vasodilation in Overweight and Obese Adults

Lifestyle modification in the form of weight reduction by caloric restriction alone or in combination with regular aerobic exercise significantly improves endothelium‐dependent vasodilation in overweight and obese adults. We determined whether regular aerobic exercise, independent of weight loss, improves endothelium‐dependent vasodilation in overweight and obese adults. Twenty overweight and obese adults (age 53 ± 1 years; BMI: 30.2 ± 0.8 kg/m²) were studied before and after a 3‐month aerobic exercise training intervention. Forearm blood flow (FBF) responses were determined (via plethysmography) in response to intra‐arterial infusion of acetylcholine and sodium nitroprusside. There were no changes in body mass or composition with the intervention. FBF responses to acetylcholine were ～35% higher (P < 0.01) after (4.1 ± 0.9 to 14.7 ± 4.3 ml/100 ml tissue/min) compared with before (4.2 ± 0.8 to 11.0 ± 3 ml/100 ml tissue/min) exercise training. FBF responses to sodium nitroprusside were unchanged. These results indicate that regular aerobic exercise improves endothelium‐dependent vasodilation in overweight and obese adults, independent of changes in body mass or composition.     

Influence of abdominal obesity on vascular endothelial function in overweight/obese adult men

It has been suggested that body fat distribution may be an important determinant of the impact of adiposity on endothelial function. We tested the hypothesis that overweight/obese adults with abdominal adiposity exhibit worse endothelial vasodilator and fibrinolytic function than overweight/obese adults without abdominal adiposity. Sixty adult men were studied: 20 normal weight (BMI: 22.3 ± 0.7 kg/m2; waist circumference (WC): 84.9 ± 2.0 cm); 20 overweight/obese with WC <102 cm (29.2 ± 0.3 kg/m2; 98.1 ± 0.7 cm); and 20 overweight/obese with WC ≥102 cm (30.0 ± 0.4 kg/m2; 106.7 ± 1.0 cm). Forearm blood flow (FBF) responses to intra-arterial acetylcholine and sodium nitroprusside (SNP) were measured. Additionally, net endothelial release of tissue-type plasminogen activator (t-PA) was determined in response to bradykinin (BK) and SNP. Overweight/obese men demonstrated lower (~30%; P < 0.01) FBF responses to acetylcholine compared with normal weight controls. However, there were no differences in FBF responses to acetylcholine between overweight/obese men with (4.1 ± 0.3-10.8 ± 1.3 ml/100 ml tissue/min) and without (4.5 ± 0.3-11.6 ± 0.8 ml/100 ml tissue/min) abdominal adiposity. Similarly, endothelial t-PA release to BK was lower (~40%; P < 0.05) in the overweight/obese men compared with normal weight controls; however, t-PA release was not different between the overweight/obese men with (-0.7 ± 0.4-40.4 ± 6.2 ng/100 ml tissue/min) and without (-0.3 ± 0.6-48 ± 7.5 ng/100 ml tissue/min) abdominal adiposity. These results indicate that abdominal obesity is not associated with greater impairment in endothelial vasodilation and fibrinolytic capacity in overweight/obese men. Excess adiposity, regardless of anatomical distribution pattern, is associated with impaired endothelial function.     

Oxidant Stress in Healthy Normal‐weight,Overweight, and Obese Individuals

This study was undertaken to investigate the association among BMI and lipid hydroperoxide (LH), total antioxidant status (TAS), superoxide dismutase (SOD), and reduced glutathione (GSH). Ninety (n = 90) healthy males and females (n = 23/67) (29 normal weight (BMI: 22.74 ± 0.25 kg/m²), 36 overweight (BMI: 27.18 ± 0.23 kg/m²), and 25 obese (33.78 ± 0.48 kg/m²)) participated in the study. Data collected included anthropometric measures, fasting blood glucose, lipid profile, LH, TAS, and enzymatic antioxidants (SOD, and reduced GSH). The results of the study showed that obese individuals had significantly increased LH levels compared to normal‐weight individuals (obese vs. normal weight (0.88 ± 0.05 vs. 0.67 ± 0.03 µmol/l, P < 0.01)) but the increased levels were not significantly different when compared to the overweight group (obese vs. overweight (0.88 ± 0.05 vs. 0.79 ± 0.05 µmol/l)). No other consistent significant differences in TAS, SOD, and GSH were identified between groups. This study concluded that only obesity and not moderate overweight elevates LH levels. Furthermore, the levels of TAS, SOD, and GSH in obesity do not explain the increased LH levels observed in obesity.     

Decreased Glucagon‐like Peptide 1 Release after Weight Loss in Overweight/Obese Subjects

Objective: Postprandial glucagon‐like peptide 1 (GLP‐1) release seems to be attenuated in obese subjects. Results on whether weight loss improves GLP‐1 release are contradictory. The aim of this study was to further investigate the effect of weight loss on basal and postprandial GLP‐1 release in overweight/obese subjects. Research Methods and Procedures: Thirty‐two overweight/obese subjects participated in a repeated measurement design before (BMI, 30.3 ± 2.8 kg/m²; waist circumference, 92.6 ± 7.8 cm; hip circumference, 111.1 ± 7.4 cm) and after a weight loss period of 6 weeks (BMI, 28.2 ± 2.7 kg/m²; waist circumference, 85.5 ± 8.5 cm; hip circumference, 102.1 ± 9.2 cm). During weight loss, subjects received a very‐low‐calorie diet (Optifast) to replace three meals per day. Subjects came to the laboratory fasted, and after a baseline blood sample, received a standard breakfast (1.9 MJ). Postprandially, blood samples were taken every one‐half hour relative to intake for 120 minutes to determine GLP‐1, insulin, glucose, and free fatty acids from plasma. Appetite ratings were obtained with visual analog scales. Results: After weight loss, postprandial GLP‐1 concentrations at 30 and 60 minutes were significantly lower than before weight loss (p < 0.05). Glucose concentrations were also lower, and free fatty acids were higher compared with before weight loss. Ratings of satiety were increased, and hunger scores were decreased after weight loss (p < 0.05). Discussion: In overweight/obese subjects, GLP‐1 concentrations after weight loss were decreased compared with before weight loss, and nutrient‐related stimulation was abolished. This might be a response to a proceeding negative energy balance. Satiety and GLP‐1 seem to be unrelated in the long term.     

Novel electrocardiographic parameters of altered repolarization in uncomplicated overweight and obesity

In addition to well‐known electrocardiographic measurements, as QT, QT dispersion, and QT apex dispersion, new parameters such as Tpeak‐Tend, Tpeak‐Tend dispersion, and Tpeak‐Tend/QT ratio have been recently introduced as indexes of increased arrhythmic risk. The aim of the present study was to test, in overweight and obese subjects not affected by conditions of comorbidity, the aforementioned markers of ventricular repolarization. We studied 60 athletic subjects with normal body weight (21 females and 39 males, BMI between 19 and 24, mean BMI 22.0 ± 2.0 kg/m², aged 14–64 years, mean age 32 ± 13.59) and 60 sedentary and overweight/obese subjects (34 overweight and 26 obese, 22 females, and 38 males, BMI between 26 and 55, mean BMI 30.7 ± 5.7 kg/m², aged 14–64, mean age 38 ± 14.49). Each subject underwent anthropometric measurements and a 12‐lead electrocardiogram, from which the following different parameters were calculated: QT, corrected QT, QT dispersion, QT apex dispersion, Tpeak‐Tend, Tpeak‐Tend dispersion and Tpeak‐Tend/QT ratio were calculated. The aforementioned repolarization markers resulted, respectively: 340.2 ± 25.1, 373.8 ± 25.9, 29 ± 16.2, 23.5 ± 14.6, 87.3 ± 12.8, 26.5 ± 16.8, and 0.22 ± 0.03 ms in control subjects and 362.5 ± 28.5, 397.4 ± 35.4, 34.5 ± 16.8, 30.7 ± 16.3, 90.5 ± 15.2, 27 ± 17.1, and 0.22 ± 0.04 ms in overweight/obese subjects. Neither uncomplicated obesity nor overweight were associated with a statistically significant difference in QT dispersion, QT apex dispersion, Tpeak‐Tend, Tpeak‐Tend dispersion, and Tpeak‐Tend/QT ratio; QT and corrected QT were the only parameters that showed statistically significant variations between normal weight and overweight/obese subjects.     

Long-Term BMI changes since adolescence and markers of early and advanced subclinical atherosclerosis

Although long‐term weight gain has been associated with cardiovascular risk and intima‐media thickening (IMT), no sufficient data exist on possible associations of such weight changes with more advanced stages of subclinical atherosclerosis. Moreover, the value of self‐reported weight changes, a more practical approach to assess long‐term history in adiposity status, is still a matter of debate. In this longitudinal study, long‐term changes in BMI and overweight status were assessed in 106 healthy young adults (age 40.5 ± 1.1 years, 60 males). These were a subgroup of adolescent school students who had originally been examined in 1983 initially aiming to assess cardiovascular risk factor prevalence. Markers of early (carotid IMT) and advanced (presence of plaques in the carotid and femoral arteries and ankle‐brachial index, ABI) subclinical atherosclerosis were measured in all individuals. By multivariate analysis, among other risk factors, IMT and the presence of plaques were independently determined by BMI change, while a low ABI was also determined by changes in overweight status. An adverse long term adiposity profile change (≥ +4 kg/m² and/or change into overweight/obese status from normal weight since adolescence) incrementally determined a low ABI over current risk factors. Self‐reported and actual BMI changes were correlated (r = 0.587) but their means significantly differed, while the former significantly correlated with IMT only (P = 0.032). In conclusion, an adverse long term adiposity status change was more prominently associated with advanced subclinical atherosclerosis and particularly low ABI. These results also suggest that the utility of self‐reported weight changes may be limited in primary prevention practice.     

Leptin, superoxide dismutase, and weight loss: initial leptin predicts weight loss

Objective: Our goal was to study how plasma leptin concentration, superoxide dismutase (SOD) activity, and weight loss are related in obese adults. Research Methods and Procedures: Serum leptin concentration, SOD activities, general biochemical data, and body composition measurements were obtained for 62 overweight and obese subjects before and after an 8‐week body weight reduction (BWR) regimen. The subjects were on dietary control, performed moderate aerobic and strength training exercises, and attended educational lectures. Results: The measurement results indicated that the following criteria were significantly reduced: body weight [84.4 ± 17.0 vs. 79.3 ± 16.1 (standard error) kg, p < 0.001]; BMI (31.5 ± 4.3 vs. 29.4 ± 4.2 kg/m², p < 0.001), and fat mass (33.3 ± 10.0 vs. 29.8 ± 10.4 kg, p < 0.001). Plasma leptin levels also significantly decreased from 31.5 ± 17.6 to 26.5 ± 17.2 ng/mL (p < 0.001). Additionally, SOD activity was significantly increased from 261.4 ± 66.0 to 302.7 ± 30.9 U/mL (p < 0.001). Based on linear regression analysis results, a 3.78‐ to 8.13‐kg reduction in weight can be expected after the 8‐week BWR regimen when initial leptin concentration was 5 to 30 ng/mL. Discussion: We found that an 8‐week exercise and diet program was effective in reducing weight and fat mass and, notably, had further beneficial effects on leptin resistance and SOD activity. Additionally, this study demonstrated that initial plasma leptin concentration may be used as a predictor for weight loss outcome.     

The Feet of Overweight and Obese Young Children: Are They Flat or Fat?

Objective: The purpose of this study was to determine whether the flat feet displayed by young obese and overweight children are attributable to the presence of a thicker midfoot plantar fat pad or a lowering of the longitudinal arch relative to that in non‐overweight children. Research Methods and Procedures: Foot anthropometry, an arch index derived from plantar footprints, and midfoot plantar fat pad thickness measured by ultrasound were obtained for 19 overweight/obese preschool children (mean age, 4.3 ± 0.9 years; mean height, 1.07 ± 0.1 m; mean BMI, 18.6 ± 1.2 kg/m²) and 19 non‐overweight children matched for age, height, and sex (mean age, 4.3 ± 0.7 years; mean height, 1.05 ± 0.1 m; mean BMI, 15.7 ± 0.7 kg/m²). Results: Independent t tests revealed no significant between‐subject group differences (p = 0.39) in the thickness of the midfoot plantar fat pad. However, the overweight/obese children had a significantly lower plantar arch height (0.9 ± 0.3 cm) than their non‐overweight counterparts (1.1 ± 0.2 cm; p = 0.04). Discussion: The lower plantar arch height found in the overweight/obese children suggests that the flatter feet characteristic of overweight/obese preschool children may be caused by structural changes in their foot anatomy. It is postulated that these structural changes, which may adversely affect the functional capacity of the medial longitudinal arch, might be exacerbated if excess weight bearing continues throughout childhood and into adulthood.     

Resistance training lowers exercise-induced oxidative stress and homocysteine levels in overweight and obese older adults

Objective: To compare exercise‐induced oxidative stress and levels of homocysteine and cholesterol in normal‐weight and overweight older adults after resistance exercise (RX). Research Methods and Procedures: This interventional study was conducted at a wellness center. Forty‐nine older adults (age range, 60 to 72 years) were stratified by BMI (<25 kg/m² normal weight, ≥25 kg/m² overweight/obese) and then randomly assigned to either a control non‐exercise group or an RX group. The RX group completed a 6‐month training program. Exercise‐induced lipid hydroperoxides (PEROXs) and thiobarbituric‐reactive acid substances, homocysteine, lipoprotein a, cholesterol, and high‐density lipoprotein cholesterol were measured before and after the 6‐month RX program. Results: PEROXs and thiobarbituric‐reactive acid substances were lower in both the overweight/obese and normal‐weight RX‐trained groups compared with control groups (p < 0.05). Homocysteine levels were lower in both overweight/obese and normal‐weight RX groups compared with control groups (p < 0.05). Lipoprotein a, total cholesterol, and high‐density lipoprotein cholesterol were not different in normal‐weight and overweight/obese groups before or after RX. The change in muscle strength was correlated with homocysteine at 6 months (r = ?0.452, p < 0.05), whereas the change in PEROXs was correlated with the change in body fat (r = ?0.329). Discussion: To our knowledge, these data are the first to show that RX reduces exercise‐induced oxidative stress and homocysteine regardless of adiposity, indicating that this protection can be afforded in an older, overweight/obese population as effectively as in healthy older adults. These data suggest that RX may afford some protection against emerging cardiovascular risk factors using a mode of exercise that supports body weight.     

Weight Loss Is Associated With Increased Serum 25‐Hydroxyvitamin D in Overweight or Obese Women

Low circulating concentrations of vitamin D metabolites have been associated with increased risk for several diseases and clinical conditions. Large observational studies and surveys have shown that obesity is independently associated with lower serum 25‐hydroxyvitamin D (25(OH)D) concentration. Few studies have examined the effect of weight loss on serum 25(OH)D concentration. The purpose of this study was to prospectively examine the effect of weight loss on serum 25(OH)D concentration. Data were collected from 383 overweight or obese women who participated in a 2‐year clinical trial of a weight‐loss program, in which 51% (N = 195) lost at least 5% of baseline weight by 24 months, 18% (N = 67) lost 5–10%, and 33% (N = 128) lost >10%. Women who did not lose weight at 24 months had an increase in serum 25(OH)D of 1.9 (9.7) ng/ml (mean (SD)); 25(OH)D increased by 2.7 (9.1) ng/ml for those who lost 5–10% of baseline weight; and 25(OH)D increased by 5.0 (9.2) ng/ml for those who lost >10% of baseline weight (P = 0.014). At baseline, 51% (N = 197) of participants met or exceeded the recommended serum concentration of 20 ng/ml. By study end, 64% (N = 230) of overweight or obese women met this goal, as well as 83% (N = 20) of those whose weight loss achieved a normal BMI. These findings suggest that weight loss, presumably associated with a reduction in body fat, is associated with increased serum 25(OH)D concentration in overweight or obese women.     

Enhanced Weight Loss With Pramlintide/Metreleptin: An Integrated Neurohormonal Approach to Obesity Pharmacotherapy

The neurohormonal control of body weight involves a complex interplay between long‐term adiposity signals (e.g., leptin), and short‐term satiation signals (e.g., amylin). In diet‐induced obese (DIO) rodents, amylin/leptin combination treatment led to marked, synergistic, fat‐specific weight loss. To evaluate the weight‐lowering effect of combined amylin/leptin agonism (with pramlintide/metreleptin) in human obesity, a 24‐week, randomized, double‐blind, active‐drug‐controlled, proof‐of‐concept study was conducted in obese or overweight subjects (N = 177; 63% female; 39 ± 8 years; BMI 32.0 ± 2.1 kg/m²; 93.3 ± 13.2 kg; mean ± s.d.). After a 4‐week lead‐in period with pramlintide (180 µg b.i.d. for 2 weeks, 360 µg b.i.d. thereafter) and diet (40% calorie deficit), subjects achieving 2–8% weight loss were randomized 1:2:2 to 20 weeks of treatment with metreleptin (5 mg b.i.d.), pramlintide (360 µg b.i.d.), or pramlintide/metreleptin (360 µg/5 mg b.i.d.). Combination treatment with pramlintide/metreleptin led to significantly greater weight loss from enrollment to week 20 (?12.7 ± 0.9%; least squares mean ± s.e.) than treatment with pramlintide (?8.4 ± 0.9%; P < 0.001) or metreleptin (?8.2 ± 1.3%; P < 0.01) alone (evaluable, N = 93). The greater reduction in body weight was significant as early as week 4, and weight loss continued throughout the study, without evidence of a plateau. The most common adverse events with pramlintide/metreleptin were injection site events and nausea, which were mostly mild to moderate and decreased over time. These results support further development of pramlintide/metreleptin as a novel, integrated neurohormonal approach to obesity pharmacotherapy.     

The Influence of Overweight and Obesity on Longitudinal Trends in Maternal Serum Leptin Levels During Pregnancy

Maternal obesity influences a number of metabolic factors that can affect the course of pregnancy. Among these factors, leptin plays an important role in energy metabolism and fetal development during pregnancy. Our objective was to estimate the influence of maternal overweight/obesity on variation in the maternal serum leptin profile during pregnancy. In a prospective cohort of 143 adult gravidas with singleton pregnancies presenting for general prenatal care, we measured serum leptin levels at 6–10, 10–14, 16–20, 22–26, and 32–36 weeks' gestation. The longitudinal effects of maternal prepregnancy BMI, categorized as nonoverweight (≤26.0 kg/m²) and overweight/obese (>26.0 kg/m²), on serum leptin concentration were analyzed using linear mixed models. Overweight/obese women had significantly higher serum leptin concentrations than their nonoverweight counterparts throughout pregnancy (P < 0.01). Although these concentrations increased significantly across gestation for both groups, the rate of increase was significantly smaller for overweight/obese women (P < 0.05). To investigate whether these differences merely reflected differences in weight‐gain patterns between the two groups, we examined an index of leptin concentration per unit body weight (leptin (ng/ml)/weight (kg)). Overweight/obese women had a significantly higher index throughout pregnancy (P < 0.01). However, although this index increased significantly across pregnancy for nonoverweight women, it actually decreased significantly for overweight/obese women (P < 0.01). Our results suggest that factors other than fat mass alone influence leptin concentrations in overweight/obese women compared to normal‐weight women during pregnancy. Such factors may contribute to differences in the intrauterine environment and its influence on pregnancy outcomes in the two groups.     

Increased Whole‐Body Adiposity Without a Concomitant Increase in Liver Fat is Not Associated With Augmented Metabolic Dysfunction

Aim of this study was to determine whether an increase in adiposity, without a concomitant increase in intrahepatic triglyceride (IHTG) content, is associated with a deterioration in metabolic function. To this end, multiorgan insulin sensitivity, assessed by using a two‐stage hyperinsulinemic–euglycemic clamp procedure in conjunction with stable isotopically labeled tracer infusion, and very low‐density lipoprotein (VLDL) kinetics, assessed by using stable isotopically labeled tracer infusion and mathematical modeling, were determined in 10 subjects with class I obesity (BMI: 31.6 ± 0.3 kg/m²; 37 ± 2% body fat; visceral adipose tissue (VAT): 1,225 ± 144 cm³) and 10 subjects with class III obesity (BMI: 41.5 ± 0.5 kg/m²; 43 ± 2% body fat; VAT: 2,121 ± 378 cm³), matched on age, sex, and IHTG content (14 ± 4 and 14 ± 3%, respectively). No differences between class I and class III obese groups were detected in insulin‐mediated suppression of palmitate (67 ± 3 and 65 ± 3%, respectively; P = 0.635) and glucose (67 ± 3 and 73 ± 5%, respectively; P = 0.348) rates of appearance in plasma, and the insulin‐mediated increase in glucose disposal (218 ± 18 and 193 ± 30%, respectively; P = 0.489). In addition, no differences between class I and class III obese groups were detected in secretion rates of VLDL‐triglyceride (6.5 ± 1.0 and 6.0 ± 1.4 µmol/l·min, respectively; P = 0.787) and VLDL‐apolipoprotein B‐100 (0.40 ± 0.05 and 0.41 ± 0.04 nmol/l·min, respectively; P = 0.866), and plasma clearance rates of VLDL‐triglyceride (31 (16–59) and 29 (18–46) ml/min, respectively; P = 0.888) and VLDL‐apolipoprotein B‐100 (15 (11–19) and 17 (11–25) ml/min, respectively; P = 0.608). We conclude that increased adiposity without a concomitant increase in IHTG content does not cause additional abnormalities in adipose tissue, skeletal muscle, and hepatic insulin sensitivity, or VLDL metabolism.     

Physical activity-related energy expenditure with the RT3 and TriTrac accelerometers in overweight adults

Objective: The objective was to evaluate two accelerometers, the RT3 and the TriTrac‐R3D for their ability to produce estimates of physical activity‐related energy expenditure (PAEE) in overweight/obese adults. Research Methods and Procedures: PAEE estimates from both accelerometers were obtained in two experiments. In Experiment 1, 13 overweight/obese subjects (BMI 34.2 ± 6.4 kg/m²) were monitored over 2 weeks in everyday life, PAEE being simultaneously measured by the doubly labeled water method (DLW). In Experiment 2, 8 overweight/obese subjects (BMI 34.3 ± 5.0 kg/m²) and 10 normal‐weight subjects (BMI 20.8 ± 2.1 kg/m²) were monitored during a treadmill walking protocol, PAEE being simultaneously measured by indirect calorimetry. Results: In Experiment 1, there was no significant difference between methods in mean PAEE (DLW: 704 ± 223 kcal/d, RT3: 656 ± 140 kcal/d, TriTrac‐R3D 624 ± 419 kcal/d). The relative difference between methods (accelerometer vs. DLW) was ?17.1% ± 16.7% for the RT3 and ?20.0 ± 44.6% for the TriTrac‐R3D. Correlation for PAEE between RT3 and DLW was higher than between TriTrac‐R3D and DLW (r = 0.67, p < 0.05 and r = 0.36, p = 0.25, respectively). The 95% confidence interval (CI) (kcal/d) of the mean difference between methods was large, amounting to ?385 to 145 for the RT3 and ?887 to 590 for the TriTrac‐R3D. In Experiment 2, both accelerometers were sensitive to the changes in treadmill speed, with no significant difference in mean PAEE between methods in overweight/obese subjects. Conclusions: Although both accelerometers did not provide accurate estimates of PAEE at individual levels, the data suggest that RT3 has the potential to assess PAEE at group levels in overweight/obese subjects.     

Eating Frequency is Associated With Energy Intake but Not Obesity in Midlife Women

Midlife women tend to gain weight with age, thus increasing risk of chronic disease. The purpose of this study was to examine associations between overweight/obesity and behavioral factors, including eating frequency, in a cross‐sectional national sample of midlife women (n = 1,099) (mean age = 49.7 years, and BMI = 27.7 kg/m²). Eating behaviors and food and nutrient intakes were based on a mailed 1‐day food record. BMI was calculated from self‐reported height and weight, and level of physical activity was assessed by self‐reported questionnaire. After exclusion of low‐energy reporters (32% of sample), eating frequency was not associated with overweight/obesity (P > 0.05) and was not different between BMI groups (normal, 5.21 ± 1.79; overweight, 5.16 ± 1.74; obese, 5.12 ± 1.68, P = 0.769). Adjusted logistic regression showed that eating frequency, snacking frequency, breakfast consumption, eating after 10 pm and consuming meals with children or other adults were not significantly associated with overweight/obesity. Total energy intake increased as eating frequency increased in all BMI groups, however, obese women had greater energy intake compared to normal weight women who consumed the same number of meals and snacks. Intake of fruit and vegetables, whole grains, dietary fiber, dairy, and added sugars also increased as eating frequency increased. While eating frequency was not associated with overweight/obesity, it was associated with energy intake. Thus, addressing total energy intake rather than eating frequency may be more appropriate to prevent weight gain among midlife women.     

Determine exogenous human DDAH2 gene function in rabbit bone marrow–derived endothelial progenitor cells in vitro

The in vitro amplification of endothelial progenitor cells (EPCs) is an important method because of its role in gene transferring and regenerative medicine. In this study, we isolated rabbit bone marrow–derived EPCs to further manipulation and overexpression of dimethylarginine dimethylaminohydrolase (DDAH) in EPCs. Isolated EPCs were cultured, expanded in endothelial basal medium. Morphology of EPCs and expression levels of surface markers detected using immunocytochemistry staining and through the use of flow cytometery. Endothelial progenitor cells were transfected with plasmid vectors expressing human DDAH2 (DDAH2‐EPCs). Three days after gene transfer, positive transfected‐EPCs proliferation and DDAH activity were assayed. We observed colonies conformation and endothelium‐like morphology gradually in the third week of culture. Characterization results revealed positive expression of EPC surface markers CD106, Flk‐1, vWF, and CD34 using few identification techniques. Overexpression of DDAH2 increased citrulline production after 96 hours of transfection, 235.34 ± 0.69 vs 95.26 ± 5.76 ng/mL; P = .023. These results suggest that cell population with EPC characteristics can be simply isolated from rabbit bone marrow and successfully engineered to overexpress exogenous gene. In this study, we offer a feasible method to isolate and identify EPCs from bone marrow. In addition, an efficient transfection with a plasmid vector (without risk of interference) can be constructed a hybrid structure with EPC and DDAH2 gene to examine their function in vitro.     

Effect of progestins on serum hormones,semen production,and agonistic behavior in the gerenuk (Litocranius walleri walleri)

The use of progestins to suppress endogenous testosterone production to reduce agonistic behavior and prevent semen production was studied in gerenuk. Five male gerenuk (20 months to 3 years of age), housed as a bachelor group, were treated with 3 monthly injections of medroxyprogesterone acetate (MPA; 2.5–20 mg/kg), followed by a melengestrol acetate implant (MGA; 0.3 g/kg) for 2 months. Blood samples collected monthly were assayed for serum testosterone and cortisol using enzyme‐linked immunoassays. Quantitative behavioral data were collected for 30 min 3/week starting 1 month before treatment. Body weight, testes volume, and semen traits were measured before treatment, after MPA treatment, and after MGA treatment. Results showed lower (P<0.05) mean serum testosterone concentrations after MPA (4.34 pg/ml) and MGA (5.02 pg/ml) treatment compared to pre‐treatment values (65.9 pg/ml) in four of five gerenuk. The remaining sub‐adult gerenuk had low testosterone initially (4.9 pg/ml) that did not decrease further with treatment (1.4 and 7.8 pg/ml for MPA and MGA, respectively). Mean serum cortisol concentrations decreased markedly after treatment with MPA (6.0±3.7 ng/ml) and MGA (0.8±0.3 ng/ml). Cortisol concentrations were regained rapidly post‐treatment (42.8±4.8 ng/ml) and were not significantly different from the pre‐treatment value (60.6±12.6 ng/ml; P>0.05). The mean incidence of combined aggressive/dominant behaviors (horning, sparring, supplanting, threat) was not different before and after treatment. Body weight, total numbers of spermatozoa produced per ejaculate, percent motility, and percent normal spermatozoa declined maximally 8 months after treatment. Mean testes volume decreased (P<0.05) after MGA treatment (10.53 cm³vs. 11.96 cm³ pre‐treatment). Elevated hepatic enzymes and bile acids were seen in three of five animals after progestin treatment and anorexia was noted in two males after MGA implant removal, however two of three males had elevated liver enzymes before progestin treatment began. Results show that reducing serum testosterone concentration does not seem to modify agonistic behavior in bachelor gerenuk groups. Zoo Biol 26:245–257, 2007. © 2007 Wiley‐Liss, Inc.     

Insulin Action,Regional Fat,and Myocyte Lipid: Altered Relationships with Increased Adiposity

Objective: Abdominal fat and myocyte triglyceride levels relate negatively to insulin sensitivity, but their interrelationships are inadequately characterized in the overweight. Using recent methods for measuring intramyocyte triglyceride, these relationships were studied in men with a broad range of adiposity. Research Methods and Procedures: Myocyte triglyceride content (¹H‐magnetic resonance spectroscopy of soleus and tibialis anterior muscles and biochemical assessment of vastus lateralis biopsies), regional fat distribution (DXA and abdominal magnetic resonance imaging), serum lipids, insulin action (euglycemic hyperinsulinemic clamp), and substrate oxidation rates (indirect calorimetry) were measured in 39 nondiabetic men (35.1 ± 7.8 years) with a broad range of adiposity (BMI 28.6 ± 4.1 kg/m², range 20.1 to 37.6 kg/m²). Results: Relationships between insulin‐stimulated glucose disposal and regional body fat depots appeared more appropriately described by nonlinear than linear models. When the group was subdivided using median total body fat as the cut‐point, insulin‐stimulated glucose disposal correlated negatively to all regional body fat measures (all p ≤ 0.004), serum triglycerides and free fatty acids (p < 0.02), and both soleus intramyocellular lipid (p = 0.003) and vastus lateralis triglyceride (p = 0.04) in the normal/less overweight group. In contrast, only visceral abdominal fat showed significant negative correlation with insulin‐stimulated glucose disposal in more overweight men (r = ?0.576, p = 0.01), some of whom surprisingly had lower than expected myocyte lipid levels. These findings persisted when the group was subdivided using different cut‐points or measures of adiposity. Discussion: Interrelationships among body fat depots, myocyte triglyceride, serum lipids, and insulin action are generally absent with increased adiposity. However, visceral abdominal fat, which corresponds less closely to total adiposity, remains an important predictor of insulin resistance in men with both normal and increased adiposity.     

QT Dispersion in Uncomplicated Human Obesity

Objective: Because obese patients generally may be prone to ventricular arrhythmias, this study was designed to measure the interval between Q‐ and T‐waves of the electrocardiogram (QT) interval dispersion (QTD) in uncomplicated overweight and obese patients. QTD is an electrocardiographic parameter whose prolongation is thought to be predictive of the possibility of sudden death caused by ventricular arrhythmias. To better evaluate the association between obesity per se and QTD, the study population was intentionally selected because they were free of complications. Research Methods and Procedures: QTD (defined as the difference between the maximum and the minimum QT corrected interval [QTc] across the 12‐lead electrocardiogram) was measured manually in 54 obese patients (Group A: mean body mass index [BMI] of 38.1 ± 0.9 kg/m² [SEM], 15 males and 39 females), 35 overweight patients (Group B: mean BMI of 27.3 ± 0.2 kg/m², 10 males and 25 females), and 57 normal weight healthy control subjects (Group C: mean BMI of 21.9 ± 0.2 kg/m², 17 males and 40 females). The obese and overweight patients had no heart disease, hypertension, diabetes, or impaired glucose tolerance and did not have any hormonal, hepatic, renal or electrolyte disorders. The study subjects were matched in terms of age (mean age 38.4 ± 1.2 years) and sex. Results: The QTDs were comparable among the three groups: Group A, 56.4 ± 2.6 ms; Group B, 56.7 ± 2.1 ms; and Group C, 59.4 ± 2.1 ms; not significant. The QTc intervals of Group A and Group B were similar to that of Group C (411.8 ± 3.3, 407.2 ± 3.9, and 410.3 ± 3.9 ms, respectively [not significant]) and did not correlate with BMI. An association was found between QTD and QTc (r = 0.24, p < 0.005). Using multivariate stepwise regression analysis of the study population, QTD did not correlate with age, BMI, waist circumference, or abdominal sagittal diameter. Discussion: These data suggest that QTD in uncomplicated obese or overweight subjects is comparable with that in age‐ and sex‐matched normal weight healthy controls. In this study population, no association was found between QTD and anthropometric parameters reflecting body fat distribution.