Bite size, ingestion rate, and meal size in lean and obese women.

The effect of bite size on ingestion rate, satiation, and meal size was studied in nine lean and nine obese women. On separate days, subjects were given one of three bite sizes of sandwiches and one of two bite sizes of bagels with cream cheese to eat in a laboratory lunch. Decreasing bite size significantly lowered ingestion rate for the whole meal. The effect was most pronounced at the beginning of meals. As bite size decreased from 15 to 5 g, the average ingestion rate decreased from (mean +/- SEM) 19.4 +/- 2.0 to 15.9 +/- 2.0 g/min (p < 0.001). The initial ingestion rate decreased from 30.0 +/- 2.9 to 19.6 +/- 1.7 g/min (p < 0.001). The larger the bite size, the more quickly ingestion rate decelerated; by the end of meals, ingestion rate was not different across conditions. The decrease in ingestion rate with smaller bites was offset by an increase in meal duration, such that meal size did not differ across conditions. Eating behavior of lean and obese subjects was not different. There were individual differences related to ingestion rate, but these were not related to body weight nor to meal size. These results bring into question the recommendation of behavior therapists that obese people eat more slowly in order to eat less.

Stress and the individual. Mechanisms leading to disease.

OBJECTIVE: This article presents a new formulation of the relationship between stress and the processes leading to disease. It emphasizes the hidden cost of chronic stress to the body over long time periods, which act as a predisposing factor for the effects of acute, stressful life events. It also presents a model showing how individual differences in the susceptibility to stress are tied to individual behavioral responses to environmental challenges that are coupled to physiologic and pathophysiologic responses. DATA SOURCES: Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE. DATA EXTRACTION: Independent extraction and cross-referencing by us. DATA SYNTHESIS: Stress is frequently seen as a significant contributor to disease, and clinical evidence is mounting for specific effects of stress on immune and cardiovascular systems. Yet, until recently, aspects of stress that precipitate disease have been obscure. The concept of homeostasis has failed to help us understand the hidden toll of chronic stress on the body. Rather than maintaining constancy, the physiologic systems within the body fluctuate to meet demands from external forces, a state termed allostasis. In this article, we extend the concept of allostasis over the dimension of time and we define allostatic load as the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful. CONCLUSIONS: This new formulation emphasizes the cascading relationships, beginning early in life, between environmental factors and genetic predispositions that lead to large individual differences in susceptibility to stress and, in some cases, to disease. There are now empirical studies based on this formulation, as well as new insights into mechanisms involving specific changes in neural, neuroendocrine, and immune systems. The practical implications of this formulation for clinical practice and further research are discussed.

Salt appetite: its neuroendocrine basis.

Based on the early work of Richter (1936), showing that the adrenalectomized rat kept itself alive by drinking hypertonic NaCl solutions, Epstein and Stellar (1955) demonstrated that that salt appetite was innate, not dependent on learning. A series of later papers by Epstein and his students made clear that in addition to the adrenal steroid, aldosterone, salt appetite depended upon the action of angiotensin II in the brain. Blocking either hormone in the brain reduced depletion-induced salt appetite in half; blocking both eliminated it. Two salt depletions enhanced depletion-induced salt appetite by nearly a factor of two even when the rats never had a chance to drink salt in the first depletion. With multiple depletions, need-free salt intake also increased when the rats were sodium replete, producing an chronic, elevated salt appetite. Strikingly, female rats drink almost twice as much as males and become more enhanced by prior depletions. The neural circuitry involved in the synergy of angiotensin and aldosterone is becoming clearer with lesions of the amygdala that reduce aldosterone's effects and lesions of the anterior wall of the third ventricle that reduce angiotensin's effects. The significance of salt appetite in nature, in body fluid homeostasis, and as a model system of the brain mechanisms of ingestive behavior is discussed.

Early-onset repeated dieting reduces food intake and body weight but not adiposity in dietary-obese female rats.

As dieting behavior and attempts at weight loss are becoming increasingly common in adolescent girls, we wished to determine whether early-onset repeated dieting influenced the development of obesity and its metabolic correlates. Female rats were fed a high-fat diet and subjected to six cycles of dieting and regain, beginning in the peripubertal period. Although dieted rats weighted less than nondieted high-fat fed controls at the completion of the sixth cycle, body composition analysis revealed that the two groups were equally obese. Cumulative caloric intake was less in dieted rats, suggesting that the pattern of consumption promoted by dieting helped to establish the obesity. Resting metabolic rate did not differ between the two groups. These data suggest that although early-onset repeated dieting may result in reduced body weight, the eventual level of adiposity may be unknowingly elevated, potentially leading to long-term health risks.

Neuroendocrine factors in salt appetite.

We dedicate this paper to Curt P. Richter, father of the study of salt appetite, who died recently at the age of 94. Richter first demonstrated that the adrenalectomized rat's voracious appetite for salt kept it alive (1936) and showed the same in humans (1940). Our first paper in 1955 demonstrated that salt appetite was an innate response to salt depletion. Since then, we have pursued the notion that the neuroendocrine consequences of sodium depletion create a brain state that raises salt appetite. In Epstein's laboratory, it was shown that angiotensin and aldosterone, the hormones of salt retention in the periphery, act synergistically in the brain to produce salt appetite in the rat. Block either hormone and the appetite is reduced by half; block both and the appetite is eliminated despite severe bodily need. With repeated depletions or treatments of the brain with angiotensin and aldosterone, salt ingestion increases, reaching an asymptote by the third depletion. Need-free intake of NaCl also increases, especially in female rats which ingest more NaCl than male rats. In Stellar's laboratory, running speed to salt solutions in a runway is used as a measure of salt appetite. When the appetite is raised with large doses of DOCA, a mimic of aldosterone, rats run rapidly for a taste of strong salt solutions as high as 24% (almost 4 molar). Using ingestion as a measure, the role of the atrial natriuretic peptide (ANP), an antagonist of angiotensin's physiological effect, was investigated as a modulator of salt appetite. When angiotensin is involved is producing salt appetite, following sodium depletion by a diuretic combined with a low-salt diet, ANP reduced salt intake by 40%. When salt appetite was raised by DOCA, however, ANP either had no effect or reduced salt ingestion by only 10%. The subfornical organ, the lateral preoptic area, and the central and medial nuclei of the amygdala are being investigated as major components of the limbic circuit underlying salt appetite produced by the actions of angiotensin, aldosterone and ANP in the brain.

Effects of variety on food intake of underweight, normal-weight and overweight women.

The food intake of 27 underweight, normal-weight and overweight women was monitored during laboratory luncheon meals of solid food units (SFUs), bite-sized spirals of bread with different sandwich fillings. Simultaneous, but not sequential, presentation of three SFU flavors increased intake compared to presentation of a single flavor in normal-weight and overweight women. Neither variety manipulation enhanced intake in the underweight women, who are more than the other subjects in all conditions. The fact that the foods were so similar probably reduced the effectiveness of the variety manipulations. Overweight and normal-weight subjects had different patterns of intake, but only when eating a single flavor of SFU. Only overweight subjects ate less when three flavors of SFUs were hidden from view in the apparatus used to monitor intake. This procedure prevented subjects from selecting particular flavors of SFUs. Differences in cognitive restraint probably do not explain the differences in the eating behavior of normal-weight and overweight subjects in the present study. Lack of dietary restraint or a high level of hunger may account for the different eating behavior of the underweight subjects compared to the other subjects.

Responses of lean and obese subjects to preloads, deprivation, and palatability.

The effects of preloads, deprivation, and palatability on the eating behavior of non-dieting lean and obese subjects were studied during laboratory meals, using small solid food units (SFUs) to measure the rate of ingestion over the time-course of the meals. In both weight groups, rate of intake decreased from the beginning to the end of meals. The smaller the preloads and the longer the deprivation interval, the faster subjects ate at the beginning of meals and the higher their hunger ratings were. The longest deprivation interval also increased palatability ratings, meal length, and the total amount that subjects ate. Increasing the palatability of the food increased the rate of intake at the beginning of meals, meal length, and the amount of food that subjects ate. Obese subjects were more sensitive to palatability and less responsive to deprivation than lean subjects. For example, while lean subjects became less discriminating about the palatability of the food at the beginning of meals as deprivation increased, obese subjects did not. The satiation mechanism of obese subjects was also different from lean subjects. For example, obese subjects overate after preloads while lean subjects underate compared to their baselines.

Sugar and fat: sensory and hedonic evaluation of liquid and solid foods.

Twenty-five subjects evaluated the sweetness, creaminess and fat content of liquid and solid dairy products containing between 0.1 and 52 g fat/100 g and sweetened with 0-20% sucrose weight/weight. Liquid stimuli included skim milk, whole milk, half and half, and heavy cream, while the solids included cottage cheese and cream cheese, blended and spread "jelly-roll" fashion on slices of white bread. The subjects' ratings of stimulus sweetness, creaminess, and fat content differed sharply between liquids and solids, and the assessment of fat content of solid foods appeared to be impaired. In contrast, acceptability ratings for both sets of stimuli were not substantially different: the subjects optimally preferred equivalent levels of sugar in both liquids and solids, but selected higher fat levels in solid than in liquid foods. Sensory preferences for fat in liquid stimuli may not always be indicative of preferences for fat in solid foods.

Effect of naltrexone on food intake, hunger, and satiety in obese men.

Increasing doses of naltrexone (25 to 200 mg) given over 4 consecutive days reduced intake of laboratory luncheon meals by 30% in 17 obese men. Meal size remained suppressed in the laboratory during the week following naltrexone administration. Water intake in the laboratory and body weight were not affected. Rates of ingestion and subjective ratings suggested that naltrexone reduced appetite rather than promoted early satiation. Nausea and other side effects occurred on 1 or 2 days during the naltrexone week in seven subjects whose food intake was reduced. Food intake was also reduced in seven of the remaining 10 subjects who reported no adverse reactions. These results suggest that a conditioned taste aversion or a conditioned anorexia may have developed in some subjects.

The effects of repeated cycles of weight loss and regain in rats.

This study examined the metabolic effects of weight cycling, i.e., repeated periods of weight loss followed by regain. There were three groups of adult, male Sprague-Dawley rats: (1) Chow Controls (a normal weight control group fed chow throughout); (2) Obese Controls (animals fed a high-fat diet throughout); and (3) Obese Cycling (obese animals cycled through two bouts of caloric restriction and refeeding). The cycled animals showed significant increases in food efficiency (weight gain/kcal food intake) in the second restriction and refeeding periods compared to the first, i.e., weight loss occurred at half the rate and regain at three times the rate in the second cycle. Several physiological changes were associated with this cycling effect. At the end of the experiment, cycled animals had a four-fold increase in food efficiency compared to obese animals of the same weight who had not cycled. These data suggest that frequent dieting may make subsequent weight loss more difficult. The possible metabolic and health consequences of "yo-yo" dieting are discussed.

Brain cholecystokinin as a satiety peptide.

Injection of 0.08 microgram/kg of CCK-8 into the anterior cerebral ventricles of the rat produced a significant depression in the rat's motivation for food for at least one-half hour, as measured by running speed to food rewards in a runway and by food intake in a test-meal in the rat's home cage. Doses of 0.04 microgram/kg were ineffective and doses of 0.06 microgram/kg intermediate. There was no effect of 0.08 microgram/kg on running speed to water rewards. Intraperitoneal doses of 8.0 micrograms/kg also suppressed running speed and eating.

Running to the taste of salt in mineralocorticoid-treated rats.

In the present series of studies, the running speed of rats in a runway was used to measure appetitive motivation for different concentrations of salt solutions. We found that when rats were thirsty, they were not interested in running for concentrated salt solutions; when they were rendered salt hungry by mineralocorticoid treatment in addition to the thirst, or even without thirst, they ran vigorously for salty tasting solutions, as high as 24% NaCl. The running speed is correlated with the degree of the mineralocorticoid treatment and the salt concentration. Moreover, drinking 5 cc of a 3% NaCl solution before the runway test decreases the running speed of the mineralocorticoid-treated rat. The experiments are discussed in the context of the effects of hormonal events on the movitation to ingest salt solutions.

Chews and swallows and the microstructure of eating.

The study of eating behavior in animals and humans shows that much is learned if detailed and sensitive measurement of the ingestive process can be made. It is possible to measure all chews and swallows of human subjects during a meal. This proves to be a sensitive way to measure the microstructure of a meal, reflecting hunger, palatability, and satiation. The oral sensor promises to be an unobtrusive and objective method of measuring all meals, snacks, and nibbling throughout the day. The oral sensor should provide a means of evaluating both the palatability and the satiating value of foods and the role of hunger and other manipulations of the internal environment in changing the chewing and swallowing microstructure of eating.

The failure of ventricular sodium to control sodium appetite in the rat.

Dilution of CSF sodium by infusion of hyperosmotic mannitol into the cerebral ventricles of the rat does not evoke a salt appetite, nor does the addition of sodium to the CSF of the rat suppress the preexisting salt appetites produced by the hormones of sodium conservation or by adrenalectomy. CSF sodium concentration does not control sodium appetite in the rat. The proposal that it does so in sheep should not be generalized to other species without caution.

Together intracranial angiotensin and systemic mineralocorticoid produce avidity for salt in the rat.

Rats that have no need for sodium will run to small rewards of 3% NaCl solution in a runway after they have been treated with both a mineralocorticoid and angiotensin II. When given alone at the low doses used here, neither the mineralocorticoid nor the angiotensin produce the behavior. This result encourages the idea that it is a synergy of the hormones of sodium conservation, angiotensin and aldosterone, that apprises the brain of the need for salt and generates the appetite for the taste of salt.