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Caloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood. The current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8 +/- 1.0 y), overweight (body mass index, 27.8 +/- 0.7 kg/m(2)) individuals randomized into one of three groups for a 6-mo intervention: Control, 100% of energy requirements; CR, 25% caloric restriction; and CREX, caloric restriction with exercise (CREX), 12.5% CR + 12.5% increased energy expenditure (EE). In the controls, 24-h EE was unchanged, but in CR and CREX it was significantly reduced from baseline even after adjustment for the loss of metabolic mass (CR, -135 +/- 42 kcal/d, p = 0.002 and CREX, -117 +/- 52 kcal/d, p = 0.008). Participants in the CR and CREX groups had increased expression of genes encoding proteins involved in mitochondrial function such as PPARGC1A, TFAM, eNOS, SIRT1, and PARL (all, p < 0.05). In parallel, mitochondrial DNA content increased by 35% +/- 5% in the CR group (p = 0.005) and 21% +/- 4% in the CREX group (p < 0.004), with no change in the control group (2% +/- 2%). However, the activity of key mitochondrial enzymes of the TCA (tricarboxylic acid) cycle (citrate synthase), beta-oxidation (beta-hydroxyacyl-CoA dehydrogenase), and electron transport chain (cytochrome C oxidase II) was unchanged. DNA damage was reduced from baseline in the CR (-0.56 +/- 0.11 arbitrary units, p = 0.003) and CREX (-0.45 +/- 0.12 arbitrary units, p = 0.011), but not in the controls. In primary cultures of human myotubes, a nitric oxide donor (mimicking eNOS signaling) induced mitochondrial biogenesis but failed to induce SIRT1 protein expression, suggesting that additional factors may regulate SIRT1 content during CR. The observed increase in muscle mitochondrial DNA in association with a decrease in whole body oxygen consumption and DNA damage suggests that caloric restriction improves mitochondrial function in young non-obese adults.

OBJECTIVE:--Cereal fiber intake is linked to reduced risk of type 2 diabetes in epidemiological observations. The pathogenic background of this phenomenon is unknown. Based on recent findings, we hypothesized that intake of purified insoluble oat fiber may improve whole-body insulin sensitivity. RESEARCH DESIGN AND METHODS--A randomized, controlled, single-blind, cross-over study was performed, and 17 overweight or obese subjects with normal glucose metabolism were analyzed. After consumption of nine macronutrient-matched portions of fiber-enriched bread (white bread enriched with 31.2 g insoluble fiber/day) or control (white bread) over a time period of 72 h, whole-body insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp. Energy intake was individually adjusted by providing standardized liquid meals. Hydrogen breath tests were performed to control for dietary adherence. RESULTS:--When analyzing the entire cohort, whole-body glucose disposal was improved after fiber consumption (M value 6.56 ± 0.32 vs. 6.07 ± 0.27 mg · min⁻¹ · kg⁻¹; P = 0.043). Thirteen subjects had increased hydrogen breath test concentrations after fiber consumption, indicating probable dietary adherence. Restricting analysis to these subjects, improvements in M value (6.85 ± 0.34 vs. 6.06 ± 0.32 mg · min⁻¹ · kg⁻¹; P = 0.003) and insulin sensitivity, expressed as M/I ratio (M value divided by mean serum insulin at steady state: 3.73 ± 0.23 vs. 3.21 ± 0.27; P = 0.02), after fiber consumption were more pronounced. Plasma lipids, serum magnesium, ghrelin, and adiponectin concentrations, as well as substrate utilization and body weight, were not significantly changed by fiber intake (P > 0.15). CONCLUSIONS:--Increased insoluble dietary fiber intake for 3 days significantly improved whole-body insulin sensitivity. These data suggest a potential mechanism linking cereal fiber intake and reduced risk of type 2 diabetes.

Objective: To assess weight maintenance after weight loss by consumption of yoghurt with a novel fat emulsion (Olibra) including effects on body composition, resting energy expenditure (REE), fat oxidation, hunger feelings and satiety hormones. Design: A randomized, placebo-controlled, double-blind, parallel design. A 6-week weight loss period (2.1 MJ/day) was followed by 18 weeks weight maintenance with test (Olibra) or placebo yoghurt. Subjects: Fifty overweight women (age: 18–58 years, body mass index (BMI) 25–32 kg/m 2 ). Measurements: In weeks 1, 7 and 25, a satiety test with questionnaires and blood samples for analysis of satiety hormones. In weeks 2, 8 and 26, REE, body weight and body composition. Results: During weight maintenance after significant body weight reduction, there was no significant increase in body weight in the test group (1.1±3.4 kg); the placebo group did gain weight (3.0±3.1 kg, P <0.001). Compared to the placebo group, the test group was less hungry 4 h after yoghurt consumption in week 25 ( P <0.05) and showed increased glucagon like peptide-1 values 180 min after yoghurt consumption (week 25 vs week 1, P <0.05). Measured REE as a function of fat-free mass (FFM) was significantly higher than predicted REE ( P <0.05) in week 26 for the test group, but not for the placebo group. Fat mass (FM) was significantly more decreased in the test group (6.5±4.1 kg) compared to the placebo group (4.1±3.6 kg) (week 26 vs week 2, P <0.05). Conclusion: Consumption of Olibra yoghurt improved weight maintenance compared to placebo, which can be explained by the relatively higher REE as a function of FFM, relatively higher decrease in FM and the relatively lower increase in hunger.

Objective: Inflammation plays a pivotal role in the atherosclerotic process, and some chemokines seem to be crucial in the pathogenesis of vascular damage. High-serum homocysteine, recently recognized as an independent risk factor for vascular disease might increase cytokine and chemokine levels, thus amplifying endothelial damage; moreover, it might worse insulin resistance, thus further contributing to enhance cardiovascular risk. The effect of folic acid supplementation in improving in vivo endothelial function is still debated. In this study, we investigated the effect of folic acid supplementation on insulin sensitivity and peripheral markers of inflammation in overweight healthy subjects. Design: The study was performed as an unmasked randomized placebo-controlled trial of 12 weeks duration. Subjects: Sixty healthy volunteers with normal glucose tolerance and BMI between 25 and 29 kg/m2 were enrolled. Measurements: Biochemical parameters and plasma concentrations of homocysteine and of some inflammatory molecules were measured at baseline and at the end of the study, together with an estimation of insulin sensitivity. Results: Subjects receiving folic acid supplementation showed a decrement of homocysteine and an amelioration of insulin sensitivity; this treatment was also associated with a significant drop in the circulating concentration of monocyte chemoattractant protein-1, interleukin-8 and C-reactive protein, in the absence of any significant variation of BMI or fat mass. Conclusions: In healthy overweight subjects a short-term folic acid supplementation reduces the circulating level of some inflammatory mediators independently of weight change, thus suggesting a potential therapeutic role for folic acid in the protection from atherogenesis and cardiovascular diseases.

ABSTRACT Background: Obesity is becoming increasingly common worldwide and is strongly associated with the metabolic syndrome (MetS). MetS is considered to be a cluster of risk factors that increase the risk of vascular events. Objective: In an open-label randomised study (the FenOrli study) we assessed the effect of orlistat and fenofibrate treatment, alone or in combination on reversing the diagnosis of the MetS (primary end-point) as well as on anthropometric and metabolic parameters (secondary end-points) in overweight and obese patients with MetS but no diabetes. Methods: Overweight and obese patients (N = 89, body mass index (BMI) > 28 kg/m2) with MetS [as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria] participated in the study. Patients were prescribed a low-calorie low-fat diet and were randomly allocated to receive orlistat 120 mg three times a day (tid) (O group), micronised fenofibrate 200 mg/day (F group), or orlistat 120 mg tid plus micronised fenofibrate 200 mg/day (OF group). Body weight, BMI, waist circumference, blood pressure, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL‐C), high-density lipoprotein cholesterol (HDL‐C), non-HDL‐C, triglyceride, creatinine (SCr) and uric acid (SUA) levels, as well as homeostasis model assessment (HOMA) index and liver enzyme activities were measured at baseline and after 3 months of treatment. Results: Of the 89 patients enrolled, three (one in each group) dropped out during the study due to side effects. After the 3‐month treatment period, 43.5% of patients in the O group, 47.6% in the F group and 50% in the OF group no longer met the MetS diagnostic criteria (primary end-point, p < 0.0001 vs. baseline in all treatment groups). No significant difference in the primary end-point was observed between the three treatment groups. Significant reductions in body weight, BMI, waist circumference, blood pressure, TC, LDL‐C, non-HDL‐C, triglyceride and SUA levels, as well as gamma-glutamyl transpeptidase activity and HOMA index were observed in all treatment groups. In the OF group a greater decrease in TC (–26%) and LDL‐C (–30%) was observed compared with that in the O and F groups ( p < 0.01) and a more pronounced reduction of triglycerides (–37%) compared with that in the O group ( p < 0.05). SUA levels and alkaline phosphatase activity decreased more in the F and OF groups compared with the O group ( p < 0.05). Moreover, SCr significantly increased and estimated creatinine clearance decreased in the F and OF groups but they were not significantly altered in the O group ( p < 0.01 for the comparison between O and either F or OF groups). Glucose (in groups O and OF), as well as insulin levels and HOMA index (in all groups), were significantly reduced after treatment ( p < 0.05 vs. baseline). Conclusion: The combination of orlistat and micronised fenofibrate appears to be safe and may further improve metabolic parameters in overweight and obese patients with MetS compared with each monotherapy.

OBJECTIVE:--To examine the effect of dairy calcium consumption on weight loss and improvement in cardiovascular disease (CVD) and diabetes indicators among overweight diabetic patients. RESEARCH DESIGN AND METHODS--This was an ancillary study of a 6-month randomized clinical trial assessing the effect of three isocaloric diets in type 2 diabetic patients: 1) mixed glycemic index carbohydrate diet, 2) low-glycemic index diet, and 3) modified Mediterranean diet. Low-fat dairy product consumption varied within and across the groups by personal choice. Dietary intake, weight, CVD risk factors, and diabetes indexes were measured at baseline and at 6 months. RESULTS:--A total of 259 diabetic patients were recruited with an average BMI >31 kg/m² and mean age of 55 years. No difference was found at baseline between the intervention groups in CVD risk factors, diabetes indicators, macronutrient intake, and nutrient intake from dairy products. Dairy calcium intake was associated with percentage of weight loss. Among the high tertile of dairy calcium intake, the odds ratio for weight loss of >8% was 2.4, P = 0.04, compared with the first tertile, after controlling for nondairy calcium intake, diet type, and the change in energy intake from baseline. No association was noted between dairy calcium and other health indexes except for triglyceride levels. CONCLUSIONS:--A diet rich in dairy calcium intake enhances weight reduction in type 2 diabetic patients. Such a diet could be tried in diabetic patients, especially those with difficulty adhering to other weight reduction diets.

This study investigated the effects of a soy-based low-calorie diet on weight control, body composition, and blood lipid profiles compared with a traditional low-calorie diet. Thirty obese adults (mean body mass index 29–30 kg/m 2) were randomized to two groups. The soy-based low-calorie group consumed soy protein as the only protein source, and the traditional low-calorie group consumed two-thirds animal protein and the rest plant protein in a 1200 kcal/d diet for 8 wk. A diet record was kept everyday throughout the study. Food intake was analyzed before and after the study. Anthropometric data were acquired every week, and biochemical data from before and after the 8-wk experiment were compared. Body weight, body mass index, body fat percentage, and waist circumference significantly decreased in both groups ( P < 0.05). The decrease in body fat percentage in the soy group (2.2%, 95% confidence interval 1.6–2.8) was greater than that in the traditional group (1.4%, 95% confidence interval −0.1 to 2.8). Serum total cholesterol concentrations, low-density lipoprotein cholesterol concentrations, and liver function parameters decreased in the soy-based group and were significantly different from measurements in the traditional group ( P < 0.05). No significant change in serum triacylglycerol levels, serum high-density lipoprotein cholesterol levels, and fasting glucose levels was found in the soy or traditional group. Soy-based low-calorie diets significantly decreased serum total cholesterol and low-density lipoprotein cholesterol concentrations and had a greater effect on reducing body fat percentage than traditional low-calorie diets. Thus, soy-based diets have health benefits in reducing weight and blood lipids.

Background:  This study examined physical activity opportunities and barriers at 36 geographically diverse middle schools participating in the Trial of Activity for Adolescent Girls. Methods:  Principals, physical education and health education department heads, and program leaders were interviewed to assess policies and instructional practices that support physical activity. Results:  Schools provided approximately 110 hours per year in physical education instruction. Approximately 20% of students walked or bicycled to school. Eighty‐three percent of schools offered interscholastic sports and 69% offered intramural sports. Most schools offered programs for girls, but on average, only 24 girls (∼5%) in the schools attended any programs. Only 25% of schools allowed after school free play. An overall score created to assess school environmental support for physical activity indicated that, on average, schools met 6.7 items of 10 items. Free/reduced lunch program participation versus not (p = .04), perceived priority of physical education instruction over coaching (p = .02), and safety for walking/bicycling to school (p = .02) predicted environmental support score. Conclusions:  Schools have policies and practices that support physical activity, although unfavorable practices exist. Schools must work with community partners and officials to provide environments that optimally support physical activity, especially schools that serve low‐income students.

OBJECTIVE: To evaluate whether snacking would improve weight loss and weight maintenance in overweight individuals within the context of a structured meal replacement (MR) weight loss program. DESIGN: A prospective 24 week, 2 (snacking vs nonsnacking) × 2 (MR vs meal replacement augmented with snacks (MRPS)) randomized trial. Participants were instructed to limit their total daily intake to 1200 (women) or 1500 (men) kcals. Those receiving the MR program were instructed not to snack while those in the MRPS program were told to snack three times per day. SUBJECTS: A total of 100 participants were block-randomized, based on prestudy snacking status (high vs low), to receive a standard meal replacement program (MR) or MRPS. MEASUREMENTS: Weight, height, blood pressure, lipid fractions, glucose, and insulin were assessed at the baseline, 12-, and 24 weeks. RESULTS: Completers analysis at 24 weeks demonstrated a significant time effect (F(1,46)=44.6, P <0.001), indicating that all participants lost significant amounts of weight regardless of group assignment. An intention-to-treat model resulted in similar results. By week 24, the average weight loss across groups was 4.6 kg. There also were significant improvements across all groups among completers for systolic blood pressure ( P =0.047), cholesterol ( P =0.001), LDL ( P =0.001), glucose ( P =0.004), and insulin ( P =0.001) at week 12, and glucose ( P =0.001) and insulin at week 24 ( P =0.003). CONCLUSIONS: Our results suggest that a participant's preferences for snacking did not affect their response to treatment. Snackers and nonsnackers responded equally well whether they received a standard meal replacement program or one augmented with snacks.

Objective: This study examined the acute effects of ingesting a widely used commercial formula containing extracts of bitter orange, green tea and guarana (Gx) on the metabolic rate and substrate utilisation in overweight, adult males at rest (study 1) and during treadmill walking (study 2). Subjects: Two different groups of 10 sedentary males with more than 20% body fat participated in studies 1 and 2. Design: In each study, subjects participated in two experimental trials during which they were given two 500 mg capsules containing either Gx or a placebo (P) in a counterbalanced double-blind manner. Doses of the main active ingredients were 6 mg of synephrine, 150 mg caffeine and 150 mg catechin polyphenols. Measurements: In study 1, subjects completed 7 h supine rest with baseline measures taken during the first hour, with expired gases, blood pressure, heart rate and venous blood being collected every 30 min for the remaining 6 h following ingestion of Gx or P. In study 2, subjects exercised for 60 min at 60% heart rate reserve following ingestion of Gx or P 1 h previously. Venous blood samples were collected twice at rest and at 5, 10, 15, 20, 30, 40, 50 and 60 min, with expired gas measurements taken at 4, 9, 14, 19, 29, 39, 49 and 59 min. In both studies, venous blood was analysed for NEFA, glycerol, glucose and lactate concentrations, while expired gases were used to calculate ATP production from carbohydrate and NEFA, as well as the total substrate utilised. Results and conclusion: The results did not show any significant effect of Gx ingestion on total ATP utilisation during 6 h rest or during 60 min treadmill walking. Changes were observed in the relative contributions of CHO and NEFA oxidation to ATP production in both studies, such that there was an increase in ATP production from CHO and a decrease from NEFA. The increase in CHO oxidation was shown to be as high as 30% at rest.