ObjectiveThe colonic microbiota ferment dietary fibres, producing short chain fatty acids. Recent evidence suggests that the short chain fatty acid propionate may play an important role in appetite regulation. We hypothesised that colonic delivery of propionate would increase peptide YY (PYY) and glucagon like peptide-1 (GLP-1) secretion in humans, and reduce energy intake and weight gain in overweight adults.DesignTo investigate whether propionate promotes PYY and GLP-1 secretion, a primary cultured human colonic cell model was developed. To deliver propionate specifically to the colon, we developed a novel inulin-propionate ester. An acute randomised, controlled cross-over study was used to assess the effects of this inulin-propionate ester on energy intake and plasma PYY and GLP-1 concentrations. The long-term effects of inulin-propionate ester on weight gain were subsequently assessed in a randomised, controlled 24-week study involving 60 overweight adults.ResultsPropionate significantly stimulated the release of PYY and GLP-1 from human colonic cells. Acute ingestion of 10 g inulin-propionate ester significantly increased postprandial plasma PYY and GLP-1 and reduced energy intake. Over 24 weeks, 10 g/day inulin-propionate ester supplementation significantly reduced weight gain, intra-abdominal adipose tissue distribution, intrahepatocellular lipid content and prevented the deterioration in insulin sensitivity observed in the inulin-control group.ConclusionsThese data demonstrate for the first time that increasing colonic propionate prevents weight gain in overweight adult humans.Trial registration numberNCT00750438.

AimThe aim of this trial was to investigate the mechanism of action for body weight loss with semaglutide.Materials and methodsThis 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.ResultsAfter 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.ConclusionAfter 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.

Experiments in animals suggest that the neuropeptide oxytocin acts as an anorexigenic signal in the central nervous control of food intake. In humans, however, research has almost exclusively focused on the involvement of oxytocin in the regulation of social behavior. We investigated the effect of intranasal oxytocin on ingestion and metabolic function in healthy men. Food intake in the fasted state was examined 45 min after neuropeptide administration, followed by the assessment of olfaction and reward-driven snack intake in the absence of hunger. Energy expenditure was registered by indirect calorimetry, and blood was repeatedly sampled to determine concentrations of blood glucose and hormones. Oxytocin markedly reduced snack consumption, restraining, in particular, the intake of chocolate cookies by 25%. Oxytocin, moreover, attenuated basal and postprandial levels of adrenocorticotropic hormone and cortisol and curbed the meal-related rise in plasma glucose. Energy expenditure and hunger-driven food intake as well as olfactory function were not affected. Our results indicate that oxytocin, beyond its role in social bonding, regulates nonhomeostatic, reward-related energy intake, hypothalamic-pituitary-adrenal axis activity, and the glucoregulatory response to food intake in humans. These effects can be assumed to converge with the psychosocial function of oxytocin and imply possible applications in the treatment of metabolic disorders.

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2Exercise is widely regarded as one of the most valuable components of behaviour that can influence body weight and therefore help in the prevention and management of obesity. Indeed long term controlled trials show a clear dose related effect of exercise on body weight. However, there is a suspicion, particularly fuelled by media reports, that exercise serves to increase hunger and drive up food intake thereby nullifying the energy expended through activity. Not everyone performing regular exercise will lose weight, and several investigations have demonstrated a huge individual variability in the response to exercise regimes. What accounts for this heterogeneous response? First, exercise (or physical activity) through the expenditure of energy will influence the energy balance equation with the potential to generate an energy deficit. However, energy expenditure also influences the control of appetite (i.e. the physiological and psychological regulatory processes underpinning feeding) and energy intake. This dynamic interaction means that the prediction of a resultant shift in energy balance, and therefore weight change, will be complicated. In changing EI, exercise will impact on the biological mechanisms controlling appetite. It is becoming recognized that the major influences on the expression of appetite arise from fat-free mass and fat mass, Resting Metabolic Rate, gastric adjustment to ingested food, changes in episodic peptides including insulin, ghrelin, CCK, GLP-1 and PYY, as well as tonic peptides such as leptin. Moreover there is evidence that exercise will influence all of these components which, in turn, influence the drive to eat through the modulation of hunger (a conscious sensation reflecting a mental urge to eat) and adjustments in post-prandial satiety via an interaction with food composition. The specific actions of exercise on each physiological component will vary in strength from person to person (according to individual physiological characteristics) and with the intensity and duration of exercise. Therefore, individual responses to exercise will be highly variable and difficult to predict. Background Issues

Eating is an action open to awareness by the individual; however, it cannot be claimed that processes that control the expression of eating habits are necessarily explicit. This distinction between implicit and explicit processes may enhance understanding of the expression of food reward (particularly the concepts of liking and wanting [Berridge, K. C., & Robinson, T. E. (2003). Parsing reward. Trends in Neurosciences, 26, 507-513] and its importance for human appetite control [Finlayson, G. S., King, N. A., & Blundell, J. E. (2007b). Liking vs. wanting food: Importance for human appetite control and weight regulation. Neuroscience and Biobehavioural Reviews, in press]. The present study investigated the effect of meal-induced satiation on implicit and explicit processes of liking (L) and wanting (W) by developing a computer-based procedure to measure L and W in hungry and satiated states. Explicit measures were derived from analogue ratings whilst an implicit W measure was derived from reaction time in a forced-choice procedure, which also identified food preferences. Seventy subjects (21.8+/-0.9 years, BMI: 22.2+/-0.5 kg/m2) completed the procedure before and immediately following consumption of a savoury test meal. Satiation caused explicit ratings of L and W to decrease in all food categories (p<0.01); but with a more marked decrease for savoury foods compared with sweet foods (p<0.01). Implicit W was increased for sweet categories (p<0.01), but not for savoury. Implicit and explicit measures of L and W independently correlated with preference for sweet foods. This study provides support that implicit and explicit processes of food reward can be simultaneously measured and dissociated using a test meal. Adjustments in hunger were linked to changes in explicit L and W in a manner consistent with sensory specific satiety, while a relationship between hunger and implicit W was absent. We suggest that implicit W is not systematically downregulated by the physiological consequences of food consumption in the same way as hunger and therefore may be largely independent of homoeostatic processes influencing intake.

Current train of thought in appetite research is favouring an interest in non-homeostatic or hedonic (reward) mechanisms in relation to overconsumption and energy balance. This tendency is supported by advances in neurobiology that precede the emergence of a new conceptual approach to reward where affect and motivation (liking and wanting) can be seen as the major force in guiding human eating behaviour. In this review, current progress in applying processes of liking and wanting to the study of human appetite are examined by discussing the following issues: How can these concepts be operationalised for use in human research to reflect the neural mechanisms by which they may be influenced? Do liking and wanting operate independently to produce functionally significant changes in behaviour? Can liking and wanting be truly experimentally separated or will an expression of one inevitably contain elements of the other? The review contains a re-examination of selected human appetite research before exploring more recent methodological approaches to the study of liking and wanting in appetite control. In addition, some theoretical developments are described in four diverse models that may enhance current understanding of the role of these processes in guiding ingestive behaviour. Finally, the implications of a dual process modulation of food reward for weight gain and obesity are discussed. The review concludes that processes of liking and wanting are likely to have independent roles in characterising susceptibility to weight gain. Further research into the dissociation of liking and wanting through implicit and explicit levels of processing would help to disclose the relative importance of these components of reward for appetite control and weight regulation.

The idea of body weight regulation implies that a biological mechanism exerts control over energy expenditure and food intake. This is a central tenet of energy homeostasis. However, the source and identity of the controlling mechanism have not been identified, although it is often presumed to be some long-acting signal related to body fat, such as leptin. Using a comprehensive experimental platform, we have investigated the relationship between biological and behavioural variables in two separate studies over a 12-week intervention period in obese adults (total n 92). All variables have been measured objectively and with a similar degree of scientific control and precision, including anthropometric factors, body composition, RMR and accumulative energy consumed at individual meals across the whole day. Results showed that meal size and daily energy intake (EI) were significantly correlated with fat-free mass (FFM, P values ,0·02-0·05) but not with fat mass (FM) or BMI (P values 0·11-0·45) (study 1, n 58). In study 2 (n 34), FFM (but not FM or BMI) predicted meal size and daily EI under two distinct dietary conditions (high-fat and low-fat). These data appear to indicate that, under these circumstances, some signal associated with lean mass (but not FM) exerts a determining effect over self-selected food consumption. This signal may be postulated to interact with a separate class of signals generated by FM. This finding may have implications for investigations of the molecular control of food intake and body weight and for the management of obesity.