John E. Blundell

Fat as a risk factor for overconsumption: satiation, satiety, and patterns of eating.

Many people experience great difficulty in preventing energy intake from outstripping energy expenditure. Eating high-fat foods can facilitate the development of short-term positive energy balances by influencing satiation and satiety, the processes that control the size of eating episodes and the strength of postingestive appetite inhibition, respectively. An important feature of these processes is the relative potency of orosensory, postingestive (preabsorptive), and postabsorptive signals. Foods high in dietary fat have a weak effect on satiation, which leads to a form of passive overconsumption, and a disproportionately weak effect on satiety (joule-for-joule compared with protein and carbohydrate). This overconsumption (high-fat hyperphagia) is dependent upon both the high energy density and the potent sensory qualities (high palatability) of high-fat foods. A positive fat balance does not appear to generate a tendency for behavioral compensation, and there appears to be almost no autoregulatory link between fat oxidation and fat intake. The Leeds High Fat Study has found a higher frequency of obesity among high-fat than low-fat consumers, but the relationship between fat consumption and obesity is not a biologic imperative: analysis of the pathways between daily fat intakes and patterns of eating has revealed high-risk eating episodes. The physiologic responses to fat ingestion appear to be weak compared with the potent orosensory properties of high-fat foods, and such responses cannot prevent overconsumption. A first stage in a health program should be to prevent passive overconsumption.

Resistance and susceptibility to weight gain: Individual variability in response to a high-fat diet

An obesigenic environment is a potent force for promoting weight gain. However, not all people exposed to such an environment become obese; some remain lean. This means that some people are susceptible to weight gain (in a weight-promoting environment) and others are resistant. Identifying the characteristics of appetite control and food motivation in these two groups could throw light on the causes of weight gain and how this can be either treated or prevented. We have investigated the issue experimentally by identifying people who habitually consume a high-fat diet (greater than 43% fat energy). These individuals have been termed high-fat phenotypes. We have compared individuals, of the same age (mean=37 years old) and gender (male), who have gained weight (BMI=34) or who have remained lean (BMI=22). The susceptible individuals are characterised by a cluster of characteristics including a weak satiety response to fatty meals, a maintained preference for high-fat over low-energy foods in the post-ingestive satiety period, a strong hedonic attraction to palatable foods and to eating, and high scores on the TFEQ factors of Disinhibition and Hunger. The analysis of large databases suggests that this profile of factors contributes to an average daily positive energy balance from food of approximately 0.5 MJ. This profile of characteristics helps to define the symptomatology of a thrifty phenotype.

Is susceptibility to weight gain characterized by homeostatic or hedonic risk factors for overconsumption

In any particular group of people-living in the same culture-some gain weight whilst others do not. Overconsumption of food is one factor contributing to this susceptibility to weight gain. Because all individuals are exposed to a similar range of environmental appetite-stimulating factors, the variability in overconsumption must be due to variability in intrinsic psychobiological processes. Such variability is an inevitable feature of living organisms. This essay explores whether susceptibility to weight gain is caused by variation in homeostatic processes-such as weak satiety responses to fat, or by hedonic processes-such as hyperresponsivity to the sensory properties of food. The question also arises whether the homeostatic or hedonic processes function separately and independently, or whether they interact. The answer to these questions can throw light upon the organization of behaviours associated with weight control, and can help to develop strategies to prevent weight gain. The theme of this essay was inspired by Gerry Smiths conceptual and experimental work on both homeostatic and hedonic mechanisms implicated in the control of food intake.

Effects of anorexie drugs on food intake, food selection and preferences and hunger motivation and subjective experiences

Two anorexic drugs with contrasting neurochemical profiles—amphetamine and fenfluramine—have been incorporated into the experimental technique of double dissociation to explore relationships between certain features of feeding behaviour and subjective experiences surrounding eating. In general, the drugs brought about opposing effects on behaviour and subjective states. A test meal revealed that amphetamine gave rise to a marked suppression of protein consumption whereas fenfluramine exerted a greater suppression on carbohydrate intake. Similar directional effects were observed on a food preference questionnaire, and it is noted that subjective preferences were a more sensitive indicator of the presence of an active drug than actual behaviour. The drug treatments exerted quite different effects on ratings of hunger, various subjective feelings and bodily sensations. Amphetamine brought about prominent effects on the appetitive phase of eating, whereas fenfluramine appeared to enhance or prolong the post-prandial state. The strength of the correlation between hunger and eating varied markedly between the conditions. Taken together these findings are in good agreement with the results of research on animals and they suggest that certain drugs may be useful as tools to explore processes influencing feeding activities.

Serotonin and appetite

The proposition that serotonin may be involved in the control of intake of food and the expression of appetite is less than 10 years old. Indeed, in a 600 page anthology of serotonin and behaviour published in 1973 (Barchas and Usdin, 1973) neither feeding behaviour nor food intake were included in the subject index. This late development of the link between serotonin and feeding is surprising. First, serotonin systems occupy a strategic anatomical location, projecting to and coursing through hypothalamic zones (Azmitia, 1978), where they could be expected to contribute to the dramatic changes in food consumption and body weight following experimentally-induced hypothalamic damage. Second, serotonergic neurones are widely distributed in the gut (Gershon and Dreyfus, 1977; Ahlman, 1976; Fozard, 1984) where modifications of gastrointestinal functioning would give rise to repercussions in feeding activity. Although the earliest conceptualisations of neurochemical models of feeding control emphasised noradrenaline (Grossman, 1962; Booth, 1967) or dopamine (Ungerstedt, 1971; Marshall, Richardson and Teitelbaum, 1974) more recently two reviews have been specifically devoted to the role of serotonin (Blundell, 1977, 1979), whilst other reviews have given considerable attention to the issue (Hoebel, 1977; Coscina, 1977; Leibowitz, 1980) or have dealt with specialised aspects (e.g. Garattini, 1978). There is now no doubt that certain experimental manipulations of serotonergic metabolism produce marked effects on food consumption and less potent effects on other aspects of feeding behaviour. Do these results mean that some serotonin-containing neurones play a role in the natural regulatory system which serves to match an organism’s nutritional intake to its bodily requirements? The present review will draw together recent research findings and suggest an appropriate interpretation of the data. It should be mentioned immediately that research on serotonin and feeding is progressing only gradually and has not yet been embraced by work on the characterisation of receptor subtypes. There appear to be two reasons for this. First, researchers have been preoccupied with establishing the validity and reliability of the basic relationship between serotonin adjustments and food intake. Second, there has been a concern to verify that any relationship involves a rational link between nutritional factors and neurochemical systems and is not dependent upon the mediation of a third factor such as changes in temperature, arousal or sedation. It is appropriate that a settlement of these methodological issues should precede the investigation of any association between feeding and a particular sub-type.

Appetite control: methodological aspects of the evaluation of foods

This report describes a set of scientific procedures used to assess the impact of foods and food ingredients on the expression of appetite (psychological and behavioural). An overarching priority has been to enable potential evaluators of health claims about foods to identify justified claims and to exclude claims that are not supported by scientific evidence for the effect cited. This priority follows precisely from the principles set down in the PASSCLAIM report. The report allows the evaluation of the strength of health claims, about the effects of foods on appetite, which can be sustained on the basis of the commonly used scientific designs and experimental procedures. The report includes different designs for assessing effects on satiation as opposed to satiety, detailed coverage of the extent to which a change in hunger can stand alone as a measure of appetite control and an extensive discussion of the statistical procedures appropriate for handling data in this field of research. Because research in this area is continually evolving, new improved methodologies may emerge over time and will need to be incorporated into the framework. One main objective of the report has been to produce guidance on good practice in carrying out appetite research, and not to set down a series of commandments that must be followed.

The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings

This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more artificial) conditions of the laboratory where the signal:noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a significantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably.

Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in obese men

BACKGROUND: Peripheral administration of glucagon-like peptide-1 (GLP-1) for four hours, to normal weight and obese humans, decreases food intake and suppresses appetite.OBJECTIVE: The aim of this study was to assess the effect of an eight hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese subjects.DESIGN: Randomised, blinded cross-over design with intravenous infusion of GLP-1 (0.75 pmol·kg−1·min−1) or saline.SUBJECTS: Eight obese (body mass index, BMI, 45.5±2.3 kg/m2) male subjects.MEASUREMENTS: Ad libitum energy intake at lunch (12.00 h) and dinner (16.00 h) after an energy fixed breakfast (2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS) immediately before and after meals and hourly in-between. Blood samples for the analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying after breakfast and lunch using a paracetamol absorption technique.RESULTS: Hunger ratings were significantly lower with GLP-1 infusion. The summed ad libitum energy intake at lunch and dinner was reduced by 1.7±0.5 MJ (21±6%) by GLP-1 infusion (P=0.01). Gastric emptying was delayed by GLP-1 infusion, and plasma glucose concentrations decreased (baseline: 6.6±0.35 mmol/L; nadir: 5.3±0.15 mmol/L). No nausea was recorded during GLP-1 infusion.CONCLUSIONS: Our results demonstrate that GLP-1 decreases feelings of hunger and reduces energy intake in obese humans. One possible mechanism for this finding might be an increased satiety primarily mediated by gastric vagal afferent signals.

Assessing dietary intake: Who, what and why of under-reporting.

Under-reporting of food intake is one of the fundamental obstacles preventing the collection of accurate habitual dietary intake data. The prevalence of under-reporting in large nutritional surveys ranges from 18 to 54% of the whole sample, but can be as high as 70% in particular subgroups. This wide variation between studies is partly due to different criteria used to identify under-reporters and also to non-uniformity of under-reporting across populations. The most consistent differences found are between men and women and between groups differing in body mass index. Women are more likely to under-report than men, and under-reporting is more common among overweight and obese individuals. Other associated characteristics, for which there is less consistent evidence, include age, smoking habits, level of education, social class, physical activity and dietary restraint. Determining whether under-reporting is specific to macronutrients or food is problematic, as most methods identify only low energy intakes. Studies that have attempted to measure under-reporting specific to macronutrients express nutrients as percentage of energy and have tended to find carbohydrate under-reported and protein over-reported. However, care must be taken when interpreting these results, especially when data are expressed as percentages. A logical conclusion is that food items with a negative health image (e.g. cakes, sweets, confectionery) are more likely to be under-reported, whereas those with a positive health image are more likely to be over-reported (e.g. fruits and vegetables). This also suggests that dietary fat is likely to be under-reported. However, it is necessary to distinguish between under-reporting and genuine under-eating for the duration of data collection. The key to understanding this problem, but one that has been widely neglected, concerns the processes that cause people to under-report their food intakes. The little work that has been done has simply confirmed the complexity of this issue. The importance of obtaining accurate estimates of habitual dietary intakes so as to assess health correlates of food consumption can be contrasted with the poor quality of data collected. This phenomenon should be considered a priority research area. Moreover, misreporting is not simply a nutritionists problem, but requires a multidisciplinary approach (including psychology, sociology and physiology) to advance the understanding of under-reporting in dietary intake studies.

Serotonergic drugs : effects on appetite expression and use for the treatment of obesity.

Over 35 years of research suggests that endogenous hypothalamic serotonin (5-hydroxytryptamine) plays an important part in within-meal satiation and post-meal satiety processes. Thus, the serotonin system has provided a viable target for weight control, critical to the action of at least two effective anti-obesity treatments, both producing clinically significant weight loss over a year or more. Numerous serotonin receptor subtypes have been identified; of these, serotonin 5-HT1B and 5-HT2C receptors have been specifically recognised as mediators of serotonin-induced satiety.A number of serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs), dexfenfluramine and 5-HT2C receptor agonists, have been shown to significantly attenuate rodent bodyweight gain. This effect is strongly associated with marked hypophagia and is probably mediated by the hypothalamic melanocortin system. Additionally, sibutramine, dexfenfluramine, fluoxetine and the 5-HT2C receptor agonist chlorophenylpiperazine (mCPP) have all been shown to modify appetite in both lean and obese humans, resulting in reduced caloric intake. Clinical studies demonstrate serotonergic drugs specifically reduce appetite prior to and following the consumption of fixed caloric loads, and cause a reduction in pre-meal appetite and caloric intake at ad libitum meals. Weight loss in the obese has also been produced by treatment with both the serotonin precursor 5-hydroxytryptophan and the preferential 5-HT2C receptor agonist mCPP.A new generation of 5-HT2C receptor selective agonists have been developed and at least one, lorcaserin (APD356), is currently undergoing clinical trials. In addition, 5-HT6 receptor antagonists such as PRX-07034 and BVT74316 have been shown to potently reduce food intake and bodyweight gain in rodent models and have recently entered clinical trials. However, the role of the 5-HT6 receptor in the expression of appetite remains to be determined. The hope is that these drugs will not only be free of their predecessors’ adverse effect profiles, but will also be equally or more effective at regulating appetite and controlling bodyweight.