The importance of fat-free mass and constituent tissue-organs in the control of human appetite.

PURPOSE OF REVIEW: Traditional models of human appetite focus on the contribution of adipose tissue and the gastrointestinal tract, both of which exert mainly inhibitory influences. The purpose of this review is to consider the biological factors that influence the drive to eat. RECENT FINDINGS: Fat-free mass is positively associated with objectively measured meal size and daily energy intake. These findings have been replicated in multiple populations across the life-course in laboratory and free-living studies. Studies have shown that the effect of fat-free mass is statistically mediated by resting metabolic rate, suggesting that energy expenditure per se may influence energy intake. A recent MRI study has reported that fasting hunger was associated with high metabolic rate organ (heart, liver, brain, kidneys) and skeletal muscle mass. Integrating measures of body composition at the tissue-organ level and markers of their metabolic function with appetitive measures could provide novel insight into the mechanisms that influence appetite. SUMMARY: These recent findings suggest that fat-free mass and resting metabolic rate are determinants of energy intake. Consideration of fat-free mass and energy expenditure as physiological sources of appetitive signals helps reconcile the mechanisms underpinning the inhibition of eating with those that drive eating.

The complex pattern of the effects of prolonged frequent exercise on appetite control, and implications for obesity.

From a public health perspective, much of the interest in the relationship between exercise and appetite rests on the implications for energy balance and obesity. Energy balance reflects a dynamic 2-way interaction between energy expenditure (EE) and energy intake (EI). Physical activity and exercise, and appetite are the behavioural components of EE and EI, respectively. Beyond EE, exercise is a powerful and complex physiological stimulus acting on several bodily systems. There are multiple effects of frequent and prolonged exercise on appetite which include inter alia an increase in fasting hunger, an enhancement of post-prandial satiety, a modulation of the hedonic responses to food and improvements in eating behaviour traits. These lead to variable adjustments in EI and in a reduction in the susceptibility to overconsumption. Frequent and prolonged physical activity and exercise behaviour can strengthen and sensitise the appetite control system, whilst physical inactivity and sedentariness (low level of EE) fails to downregulate EI and can permit overconsumption. Not all of the effects of exercise operate uniformly to drive appetite in the same direction. The complexity of the interaction between EE and EI means that the effects of prolonged exercise are characterised by substantial individual heterogeneity. This leads to variable effects on energy balance and body mass.

Fat-Free Mass and Total Daily Energy Expenditure Estimated Using Doubly Labeled Water Predict Energy Intake in a Large Sample of Community-Dwelling Older Adults.

BACKGROUND: Up to 30% of community-based older adults report reduced appetite and energy intake (EI), but previous research examining the underlying physiological mechanisms has focused on the mechanisms that suppress eating rather than the hunger drive and EI. OBJECTIVES: We examined the associations between fat-free mass (FFM), physical activity (PA), total daily energy expenditure (TDEE), and self-reported EI in older adults. METHODS: The present study was a secondary analysis of the Interactive Diet and Activity Tracking in AARP study. Body composition (deuterium dilution), PA (accelerometry), and TDEE (doubly labeled water) were measured in 590 older adults (age, 63.1 ± 5.9 years; BMI, 28.1 ± 4.9 kg/m2). The total daily EI was estimated from a single 24-hour dietary recall (EIsingle; ±1 month of PA and TDEE measurement) and the mean of up to 6 recalls over a 12-month period (EImean), with misreporters classified using the 95% CIs between the EImean and TDEE. RESULTS: After controlling for age and sex, linear regression demonstrated that FFM and TDEE predicted EI when estimated from a single 24-hour dietary recall (P < 0.05), from the mean of up to 6 dietary recalls (P < 0.05), and after the removal of those classified as underreporters (P < 0.001). Age moderated the associations between FFM and EIsingle (P < 0.001), FFM and EImean (P < 0.001), and TDEE with EIsingle (P = 0.016), with associations becoming weaker across age quintiles. CONCLUSIONS: These data suggest that the total daily EI is proportional to the FFM and TDEE, but not fat mass, in older adults. These associations may reflect an underling drive to eat that influences the daily food intake. While the associations between FFM or TDEE and EI existed across all age quintiles, these associations weakened with increasing age.

Fat-Free Mass and Total Daily Energy Expenditure Estimated Using Doubly Labeled Water Predict Energy Intake in a Large Sample of Community-Dwelling Older Adults.

BACKGROUND: Up to 30% of community-based older adults report reduced appetite and energy intake (EI), but previous research examining the underlying physiological mechanisms has focused on the mechanisms that suppress eating rather than the hunger drive and EI. OBJECTIVES: We examined the associations between fat-free mass (FFM), physical activity (PA), total daily energy expenditure (TDEE), and self-reported EI in older adults. METHODS: The present study was a secondary analysis of the Interactive Diet and Activity Tracking in AARP study. Body composition (deuterium dilution), PA (accelerometry), and TDEE (doubly labeled water) were measured in 590 older adults (age, 63.1 ± 5.9 years; BMI, 28.1 ± 4.9 kg/m2). The total daily EI was estimated from a single 24-hour dietary recall (EIsingle; ±1 month of PA and TDEE measurement) and the mean of up to 6 recalls over a 12-month period (EImean), with misreporters classified using the 95% CIs between the EImean and TDEE. RESULTS: After controlling for age and sex, linear regression demonstrated that FFM and TDEE predicted EI when estimated from a single 24-hour dietary recall (P < 0.05), from the mean of up to 6 dietary recalls (P < 0.05), and after the removal of those classified as underreporters (P < 0.001). Age moderated the associations between FFM and EIsingle (P < 0.001), FFM and EImean (P < 0.001), and TDEE with EIsingle (P = 0.016), with associations becoming weaker across age quintiles. CONCLUSIONS: These data suggest that the total daily EI is proportional to the FFM and TDEE, but not fat mass, in older adults. These associations may reflect an underling drive to eat that influences the daily food intake. While the associations between FFM or TDEE and EI existed across all age quintiles, these associations weakened with increasing age.

Increases in physical activity are associated with a faster rate of weight loss during dietary energy restriction in women with overweight and obesity.

This secondary analysis examined the influence of changes in physical activity (PA), sedentary time and energy expenditure (EE) during dietary energy restriction on the rate of weight loss (WL) and 1-year follow-up weight change in women with overweight/obesity.Measurements of body weight and composition (air-displacement plethysmography), resting metabolic rate (indirect calorimetry), total daily (TDEE) and activity EE (AEE), minutes of PA and sedentary time (PA monitor) were taken at baseline, after 2 weeks, after ≥5% WL or 12 weeks of continuous (25% daily energy deficit) or intermittent (75% daily energy deficit alternated with ad libitum day) energy restriction, and at 1-year post-WL. The rate of WL was calculated as total %WL/number of dieting weeks. Data from both groups were combined for analyses.Thirty-seven participants (age=35±10y; BMI=29.1±2.3kg/m2) completed the intervention (WL=-5.9±1.6%) and 18 returned at 1-year post-WL (weight change=+4.5±5.2%). Changes in sedentary time at 2 weeks were associated with the rate of WL during energy restriction (r=-0.38; p=0.03). Changes in total (r=0.54; p<0.01), light (r=0.43; p=0.01) and moderate-to-vigorous PA (r=0.55; p<0.01), sedentary time (r=-0.52; p<0.01), steps per day (r=0.39; p=0.02), TDEE (r=0.46; p<0.01) and AEE (r=0.51; p<0.01) during energy restriction were associated with the rate of WL. Changes in total (r=-0.50; p=0.04) and moderate-to-vigorous PA (r=-0.61; p=0.01) between post-WL and follow-up were associated with 1-year weight change (r=-0.51; p=0.04).These findings highlight that PA and sedentary time could act as modifiable behavioural targets to promote better weight outcomes during dietary energy restriction and/or weight maintenance.

Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes.

AIM: To evaluate the effect of oral semaglutide on energy intake and appetite in subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, two-period cross-over trial, 15 subjects with T2D received 12 weeks of treatment with once-daily oral semaglutide (4-week dose escalation from 3 to 7 to 14 mg) followed by placebo, or vice versa. Energy intake was measured during an ad libitum lunch, evening meal and snack box after a standard breakfast. Appetite ratings were measured using a visual analogue scale after standard and fat-rich breakfasts. Other assessments included eating and craving control (using the Control of Eating Questionnaire), and changes in body weight and composition. RESULTS: Following a standard breakfast, total daily ad libitum energy intake was significantly lower (38.9%) with oral semaglutide versus placebo in 13 evaluable subjects (estimated treatment difference, -5096.0 kJ; 95% CI -7000.0, -3192.1; P = .0001). After a fat-rich breakfast, there were significant differences in favour of oral semaglutide versus placebo for measures of satiety, hunger and for overall appetite score, with no significant differences following a standard breakfast. Fewer food cravings and better eating control were seen with oral semaglutide versus placebo. Overall, mean body weight decreased by 2.7 kg with oral semaglutide and 0.1 kg with placebo, mostly attributable to body fat mass loss. CONCLUSION: After 12 weeks of treatment, ad libitum energy intake was lower with oral semaglutide versus placebo, resulting in reduced body fat mass, and was associated with increased satiety and fullness after a fat-rich breakfast, and improved eating control. TRIAL REGISTRATION NUMBER: NCT02773381.

Effects of oral lubrication on satiety, satiation and salivary biomarkers in model foods: A pilot study.

With a dramatic increase in overweight and population with obesity over the last decades, there is an imminent need to tackle this issue using novel strategies. Addressing obesity issues by generating satiety in food to reduce energy intake has been one of those prominent strategies and often textural interventions have been used to generate satiety, specifically in short-term trials. This study aimed to investigate the role of preloads varying in their oral lubricating properties on appetite sensations, food intake, salivary friction and concentration of salivary biomarkers (proteins, α-amylase and mucins) in collected human saliva (n = 17 healthy participants). The preloads were model foods (flavoured hydrogels) either high or low in their lubricating properties, assessed both by instrumental and sensorial measurements. The results showed that hunger and desire to eat decreased immediately after preload and remained decreased for 10 and 20 min, respectively, after preload in the high lubricating condition compared to control (all p < 0.05). Fullness increased immediately after preload and remained increased for 10 and 20 min, respectively, after preload in high lubricating condition compared to control (p < 0.05). However, after controlling the values for baseline, such significant effect of the intervention did not exist anymore. Only the effect of time is observed. Consuming high lubricating hydrogels showed no effect on food intake and salivary biomarkers in this pilot study. Salivary lubrication correlated with feeling of fullness. Considering the issue of large time-interval (30 min) between preload and next meal in this study, it is worthwhile investigating the immediate effects of oral lubrication on appetite control, food intake and salivary biomarkers.

Matched Weight Loss Through Intermittent or Continuous Energy Restriction Does Not Lead To Compensatory Increases in Appetite and Eating Behavior in a Randomized Controlled Trial in Women with Overweight and Obesity.

BACKGROUND: Continuous energy restriction (CER) is purported to be problematic because of reductions in fat-free mass (FFM), compensatory motivation to overeat, and weakened satiety. Intermittent energy restriction (IER) is an alternative behavioral weight loss (WL) strategy that may mitigate some of these limitations. OBJECTIVE: The objective of the DIVA study was to compare the effects of CER and IER on appetite when the degree of WL (≥5%) is matched. METHODS: Women with overweight/obesity (BMI 25.0-34.9 kg/m2; age 18-55 y) were recruited for this controlled-feeding RCT via CER (25% daily energy restriction) or IER (alternating ad libitum and 75% energy restriction days). Probe days were conducted at baseline and post-intervention to assess body composition, ad libitum energy intake and subjective appetite in response to a fixed-energy breakfast, and eating behavior traits. After baseline measurements, participants were allocated to CER (n = 22) or IER (n = 24). Per protocol analyses (≥5% WL within 12 wk) were conducted with use of repeated measures ANOVA. RESULTS: Thirty of 37 completers reached ≥5% WL [CER (n = 18): 6.3 ± 0.8% in 57 ± 16 d, IER (n = 12): 6.6 ± 1.1% in 67 ± 13 d; % WL P = 0.43 and days P = 0.10]. Fat mass [-3.9 (95% CI: -4.3, -3.4) kg] and FFM [-1.3 (95% CI: -1.6, -1.0) kg] were reduced post-WL (P < 0.001), with no group differences. Self-selected meal size decreased post-WL in CER (P = 0.03) but not in IER (P = 0.19). Hunger AUC decreased post-WL (P < 0.05), with no group differences. Satiety quotient remained unchanged and was similar in both groups. Both interventions improved dietary restraint, craving control, susceptibility to hunger, and binge eating (P < 0.001). CONCLUSIONS: Controlled ≥5% WL via CER or IER did not differentially affect changes in body composition, reductions in hunger, and improvements in eating behavior traits. This suggests that neither CER nor IER lead to compensatory adaptations in appetite in women with overweight/obesity. This trial was registered at clinicaltrials.gov as NCT03447600.

Validation of the Activity Preference Assessment: a tool for quantifying children's implicit preferences for sedentary and physical activities.

BACKGROUND: High levels of sedentary behavior and low physical activity are associated with poor health, and the cognitive determinants of these behaviors in children and adolescents are not well understood. To address this gap, we developed a novel, non-verbal, computer-based assessment to quantify the degree to which youth prefer to be sedentary relative to physically active in their leisure time. METHODS: The Activity Preference Assessment (APA) uses a forced-choice paradigm to understand implicit decision-making processes when presented with common sedentary and physical activities. The APA bias score ranges from - 100 to + 100, with positive scores indicating a relative preference for sedentary activities, and negative scores representing a preference for physical activities. In 60 children ages 8-17 years, we assessed the validity of this behavioral task against a free-choice play observation, accelerometry-measured activity, anthropometrics and body composition, and cardiorespiratory fitness. We explored neighborhood, family, and individual-level factors that may influence implicit activity preferences. Test-retest reliability was assessed over one week. RESULTS: The majority of children (67%) preferred sedentary relative to physical activities. APA bias scores were positively associated with sedentary time during free-choice play. In girls, bias scores were negatively associated with average daily MVPA. APA bias scores were positively associated with body fat and negatively associated with cardiorespiratory fitness. These findings were independent of age, sex, and race/ethnicity. Neighborhood access to physical activity spaces, the number of people in the home, perceived physical self-competence (e.g., coordination, strength), and self-reported depressive symptoms were associated with activity preferences. The intra-class correlation for test-retest reliability was r = 0.59. CONCLUSIONS: The APA shows promise as a novel tool for quantifying children's relative preference for sedentary versus physical activities. Implicit bias scores from the APA are clinically meaningful, as shown by significant associations with adiposity and cardiorespiratory fitness. Future longitudinal studies should examine the directionality of the association between preferences and health markers, and the degree to which implicit activity preferences are modifiable. Importantly, the task only takes an average of 10 min to complete, highlighting a potential role as an efficient screening tool for the propensity to be sedentary versus physically active. TRIAL REGISTRATION: ClinicalTrials.gov NCT03624582 .

Biological and psychological mediators of the relationships between fat mass, fat-free mass and energy intake.

BACKGROUND: While recent studies in humans indicate that fat-free mass (FFM) is closely associated with energy intake (EI) when in energy balance, associations between fat mass (FM) and EI are inconsistent. OBJECTIVES: The present study used a cross-sectional design to examine the indirect and direct effects of FFM, FM and resting metabolic rate (RMR) on EI in individuals at or close to energy balance. METHODS: Data for 242 individuals (114 males; 128 females; BMI = 25.7 ± 4.9 kg/m2) were collated from the non-intervention baseline conditions of five studies employing common measures of body composition (air-displacement plethysmography), RMR (indirect calorimetry) and psychometric measures of eating behaviours (Dutch Eating Behaviour Questionnaire). Daily EI (weighed dietary records) and energy expenditure (flex heart rate) were measured for 6-7 days. Sub-analyses were conducted in 71 individuals who had additional measures of body composition (dual-energy X-ray absorptiometry) and fasting glucose, insulin and leptin. RESULTS: After adjusting for age, sex and study, linear regression and mediation analyses indicated that the effect of FFM on EI was mediated by RMR (P < 0.05). FM also independently predicted EI, with path analysis indicating a positive indirect association (mediated by RMR; P < 0.05), and a stronger direct negative association (P < 0.05). Leptin, insulin and insulin resistance failed to predict EI, but cognitive restraint was a determinant of EI and partially mediated the association between FM and EI (P < 0.05). CONCLUSIONS: While the association between FFM and EI was mediated by RMR, FM influenced EI via two separate and opposing pathways; an indirect 'excitatory' effect (again, mediated by RMR), and a stronger direct 'inhibitory' effect. Psychological factors such as cognitive restraint remain robust predictors of EI when considered alongside physiological determinants of EI, and indeed, have the potential to play a mediating role in the overall expression of EI.

Activity energy expenditure is an independent predictor of energy intake in humans.

BACKGROUND: There is evidence that the energetic demand of metabolically active tissue is associated with day-to-day food intake (EI). However, the extent to which behavioural components of total daily energy expenditure (EE) such as activity energy expenditure (AEE) are also associated with EI is unknown. Therefore, the present study examined the cross-sectional associations between body composition, resting metabolic rate (RMR), AEE and EI. METHODS: Data for 242 individuals (114 males; 128 females; BMI = 25.7 ± 4.9 kg/m2) were collated from the baseline control conditions of five studies employing common measures of body composition (air displacement plethysmography) and RMR (indirect calorimetry). Daily EI (weighed-dietary records) and EE (FLEX heart rate) were measured over 6-7 days, and AEE was calculated as total daily EE minus RMR. RESULTS: Linear regression indicated that RMR (ß = 0.39; P < 0.001), fat mass (ß = -0.26; P < 0.001) and AEE (ß = 0.18; P = 0.002) were independent predictors of mean daily EI, with AEE adding ≈3% of variance to the model after controlling for age, sex and study (F(10, 231) = 18.532, P < 0.001; R2 = 0.445). Path analyses indicated that the effect of FFM on mean daily EI was mediated by RMR (P < 0.05), while direct (ß = 0.19; P < 0.001) and indirect (ß = 0.20; P = 0.001) associations between AEE and mean daily EI were observed. CONCLUSIONS: When physical activity was allowed to vary under free-living conditions, AEE was associated with mean daily EI independently of other biological determinants of EI arising from body composition and RMR. These data suggest that EE per se exerts influence over daily food intake, with both metabolic (RMR) and behavioral (AEE) components of total daily EE potentially influencing EI via their contribution to daily energy requirements.

Women with a low-satiety phenotype show impaired appetite control and greater resistance to weight loss.

This trial compared weight loss outcomes over 14 weeks in women showing low- or high-satiety responsiveness (low- or high-satiety phenotype (LSP, HSP)) measured by a standardised protocol. Food preferences and energy intake (EI) after low and high energy-density (LED, HED) meals were also assessed. Ninety-six women (n 52 analysed; 41·24 (SD 12·54) years; 34·02 (sd 3·58) kg/m2) engaged in one of two weight loss programmes underwent LED and HED laboratory test days during weeks 3 and 12. Preferences for LED and HED food (Leeds Food Preference Questionnaire) and ad libitum evening meal and snack EI were assessed in response to equienergetic LED and HED breakfasts and lunches. Weekly questionnaires assessed control over eating and ease of adherence to the programme. Satiety quotients based on subjective fullness ratings post LED and HED breakfasts determined LSP (n 26) and HSP (n 26) by tertile splits. Results showed that the LSP lost less weight and had smaller reductions in waist circumference compared with HSP. The LSP showed greater preferences for HED foods, and under HED conditions, consumed more snacks (kJ) compared with HSP. Snack EI did not differ under LED conditions. LSP reported less control over eating and reported more difficulty with programme adherence. In conclusion, low-satiety responsiveness is detrimental for weight loss. LED meals can improve self-regulation of EI in the LSP, which may be beneficial for longer-term weight control.

The case of GWAS of obesity: does body weight control play by the rules?

As yet, genome-wide association studies (GWAS) have not added much to our understanding of the mechanisms of body weight control and of the etiology of obesity. This shortcoming is widely attributed to the complexity of the issues. The appeal of this explanation notwithstanding, we surmise that (i) an oversimplification of the phenotype (namely by the use of crude anthropometric traits) and (ii) a lack of sound concepts of body weight control and, thus, a lack of a clear research focus have impeded better insights most. The idea of searching for polygenetic mechanisms underlying common forms of obesity was born out of the impressive findings made for monogenetic forms of extreme obesity. In the case of common obesity, however, observational studies on normal weight and overweight subjects never provided any strong evidence for a tight internal control of body weight. In addition, empirical studies of weight changes in normal weight and overweight subjects revealed an intra-individual variance that was similar to inter-individual variance suggesting the absence of tight control of body weight. Not least, this lack of coerciveness is reflected by the present obesity epidemic. Finally, data on detailed body composition highlight that body weight is too heterogeneous a phenotype to be controlled as a single entity. In summary GWAS of obesity using crude anthropometric traits have likely been misled by popular heritability estimates that may have been inflated in the first place. To facilitate more robust and useful insights into the mechanisms of internal control of human body weight and, consequently, the genetic basis of obesity, we argue in favor of a broad discussion between scientists from the areas of integrative physiologic and of genomics. This discussion should aim at better conceived studies employing biologically more meaningful phenotypes based on in depth body composition analysis. To advance the scientific community-including the editors of our top journals-needs a re-launch of future GWAS of obesity.

A Low Energy-Dense Diet in the Context of a Weight-Management Program Affects Appetite Control in Overweight and Obese Women.

Background: Low energy-dense (LED) foods reduce energy intake (EI); whether this effect is sustained over time and during weight loss is unknown. Objective: This trial examined the effects of LED compared with high energy-dense (HED) meals on appetite, EI, and control over eating in the laboratory and during a weight-management program that encourages unrestricted intake of LED foods [Slimming World, UK (SW)] compared with a self-led Standard Care program [NHS weight-loss plan (SC)]. Methods: Overweight and obese women [n = 96; mean ± SD age: 41.03 ± 12.61 y; mean ± SD body mass index (in kg/m2): 34.00 ± 3.61] were recruited from the SW or SC programs. Primary outcomes included appetite, food preferences (liking and wanting for LED and HED foods), cravings, and evening meal EI (LED, HED) in response to calorie-matched LED (≤0.8 kcal/g) and HED (≥2.5 kcal/g) breakfast and lunch meals. Probe-day tests were conducted at weeks 3 and 4 and repeated at weeks 12 and 13 in a within-day crossover design. Secondary outcomes, including body weight and program experience, were measured from weeks 1 to 14 in a parallel-group design. Dietary compliance was monitored with the use of weighed food diaries at weeks 3 and 12. Results: Intention-to-treat (ITT) and completers analyses showed that the SW group lost more weight than the SC group [ITT: -5.9% (95% CI: -4.7%, -7.2%) compared with -3.5% (-2.3%, -4.8%), P < 0.05; completers: -6.2% (-4.8%, -7.6%) compared with 3.9% (-2.5%, -5.2%), P < 0.05]. The SW group reported greater control over eating and more motivation to continue the program compared with the SC group. LED meals increased sensations of fullness and reduced hunger on probe days (P < 0.001). Total-day EI was 1057 ± 73 kcal less (95% CI: 912, 1203 kcal; 36%) under LED compared with HED conditions (P < .001). Liking for LED and HED foods and wanting for HED foods were lower before lunch under LED compared with HED conditions, and liking decreased to a greater extent after the LED lunch. The SW group reported fewer cravings under LED compared with HED conditions (P < 0.05). On probe days, appetite and EI outcomes did not differ between weeks 3 and 12 or between the SW and SC groups. Conclusion: LED meals improve appetite control in women attempting weight loss and the effect is sustainable. Consumption of LED meals likely contributed to weight loss in the SW program. This study was registered at clinicaltrials.gov as NCT02012426.

Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity.

AIM: To investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled, 2-period, crossover trial. Subjects with obesity (N = 30) received once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, or placebo. After each 12-week treatment period, glucose and lipid metabolism were assessed before and after standardized meals. Gastric emptying (paracetamol absorption test) and peptide YY (PYY) response were also assessed. RESULTS: Semaglutide treatment significantly lowered fasting concentrations of glucose and glucagon, and increased insulin vs placebo (estimated treatment ratio: 0.95 [95% confidence interval: 0.91, 0.98]; 0.86 [0.75, 0.98]; 1.45 [1.20, 1.75], respectively). Postprandial glucose metabolism significantly improved with semaglutide vs placebo (incremental area under the curve 0 to 5 hours [iAUC0-5h ]; estimated treatment difference: glucose -1.34 mmol h/L [-2.42, -0.27]; insulin -921 pmol h/L [-1461, -381]; C-peptide -1.42 nmol h/L [-2.33, -0.51]). Fasting and postprandial lipid metabolism improved with semaglutide vs placebo. First-hour gastric emptying after the meal was delayed with semaglutide vs placebo (AUC0-1h ; estimated treatment ratio: 0.73 [0.61, 0.87]); this may have contributed to the lower postprandial glucose increase in semaglutide-treated subjects. Overall gastric emptying (AUC0-5h ) was not statistically different between treatments. Fasting and postprandial PYY responses were significantly lower with semaglutide vs placebo (P = .0397 and P = .0097, respectively). CONCLUSION: Semaglutide improved fasting and postprandial glucose and lipid metabolism. Overall gastric emptying was similar to that with placebo; however, the observed first-hour delay with semaglutide may contribute to a slower entry of glucose into the circulation.

Energy depletion by 24-h fast leads to compensatory appetite responses compared with matched energy depletion by exercise in healthy young males.

Although there is a growing interest for the effects of intermittent fasting on energy balance, this study aimed to compare appetite, energy intake and food reward responses with an energy depletion induced either by 24-h food restriction or an equivalent deficit with exercise in healthy males. In all, twelve healthy lean males (21·5 (sd 0·5) years old; BMI: 22·5 (sd 1·7) kg/m2) participated in this study. Body composition, aerobic capacity, food preferences and energy intake were assessed. They randomly completed three conditions: (i) no depletion (CON); (ii) full 24-h energy restrictions (Def-EI); and (iii) exercise condition (Def-EX). Ad libitum energy intake and food reward were assessed at the end of each session. Appetite feelings were assessed regularly. Ad libitum energy intake was higher on Def-EI (7330 (sd 2975) kJ (1752 (sd 711) kcal) compared with that on CON (5301 (sd 1205) kJ (1267 (sd 288) kcal)) (P<0·05), with no difference between CON and Def-EX (6238 (sd 1741) kJ (1491 (sd 416) kcal) (P=0·38) and between Def-EX and Def-EI (P=0·22). There was no difference in the percent energy ingested from macronutrients. Hunger was lower on CON and Def-EX compared with Def-EI (P<0·001). Satiety was higher on CON and Def-EI compared with that on Def-EX (P<0·001). There was a significant interaction condition × time for food choice fat bias (P=0·04), showing a greater preference for high-fat v. low-fat food during Def-EI and Def-EX. Although 24-h fasting leads to increased energy intake at the following test meal (without total daily energy intake difference), increased hunger profile and decreased post-meal food choice fat bias, such nutritional responses are not observed after a similar deficit induced by exercise.

Development and validation of the Child Three-Factor Eating Questionnaire (CTFEQr17).

OBJECTIVE: To develop and validate a child and adolescent version of the Three-Factor Eating Questionnaire (CTFEQr17) and to assess its psychometric properties and factor structure. We also examined associations between the CTFEQr17 and BMI and food preferences. DESIGN: A two-phase approach was utilized, employing both qualitative and quantitative methodologies. SETTING: Primary and secondary schools, UK. SUBJECTS: In phase 1, seventy-six children (thirty-nine boys; mean age 12·3 (sd 1·4) years) were interviewed to ascertain their understanding of the original TFEQr21 and to develop accessible and understandable items to create the CTFEQr17. In phase 2, 433 children (230 boys; mean age 12·0 (sd 1·7) years) completed the CTFEQr17 and a food preference questionnaire, a sub-sample (n 253; 131 boys) had their height and weight measured, and forty-five children (twenty-three boys) were interviewed to determine their understanding of the CTFEQr17. RESULTS: The CTFEQr17 showed good internal consistency (Cronbach's α=0·85) and the three-factor structure was retained: cognitive restraint (CR), uncontrolled eating (UE) and emotional eating (EE). Qualitative data demonstrated a high level of understanding of the questionnaire (95 %). High CR was found to be significantly associated with a higher body weight, BMI and BMI percentile. High UE and EE scores were related to a preference for high-fat savoury and high-fat sweet foods. The relationships between CTFEQr17, anthropometry and food preferences were stronger for girls than boys. CONCLUSIONS: The CTFEQr17 is a psychometrically sound questionnaire for use in children and adolescents, and associated with anthropometric and food preference measures.

Weight loss decreases self-reported appetite and alters food preferences in overweight and obese adults: Observational data from the DiOGenes study.

People with obesity often struggle to maintain their weight loss after a weight loss period. Furthermore, the effect of weight loss on appetite and food preferences remains unclear. Hence this study investigated the effect of weight loss on subjective appetite and food preferences in healthy, overweight and obese volunteers. A subgroup of adult participants (n = 123) from the Diet Obesity and Genes (DiOGenes) study (subgroup A) was recruited from across six European countries. Participants lost ≥8% of initial body weight during an 8-week low calorie diet (LCD). Subjective appetite and food preferences were measured before and after the LCD, in response to a standardized meal test, using visual analogue rating scales (VAS) and the Leeds Food Choice Questionnaire (FCQ). After the LCD, participants reported increased fullness (p < 0.05), decreased desire to eat (p < 0.05) and decreased prospective consumption (p < 0.05) after consuming the test meal. An interaction effect (visit x time) was found for hunger ratings (p < 0.05). Area under the curve (AUC) for hunger, desire to eat and prospective consumption was decreased by 18.1%, 20.2% and 21.1% respectively whereas AUC for fullness increased by 13.9%. Preference for low-energy products measured by the Food Preference Checklist (FPC) decreased by 1.9% before the test meal and by 13.5% after the test meal (p < 0.05). High-carbohydrate and high-fat preference decreased by 11.4% and 16.2% before the test meal and by 17.4% and 22.7% after the meal (p < 0.05). No other effects were observed. These results suggest that LCD induced weight loss decreases the appetite perceptions of overweight volunteers whilst decreasing their preference for high-fat-, high-carbohydrate-, and low-energy products.

Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity.

AIM: The aim of this trial was to investigate the mechanism of action for body weight loss with semaglutide. MATERIALS AND METHODS: This randomised, double-blind, placebo-controlled, two-period crossover trial investigated the effects of 12 weeks of treatment with once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, in 30 subjects with obesity. Ad libitum energy intake, ratings of appetite, thirst, nausea and well-being, control of eating, food preference, resting metabolic rate, body weight and body composition were assessed. RESULTS: After a standardised breakfast, semaglutide, compared with placebo, led to a lower ad libitum energy intake during lunch (-1255 kJ; P < .0001) and during the subsequent evening meal ( P = .0401) and snacks ( P = .0034), resulting in a 24% reduction in total energy intake across all ad libitum meals throughout the day (-3036 kJ; P < .0001). Fasting overall appetite suppression scores were improved with semaglutide vs placebo, while nausea ratings were similar. Semaglutide was associated with less hunger and food cravings, better control of eating and a lower preference for high-fat foods. Resting metabolic rate, adjusted for lean body mass, did not differ between treatments. Semaglutide led to a reduction from baseline in mean body weight of 5.0 kg, predominantly from body fat mass. CONCLUSION: After 12 weeks of treatment, ad libitum energy intake was substantially lower with semaglutide vs placebo with a corresponding loss of body weight observed with semaglutide. In addition to reduced energy intake, likely mechanisms for semaglutide-induced weight loss included less appetite and food cravings, better control of eating and lower relative preference for fatty, energy-dense foods.

Impact of physical activity level and dietary fat content on passive overconsumption of energy in non-obese adults.

BACKGROUND: Passive overconsumption is the increase in energy intake driven by the high-fat energy-dense food environment. This can be explained in part because dietary fat has a weaker effect on satiation (i.e. process that terminates feeding). Habitually active individuals show improved satiety (i.e. process involved in post-meal suppression of hunger) but any improvement in satiation is unknown. Here we examined whether habitual physical activity mitigates passive overconsumption through enhanced satiation in response to a high-fat meal. METHODS: Twenty-one non-obese individuals with high levels of physical activity (HiPA) and 19 individuals with low levels of physical activity (LoPA) matched for body mass index (mean = 22.8 kg/m2) were recruited. Passive overconsumption was assessed by comparing ad libitum energy intake from covertly manipulated high-fat (HFAT; 50% fat) or high-carbohydrate (HCHO; 70% carbohydrate) meals in a randomized crossover design. Habitual physical activity was assessed using SenseWear accelerometers (SWA). Body composition, resting metabolic rate, eating behaviour traits, fasting appetite-related peptides and hedonic food reward were also measured. RESULTS: In the whole sample, passive overconsumption was observed with greater energy intake at HFAT compared to HCHO (p < 0.01), without any differences between activity groups (p > 0.05). SWA confirmed that HiPA were more active than LoPA (p < 0.01). HiPA had lower body fat and greater fat-free mass than LoPA (p < 0.05 for both) but did not differ in resting metabolic rate, eating behaviour traits, appetite-related peptides or food reward (p > 0.05 for all). CONCLUSIONS: Non-obese individuals with high or low physical activity levels but matched for BMI showed similar susceptibility to passive overconsumption when consuming an ad libitum high-fat compared to a high-carbohydrate meal. This occurred despite increased total daily energy expenditure and improved body composition in HiPA. Greater differences in body composition and/or physical activity levels may be required to impact on satiation.