Biomedical subjects

John E Blundell

Publications and source records attributed to John E Blundell.

11 recordsLinked to original sources

PubMed2007

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.

Animals↗

PubMed2006

Is it possible to dissociate 'liking' and 'wanting' for foods in humans? A novel experimental procedure.

Berridge's model (e.g. [Berridge KC. Food reward: Brain substrates of wanting and liking. Neurosci Biobehav Rev 1996;20:1-25.; Berridge KC, Robinson T E. Parsing reward. Trends Neurosci 2003;26:507-513.; Berridge KC. Motivation concepts in behavioral neuroscience. Physiol Behav 2004;81:179-209]) outlines the brain substrates thought to mediate food reward with distinct 'liking' (hedonic/affective) and 'wanting' (incentive salience/motivation) components. Understanding the dual aspects of food reward could throw light on food choice, appetite control and overconsumption. The present study reports the development of a procedure to measure these processes in humans. A computer-based paradigm was used to assess 'liking' (through pleasantness ratings) and 'wanting' (through forced-choice photographic procedure) for foods that varied in fat (high or low) and taste (savoury or sweet). 60 participants completed the program when hungry and after an ad libitum meal. Findings indicate a state (hungry-satiated)-dependent, partial dissociation between 'liking' and 'wanting' for generic food categories. In the hungry state, participants 'wanted' high-fat savoury>low-fat savoury with no corresponding difference in 'liking', and 'liked' high-fat sweet>low-fat sweet but did not differ in 'wanting' for these foods. In the satiated state, participants 'liked', but did not 'want', high-fat savoury>low-fat savoury, and 'wanted' but did not 'like' low-fat sweet>high-fat sweet. More differences in 'liking' and 'wanting' were observed when hungry than when satiated. This procedure provides the first step in proof of concept that 'liking' and 'wanting' can be dissociated in humans and can be further developed for foods varying along different dimensions. Other experimental procedures may also be devised to separate 'liking' and 'wanting'.

Adolescent↗

PubMed2006

Further evidence of association of OPRD1 & HTR1D polymorphisms with susceptibility to anorexia nervosa.

BACKGROUND: A recent study reported strong evidence for the involvement of a region on human chromosome 1 and genetic susceptibility to anorexia nervosa (AN). A more detailed analysis of this region has suggested 2 genes that may account for this susceptibility. These data suggest that polymorphisms in both the serotonin 1D (HTR1D) and opioid delta 1 (OPRD1) receptor genes show a significant association with restricting AN (RAN). METHODS: In the current study, we have conducted an independent association study on 226 females meeting DSM-IV criteria for AN and 678 matched volunteers. RESULTS: We genotyped 4 SNPs in HTR1D and 6 SNPs in OPRD1. 3 SNPs were found to be associated with both RAN and binge-purge AN (BPAN) within the gene for OPRD1. We also found evidence of association between 2 polymorphisms within HTR1D and RAN. CONCLUSIONS: These data support the hypothesis that polymorphisms within this region form a component of the genetic basis to susceptibility to RAN. However, further work is required to understand the processes that may be mediated by these genes.

Adult↗

PubMed2006

Perspective on the central control of appetite.

Within the last 10 to 15 years, a number of discoveries have revised the way in which scientists view the role of the brain in the control of food intake (1). One aspect of the brain's influence is often characterized as the control of energy homeostasis. This term accounts for a number of factors arising from experimental studies on molecules and food consumption but seems to stop well short of explaining how brain processes articulate the variety of patterns of human feeding. It should be kept in mind that eating is 100% behavior, and this activity links the internal world of molecules and physiological processes with the external world of physical and cultural systems. It is not always clear the extent to which human eating patterns are a function of physiological or environmental pressure; this is, of course,the subject of extensive experimental study and debate. Because much of the current scientific activity on neural control of feeding is driven by the need to understand (and deal with) the causes of obesity, it will be necessary, at some stage, to reconcile the effects of the physiological mechanism believed to be responsible for eating control in the obese with the actual patterns of eating displayed (eating phenotypes) by obese people. Ultimately, the mechanisms and the behavioral phenotypes must match up. Initially, it is useful to consider which components of energy homeostasis are codified in specific molecular processes and neural pathways and to describe how the integration of diverse signaling systems (the codification) is translated into the expression of behavior and the accompanying subjective sensations.

Appetite Regulation↗

PubMed2005

Evaluation of the independent and combined effects of xylitol and polydextrose consumed as a snack on hunger and energy intake over 10 d.

The study assessed the independent and combined effect of two specialty carbohydrates (polydextrose and xylitol) on appetite. Eight female and seven male lean volunteers were recruited from the University of Leeds campus. Using a repeated measures design, volunteers completed four conditions in a counterbalanced order. Each condition varied according to the yoghurt formulation administered: a control yoghurt (C, yoghurt+25 g sucrose) and three experimental yoghurts (X, yoghurt+25 g xylitol; P, yoghurt+25 g polydextrose; and XP, yoghurt+12.5 g xylitol and 12.5 g polydextrose). Each condition lasted for 10 d during which volunteers consumed 200 g yoghurt on each day. On days 1 and 10, the short- and medium-term effects of yoghurt consumption were assessed by measuring ad libitum lunch intake and subjective motivation to eat. The three experimental yoghurts (X, P and XP) induced a slight suppression of energy intake compared with the control (C) yoghurt, but the differences were not statistically significant. However, when the energy content of the yoghurt pre-loads were accounted for, there was a significant suppression of energy intake for P compared with C (P=0.002). The XP yoghurt induced a significantly stronger satiating effect (increase in subjective fullness) compared with C, both with (P=0.003) and without (P<0.001) the differential in energy content of the yoghurt pre-loads accounted for. The study demonstrated that pre-loads of xylitol and polydextrose caused a mild increase in satiety and suppression of energy intake, and that the effects persist after repeated daily administration. The effects exerted by the formulations containing xylitol and polydextrose did not arise from the differences in energy content of the yoghurt per se. Therefore, the usefulness of xylitol and polydextrose as ingredients in functional foods for appetite control are as a result of their lower energy content and suppression of appetite.

Adult↗

PubMed2005

Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity.

The pivotal role of 5-HT in the control of appetite was formally proposed nearly 30 years ago. In particular endogenous hypothalamic 5-HT has been implicated in the processes of within meal satiation and the end state of post meal satiety. Of the numerous 5-HT receptor subtypes currently identified, 5-HT(1B) and 5-HT(2C) receptors are believed to mediate the 5-HT induced satiety. 5-HT drugs such as d-fenfluramine, selective serotoninergic reuptake inhibitor (SSRIs) and 5-HT(2C) receptor agonists have all been shown to significantly attenuate rodent body weight gain, an effect strongly associated with marked hypophagia. D-Fenfluramine, sibutramine, fluoxetine and the 5-HT(2C) receptor agonist mCPP have also all been shown to reduce caloric intake by modifying appetite in both lean and obese humans. Specifically, 5-HT drugs reduce appetite prior to and after the consumption of fixed caloric loads, and reduce pre meal appetite and caloric intake at ad libitum meals. Clinically significant weight loss over a year or more can be produced by both d-fenfluramine and sibutramine treatment, but apparently not by the SSRI fluoxetine. Treatment with the preferential 5-HT(2C) receptor agonist mCPP and the serotonin precursor 5-HTP has also been shown to produce weight loss in the obese. Issues around the actual and possible side effects of these compounds, and in the case of d-fenfluramine toxicity, have led to a search for drugs that act selectively on the CNS 5-HT receptors critical to the satiety response. Currently, a new generation of 5-HT(2C) selective agonists have been developed (including Ro 60-0175, Org 12962, VER-3323, BVT-933 and YM348) and at least one, ADP356, is currently undergoing clinical trials. Hopefully, such drugs will be as or even more effective at regulating appetite and controlling body weight, and will also be free of their predecessors' side effect.

Animals↗

PubMed2004

PASSCLAIM--mental state and performance.

BACKGROUND: The intake of food and drink can influence brain functions, which in turn may have effects on mental state and performance. Therefore, in principle claims to improve mood or specific aspects of cognitive performance by the consumption of functional foods are possible and indeed are currently found on the market. AIM: The paper reviews existing methodologies, which may be used to substantiate and validate such claims of desirable effects of foods on mental state and performance. RESULTS: Mood, arousal, activation, vigilance, attention, sleep, motivation, effort, perception, memory and intelligence have been identified as relevant aspects of mental state and performance. The basic scientific concepts within this field as well as the methodologies to measure these concepts have been reviewed and described. CONCLUSIONS: From this review it is concluded that, in principle, the phenomena in these fields are no different to those in other fields of life science. The scientific methods and protocols described in this report can positively demonstrate the effects of foods on mental state and performance in a scientifically valid way. A claim on mental state and performance like other claims must be based on scientific evidence. This report confirms that methodologies do exist to generate sound scientific evidence in this area. Therefore, claims on the enhancement of specific mental functions can and should be substantiated and validated using the methodologies described in this review.

Affect↗

PubMed2004

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 Smith's conceptual and experimental work on both homeostatic and hedonic mechanisms implicated in the control of food intake.

Disease Susceptibility↗

PubMed2004

Palatability: response to nutritional need or need-free stimulation of appetite?

The traditional view of palatability was that it reflected some underlying nutritional deficit and was part of a homeostatically driven motivational system. However, this idea does not fit with the common observation that palatability can lead to short-term overconsumption. Here, we attempt to re-evaluate the basis of palatability, first by reviewing the role of salt-need both in the expression of liking for salty tastes, and paradoxically, in dissociating need from palatability, and second by examining the role of palatability in short-term control of appetite. Despite the clarity of this system in animals, however, most salt (NaCl) intake in man occurs in a need-free state. Similar conclusions can be drawn in relation to the palatability of food in general. Importantly, the neural systems underlying the hedonic system relating to palatability and homeostatic controls of eating are separate, involving distinct brain structures and neurochemicals. If palatability was a component of homeostatic control, reducing need-state should reduce palatability. However, this is not so, and if anything palatability exerts a stronger stimulatory effect on eating when sated, and over-consumption induced by palatability may contribute to obesity. Differential responsivity to palatability may be a component of the obese phenotype, perhaps through sensitisation of the neural structures related to hedonic aspects of eating. Together, these disparate data clearly indicate that palatability is not a simple reflection of need state, but acts to promote intake through a distinct hedonic system, which has inputs from a variety of other systems, including those regulating need. This conclusion leads to the possibility of novel therapies for obesity based on modulation of hedonic rather than homeostatic controls. Potential developments are discussed.

Appetite Regulation↗

PubMed2004

A decrease in physical activity affects appetite, energy, and nutrient balance in lean men feeding ad libitum.

BACKGROUND: It is not clear how decreased activity quantitatively affects energy balance (EB) in subjects feeding ad libitum. OBJECTIVE: We assessed the effect of an imposed sedentary routine on appetite, energy intake (EI), EB, and nutrient balance in lean men for 7 d. DESIGN: Six men with a mean (+/-SD) age of 23.0 +/- 2.3 y, weight of 69.2 +/- 11.4 kg, and height of 1.76 +/- 0.07 m were each studied twice during a sedentary [1.4 x resting metabolic rate (RMR)] and a moderately active (1.8 x RMR) regimen. During each treatment, they resided in the whole-body indirect calorimeter for the 7 d and had ad libitum access to a medium-fat diet of constant, measurable composition. Meal size, frequency, and composition were continually monitored. Motivation to eat was recorded during waking hours. Subjects were weighed in light clothing each morning, and their weight was corrected to nude. RESULTS: Energy expenditure was 9.7 and 12.8 MJ/d [P < 0.01; SE of the difference between means (SED) = 0.41] during the sedentary and active regimens, respectively. EI was 13.5 and 14.4 MJ/d (P = 0.463, SED = 1.06), respectively. There was no regimen effect on hunger, appetite, or body weight. By day 7, cumulative EB was 26.3 and 11.1 MJ, respectively. CONCLUSIONS: Reducing a level of physical activity from 1.8 to 1.4 x RMR can markedly affect EB. A sedentary routine does not induce a compensatory reduction of EI and leads to a significantly positive EB, most of which is stored as fat.

Adult↗

PubMed2003

Highlighting the positive impact of increasing feeding frequency on metabolism and weight management.

Research on feeding frequency started more than 20 years ago and some studies have shown evidence of nutritional benefits, especially on metabolism and body weight management. Advice on feeding frequency could play an important role in public health policies by reducing levels of overweight and obesity, the prevalence of which has dangerously increased in most countries over the last few decades. The 17th International Congress of Nutrition brought to the forefront the benefits of increasing feeding frequency (i.e. keeping the same total daily energy intake but dividing it into more frequent meals than usual). Recent epidemiological studies, mostly carried out in France, have provided evidence on the beneficial effects of a fourth meal for those individuals who habitually choose this pattern. Supported by metabolic data, these findings have now been supported by experimental studies. The "goûter", commonly eaten in the afternoon in France by most children and many adults, has the biological characteristics of a meal because it is eaten in response to hunger. Suppressing the "goûter" in "habitual fourth meal eaters" soon leads to an increase in Body Mass Index (BMI). Further, people who are regular "goûter" eaters have a higher carbohydrate intake and better metabolic profile than other adults, even though their total energy intake is not greater. Increased feeding frequency leads to a reduction in the total secretion of insulin, an improvement in insulin resistance and a better blood glucose control, as well as an improvement in the blood lipid profile. The experts agreed that, as long as we do not consume more energy than we use up and we only eat when we are hungry, it may be useful to split our total energy intake into as many meals as our social pattern allows. However, the pattern of eating cannot be completely dissociated from the composition of foods consumed. Therefore within this energy intake, we must take care to consume not only a good balance of macronutrients with high carbohydrate and low fat levels, but also ensure that we get an adequate intake of essential micronutrients. "What you eat" and "When you eat it" are public health messages to communicate: frequent consumption of low energy dense high carbohydrate foods, rich in micronutrients, must be encouraged ensuring that energy intakes are not greater than energy expenditures and that eating episodes occur in a hunger state.

Body Weight↗