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 effects of weight loss strategies on gastric emptying and appetite control

The gastrointestinal tract plays an important role in the improved appetite control and weight loss in response to bariatric surgery. Other strategies which similarly alter gastrointestinal responses to food intake could contribute to successful weight management. The aim of this review is to discuss the effects of surgical, pharmacological and behavioural weight loss interventions on gastrointestinal targets of appetite control, including gastric emptying. Gastrointestinal peptides are also discussed because of their integrative relationship in appetite control. This review shows that different strategies exert diverse effects and there is no consensus on the optimal strategy for manipulating gastric emptying to improve appetite control. Emerging evidence from surgical procedures (e.g., sleeve gastrectomy and Roux en-Y gastric bypass) suggests a faster emptying rate and earlier delivery of nutrients to the distal small intestine may improve appetite control. Energy restriction slows gastric emptying, while the effect of exercise-induced weight loss on gastric emptying remains to be established. The limited evidence suggests that chronic exercise is associated with faster gastric emptying which we hypothesise will impact on appetite control and energy balance. Understanding how behavioural weight loss interventions (e.g., diet and exercise) alter gastrointestinal targets of appetite control may be important to improve their success in weight management.

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.

Isoenergetic replacement of dietary saturated with monounsaturated fat via macadamia nuts enhances endothelial function in overweight subjects

Background & aims: - Excess adiposity (overweight) is one of numerous risk factors for cardiometabolic disease. Most risk reduction strategies for overweight rely on weight loss through dietary energy restriction. However, since the evidence base for long-term successful weight loss interventions is scant, it is important to identify strategies for risk reduction independent of weight loss. The aim of this study was to compare the effects of isoenergetic substitution of dietary saturated fat (SFA) with monounsaturated fat (MUFA) via macadamia nuts on coronary risk compared to usual diet in overweight adults. Methods: - A randomised controlled trial design, maintaining usual energy intake, but manipulating dietary lipid profile in a group of 64 (54 female, 10 male) overweight (BMI > 25), otherwise healthy, subjects. For the intervention group, energy intakes of usual (baseline) diets were calculated from multiple 3 day diet diaries, and SFA was replaced with MUFA (target: 50%E from fat as MUFA) by altering dietary SFA sources and adding macadamia nuts to the diet. Both control and intervention groups received advice on national guidelines for physical activity and adhered to the same protocol for diet diary record keeping and trial consultations. Anthropometric and clinical measures were taken at baseline and at 10 weeks. Results: A significant increase in brachial artery flow-mediated dilation (p < 0.05) was seen in the monounsaturated diet group at week 10 compared to baseline. This corresponded to significant decreases in waist circumference, total cholesterol (p < 0.05), plasma leptin and ICAM-1 (p < 0.01). Conclusions: - In patient subgroups where adherence to dietary energy-reduction is poor, isoenergetic interventions may improve endothelial function and other coronary risk factors without changes in body weight. This trial was registered with the Australia New Zealand Clinical Trial Registry (ACTRN12607000106437).

'Sarcobesity' : a metabolic conundrum

Two independent but inter-related conditions that have a growing impact on healthy life expectancy and health care costs in developed nations are an age-related loss of muscle mass (i.e., sarcopenia) and obesity. Sarcopenia is commonly exacerbated in overweight and obese individuals. Progression towards obesity promotes an increase in fat mass and a concomitant decrease in muscle mass, producing an unfavourable ratio of fat to muscle. The coexistence of diminished muscle mass and increased fat mass (so-called 'sarcobesity') is ultimately manifested by impaired mobility and/or development of life-style-related diseases. Accordingly, the critical health issue for a large proportion of adults in developed nations is how to lose fat mass while preserving muscle mass. Lifestyle interventions to prevent or treat sarcobesity include energy-restricted diets and exercise. The optimal energy deficit to reduce body mass is controversial. While energy restriction in isolation is an effective short-term strategy for rapid and substantial weight loss, it results in a reduction of both fat and muscle mass and therefore ultimately predisposes one to an unfavourable body composition. Aerobic exercise promotes beneficial changes in whole-body metabolism and reduces fat mass, while resistance exercise preserves lean (muscle) mass. Current evidence strongly supports the inclusion of resistance and aerobic exercise to complement mild energy-restricted high-protein diets for healthy weight loss as a primary intervention for sarcobesity.

Comparing the medium-term effects of exercise or dietary restriction on appetite regulation and compensatory responses

Previous studies have shown that exercise (Ex) interventions create a stronger coupling between energy intake (EI) and energy expenditure (EE) leading to increased homeostasis of the energy-balance (EB) regulatory system compared to a diet intervention where an un-coupling between EI and EE occurs. The benefits of weight loss from Ex and diet interventions greatly depend on compensatory responses. The present study investigated an 8-week medium-term Ex and diet intervention program (Ex intervention comprised of 500kcal EE five days per week over four weeks at 65-75% maximal heart rate, whereas the diet intervention comprised of a 500kcal decrease in EI five days per week over four weeks) and its effects on compensatory responses and appetite regulation among healthy individuals using a between- and within-subjects design. Effects of an acute dietary manipulation on appetite and compensatory behaviours and whether a diet and/or Ex intervention pre-disposes individuals to disturbances in EB homeostasis were tested. Energy intake at an ad libitum lunch test meal after a breakfast high- and low-energy pre-load (the high energy pre-load contained 556kcal and the low energy pre-load contained 239kcal) were measured at the Baseline (Weeks -4 to 0) and Intervention (Weeks 0 to 4) phases in 13 healthy volunteers (three males and ten females; mean age 35 years [sd + 9] and mean BMI 25 kg/m2 [sd + 3.8]) [participants in each group included Ex=7, diet=5 (one female in the diet group dropped out midway), thus, 12 participants completed the study]. At Weeks -4, 0 and 4, visual analogue scales (VAS) were used to assess hunger and satiety and liking and wanting (L&W) for nutrient and taste preferences using a computer-based system (E-Prime v1.1.4). Ad libitum test meal EI was consistently lower after the HE pre-load compared to the LE pre-load. However, this was not consistent during the diet intervention however. A pre-load x group interaction on ad libitum test meal EI revealed that during the intervention phase the Ex group showed an improved sensitivity to detect the energy content between the two pre-loads and improved compensation for the ad libitum test meal whereas the diet group’s ability to differentiate between the two pre-loads decreased and showed poorer compensation (F[1,10]=2.88, p-value not significant). This study supports previous findings of the effect Ex and diet interventions have on appetite and compensatory responses; Ex increases and diet decreases energy balance sensitivity.

Clinical Accuracy of the MedGem Indirect Calorimeter for Measuring Resting Energy Expenditure in Cancer Patients

OBJECTIVE: To compare, in patients with cancer and in healthy subjects, measured resting energy expenditure (REE) from traditional indirect calorimetry to a new portable device (MedGem) and predicted REE. DESIGN: Cross-sectional clinical validation study. SETTING: Private radiation oncology centre, Brisbane, Australia. SUBJECTS: Cancer patients (n = 18) and healthy subjects (n = 17) aged 37-86 y, with body mass indices ranging from 18 to 42 kg/m(2). INTERVENTIONS: Oxygen consumption (VO(2)) and REE were measured by VMax229 (VM) and MedGem (MG) indirect calorimeters in random order after a 12-h fast and 30-min rest. REE was also calculated from the MG without adjustment for nitrogen excretion (MGN) and estimated from Harris-Benedict prediction equations. Data were analysed using the Bland and Altman approach, based on a clinically acceptable difference between methods of 5%. RESULTS: The mean bias (MGN-VM) was 10% and limits of agreement were -42 to 21% for cancer patients; mean bias -5% with limits of -45 to 35% for healthy subjects. Less than half of the cancer patients (n = 7, 46.7%) and only a third (n = 5, 33.3%) of healthy subjects had measured REE by MGN within clinically acceptable limits of VM. Predicted REE showed a mean bias (HB-VM) of -5% for cancer patients and 4% for healthy subjects, with limits of agreement of -30 to 20% and -27 to 34%, respectively. CONCLUSIONS: Limits of agreement for the MG and Harris Benedict equations compared to traditional indirect calorimetry were similar but wide, indicating poor clinical accuracy for determining the REE of individual cancer patients and healthy subjects.