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Biomedical subjects

C L Lawton

Publications and source records attributed to C L Lawton.

18 recordsLinked to original sources

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.

Appetite↗

The degree of saturation of fatty acids influences post-ingestive satiety.

Two studies were designed to compare the effects on post-ingestive satiety of manipulating the degree of saturation of fatty acids, at a fixed chain length (18 C atoms), in a fixed energy (5.68 MJ for males; 3.97 MJ for females), high-fat (55% energy) lunch meal. Two different groups of twenty subjects (ten males and ten females) took part in each study. All forty subjects were of normal weight and aged between 18 and 36 years. Study 1 compared the effects of fat A (oleic blend, high in monounsaturated fatty acids (MUFA)) with those of fat B (linoleic blend, high in polyunsaturated fatty acids (PUFA)) and fat C (stearic-oleic blend, high in saturated fatty acids (SFA)). Study 2, which was designed to confirm and extend the findings of Study 1, compared the effects of fats A, B and C with those of fat D (a linoleic-oleic blend). Energy and nutrient intakes were monitored for the rest of the day and for the following day. Profiles of hunger, fullness and other sensations were monitored by continuous tracking and end-of-day questionnaires. In each meal the fat content was exclusively composed of one particular type (A, B, C or D) and was divided equally between the main course and dessert. Study 1 revealed a significant effect of fat type (degree of saturation) on intake of nutrients at the following (dinner) meal (smallest F[2,36] 3.38, P < 0.05), on post-ingestive ratings of motivation to eat (smallest F[2,36] 4.18, P = 0.02) and on energy intake over the whole test day (F[2,36] 3.39, P < 0.01). Subjects consumed significantly more energy after consumption of the lunch containing fat A than after the lunches containing fats B or C and there was a trend for these effects to continue into the second day. In Study 2, fat C produced more similar effects on appetite to fat A and there was a tendency for subjects to consume more over the whole test day when they had consumed the lunch containing fat A than when they had consumed the lunch containing fat B. Furthermore, when the data from fat conditions A and B in both studies were combined (n 40) the results of Study 1 were confirmed. Overall, the results of these short-term studies indicate that PUFA may exert a relatively stronger control over appetite than MUFA and SFA.

Adolescent↗

Comparison of high-fat and high-carbohydrate foods in a meal or snack on short-term fat and energy intakes in obese women.

The present study aimed to compare the action of high-fat and high-carbohydrate (CHO) foods on meal size (satiation) and post-meal satiety in obese women. A within-subjects design was used; each participant received all four nutritional challenges. Fifteen healthy obese women (age 21-56 years, BMI 35-48 kg/m2) participated; thirteen completed all four test days. On two test days, participants were exposed to a nutritional challenge comprising an ad libitum high-fat or high-CHO lunch. On the other two test days they were exposed to a challenge comprising an ad libitum sweet high-fat or high-CHO mid-afternoon snack. Energy and macronutrient intakes were measured at each eating episode. Visual analogue rating scales were completed periodically to record subjective feelings of appetite. When offered a high-CHO selection of foods at lunch and mid-afternoon participants consumed less energy than when offered a high-fat selection. However, post-meal satiety was similar. Total test-day energy intake was significantly higher when high-fat foods were consumed at lunch, but not as a snack. Consumption of high-fat foods at a lunch and snack increased the amount of fat consumed over the whole test day. In conclusion, energy intake of an eating episode was influenced by nutrient composition in this group of obese women. Consumption of high-fat foods at lunch or as a snack led to overconsumption relative to high-CHO foods. However, high-fat foods at meals may have greater potential to influence daily intake than at snacks, probably because meals are larger eating episodes and therefore give greater opportunity to overconsume.

Adult↗

The effects of high-carbohydrate vs high-fat breakfasts on feelings of fullness and alertness, and subsequent food intake.

Fourteen subjects consumed four realistic isoenergetic (2035 kJ) breakfasts, varying in macronutrient content (two fat-rich, two carbohydrate-rich (low- and high-fibre)), in random order on separate mornings. After breakfast, subjects left the laboratory and completed appetite and alertness ratings at specific times and recorded all subsequent fluid and food intake for the rest of the day. The high-fibre, carbohydrate-rich breakfast was the least palatable but most filling meal and was associated with less food intake during the morning and at lunch. Hunger returned at a slower rate after this meal than after the low-fibre, carbohydrate-rich meal. Both fat-rich breakfasts were more palatable but less satiating than the carbohydrate-rich meals and were followed by greater food intake during the morning, which may be a compensatory response to ingest a sufficient amount of food and/or carbohydrate to match the level of fullness produced by the subjects' habitual breakfasts. By the end of the day, the average total energy intake was significantly greater after the fat-rich EB meal than after the high-fibre, carbohydrate-rich meal (P < 0.05). Total day fat intakes were also significantly greater when the high-fat breakfasts were eaten. For every individual test, alertness ratings increased immediately after breakfast was consumed. On average, the high-fibre carbohydrate-rich meal was associated with the highest post-breakfast alertness ratings and with the greatest cumulative amount of alertness during the period between breakfast and lunch (AUC). Alertness AUC values up until lunch correlated positively with fullness AUC values (r = 0.36, P < 0.01, n = 56). The results confirm the relatively weak satiating power of fat-rich meals observed in controlled laboratory-based studies and indicate that a high-fibre, carbohydrate-rich breakfast may assist weight control efforts by maintaining fullness. Further research is required to determine whether satiety directly enhances alertness and whether low-GI carbohydrate-rich meals enhance alertness to a greater degree than high-GI meals.

Adult↗

A medium-term intervention study on the impact of high- and low-fat snacks varying in sweetness and fat content: large shifts in daily fat intake but good compensation for daily energy intake.

Thirty-six normal-weight, habitual snackers (eighteen males, eighteen females) completed a medium-term intervention study designed to examine the tendency of four different types of snacks, varying in nutrient (low- (LF) or high-fat (HF) and sensory properties (sweet (SW) or non-sweet (NSW)), to influence the control of appetite and to adjust daily energy intake. Subjects were exposed to each snack category for a 3-week period and were asked to consume a minimum number of snacks each day so that at least 25% of their daily energy intake would be derived from the test snacks. Energy and macronutrient intakes from the test snacks were calculated every day and also from other eating episodes (using 3 d food diary records) during the third week of snack exposure. Subjects consumed more energy/d from the SW snacks than from the NSW snacks, with most energy being consumed from the HF/SW snacks (3213 kJ) and least energy from the LF/NSW snacks (1628 kJ). This differential snack intake remained stable across the whole snack exposure period. Total daily energy intake did not differ significantly during exposure to any of the four snack types. Furthermore, the encouragement to eat freely from the test snacks did not lead to daily overconsumption of energy when compared with pre-study intakes. Hence, the level of snack consumption was largely compensated for by the energy consumed from the rest of the eating pattern. Although daily energy intake during exposure to the HF snacks was an average of 364 kJ higher (NS) than that during exposure to the LF snacks, the clearest and most significant effect of snack consumption was on daily macronutrient intake. Appreciable consumption of the HF snacks raised the percentage of total daily energy intake consumed as fat from 37 to 41% (P < 0.01). In contrast, the LF snacks reduced daily fat intake to 33.5% (LF/SW, P < 0.05; LF/NSW, NS) of total daily energy. The results, therefore, suggest that, in habitual snackers, generous consumption of LF snacks, when compared with HF snacks, is an effective strategy to reduce fat intake so that it approaches the recommendations of dietary guidelines without increasing total daily energy intake.

Adolescent↗

The role of reduced fat diets and fat substitutes in the regulation of energy and fat intake and body weight.

The suggested link between a high intake of dietary fat and obesity has led to a proliferation on the market of reduced fat foods. The preceding year has seen the publication of more long-term studies investigating the effects of reduced fat and fat substituted foods on energy intake, fat intake and body weight. Effects on the proportion of the diet consumed as fat are encouraging (with most studies showing a decrease towards dietary recommendations), whilst effects on energy intake and body weight remain equivocal.

Body Weight↗

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.

Animals↗

Control of human appetite: implications for the intake of dietary fat.

The human appetite system contains central and peripheral mechanisms that interact with environmental features, especially with the physical and nutrient composition of the food supply. Foods varying in nutrient composition exert different physiologic effects, some of which function as satiety signals. High-fat diets (low food quotient) lead to high levels of energy intake. This effect is termed passive overconsumption and overcomes fat-induced physiological satiety signals. High-fat foods exert a weak effect on satiation (intra-meal satiety), and fat has a weaker effect, joule for joule, on postingestive satiety than do other macronutrients. The frequency of obesity is greater among high-fat than low-fat consumers. However, the development of obesity on a high-fat diet is not a biological inevitability. The investigation of people who resist the weight-inducing properties of high-fat diets is a key research strategy. Understanding the appetite control system suggests behavioral, nutritional, and pharmacologic strategies for modifying dietary fat intake.

Appetite↗

Serotoninergic manipulation, meal-induced satiety and eating pattern: effect of fluoxetine in obese female subjects.

Twelve nondepressed healthy female obese subjects (BMI > 30 kg/m2) took part in a study which conformed to a double-blind randomized crossover design. Each subject acted as her own control across 2 weeks of treatment with either 60 mg of the 5-HT reuptake inhibitor fluoxetine or matching placebo. On days 7 and 14 of both treatment phases subjects were provided with fixed energy lunch meals high in either CHO or fat. The effect of these meals on satiety during the fluoxetine and placebo phases was assessed by a battery of procedures. Subjects felt less hungry after consuming the high CHO meal than after consuming the high-fat meal. They also felt less hungry when taking fluoxetine than when taking the placebo. Analysis of energy intake from the test meal revealed a main effect of prior lunch meal type (high CHO or high fat) and a main effect of drug treatment. Subjects consumed an average of 574 kcal following the high CHO meal compared to 689 kcal following the high-fat meal. Subjects also consumed an average of 532 kcal when taking fluoxetine compared to 730 kcal when taking the placebo. Fluoxetine did not exert any significant effects on macronutrient selection. Mean daily energy intake, calculated from food diary records, was 1881 kcal when subjects were taking the placebo compared to 1460 kcal when taking fluoxetine (a reduction of 22.4%). Fluoxetine treatment produced a significant weight loss of 1.97 kg over the two weeks of treatment compared to a weight loss of only 0.04 kg on placebo.

Adult↗

Serotonin, eating behavior, and fat intake.

There is an intimate relationship between nutritional intake (eating) and serotonin activity. Experimental manipulations (mainly neuropharmacological) of serotonin influence the pattern of eating behavior, subjective feelings of appetite motivation, and the response to nutritional challenges. Similarly, nutritional manipulations (food restriction, dieting, or altered nutrient supply) change the sensitivity of the serotonin network. Traditionally, serotonin has been linked to the macronutrient carbohydrate via the intermediary step of plasma amino acid ratios. However, it has also been demonstrated that 5-HT drugs will reduce energy intake and reverse body weight gain in rats exposed to weight increasing high fat diets. 5-HT drugs can also reduce food intake and block weight gain of rats on a high fat cafeteria diet. Some diet selection studies in rats indicate that the most prominent reduction of macronutrient intake is for fat. These data indicate that 5-HT activity can bring about a reduction in fat consumption. In turn, different types of dietary fat can alter brain 5-HT activity. In human studies the methodology of food choice experiments has often precluded the detection of an effect of 5-HT manipulation on fat intake. However, there is evidence that in obese and lean subjects some 5-HT drugs can readily reduce the intake of high fat foods. Data also suggest that 5-HT activation can lead to a selective avoidance of fat in the diet. These effects of 5-HT on the intake of dietary fat may involve a pre-absorptive mechanism and there is evidence that 5-HT is linked to cholecystokinin and enterostatin. These proposals have theoretical and practical implications and suggest possible strategies to intensify or advance fat-induced satiety signals.

Animals↗

Serotonin and dietary fat intake: effects of dexfenfluramine.

Traditionally, serotonin (5-HT) has been most commonly linked with carbohydrate (CHO) intake. However, in recent years it has been demonstrated that serotoninergic drugs such as dexfenfluramine also reduce energy intake and reverse body weight gain in rats exposed to weight-increasing high-fat diets. Dexfenfluramine is also effective in decreasing food intake and body weight gain of rats that gain weight on a high-fat cafeteria diet. The basic science studies indicate that serotoninergic activity--induced by dexfenfluramine--can act as a sufficient stimulus for the reduction of fat consumption. High-fat diets do not appear to impede the suppressive effect of dexfenfluramine on food intake. In human studies with dexfenfluramine, it has often been the case that the fat content of test foods has been held constant--with only protein and CHO allowed to vary. These studies therefore cannot display any direct effect on fat. However, when food choice is not limited by experimental constraints, a significant reduction of fat intake by dexfenfluramine has been demonstrated in obese patients. In other experimental studies, dexfenfluramine has suppressed fat intake to a greater extent than other macronutrients when free selection of foods has been permitted. Taken together, these studies demonstrate that dexfenfluramine is effective at reducing energy intake with a diet high in fat and may under certain conditions cause a selective avoidance of high-fat foods.

Animals↗

5-HT manipulation and dietary choice: variable carbohydrate (Polycose) suppression demonstrated only under specific experimental conditions.

The effects of six 5-HT anorectic agents, d-fenfluramine (5-HT releaser and reuptake inhibitor), fluoxetine (5-HT reuptake inhibitor), mCPP (5-HT1B/5-HT1C receptor agonist), RU24969 (5-HT1A/5-HT1B receptor agonist), MK212 (5-HT1C receptor agonist) and DOI (5-HT2/5-HT1C receptor agonist), and two non-5-HT anorectic agents, salbutamol (beta 2-adrenergic agonist) and d-amphetamine (catecholaminergic agonist), were examined in an experimental procedure designed to disclose selective effects on carbohydrate consumption. In this procedure, a revised version of what we have termed "The Classic Sclafani Paradigm", animals are presented with powdered Polycose as an optional carbohydrate supplement to hydrated chow (nutritionally complete diet). All drugs produced significant reductions in total (hydrated chow plus powdered Polycose) intake. However, only the 5-HT drugs DOI and fluoxetine exerted significantly stronger anorectic effects on intake of powdered Polycose than on intake of hydrated chow. d-Fenfluramine also showed a tendency to selectively suppress Polycose intake but this effect marginally failed to reach significance. These results suggest that when experimental conditions are favourable, what appears to be selective carbohydrate (Polycose) suppression can be demonstrated with certain 5-HT drugs. They also suggest that a selective effect on carbohydrate intake is not the most prominent feeding response to 5-HT drugs.

Animals↗

5-HT and carbohydrate suppression: effects of 5-HT antagonists on the action of d-fenfluramine and DOI.

The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine and the 5-HT2/5-HT1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were examined in a dietary paradigm that appears to be sensitive to 5-HT-induced carbohydrate suppression. In this paradigm, deprived rats are provided with a nutritionally complete hydrated chow mash diet together with an optional carbohydrate supplement of powdered Polycose. Both d-fenfluramine and DOI produced a clear suppression of total energy intake and carbohydrate (Polycose) intake. However, the mechanisms underlying these effects are different. The effect of d-fenfluramine in this paradigm was attenuated by the 5-HT1/5-HT2 receptor antagonist metergoline and partially attenuated by the 5-HT1A/5-HT1B receptor antagonist (+/-)cyanopindolol. In contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor antagonist ketanserin, the 5-HT3 receptor antagonist (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS-205,930), the 5-HT2/5-HT1C receptor antagonist ritanserin, or the peripheral 5-HT receptor antagonist xylamidine. However, the effect of DOI in this paradigm was significantly attenuated by ketanserin but was not antagonised by either ritanserin or (+/-)cyanopindolol. Therefore, the suppressive effect of these two 5-HT drugs on total and Polycose intake appears to be mediated, respectively, by 5-HT1B/5-HT1C receptors (d-fenfluramine) and 5-HT2 receptors (DOI).

Amphetamines↗

Dietary fat and the control of energy intake: evaluating the effects of fat on meal size and postmeal satiety.

Three separate experiments in lean subjects confirmed that a 1.52-MJ (362-kcal) carbohydrate supplement at breakfast suppressed appetite 90 min later but had no effect on a test meal given after 270 min. A 1.52-MJ (362-kcal) fat supplement produced no detectable action on measures of appetite at any time point. Therefore, fat and carbohydrate do not have identical effects on the appetite profile. In a further study in obese subjects, a novel experimental design was used to assess the satiating efficiency and compensatory response of fat. Eating from a range of either high-fat or high-carbohydrate foods, obese subjects voluntarily consumed twice as much energy from the fat items, thereby indicating a weak action of fat on satiation. In turn, this large intake of fat exerted a disproportionately weak effect on satiety. These studies suggest that the appetite-control system may have only weak inhibitory mechanisms to prevent the passive overconsumption of dietary fat. The results indicate how this action could induce a positive energy balance and lead to a gradual upward drift in body mass index.

Analysis of Variance↗

Mechanisms of appetite control and their abnormalities in obese patients.

Human appetite is a complex mixture of physiological and psychological phenomena which include feelings of hunger, total energy intake, ingestion of particular nutrients, distribution and sizes of meals and snacks, specific cravings and food preferences. These phenomena can be assembled into a profile of motivation and a pattern of eating which represents the way in which appetite fluctuates over time. The satiety cascade shows the processes through which nutrition exerts effects on the biological system and, therefore, on feelings and behaviour. Within the biological system, the control of appetite involves post-ingestive mechanisms, including signals arising from the gastrointestinal tract and the release of hormones when food is processed. Post-absorptive mechanisms include the detection of important products of digestion, such as glucose and amino acids, together with the nature of the fuel mix oxidized and other metabolic variables. In obese patients, evidence points to a defect in the control of fat intake. In these people, dietary fat exerts only a weak action on satiation and satiety; it fails to generate strong responses in the mechanisms of the satiety cascade. An imbalance between fat intake and oxidation favours weight gain. A consideration of the psychobiological system (interactions between behaviour, peripheral physiology and neurochemical profiles) suggests strategies for treating or preventing the development of weight gain in vulnerable individuals.

Appetite↗

Dietary fat and appetite control in obese subjects: weak effects on satiation and satiety.

The present study assessed the capacity of both high fat and high carbohydrate (CHO) foods to lead to overconsumption in 12 obese women (mean BMI = 42 kg/m2). Subjects were provided with either a low (527 kcal) or high (985 kcal) energy meal at midday. Energy intake was then measured in a later ad libitum dinner meal in which subjects ate from a range of either high fat or high CHO foods. Energy intake following exposure to these meals was then assessed using food intake diary records which were kept for the rest of the day and for the following 24 h. The energy manipulations at lunch gave rise to different levels in the rated intensity of hunger. At the dinner meal subjects consumed an average of 937 kcal following the high energy lunch and 1026 kcal following the low energy lunch (an increase of 10%). However, average intake from the high CHO dinner meal was only 677 kcal compared to 1336 kcal from the high fat dinner meal (an increase of 97%). Consequently the most important variable influencing dinner meal size was not level of hunger but the nutrient content of the range of foods consumed. Analysis of dinner meal intake revealed a significant interaction between lunch meal size and dinner meal type. This means that when hunger level was high subjects over-ate on the high fat but not the high CHO foods. Average post-dinner intakes following the high fat and high CHO meals did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗