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.

Diet-induced obesity : when does consumption become overconsumption?

Overconsumption is commonly implicated in the aetiology of obesity; however there is a lack of consensus on a definition and the most appropriate methodology for assessing it. The aim of this communication is to highlight the need for theoretical consensus on the assessment of overconsumption, which may lead to improved methodological standards in obesity research. In laboratory studies, overconsumption is most frequently inferred from the comparison of food intake within or between individuals against a single control. Measurement often relies on a single eating episode with limited consideration of preceding or subsequent intake. An alternative approach is to consider food intake in the context of energy requirements, within an energy balance framework. One such marker of chronic overconsumption is body weight. There is a need for agreement on the definition and measurement of overconsumption, so that its role in weight gain and obesity can be more precisely delineated.

Methodological considerations for meal-induced thermogenesis : measurement duration and reproducibility

Meal-Induced Thermogenesis (MIT) research findings are highly inconsistent, in part, due to the variety of durations and protocols used to measure MIT. We aimed to determine: 1) the proportion of a 6 h MIT response completed at 3, 4 and 5 h; 2) the associations between the shorter durations and the 6 h measure; 3) whether shorter durations improved the reproducibility of the measurement. MIT was measured in response to a 2410 KJ mixed composition meal in ten individuals (5 male, 5 female) on two occasions. Energy expenditure was measured continuously for 6 h post-meal using indirect calorimetry and MIT was calculated as the increase in energy expenditure above the pre-meal RMR. On average, 76%, 89%, and 96% of the 6 h MIT response was completed within 3, 4 and 5 h respectively, and the MIT at each of these time points was strongly correlated to the 6 h MIT (range for correlations, r = 0.990 to 0.998; p < 0.01). The between-day CV for the 6 h measurement was 33%, but was significantly lower after 3 h of measurement (CV = 26%, p = 0.02). Despite variability in the total MIT between days, the proportion of the MIT that was complete at 3, 4 and 5 h was reproducible (mean CV: 5%). While 6 h is typically required to measure the complete MIT response, 3 h measures provide sufficient information about the magnitude of the MIT response and may be applicable for measuring individuals on repeated occasions.

Shaping development through mechanical strain: The transcriptional basis of diet-induced phenotypic plasticity in a cichlid fish

Adaptive phenotypic plasticity, the ability of an organism to change its phenotype to match local environments, is increasingly recognized for its contribution to evolution. However, few empirical studies have explored the molecular basis of plastic traits. The East African cichlid fish Astatoreochromis alluaudi displays adaptive phenotypic plasticity in its pharyngeal jaw apparatus, a structure that is widely seen as an evolutionary key innovation that has contributed to the remarkable diversity of cichlid fishes. It has previously been shown that in response to different diets, the pharyngeal jaws change their size, shape and dentition: hard diets induce an adaptive robust molariform tooth phenotype with short jaws and strong internal bone structures, while soft diets induce a gracile papilliform tooth phenotype with elongated jaws and slender internal bone structures. To gain insight into the molecular underpinnings of these adaptations and enable future investigations of the role that phenotypic plasticity plays during the formation of adaptive radiations, the transcriptomes of the two divergent jaw phenotypes were examined. Our study identified a total of 187 genes whose expression differs in response to hard and soft diets, including immediate early genes, extracellular matrix genes and inflammatory factors. Transcriptome results are interpreted in light of expression of candidate genesmarkers for tooth size and shape, bone cells and mechanically sensitive pathways. This study opens up new avenues of research at new levels of biological organization into the roles of phenotypic plasticity during speciation and radiation of cichlid fishes.

Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1

Obesity and metabolic syndrome are associated with several cancers, however, the molecular mechanisms remain to be fully elucidated. Recent studies suggest that hypercholesterolemia increases intratumoral androgen signaling in prostate cancer, but it is unclear whether androgenindependent mechanisms also exist. Since hypercholesterolemia is associated with advanced, castrate-resistant prostate cancer, in this study, we aimed to determine whether and how hypercholesterolemia affects prostate cancer progression in the absence of androgen signaling. We demonstrate that diet-induced hypercholesterolemia promotes orthotopic xenograft PC-3 cell metastasis, concomitant with elevated expression of caveolin-1 and IQGAP1 in xenograft tumor tissues. In vitro cholesterol treatment of PC-3 cells stimulated migration and increased IQGAP1 and caveolin-1 protein level and localization to a detergent-resistant fraction. Down-regulation of caveolin-1 or IQGAP1 in PC-3 cells reduced migration and invasion in vitro, and hypercholesterolemia-induced metastasis in vivo. Double knock-down of caveolin-1 and IQGAP1 showed no additive effect, suggesting that caveolin-1 and IQGAP1 act via the same pathway. Taken together, our data show that hypercholesterolemia promotes prostate cancer metastasis independent of the androgen pathway, in part by increasing IQGAP1 and caveolin-1. These results have broader implications for managing metastasis of cancers in general as IQGAP1 and hypercholesterolemia are implicated in the progression of several cancers.

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet.

Ghrelin and the brain-gut axis as a pharmacological target for appetite control

Appetite regulation is highly complex and involves a large number of orexigenic and anorexigenic peptide hormones. These are small, processed, secreted peptides derived from larger prepropeptide precursors. These peptides are important targets for the development of therapeutics for obesity, a global health epidemic. As a case study, we consider the ghrelin axis. The ghrelin axis is likely to be a particularly useful drug target, as it also plays a role in energy homeostasis, adipogenesis, insulin regulation and reward associated with food intake. Ghrelin is the only known circulating gut orexigenic peptide hormone. As it appears to play a role in diet-induced obesity, blocking the action of ghrelin is likely to be effective for treating and preventing obesity. The ghrelin peptide has been targeted using a number of approaches, with ghrelin mirror-image oligonucleotides (Spiegelmers) and immunotherapy showing some promise. The ghrelin receptor, the growth hormone secretagogue receptor, may also provide a useful target and a number of antagonists and inverse agonists have been developed. A particularly promising new target is the enzyme which octanoylates ghrelin, ghrelin O-acyltransferase (GOAT), and drugs that inhibit GOAT are likely to circumvent pharmacological issues associated with approaches that directly target ghrelin or its receptor.

The effect of graded levels of exercise on energy intake and balance in free-living men, consuming their normal diet

Objective: To assess the effect of graded increases in exercised-induced energy expenditure (EE) on appetite, energy intake (EI), total daily EE and body weight in men living in their normal environment and consuming their usual diets. Design: Within-subject, repeated measures design. Six men (mean (s.d.) age 31.0 (5.0) y; weight 75.1 (15.96) kg; height 1.79 (0.10) m; body mass index (BMI) 23.3(2.4) kg/m2), were each studied three times during a 9 day protocol, corresponding to prescriptions of no exercise, (control) (Nex; 0 MJ/day), medium exercise level (Mex; ~1.6 MJ/day) and high exercise level (Hex; ~3.2 MJ/day). On days 1-2 subjects were given a medium fat (MF) maintenance diet (1.6 ´ resting metabolic rate (RMR)). Measurements: On days 3-9 subjects self-recorded dietary intake using a food diary and self-weighed intake. EE was assessed by continual heart rate monitoring, using the modified FLEX method. Subjects' HR (heart rate) was individually calibrated against submaximal VO2 during incremental exercise tests at the beginning and end of each 9 day study period. Respiratory exchange was measured by indirect calorimetry. Subjects completed hourly hunger ratings during waking hours to record subjective sensations of hunger and appetite. Body weight was measured daily. Results: EE amounted to 11.7, 12.9 and 16.8 MJ/day (F(2,10)=48.26; P<0.001 (s.e.d=0.55)) on the Nex, Mex and Hex treatments, respectively. The corresponding values for EI were 11.6, 11.8 and 11.8 MJ/day (F(2,10)=0.10; P=0.910 (s.e.d.=0.10)), respectively. There were no treatment effects on hunger, appetite or body weight, but there was evidence of weight loss on the Hex treatment. Conclusion: Increasing EE did not lead to compensation of EI over 7 days. However, total daily EE tended to decrease over time on the two exercise treatments. Lean men appear able to tolerate a considerable negative energy balance, induced by exercise, over 7 days without invoking compensatory increases in EI.

Exercise-induced energy expenditure : implications for exercise prescription and obesity

Objective: Walking is commonly recommended to help with weight management. We measured total energy expenditure (TEE) and its components to quantify the impact of increasing exercise-induced energy expenditure (ExEE) on other components of TEE. Methods: Thirteen obese women underwent an 8-week walking group intervention. TEE was quantified using doubly labeled water, ExEE was quantified using heart rate monitors, daily movement was assessed by accelerometry and resting metabolic rate was measured using indirect calorimetry. Results: Four of the 13 participants achieved the target of 1500 kcal wk−1 of ExEE and all achieved 1000 kcal wk−1. The average ExEE achieved by the group across the 8 weeks was 1434 ± 237 kcal wk−1. Vigorous physical activity, as assessed by accelerometry, increased during the intervention by an average of 30 min per day. Non-exercise activity thermogenesis (NEAT) decreased, on average, by 175 kcal d−1 (−22%) from baseline to the intervention and baseline fitness was correlated with change in NEAT. Conclusions: Potential alterations in non-exercise activity should be considered when exercise is prescribed. The provision of appropriate education on how to self-monitor daily activity levels may improve intervention outcomes in groups who are new to exercise. Practice implications: Strategies to sustain incidental and light physical activity should be offered to help empower individuals as they develop and maintain healthy and long-lasting lifestyle habits.

Interactions between energy intake and expenditure in the development and treatment of obesity.

Summary There are four interactions to consider between energy intake (EI) and energy expenditure (EE) in the development and treatment of obesity. (1) Does sedentariness alter levels of EI or subsequent EE? and (2) Do high levels of EI alter physical activity or exercise? (3) Do exercise-induced increases in EE drive EI upwards and undermine dietary approaches to weight management and (4) Do low levels of EI elevate or decrease EE? There is little evidence that sedentariness alters levels of EI. This lack of cross-talk between altered EE and EI appears to promote a positive EB. Lifestyle studies also suggest that a sedentary routine actually offers the opportunity for over-consumption. Substantive changes in non exercise activity thermogenesis are feasible, but not clearly demonstrated. Cross talk between elevated EE and EI is initially too weak and takes too long to activate, to seriously threaten dietary approaches to weight management. It appears that substantial fat loss is possible before intake begins to track a sustained elevation of EE. There is more evidence that low levels of EI does lower physical activity levels, in relatively lean men under conditions of acute or prolonged semi-starvation and in dieting obese subjects. During altered EB there are a number of small but significant changes in the components of EE, including (i) sleeping and basal metabolic rate, (ii) energy cost of weight change alters as weight is gained or lost, (iii) exercise efficiency, (iv) energy cost of weight bearing activities, (v) during substantive overfeeding diet composition (fat versus carbohydrate) will influence the energy cost of nutrient storage by ~ 15%. The responses (i-v) above are all “obligatory” responses. Altered EB can also stimulate facultative behavioural responses, as a consequence of cross-talk between EI and EE. Altered EB will lead to changes in the mode duration and intensity of physical activities. Feeding behaviour can also change. The degree of inter-individual variability in these responses will define the scope within which various mechanisms of EB compensation can operate. The relative importance of “obligatory” versus facultative, behavioural responses -as components of EB control- need to be defined.

The effect of exercise intensity on fat oxidation and non-exercise activity thermogenesis in overweight/obese men

It is frequently reported that the actual weight loss achieved through exercise interventions is less than theoretically expected. Amongst other compensatory adjustments that accompany exercise training (e.g., increases in resting metabolic rate and energy intake), a possible cause of the less than expected weight loss is a failure to produce a marked increase in total daily energy expenditure due to a compensatory reduction in non-exercise activity thermogenesis (NEAT). Therefore, there is a need to understand how behaviour is modified in response to exercise interventions. The proposed benefits of exercise training are numerous, including changes to fat oxidation. Given that a diminished capacity to oxidise fat could be a factor in the aetiology of obesity, an exercise training intensity that optimises fat oxidation in overweight/obese individuals would improve impaired fat oxidation, and potentially reduce health risks that are associated with obesity. To improve our understanding of the effectiveness of exercise for weight management, it is important to ensure exercise intensity is appropriately prescribed, and to identify and monitor potential compensatory behavioural changes consequent to exercise training. In line with the gaps in the literature, three studies were performed. The aim of Study 1 was to determine the effect of acute bouts of moderate- and high-intensity walking exercise on NEAT in overweight and obese men. Sixteen participants performed a single bout of either moderate-intensity walking exercise (MIE) or high-intensity walking exercise (HIE) on two separate occasions. The MIE consisted of walking for 60-min on a motorised treadmill at 6 km.h-1. The 60-min HIE session consisted of walking in 5-min intervals at 6 km.h-1 and 10% grade followed by 5-min at 0% grade. NEAT was assessed by accelerometer three days before, on the day of, and three days after the exercise sessions. There was no significant difference in NEAT vector magnitude (counts.min-1) between the pre-exercise period (days 1-3) and the exercise day (day 4) for either protocol. In addition, there was no change in NEAT during the three days following the MIE session, however NEAT increased by 16% on day 7 (post-exercise) compared with the exercise day (P = 0.32). During the post-exercise period following the HIE session, NEAT was increased by 25% on day 7 compared with the exercise day (P = 0.08), and by 30-33% compared with the pre-exercise period (day 1, day 2 and day 3); P = 0.03, 0.03, 0.02, respectively. To conclude, a single bout of either MIE or HIE did not alter NEAT on the exercise day or on the first two days following the exercise session. However, extending the monitoring of NEAT allowed the detection of a 48 hour delay in increased NEAT after performing HIE. A longer-term intervention is needed to determine the effect of accumulated exercise sessions over a week on NEAT. In Study 2, there were two primary aims. The first aim was to test the reliability of a discontinuous incremental exercise protocol (DISCON-FATmax) to identify the workload at which fat oxidation is maximised (FATmax). Ten overweight and obese sedentary male men (mean BMI of 29.5 ¡Ó 4.5 kg/m2 and mean age of 28.0 ¡Ó 5.3 y) participated in this study and performed two identical DISCON-FATmax tests one week apart. Each test consisted of alternate 4-min exercise and 2-min rest intervals on a cycle ergometer. The starting work load of 28 W was increased every 4-min using 14 W increments followed by 2-min rest intervals. When the respiratory exchange ratio was consistently >1.0, the workload was increased by 14 W every 2-min until volitional exhaustion. Fat oxidation was measured by indirect calorimetry. The mean FATmax, ƒtV O2peak, %ƒtV O2peak and %Wmax at which FATmax occurred during the two tests were 0.23 ¡Ó 0.09 and 0.18 ¡Ó 0.08 (g.min-1); 29.7 ¡Ó 7.8 and 28.3 ¡Ó 7.5 (ml.kg-1.min-1); 42.3 ¡Ó 7.2 and 42.6 ¡Ó 10.2 (%ƒtV O2max) and 36.4 ¡Ó 8.5 and 35.4 ¡Ó 10.9 (%), respectively. A paired-samples T-test revealed a significant difference in FATmax (g.min-1) between the tests (t = 2.65, P = 0.03). The mean difference in FATmax was 0.05 (g.min-1) with the 95% confidence interval ranging from 0.01 to 0.18. Paired-samples T-test, however, revealed no significant difference in the workloads (i.e. W) between the tests, t (9) = 0.70, P = 0.4. The intra-class correlation coefficient for FATmax (g.min-1) between the tests was 0.84 (95% confidence interval: 0.36-0.96, P < 0.01). However, Bland-Altman analysis revealed a large disagreement in FATmax (g.min-1) related to W between the two tests; 11 ¡Ó 14 (W) (4.1 ¡Ó 5.3 ƒtV O2peak (%)).These data demonstrate two important phenomena associated with exercise-induced substrate oxidation; firstly, that maximal fat oxidation derived from a discontinuous FATmax protocol differed statistically between repeated tests, and secondly, there was large variability in the workload corresponding with FATmax. The second aim of Study 2 was to test the validity of a DISCON-FATmax protocol by comparing maximal fat oxidation (g.min-1) determined by DISCON-FATmax with fat oxidation (g.min-1) during a continuous exercise protocol using a constant load (CONEX). Ten overweight and obese sedentary males (BMI = 29.5 ¡Ó 4.5 kg/m2; age = 28.0 ¡Ó 4.5 y) with a ƒtV O2max of 29.1 ¡Ó 7.5 ml.kg-1.min-1 performed a DISCON-FATmax test consisting of alternate 4-min exercise and 2-min rest intervals on a cycle ergometer. The 1-h CONEX protocol used the workload from the DISCON-FATmax to determine FATmax. The mean FATmax, ƒtV O2max, %ƒtV O2max and workload at which FATmax occurred during the DISCON-FATmax were 0.23 ¡Ó 0.09 (g.min-1); 29.1 ¡Ó 7.5 (ml.kg-1.min-1); 43.8 ¡Ó 7.3 (%ƒtV O2max) and 58.8 ¡Ó 19.6 (W), respectively. The mean fat oxidation during the 1-h CONEX protocol was 0.19 ¡Ó 0.07 (g.min-1). A paired-samples T-test revealed no significant difference in fat oxidation (g.min-1) between DISCON-FATmax and CONEX, t (9) = 1.85, P = 0.097 (two-tailed). There was also no significant correlation in fat oxidation between the DISCON-FATmax and CONEX (R=0.51, P = 0.14). Bland- Altman analysis revealed a large disagreement in fat oxidation between the DISCONFATmax and CONEX; the upper limit of agreement was 0.13 (g.min-1) and the lower limit of agreement was ¡V0.03 (g.min-1). These data suggest that the CONEX and DISCONFATmax protocols did not elicit different rates of fat oxidation (g.min-1). However, the individual variability in fat oxidation was large, particularly in the DISCON-FATmax test. Further research is needed to ascertain the validity of graded exercise tests for predicting fat oxidation during constant load exercise sessions. The aim of Study 3 was to compare the impact of two different intensities of four weeks of exercise training on fat oxidation, NEAT, and appetite in overweight and obese men. Using a cross-over design 11 participants (BMI = 29 ¡Ó 4 kg/m2; age = 27 ¡Ó 4 y) participated in a training study and were randomly assigned initially to: [1] a lowintensity (45%ƒtV O2max) exercise (LIT) or [2] a high-intensity interval (alternate 30 s at 90%ƒtV O2max followed by 30 s rest) exercise (HIIT) 40-min duration, three times a week. Participants completed four weeks of supervised training and between cross-over had a two week washout period. At baseline and the end of each exercise intervention,ƒtV O2max, fat oxidation, and NEAT were measured. Fat oxidation was determined during a standard 30-min continuous exercise bout at 45%ƒtV O2max. During the steady state exercise expired gases were measured intermittently for 5-min periods and HR was monitored continuously. In each training period, NEAT was measured for seven consecutive days using an accelerometer (RT3) the week before, at week 3 and the week after training. Subjective appetite sensations and food preferences were measured immediately before and after the first exercise session every week for four weeks during both LIT and HIIT. The mean fat oxidation rate during the standard continuous exercise bout at baseline for both LIT and HIIT was 0.14 ¡Ó 0.08 (g.min-1). After four weeks of exercise training, the mean fat oxidation was 0.178 ¡Ó 0.04 and 0.183 ¡Ó 0.04 g.min-1 for LIT and HIIT, respectively. The mean NEAT (counts.min-1) was 45 ¡Ó 18 at baseline, 55 ¡Ó 22 and 44 ¡Ó 16 during training, and 51 ¡Ó 14 and 50 ¡Ó 21 after training for LIT and HIIT, respectively. There was no significant difference in fat oxidation between LIT and HIIT. Moreover, although not statistically significant, there was some evidence to suggest that LIT and HIIT tend to increase fat oxidation during exercise at 45% ƒtV O2max (P = 0.14 and 0.08, respectively). The order of training treatment did not significantly influence changes in fat oxidation, NEAT, and appetite. NEAT (counts.min-1) was not significantly different in the week following training for either LIT or HIIT. Although not statistically significant (P = 0.08), NEAT was 20% lower during week 3 of exercise training in HIIT compared with LIT. Examination of appetite sensations revealed differences in the intensity of hunger, with higher ratings after LIT compared with HIIT. No differences were found in preferences for high-fat sweet foods between LIT and HIIT. In conclusion, the results of this thesis suggest that while fat oxidation during steady state exercise was not affected by the level of exercise intensity, there is strong evidence to suggest that intense exercise could have a debilitative effect on NEAT.

Does metabolic compensation explain the majority of less-than-expected weight loss in obese adults during a short-term severe diet and exercise intervention?

Objective: We investigated to what extent changes in metabolic rate and composition of weight loss explained the less-than-expected weight loss in obese men and women during a diet-plus-exercise intervention. Design: 16 obese men and women (41 ± 9 years; BMI 39 ± 6 kg/m2) were investigated in energy balance before, after and twice during a 12-week VLED (565–650 kcal/day) plus exercise (aerobic plus resistance training) intervention. The relative energy deficit (EDef) from baseline requirements was severe (74-87%). Body composition was measured by deuterium dilution and DXA and resting metabolic rate (RMR) by indirect calorimetry. Fat mass (FM) and fat-free mass (FFM) were converted into energy equivalents using constants: 9.45 kcal/gFM and 1.13 kcal/gFFM. Predicted weight loss was calculated from the energy deficit using the '7700 kcal/kg rule'. Results: Changes in weight (-18.6 ± 5.0 kg), FM (-15.5 ± 4.3 kg), and FFM (-3.1 ± 1.9 kg) did not differ between genders. Measured weight loss was on average 67% of the predicted value, but ranged from 39 to 94%. Relative EDef was correlated with the decrease in RMR (R=0.70, P<0.01) and the decrease in RMR correlated with the difference between actual and expected weight loss (R=0.51, P<0.01). Changes in metabolic rate explained on average 67% of the less-than-expected weight loss, and variability in the proportion of weight lost as FM accounted for a further 5%. On average, after adjustment for changes in metabolic rate and body composition of weight lost, actual weight loss reached 90% of predicted values. Conclusion: Although weight loss was 33% lower than predicted at baseline from standard energy equivalents, the majority of this differential was explained by physiological variables. While lower-than-expected weight loss is often attributed to incomplete adherence to prescribed interventions, the influence of baseline calculation errors and metabolic down-regulation should not be discounted.

Cross-sectional survey of the health behaviour of southeast Queensland women with cancer-treatment induced menopause : Implications for cancer and primary care nurses

Purpose Women who experience cancer treatment-induced menopause are at risk of long-term chronic morbidity. This risk can be prevented or offset with adherence to health promotion and risk reduction guidelines. The purpose of this study was to explore health behaviours in younger female survivors of cancer and the variables (quality of life and psychological distress) believed to moderate health behaviours. Design Cross-sectional survey of a convenience sample of women (n = 85) in southeast Queensland. Methods Health behaviour and health status were elicited with items from the Australian Health Survey and the Behavioural Risk Factor Surveillance System. The WHO Quality of Life (Brief) measured participants’ self-reported quality of life and their satisfaction with their health. The Brief Symptom Inventory-18 measured psychological distress. Findings Higher self-reported health status was associated with regular exercise and better quality of life. However, a substantial proportion of participants did not engage in the physical activity, dietary or cervical screening practices recommended by Australian guidelines. Conclusions The participants require education regarding the benefits of diet, exercise, weight loss and decreased alcohol intake, as well as information on future health risks and possible comorbidities. These education sessions could be addressed by a nurse-led health promotion model of care at the time of discharge or in the community.