Early improvement in food cravings are associated with long-term weight loss success in a large clinical sample.

BACKGROUND: Food cravings are associated with dysregulated eating behaviour and obesity, and may impede successful weight loss attempts. Gaining control over food craving is therefore a component in the management of obesity. The current paper examined whether early changes in control over food craving (assessed using the Craving Control subscale on the Control of Eating Questionnaire (CoEQ)) was predictive of weight loss in four phase 3 clinical trials investigating a sustained-release combination of naltrexone/bupropion (NB) in obese adults. The underlying component structure of the CoEQ was also examined. METHOD: In an integrated analysis of four 56-week phase 3 clinical trials, subjects completed the CoEQ and had their body weight measured at baseline and at weeks 8, 16, 28 and 56. All analyses were conducted on subjects who had complete weight and CoEQ measurements at baseline and week 56, and had completed 56 weeks of NB (n=1310) or placebo (n=736). A latent growth curve model was used to examine whether early changes in the CoEQ subscales were associated with decreases in weight loss over time. Confirmatory factor analysis (CFA) was used to determine the psychometric properties of the CoEQ. RESULTS: The factor structure of the CoEQ was consistent with previous findings with a four-factor solution being confirmed: Craving Control, Positive Mood, Craving for Sweet and Craving for Savoury with good internal consistency (Cronbach's α=0.72-0.92). Subjects with the greatest improvement in Craving Control at week 8 exhibited a greater weight loss at week 56. CONCLUSIONS: These findings highlight the importance of the experience of food cravings in the treatment of obesity and support the use of the CoEQ as a psychometric tool for the measurement of food cravings in research and the pharmacological management of obesity.

Physical activity, eating traits and weight in young adulthood: a cross-sectional and longitudinal study.

OBJECTIVE: To investigate the association between eating traits (e.g. dietary restraint or opportunistic eating) and weight - both cross-sectionally and longitudinally - and whether physical activity (PA) moderates these associations. METHODS: Two-hundred seventy young adults (21-35 years; BMI: 25.40 kg/m2 [SD = 3.90 kg/m2]; 48.90% female) participated in this 12-month observational cohort study. Cognitive Restraint (CR), Disinhibition (DI) and Hunger (HU) were measured using the Three-Factor Eating Questionnaire at baseline and 12 months. Participants were measured at quarterly intervals for objectively measured PA and anthropometrics. Cross-sectional and longitudinal models determined if eating traits were associated with weight or weight change, and whether these associations were moderated by PA. RESULTS: At baseline, higher CR (B = 0.429, p < 0.01) and DI (B = 0.942, p < 0.01) were associated with higher weight. The associations of DI (B = -0.008 p = 0.02) and HU (B = -0.006, p = 0.04) with weight were moderated by PA at baseline. The longitudinal model for CR determined PA altered the relationship between change in CR and weight change (B = 0.004, p < 0.01). CONCLUSIONS: Eating traits and PA are associated with weight and weight change. However, to elucidate how PA and eating traits directly affect weight changes, future weight loss interventions should investigate whether improving eating traits and concomitantly increasing PA amplify weight loss.

Exercise, appetite and weight management: understanding the compensatory responses in eating behaviour and how they contribute to variability in exercise-induced weight loss.

Does exercise promote weight loss? One of the key problems with studies assessing the efficacy of exercise as a method of weight management and obesity is that mean data are presented and the individual variability in response is overlooked. Recent data have highlighted the need to demonstrate and characterise the individual variability in response to exercise. Do people who exercise compensate for the increase in energy expenditure via compensatory increases in hunger and food intake? The authors address the physiological, psychological and behavioural factors potentially involved in the relationship between exercise and appetite, and identify the research questions that remain unanswered. A negative consequence of the phenomena of individual variability and compensatory responses has been the focus on those who lose little weight in response to exercise; this has been used unreasonably as evidence to suggest that exercise is a futile method of controlling weight and managing obesity. Most of the evidence suggests that exercise is useful for improving body composition and health. For example, when exercise-induced mean weight loss is <1.0 kg, significant improvements in aerobic capacity (+6.3 ml/kg/min), systolic (-6.00 mm Hg) and diastolic (-3.9 mm Hg) blood pressure, waist circumference (-3.7 cm) and positive mood still occur. However, people will vary in their responses to exercise; understanding and characterising this variability will help tailor weight loss strategies to suit individuals.

Interaction between disinhibition and restraint: Implications for body weight and eating disturbance.

An increase in obesity is usually accompanied by an increase in eating disturbances. Susceptibility to these states may arise from different combinations of underlying traits: Three Factor Eating Questionnaire (TFEQ) Restraint and Disinhibition. Two studies were conducted to examine the interaction between these traits; one on-line study (n=351) and one laboratory-based study (n=120). Participants completed a battery of questionnaires and provided self-report measures of body weight and physical activity. A combination of high Disinhibition and high Restraint was associated with a problematic eating behaviour profile (EAT-26), and a higher rate of smoking and alcohol consumption. A combination of high Disinhibition and low Restraint was associated with a higher susceptibility to weight gain and a higher sedentary behaviour. These data show that different combinations of Disinhibition and Restraint are associated with distinct weight and behaviour outcomes.

The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat.

CONTEXT: The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic and anorexigenic peptides. OBJECTIVE: The aim of the study was to investigate the effects of medium-term exercise on fasting/postprandial levels of appetite-related hormones and subjective appetite sensations in overweight/obese individuals. DESIGN AND SETTING: We conducted a longitudinal study in a university research center. PARTICIPANTS AND INTERVENTION: Twenty-two sedentary overweight/obese individuals (age, 36.9 +/- 8.3 yr; body mass index, 31.3 +/- 3.3 kg/m(2)) took part in a 12-wk supervised exercise programme (five times per week, 75% maximal heart rate) and were requested not to change their food intake during the study. MAIN OUTCOME MEASURES: We measured changes in body weight and fasting/postprandial plasma levels of glucose, insulin, total ghrelin, acylated ghrelin (AG), peptide YY, and glucagon-like peptide-1 and feelings of appetite. RESULTS: Exercise resulted in a significant reduction in body weight and fasting insulin and an increase in AG plasma levels and fasting hunger sensations. A significant reduction in postprandial insulin plasma levels and a tendency toward an increase in the delayed release of glucagon-like peptide-1 (90-180 min) were also observed after exercise, as well as a significant increase (127%) in the suppression of AG postprandially. CONCLUSIONS: Exercise-induced weight loss is associated with physiological and biopsychological changes toward an increased drive to eat in the fasting state. However, this seems to be balanced by an improved satiety response to a meal and improved sensitivity of the appetite control system.

Overconsumption and obesity: peptides and susceptibility to weight gain.

Physiological control of feeding is mediated by tonic and episodic signalling systems. These are sometimes thought of as long-term and short-term control. Tonic signals arise from tissue stores whereas episodic signals oscillate periodically with the consumption of food. These physiological controls are paralleled in the motivation to eat by long-acting enduring traits (such as disinhibition) and by short-acting states (such as hunger). Peptides are usually envisaged to exert an action on appetite control through the modulation of states such as hunger and satiety (fullness). Here we provide evidence that peptides involved in tonic regulation--such as leptin--may express a control over appetite motivation through an effect on traits that confer a constant readiness to eat, whereas episodic peptides such as GLP-1 influence appetite motivation through a state such as hunger. The distinction between tonic and episodic regulation, and between traits and states has implications for understanding overconsumption and the susceptibility to weight gain.

PYY3-36 as an anti-obesity drug target.

The neuropeptide Y (NPY)/peptide YY (PYY) system has been implicated in the physiology of obesity for several decades. More recently ignited enormous interest in PYY3-36, an endogenous Y2-receptor agonist, as a promising anti-obesity compound. Despite this interest, there have been remarkably few subsequent reports reproducing or extending the initial findings, while at the same time studies finding no anti-obesity effects have surfaced. Out of 41 different rodent studies conducted (in 16 independent labs worldwide), 33 (83%) were unable to reproduce the reported effects and obtained no change or sometimes increased food intake, despite use of the same experimental conditions (i.e. adaptation protocols, routes of drug administration and doses, rodent strains, diets, drug vendors, light cycles, room temperatures). Among studies by authors in the original study, procedural caveats are reported under which positive effects may be obtained. Currently, data speak against a sustained decrease in food intake, body fat, or body weight gain following PYY3-36 administration and make the previously suggested role of the hypothalamic melanocortin system unlikely as is the existence of PYY deficiency in human obesity. We review the studies that are in the public domain which support or challenge PYY3-36 as a potential anti-obesity target.

Cross talk between physical activity and appetite control: does physical activity stimulate appetite?

Physical activity has the potential to modulate appetite control by improving the sensitivity of the physiological satiety signalling system, by adjusting macronutrient preferences or food choices and by altering the hedonic response to food. There is evidence for all these actions. Concerning the impact of physical activity on energy balance, there exists a belief that physical activity drives up hunger and increases food intake, thereby rendering it futile as a method of weight control. There is, however, no evidence for such an immediate or automatic effect. Short (1-2 d)-term and medium (7-16 d)-term studies demonstrate that men and women can tolerate substantial negative energy balances of < or = 4 MJ energy cost/d when performing physical activity programmes. Consequently, the immediate effect of taking up exercise is weight loss (although this outcome is sometimes difficult to assess due to changes in body composition or fluid compartmentalization). However, subsequently food intake begins to increase in order to provide compensation for about 30% of the energy expended in activity. This compensation (up to 16 d) is partial and incomplete. Moreover, subjects separate into compensators and non-compensators. The exact nature of these differences in compensation and whether it is actually reflective of non-compliance with protocols is yet to be determined. Some subjects (men and women) performing activity with a cost of < or = 4 MJ/d for 14 d, show no change in daily energy intake. Conversely, it can be demonstrated that when active individuals are forced into a sedentary routine food intake does not decrease to a lower level to match the reduced energy expenditure. Consequently, this situation creates a substantial positive energy balance accompanied by weight gain. The next stage is to further characterize the compensators and non-compensators, and to identify the mechanisms (physiological or behavioural) that are responsible for the rate of compensation and its limits.

SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats.

Intracerebroventricular (i.c.v.) administration of the novel hypothalamic neuropeptide orexin-A stimulates food intake in rats, and delays the onset of behavioural satiety (i.e. the natural transition from feeding to resting). Furthermore, preliminary findings with the selective orexin-1 receptor antagonist, SB-334867, suggest that orexin-A regulation of food intake is mediated via the orexin-1 receptor. At present, however, little is known about either the intrinsic effects of SB-334867 on the normal structure of feeding behaviour, or its effects upon orexin-A-induced behavioural change. In the present study, we have employed a continuous monitoring technique to characterize the effects of SB-334867 (3-30 mg/kg, i.p.) on the microstructure of rat behaviour during a 1-h test with palatable wet mash. Administered alone, SB-334867 (30 mg/kg, but not lower doses) significantly reduced food intake and most active behaviours (eating, grooming, sniffing, locomotion and rearing), while increasing resting. Although suggestive of a behaviourally nonselective (i.e. sedative) action, the structure of feeding behaviour was well-preserved at this dose level, with the reduction in behavioural output clearly attributable to an earlier onset of behavioural satiety. As previously reported, orexin-A (10 microg per rat i.c.v.) stimulated food intake, increased grooming and delayed the onset of behavioural satiety. Pretreatment with SB-334867 dose-dependently blocked these effects of orexin-A, with significant antagonism evident at dose levels (3-10 mg/kg) below those required to produce intrinsic behavioural effects under present test conditions. Together, these findings strongly support the view that orexin-A is involved in the regulation of feeding patterns and that this influence is mediated through the orexin-1 receptor.

Physical activity and regulation of food intake: current evidence.

OBJECTIVE: The evidence was reviewed on how physical activity could influence the regulation of food intake by either adjusting the sensitivity of appetite control mechanisms or by generating an energy deficit that could adjust the drive to eat. DESIGN: Interventionist and correlational studies that had a significant influence on the relationship between physical activity and food intake were reviewed. Interventionist studies involve a deliberate imposition of physical activity with subsequent monitoring of the eating response. Correlational studies make use of naturally occurring differences in the levels of physical activity (between and within subjects) with simultaneous assessment of energy expenditure and intake. SUBJECTS: Studies using lean, overweight, and obese men and women were included. RESULTS: Only 19% of interventionist studies report an increase in energy intake after exercise; 65% show no change and 16% show a decrease in appetite. Of the correlational studies, approximately half show no relationship between energy expenditure and intake. These data indicate a rather loose coupling between energy expenditure and intake. A common sense view is that exercise is futile as a form of weight control because the energy deficit drives a compensatory increase in food intake. However, evidence shows that this is not generally true. One positive aspect of this is that raising energy expenditure through physical activity (or maintaining an active life style) can cause weight loss or prevent weight gain. A negative feature is that when people become sedentary after a period of high activity, food intake is not "down-regulated" to balance a reduced energy expenditure. CONCLUSION: Evidence suggests that a high level of physical activity can aid weight control either by improving the matching of food intake to energy expenditure (regulation) or by raising expenditure so that it is difficult for people to eat themselves into a positive energy balance.

Uncoupling the effects of energy expenditure and energy intake: appetite response to short-term energy deficit induced by meal omission and physical activity.

The effects of two methods of inducing an acute energy deficit (exercise and a low-energy breakfast) on appetite were investigated in 11 healthy females, all of whom were regular exercisers and regular breakfast eaters. There were four experimental days: with exercise and a high-energy (500 kcal) breakfast (EHB), exercise and a low-energy (64 kcal) breakfast (ELB), no exercise and a high-energy breakfast (NEHB) and no exercise and a low-energy breakfast (NELB). Hunger and moods were monitored each hour from 8 a. m. until 5 p.m. Energy and macronutrient intake were measured during an ad libitum lunch test meal 4 h after the exercise and breakfast. Heart rate was continuously monitored using the Polar sport tester. The low-energy breakfasts (ELB and NELB) led to increased hunger during the morning and an increase in energy intake at lunch compared with the high-energy breakfasts. Subjects also experienced significantly more food cravings after LBs than after HBs. Exercise failed to have any significant effect on these variables. Thus, two methods of inducing a short-term energy deficit had markedly different effects on appetite. The low-energy breakfast presumably fails to generate the inhibitory satiety signals induced by the 500 kcal breakfast, whereas the metabolic effects of an exercise session failed to generate excitatory signals to hunger and food intake.

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.

The 5-HT2 receptor agonist MK-212 reduces food intake and increases resting but prevents the behavioural satiety sequence.

The 5-HT2c receptor is implicated in the relationship between serotonin and satiety. However, anorexia induced by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) has been shown to delay, not advance behaviours associated with the onset of satiety, fragmenting eating behaviour, 6-chloro-2-(1-piperazinyl)pryazine (MK-212) is also a selective agonist at the 5-HT2 receptor sites. MK-212 has greater affinity for 5-HT2c receptor sites than DOI. The effects of an ED50 dose of MK-212 (5.0 mg/kg i.p.) on the eating and other behaviours of the fasted rat were continuously monitored following the presentation of food. Continuous monitoring provides the most powerful and valid form of behavioural analysis. Temporal profiles of behaviour duration (dur) and frequency (frq) were generated. Food intake was reduced 54% by MK-212 (p < .001). The frequency of grooming was reduced (p < .01). Locomotion (dur p < .001, frq p < .001), rearing (dur p < .0005, frq p < .005) and sniffing (dur p < .05, frq p < .0001) were all reduced. The duration of resting increased (p < 0.01). This is consistent with enhanced satiety. However, the Behavioural Satiety Sequence was not present after the administration of MK-212 (5.0 mg/kg). The temporal structure of behaviour produced by MK-212 was quite different from that produced by pre-feeding. Initially resting dominated the behavioural profile. Eating increased over time from a suppressed state in the initial stages of the observation period. This lack of appearance of the Behavioural Satiety Sequence is more similar to a state of hyper-sedation than to DOI induced hyper-activity. The time course of this sedation would not have been picked up by a simple categorical analysis of behaviour. Hence, temporal analysis is an essential tool in understanding of drug induced anorexia.

Overconsumption as a cause of weight gain: behavioural-physiological interactions in the control of food intake (appetite).

There is an asymmetry in the operation of physiological processes that maintain body weight. The body exerts a strong defence against undernutrition and weight loss, but applies a much weaker resistance to overconsumption and weight gain. These principles influence how appetite control operates and this constitutes one form of vulnerability to weight gain. The expression of appetite is reflected in an episodic pattern of eating behaviour, the selection of dietary commodities and an associated profile of conscious sensations such as hunger, preferences, aversions and fullness. The onset and termination of eating episodes are subject to facilitatory and inhibitory physiological processes, and are held in place by strong environmental contingencies and habitual routines. Energy intake resulting from physiological and environmental control of behaviour is generally in balance with energy expenditure, although changes in energy expenditure do not inevitably trigger changes in food intake. Excess energy intake over expenditure may be due to aberrant positive drive to seek energy or a permissive response to strong external stimuli. The former could arise from a defect in a lipostatic regulatory system, and the latter from the weakness of inhibitory signals or from strong facilitatory responses to superpotent physical features of food. Taste and textural qualities of food give rise to hedonic responses via opioidergic and aminergic systems. Inhibitory responses to macronutrients include adjustment of gastric volume, rate of gastric emptying, release of cholecystokinin and enterostatin, and changes in plasma levels of products of digestion. These peripheral responses lead to a series of changes in brain neurotransmitter networks. Proteins, fats and carbohydrates generate different sets of physiological responses that produce different effects on the intensity and duration of satiety. The nutrient composition of food and the overall energy density influence control of meal size and post-ingestive inhibition. Particular sensory and nutrient combinations in foods can facilitate passive overconsumption. Overriding physiological satiety signals can lead to a positive energy balance and weight gain.

Experimental animal models of eating disorders. Recent pharmacological studies.

Until recently, the amount of standardized laboratory food eaten--during a short period of time--by starved young and lean animals was the only parameter used to determine the effects of drugs on feeding behaviours. Now with the introduction of recent physio-pathological concepts and new behavioural designs the information obtained from pharmacological studies is much more elaborate. It concerns not only the ingestive behaviours but also the peri-prandial behaviours. It gives specific indications on how the effects of different drugs may be affected by changes in the "milieu intérieur" and by the characteristics of environmental factors. Different experimental models are described; results obtained with these models are discussed.

Meal patterns and food selection during the development of obesity in rats fed a cafeteria diet.

Offering preferred foods in addition to laboratory chow led immediately to a marked increase in both mean meal size (MMS) and meal frequency (MF). As body weight increased over a 5 months period, MF declined to a low level but MMS remained high. Within a majority of meals there was substantial consumption of only one food item. Nonetheless, when "mixed" meals were eaten these were usually larger than "exclusive" meals. With more than one preferred food available there was a significant tendency to alternate consumption of food types from one meal to the next. This disappeared at inter-meal intervals longer than 90 minutes. With one preferred food available, only MMS (and not MF) was increased and the degree of hyperphagia and obesity were reduced. The findings suggest the following conclusions: Both palatability (preference value for a particular food) and variety (availability of different types of food) have incremental, but distinguishable, effects on food consumption and mean parameters. Palatability mainly influences meal size, whereas variety exerts an effect on meal size and inter-meal interval. However, the potential effect of variety on overall intake is probably somewhat reduced by the tendency to eat only one type of food in each meal. Obesity has an inhibitory influence on feeding, operating primarily through a reduction in mean frequency.