Effect of chronic exercise on appetite control in overweight and obese individuals

Purpose: The effect of exercise on body mass is likely to be partially mediated through changes in appetite control. However, no studies have examined the effect of chronic exercise on obestatin and cholecystokinin (CCK) plasma concentrations or the sensitivity to detect differences in preload energy in obese individuals. The objective of this study was to investigate the effects of chronic exercise on 1) fasting and postprandial plasma concentrations of obestatin, CCK, leptin, and glucose insulinotropic peptide (GIP) and 2) the accuracy of energy compensation in response to covert preload manipulation. Methods: This study used a 12-wk supervised exercise program in 22 sedentary overweight/obese individuals. Fasting/postprandial plasma concentrations of obestatin, CCK, leptin, and GIP were assessed before and after the intervention. Energy compensation at a 30-min test meal after a high-energy (607 kcal) or a low-energy (246 kcal) preload and for the rest of the day (cumulative energy intake [EI]) was also measured. Results: There was a significant reduction in the plasma concentration of fasting plasma GIP and both fasting and postprandial leptin concentrations after the exercise intervention (P < 0.05 for all). No significant changes were observed for CCK or obestatin. A significant preload–exercise interaction (P = 0.011) was observed on cumulative EI and energy compensation for the same period (−87% ± 196% vs 68% ± 165%, P = 0.011). Weight loss (3.5 ± 1.4 kg, P < 0.0001) was not correlated with changes in energy compensation. Conclusions: This study suggests that exercise improves the accuracy of compensation for previous EI, independent of weight loss. Unexpectedly, and in contrast to GIP and leptin, exercise-induced weight loss had no effect on obestatin or CCK concentrations.

Meal induced thermogenesis and appetite : methodological issues and responses to energy restriction

Diet Induced Thermogenesis (DIT) is the energy expended consequent to meal consumption, and reflects the energy required for the processing and digestion of food consumed throughout each day. Although DIT is the total energy expended across a day in digestive processes to a number of meals, most studies measure thermogenesis in response to a single meal (Meal Induced Thermogenesis: MIT) as a representation of an individual’s thermogenic response to acute food ingestion. As a component of energy expenditure, DIT may have a contributing role in weight gain and weight loss. While the evidence is inconsistent, research has tended to reveal a suppressed MIT response in obese compared to lean individuals, which identifies individuals with an efficient storage of food energy, hence a greater tendency for weight gain. Appetite is another factor regulating body weight through its influence on energy intake. Preliminary research has shown a potential link between MIT and postprandial appetite as both are responses to food ingestion and have a similar response dependent upon the macronutrient content of food. There is a growing interest in understanding how both MIT and appetite are modified with changes in diet, activity levels and body size. However, the findings from MIT research have been highly inconsistent, potentially due to the vastly divergent protocols used for its measurement. Therefore, the main theme of this thesis was firstly, to address some of the methodological issues associated with measuring MIT. Additionally this thesis aimed to measure postprandial appetite simultaneously to MIT to test for any relationships between these meal-induced variables and to assess changes that occur in MIT and postprandial appetite during periods of energy restriction (ER) and following weight loss. Two separate studies were conducted to achieve these aims. Based on the increasing prevalence of obesity, it is important to develop accurate methodologies for measuring the components potentially contributing to its development and to understand the variability within these variables. Therefore, the aim of Study One was to establish a protocol for measuring the thermogenic response to a single test meal (MIT), as a representation of DIT across a day. This was done by determining the reproducibility of MIT with a continuous measurement protocol and determining the effect of measurement duration. The benefit of a fixed resting metabolic rate (RMR), which is a single measure of RMR used to calculate each subsequent measure of MIT, compared to separate baseline RMRs, which are separate measures of RMR measured immediately prior to each MIT test meal to calculate each measure of MIT, was also assessed to determine the method with greater reproducibility. Subsidiary aims were to measure postprandial appetite simultaneously to MIT, to determine its reproducibility between days and to assess potential relationships between these two variables. Ten healthy individuals (5 males, 5 females, age = 30.2 ± 7.6 years, BMI = 22.3 ± 1.9 kg/m2, %Fat Mass = 27.6 ± 5.9%) undertook three testing sessions within a 1-4 week time period. During the first visit, participants had their body composition measured using DXA for descriptive purposes, then had an initial 30-minute measure of RMR to familiarise them with the testing and to be used as a fixed baseline for calculating MIT. During the second and third testing sessions, MIT was measured. Measures of RMR and MIT were undertaken using a metabolic cart with a ventilated hood to measure energy expenditure via indirect calorimetry with participants in a semi-reclined position. The procedure on each MIT test day was: 1) a baseline RMR measured for 30 minutes, 2) a 15-minute break in the measure to consume a standard 576 kcal breakfast (54.3% CHO, 14.3% PRO, 31.4% FAT), comprising muesli, milk toast, butter, jam and juice, and 3) six hours of measuring MIT with two, ten-minute breaks at 3 and 4.5 hours for participants to visit the bathroom. On the MIT test days, pre and post breakfast then at 45-minute intervals, participants rated their subjective appetite, alertness and comfort on visual analogue scales (VAS). Prior to each test, participants were required to be fasted for 12 hours, and have undertaken no high intensity physical activity for the previous 48 hours. Despite no significant group changes in the MIT response between days, individual variability was high with an average between-day CV of 33%, which was not significantly improved by the use of a fixed RMR to 31%. The 95% limits of agreements which ranged from 9.9% of energy intake (%EI) to -10.7%EI with the baseline RMRs and between 9.6%EI to -12.4%EI with the fixed RMR, indicated very large changes relative to the size of the average MIT response (MIT 1: 8.4%EI, 13.3%EI; MIT 2: 8.8%EI, 14.7%EI; baseline and fixed RMRs respectively). After just three hours, the between-day CV with the baseline RMR was 26%, which may indicate an enhanced MIT reproducibility with shorter measurement durations. On average, 76, 89, and 96% of the six-hour MIT response was completed within three, four and five hours, respectively. Strong correlations were found between MIT at each of these time points and the total six-hour MIT (range for correlations r = 0.990 to 0.998; P < 0.01). The reproducibility of the proportion of the six-hour MIT completed at 3, 4 and 5 hours was reproducible (between-day CVs ≤ 8.5%). This indicated the suitability to use shorter durations on repeated occasions and a similar percent of the total response to be completed. There was a lack of strong evidence of any relationship between the magnitude of the MIT response and subjective postprandial appetite. Given a six-hour protocol places a considerable burden on participants, these results suggests that a post-meal measurement period of only three hours is sufficient to produce valid information on the metabolic response to a meal. However while there was no mean change in MIT between test days, individual variability was large. Further research is required to better understand which factors best explain the between-day variability in this physiological measure. With such a high prevalence of obesity, dieting has become a necessity to reduce body weight. However, during periods of ER, metabolic and appetite adaptations can occur which may impede weight loss. Understanding how metabolic and appetite factors change during ER and weight loss is important for designing optimal weight loss protocols. The purpose of Study Two was to measure the changes in the MIT response and subjective postprandial appetite during either continuous (CONT) or intermittent (INT) ER and following post diet energy balance (post-diet EB). Thirty-six obese male participants were randomly assigned to either the CONT (Age = 38.6 ± 7.0 years, weight = 109.8 ± 9.2 kg, % fat mass = 38.2 ± 5.2%) or INT diet groups (Age = 39.1 ± 9.1 years, weight = 107.1 ± 12.5 kg, % fat mass = 39.6 ± 6.8%). The study was divided into three phases: a four-week baseline (BL) phase where participants were provided with a diet to maintain body weight, an ER phase lasting either 16 (CONT) or 30 (INT) weeks, where participants were provided with a diet which supplied 67% of their energy balance requirements to induce weight loss and an eight-week post-diet EB phase, providing a diet to maintain body weight post weight loss. The INT ER phase was delivered as eight, two-week blocks of ER interspersed with two-week blocks designed to achieve weight maintenance. Energy requirements for each phase were predicted based on measured RMR, and adjusted throughout the study to account for changes in RMR. All participants completed MIT and appetite tests during BL and the ER phase. Nine CONT and 15 INT participants completed the post-diet EB MIT and 14 INT and 15 CONT participants completed the post-diet EB appetite tests. The MIT test day protocol was as follows: 1) a baseline RMR measured for 30 minutes, 2) a 15-minute break in the measure to consume a standard breakfast meal (874 kcal, 53.3% CHO, 14.5% PRO, 32.2% FAT), and 3) three hours of measuring MIT. MIT was calculated as the energy expenditure above the pre-meal RMR. Appetite test days were undertaken on a separate day using the same 576 kcal breakfast used in Study One. VAS were used to assess appetite pre and post breakfast, at one hour post breakfast then a further three times at 45-minute intervals. Appetite ratings were calculated for hunger and fullness as both the intra-meal change in appetite and the AUC. The three-hour MIT response at BL, ER and post-diet EB respectively were 5.4 ± 1.4%EI, 5.1 ± 1.3%EI and 5.0 ± 0.8%EI for the CONT group and 4.4 ± 1.0%EI, 4.7 ± 1.0%EI and 4.8 ± 0.8%EI for the INT group. Compared to BL, neither group had significant changes in their MIT response during ER or post-diet EB. There were no significant time by group interactions (p = 0.17) indicating a similar response to ER and post-diet EB in both groups. Contrary to what was hypothesised, there was a significant increase in postprandial AUC fullness in response to ER in both groups (p < 0.05). However, there were no significant changes in any of the other postprandial hunger or fullness variables. Despite no changes in MIT in both the CONT or INT group in response to ER or post-diet EB and only a minor increase in postprandial AUC fullness, the individual changes in MIT and postprandial appetite in response to ER were large. However those with the greatest MIT changes did not have the greatest changes in postprandial appetite. This study shows that postprandial appetite and MIT are unlikely to be altered during ER and are unlikely to hinder weight loss. Additionally, there were no changes in MIT in response to weight loss, indicating that body weight did not influence the magnitude of the MIT response. There were large individual changes in both variables, however further research is required to determine whether these changes were real compensatory changes to ER or simply between-day variation. Overall, the results of this thesis add to the current literature by showing the large variability of continuous MIT measurements, which make it difficult to compare MIT between groups and in response to diet interventions. This thesis was able to provide evidence to suggest that shorter measures may provide equally valid information about the total MIT response and can therefore be utilised in future research in order to reduce the burden of long measurements durations. This thesis indicates that MIT and postprandial subjective appetite are most likely independent of each other. This thesis also shows that, on average, energy restriction was not associated with compensatory changes in MIT and postprandial appetite that would have impeded weight loss. However, the large inter-individual variability supports the need to examine individual responses in more detail.

The role of intensity of interval training on fat oxidation and eating behaviour in overweight/obese men

The increasing prevalence of obesity in society has been associated with a number of atherogenic risk factors such as insulin resistance. Aerobic training is often recommended as a strategy to induce weight loss, with a greater impact of high-intensity levels on cardiovascular function and insulin sensitivity, and a greater impact of moderate-intensity levels on fat oxidation. Anaerobic high-intensity (supramaximal) interval training has been advocated to improve cardiovascular function, insulin sensitivity and fat oxidation. However, obese individuals tend to have a lower tolerance of high-intensity exercise due to discomfort. Furthermore, some obese individuals may compensate for the increased energy expenditure by eating more and/or becoming less active. Recently, both moderate- and high-intensity aerobic interval training have been advocated as alternative approaches. However, it is still uncertain as to which approach is more effective in terms of increasing fat oxidation given the issues with levels of fitness and motivation, and compensatory behaviours. Accordingly, the objectives of this thesis were to compare the influence of moderate- and high-intensity interval training on fat oxidation and eating behaviour in overweight/obese men. Two exercise interventions were undertaken by 10-12 overweight/obese men to compare their responses to study variables, including fat oxidation and eating behaviour during moderate- and high-intensity interval training (MIIT and HIIT). The acute training intervention was a methodological study designed to examine the validity of using exercise intensity from the graded exercise test (GXT) - which measured the intensity that elicits maximal fat oxidation (FATmax) - to prescribe interval training during 30-min MIIT. The 30-min MIIT session involved 5-min repetitions of workloads 20% below and 20% above the FATmax. The acute intervention was extended to involve HIIT in a cross-over design to compare the influence of MIIT and HIIT on eating behaviour using subjective appetite sensation and food preference through the liking and wanting test. The HIIT consisted of 15-sec interval training at 85 %VO2peak interspersed by 15-sec unloaded recovery, with a total mechanical work equal to MIIT. The medium term training intervention was a cross-over 4-week (12 sessions) MIIT and HIIT exercise training with a 6-week detraining washout period. The MIIT sessions consisted of 5-min cycling stages at ±20% of mechanical work at 45 %VO2peak, and the HIIT sessions consisted of repetitive 30-sec work at 90 %VO2peak and 30-sec interval rests, during identical exercise sessions of between 30 and 45 mins. Assessments included a constant-load test (45 %VO2peak for 45 mins) followed by 60-min recovery at baseline and the end of 4-week training, to determine fat oxidation rate. Participants’ responses to exercise were measured using blood lactate (BLa), heart rate (HR) and rating of perceived exertion (RPE) and were measured during the constant-load test and in the first intervention training session of every week during training. Eating behaviour responses were assessed by measuring subjective appetite sensations, liking and wanting and ad libitum energy intake. Results of the acute intervention showed that FATmax is a valid method to estimate VO2 and BLa, but is not valid to estimate HR and RPE in the MIIT session. While the average rate of fat oxidation during 30-min MIIT was comparable with the rate of fat oxidation at FATmax (0.16 ±0.09 and 0.14 ±0.08 g/min, respectively), fat oxidation was significantly higher at minute 25 of MIIT (P≤0.01). In addition, there was no significant difference between MIIT and HIIT in the rate of appetite sensations after exercise, but there was a tendency towards a lower rate of hunger after HIIT. Different intensities of interval exercise also did not affect explicit liking or implicit wanting. Results of the medium-term intervention indicated that current interval training levels did not affect body composition, fasting insulin and fasting glucose. Maximal aerobic capacity significantly increased (P≤0.01) (2.8 and 7.0% after MIIT and HIIT respectively) during GXT, and fat oxidation significantly increased (P≤0.01) (96 and 43% after MIIT and HIIT respectively) during the acute constant-load exercise test. RPE significantly decreased after HIIT greater than MIIT (P≤0.05), and the decrease in BLa was greater during the constant-load test after HIIT than MIIT, but this difference did not reach statistical significance (P=0.09). In addition, following constant-load exercise, exercise-induced hunger and desire to eat decreased after HIIT greater than MIIT but were not significant (p value for desire to eat was 0.07). Exercise-induced liking of high-fat sweet (HFSW) and high-fat non-sweet (HFNS) foods increased after MIIT and decreased after HIIT (p value for HFNS was 0.09). The intervention explained 12.4% of the change in fat intake (p = 0.07). This research is significant in that it confirmed two points in the acute study. While the rate of fat oxidation increased during MIIT, the average rate of fat oxidation during 30-min MIIT was comparable with the rate of fat oxidation at FATmax. In addition, manipulating the intensity of acute interval exercise did not affect appetite sensations and liking and wanting. In the medium-term intervention, constant-load exercise-induced fat oxidation significantly increased after interval training, independent of exercise intensity. In addition, desire to eat, explicit liking for HFNS and fat intake collectively confirmed that MIIT is accompanied by a greater compensation of eating behaviour than HIIT. Findings from this research will assist in developing exercise strategies to provide obese men with various training options. In addition, the finding that overweight/obese men expressed a lower RPE and decreased BLa after HIIT compared with MIIT is contrary to the view that obese individuals may not tolerate high-intensity interval training. Therefore, high-intensity interval training can be advocated among the obese adult male population. Future studies may extend this work by using a longer-term intervention.

Individual variability in compensatory eating following acute exercise in overweight and obese women

Background While compensatory eating following acute aerobic exercise is highly variable, little is known about the underling mechanisms that contribute to alterations in exercise-induced eating behaviour. Methods Overweight and obese women (BMI = 29.6 ± 4.0kg.m2) performed a bout of cycling individually tailored to expend 400kcal (EX), or a time-matched no exercise control condition in a randomised, counter-balanced order. Sixty minutes after the cessation of exercise, an ad libitum test meal was provided. Substrate oxidation and subjective appetite ratings were measured during exercise/time-matched rest, and during the period between the cessation of exercise and food consumption. Results While ad libitum EI did not differ between EX and the control condition (666.0 ± 203.9kcal vs. 664.6 ± 174.4kcal, respectively; ns), there was marked individual variability in compensatory energy intake (EI). The difference in EI between EX and the control condition ranged from -234.3 to +278.5kcal. Carbohydrate oxidation during exercise was positively associated with post-exercise EI, accounting for 37% of the variance in EI (r = 0.57; p = 0.02). Conclusions These data indicate that capacity of acute exercise to create a short-term energy deficit in overweight and obese women is highly variable. Furthermore, exercise-induced CHO oxidation can explain part of the variability in acute exercise-induced compensatory eating. Post-exercise compensatory eating could serve as an adaptive response to facilitate the restoration of carbohydrate balance.

The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake

BACKGROUND/OBJECTIVEs A decline in resting energy expenditure (REE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (EI). SUBJECTS/METHODS Thirty overweight and obese women (body mass index (BMI)=30.6±3.6 kg/m2) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, EI and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured REE was also calculated post intervention (MApost), with REE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI=31.0±3.9 kg/m2). RESULTS Although mean predicted and measured REE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in REE (−102.9±77.5 kcal per day). MApost was associated with the change in leptin (r=0.47; P=0.04), and the change in resting fat (r=0.52; P=0.01) and carbohydrate oxidation (r=−0.44; P=0.02). Furthermore, MApost was also associated with the change in EI following EX (r=−0.44; P=0.01). CONCLUSIONS Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in REE also experienced an upregulation in EI, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

Interval training intensity affects energy intake compensation in obese men

Abstract PURPOSE: Compensatory responses may attenuate the effectiveness of exercise training in weight management. The aim of this study was to compare the effect of moderate- and high-intensity interval training on eating behavior compensation. METHODS: Using a crossover design, 10 overweight and obese men participated in 4-week moderate (MIIT) and high (HIIT) intensity interval training. MIIT consisted of 5-min cycling stages at ± 20% of mechanical work at 45%VO(2)peak, and HIIT consisted of alternate 30-s work at 90%VO(2)peak and 30-s rests, for 30 to 45 min. Assessments included a constant-load exercise test at 45%VO(2)peak for 45 min followed by 60-min recovery. Appetite sensations were measured during the exercise test using a Visual Analog Scale. Food preferences (liking and wanting) were assessed using a computer-based paradigm, and this paradigm uses 20 photographic food stimuli varying along two dimensions, fat (high or low) and taste (sweet or nonsweet). An ad libitum test meal was provided after the constant-load exercise test. RESULTS: Exercise-induced hunger and desire to eat decreased after HIIT, and the difference between MIIT and HIIT in desire to eat approached significance (p = .07). Exercise-induced liking for high-fat nonsweet food tended to increase after MIIT and decreased after HIIT (p = .09). Fat intake decreased by 16% after HIIT, and increased by 38% after MIIT, with the difference between MIIT and HIIT approaching significance (p = .07). CONCLUSIONS: This study provides evidence that energy intake compensation differs between MIIT and HIIT.

The E3 ubiquitin ligase Pellino3 protects against obesity-induced inflammation and insulin resistance

Diet-induced obesity can induce low-level inflammation and insulin resistance. Interleukin-1β (IL-1β) is one of the key proinflammatory cytokines that contributes to the generation of insulin resistance and diabetes, but the mechanisms that regulate obesity-driven inflammation are ill defined. Here we found reduced expression of the E3 ubiquitin ligase Pellino3 in human abdominal adipose tissue from obese subjects and in adipose tissue of mice fed a high-fat diet and showing signs of insulin resistance. Pellino3-deficient mice demonstrated exacerbated high-fat-diet-induced inflammation, IL-1β expression, and insulin resistance. Mechanistically, Pellino3 negatively regulated TNF receptor associated 6 (TRAF6)-mediated ubiquitination and stabilization of hypoxia-inducible factor 1α (HIF1α), resulting in reduced HIF1α-induced expression of IL-1β. Our studies identify a regulatory mechanism controlling diet-induced insulin resistance by highlighting a critical role for Pellino3 in regulating IL-1β expression with implications for diseases like type 2 diabetes.

Quantifying diet-induced metabolic changes of the human gut microbiome

The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention.

Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity.

AIMS: Aldosterone plays a crucial role in cardiovascular disease. 'Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the 'endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. METHODS AND RESULTS: C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high 'endogenous' aldosterone) and in 'exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. CONCLUSION: Obesity-induced endothelial dysfunction depends on the 'endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complications.

Obese and fit adolescents have lower blood pressure levels than obese and unfit counterparts.

The aim of the study was to assess the effects of physical fitness on the relationships between body mass index (BMI) and body fat (BF) on blood pressure (BP) levels. Cross-sectional study conducted in 25 schools of Lisbon (Portugal), including 2041 boys and 1995 girls aged 10-18. BF was assessed by bioimpedance. Cardiovascular fitness was assessed by the 20-meter shuttle run and classified as fit/unfit. Obesity (BMI or BF defined) was defined according to international criteria. In both sexes, BMI was positively related with systolic and diastolic BP, while BF was only positively related with diastolic BP z-scores. No interaction was found between fitness and BMI categories regarding BP levels, while for BF a significant interaction was found. Being fit reduced the BF-induced increase in the Odds ratio (OR) of presenting with high BP: OR (95% confidence interval) 1.01 (0.73-1.40) and 0.99 (0.70-1.38) for overweight and obese fit boys, respectively, the corresponding values for unfit overweight and obese boys being 1.33 (0.94-1.90) and 1.75 (1.34-2.28), respectively. The values were 0.88 (0.57-1.35) and 1.66 (0.98-2.80) for overweight and obese fit girls, respectively, the corresponding values for unfit overweight and obese being 1.63 (1.12-2.37) and 1.90 (1.32-2.73) respectively. No interaction was found between fitness and BMI-defined overweight and obesity. Being fit reduces the negative impact of BF on BP levels and high BP status in adolescents. This protective effect was not found with BMI.

Dipeptidyl peptidase IV in the hypothalamus and hippocampus of monosodium glutamate obese and food-deprived rats

Proline-specific dipeptidyl peptidases are emerging as a protease family with important roles in the regulation of signaling by peptide hormones related to energy balance. The treatment of neonatal rats with monosodium glutamate (MSG) is known to produce a selective damage on the arcuate nucleus with development of obesity. This study investigates the relationship among dipeptidyl peptidase IV (DPPIV) hydrolyzing activity, CD26 protein, fasting, and MSG model of obesity in 2 areas of the central nervous system. Dipeptidyl peptidase IV and CD26 were, respectively, evaluated by fluorometry, and enzyme-linked immunosorbent assay and reverse transcriptase polymerase chain reaction in soluble (SF) and membrane-bound (MF) fractions from the hypothalamus and hippocampus of MSG-treated and normal rats, submitted or not to food deprivation (FD). Dipeptidyl peptidase IV in both areas was distinguished kinetically as insensitive (DI) and sensitive (DS) to diprotin A. Compared with the controls, MSG and/or FD decreased the activity of DPPIV-DI in the SF and MF from the hypothalamus, as well as the activity of DPPIV-DS in the SF from the hypothalamus and in the MF from the hippocampus. Monosodium glutamate and/or FD increased the activity of DPPIV-DI in the MF from the hippocampus. The monoclonal protein expression of membrane CD26 by enzyme-linked immunosorbent assay decreased in the hypothalamus and increased in the hippocampus of MSG and/or FD relative to the controls. The existence of DPPIV-like activity with different sensitivities to diprotin A and the identity of insensitive with CD26 were demonstrated for the first time in the central nervous system. Data also demonstrated the involvement of DPPIV-DI/CD26 hydrolyzing activity in the energy balance probably through the regulation of neuropeptide Y and beta-endorphin levels in the hypothalamus and hippocampus. (C) 2011 Elsevier Inc. All rights reserved.

Alterations of NADPH Oxidase Activity in Rat Pancreatic Islets Induced by a High-Fat Diet

Objective: The aim of this study was to evaluate the effect of a high-fat diet (HFD) on nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in rat pancreatic islets. We investigated if changes in NADPH oxidase are connected to beta cell dysfunction reported in obese animals. Methods: Male Wistar rats were fed a HFD or control diet for 3 months. DNA fragmentation, insulin secretion, and [U-(14)C] glucose oxidation were examined in isolated pancreatic islets. The oxidative stress markers nitrotyrosine and 4-hydroxy-2-nonenal were assessed by immunohistochemistry. The protein content of gp91(phox) and p47(phox) was evaluated by Western blotting. Production of reactive oxygen species (ROS) was determined by a fluorescence assay using hydroethidine. Results: Occurrence of DNA fragmentation was reduced in pancreatic islets from HFD rats. There were no differences in oxidative stress markers between the groups. Glucose oxidation and insulin secretion were elevated due to high glucose in pancreatic islets from HFD rats. Protein concentrations of p47(phox) and gp91(phox) subunits were reduced and ROS production was diminished in pancreatic islets from HFD rats. Conclusions: The diminished content of NADPH oxidase subunits and ROS concentrations may be associated with increased glucose oxidation and insulin secretion in an attempt to compensate for the peripheral insulin resistance elicited by the HFD.

Oxidative stress and inflammatory mediators contribute to endothelial dysfunction in high-fat diet-induced obesity in mice

Objective We investigated the effects of high-fat diet-induced obesity on vascular proinflammatory factors and oxidative stress on endothelium-dependent relaxation of the aorta. Methods Female Swiss mice were submitted to a high-fat diet for 16 weeks. At the end of the experimental period, we evaluated blood pressure, relaxation in response to acetylcholine in aortic rings in the absence and the presence of the superoxide anion scavenger, superoxide dismutase (SOD, 150 U/ml), and the nuclear factor (NF)-kappa B inhibitor, sodium salicylate (5 mmol/l). Aortic protein expression of endothelial nitric oxide synthase, Cu/Zn-SOD, NF-kappa B, I kappa B-alpha, and proinflammatory cytokines were also evaluated. Results Obese mice presented higher systolic and diastolic blood pressure than control mice (P<0.05). The relaxation of aortas to acetylcholine, but not to sodium nitroprusside, was significantly decreased in obese mice and was corrected by both SOD and sodium salicylate (P<0.05). The protein expression of endothelial nitric oxide synthase and Cu/Zn-SOD was significantly decreased in aorta from obese mice (P<0.05). Total p65 NF-kappa B subunit protein expression was not affected by obesity, but the protein expression of NF-kappa B inhibitor I kappa B-alpha was lower in aorta from obese mice (P<0.05). There were no significant differences in the interleukin (IL)-1 beta and IL-6 protein expression between groups. In contrast, the expression of TNF-alpha was significantly increased in aortas from obese mice. Conclusion Our resultssuggest that the reducedantioxidant defense and the local NF-kappa B pathway play an important role in the impairment of endothelium-dependent relaxation in aorta from obese mice. J Hypertens 28: 2111-2119 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Exercise Training Reduces Insulin Resistance and Upregulates the mTOR/p70S6k Pathway in Cardiac Muscle of Diet-Induced Obesity Rats

Obesity and insulin resistance are rapidly expanding public health problems. These disturbances are related to many diseases, including heart pathology. Acting through the Akt/mTOR pathway, insulin has numerous and important physiological functions, such as the induction of growth and survival of many cell types and cardiac hypertrophy. However, obesity and insulin resistance can alter mTOR/p70S6k. Exercise training is known to induce this pathway, but never in the heart of diet-induced obesity subjects. To evaluate the effect of exercise training on mTOR/p70S6k in the heart of obese Wistar rats, we analyzed the effects of 12 weeks of swimming on obese rats, induced by a high-fat diet. Exercise training reduced epididymal fat, fasting serum insulin and plasma glucose disappearance. Western blot analyses showed that exercise training increased the ability of insulin to phosphorylate intracellular molecules such as Akt (2.3-fold) and Foxo1 (1.7-fold). Moreover, reduced activities and expressions of proteins, induced by the high-fat diet in rats, such as phospho-JNK (1.9-fold), NF-kB (1.6-fold) and PTP-1B (1.5-fold), were observed. Finally, exercise training increased the activities of the transduction pathways of insulin-dependent protein synthesis, as shown by increases in Raptor phosphorylation (1.7-fold), p70S6k phosphorylation (1.9-fold), and 4E-BP1 phosphorylation (1.4-fold) and a reduction in atrogin-1 expression (2.1-fold). Results demonstrate a pivotal regulatory role of exercise training on the Akt/ mTOR pathway, in turn, promoting protein synthesis and antagonizing protein degradation. J. Cell. Physiol. 226: 666-674, 2011. (C) 2010 Wiley-Liss, Inc.

Depot-specific modulation of adipokine levels in rat adipose tissue by diet-induced obesity: The effect of aerobic training and energy restriction

The present study examined the effects of aerobic training and energy restriction on adipokines levels in mesenteric (MEAT) and retroperitoneal (RPAT) white adipose tissue from obese rats. Male Wistar rats were fed with standard laboratory diet (Control group) or high fat diet (HFD). After 15 weeks, HFD rats were randomly assigned to the following groups: rats submitted to HFD, which were sedentary (sedentary HFD, n = 8) or trained (trained HFD, n = 8); or submitted to energy-restriction (ER), which were sedentary (sedentary ER, n = 8) or trained (trained ER, n = 8). Trained rats ran on a treadmill at 55% VO(2max) for 60 min/day, 5 days/week, for 10 weeks. ER rats were submitted to a reduction of 20% daily caloric ingestion compared to the Control group. ER and aerobic training decreased body weight, MEAT and RPAT absolute weight, and fat mass. IL-6, IL-10 and TNF-alpha levels were decreased and adiponectin did not change in RPAT in response to ER protocol. On the other hand, ER and the aerobic training protocol decreased IL-6, TNF-alpha and adiponectin levels in MEAT. Absolute MEAT weight showed a positive correlation with IL-6 (r = 0.464), INF-alpha (r = 0.508); and adiponectin (r = 0.342). These results suggest a tissue-specific heterogeneous response in adipokines level. The combination of the protocols (aerobic training and energy restriction) did not induce an enhanced effect. Published by Elsevier Ltd.