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Effects of sibutramine on binge eating, hunger, and fullness in a laboratory human feeding paradigm.

OBJECTIVE: The purpose of this study was to evaluate the effects of sibutramine vs. placebo on binge-eating behavior, hunger, and satiety in patients who had problems with binge eating. RESEARCH METHODS AND PROCEDURES: Seven adult subjects who had problems with binge eating (mean age, 42 years) were randomly assigned to receive alternating sibutramine and placebo in a double-blind placebo-controlled crossover study. This involved two 4-week dosing periods separated by a 2-week washout. RESULTS: Subjects lost weight on sibutramine but not on placebo. There was a significant difference in the number of kilocalories consumed between the sibutramine and placebo conditions, with a significant reduction of intake during binge-eating episodes on sibutramine. DISCUSSION: Sibutramine suppresses intake during binge-eating episodes. This effect is demonstrable in a human feeding laboratory paradigm.

Adult↗

Eating in the absence of hunger: a genetic marker for childhood obesity in prepubertal boys?

OBJECTIVE: Eating in the absence of hunger (EAH) may be a behavioral trait through which obesity-promoting genes promote positive energy balance. The primary aim of this study was to compare children born at high vs. low risk for obesity with respect to EAH at 5 years of age. RESEARCH METHODS AND PROCEDURES: This was an observational investigation of families enrolled in the University of Pennsylvania and The Children's Hospital of Philadelphia's Infant Growth Study. Five-year-old children born at high (N = 28) or low (N = 25) risk for obesity on the basis of maternal prepregnancy body weight were evaluated at a hospital-based laboratory. Children consumed 11 snack foods ad libitum after consuming an ad libitum dinner and reporting fullness. Parents reported on snack foods at home and their own eating styles. Nutritive sucking at 3 months of age was evaluated by computerized apparatus. RESULTS: EAH in high-risk boys (mean +/- standard error = 326 +/- 66 kJ] was more than twice that of low-risk boys (mean +/- standard error = 151 +/- 39 kJ), p = 0.03. Among girls, there was a trend for EAH to be associated with increased parental limitations on daughter snack food consumption at home (p = 0.06). EAH was unrelated to 3-month sucking behavior. DISCUSSION: Genes that promote childhood obesity may partially exert their influence through EAH, an effect that was limited to boys born at risk for obesity. The unique influences of genes and home environment on this trait should be disaggregated in subsequent studies.

Birth Weight↗

Reciprocal hunger-regulating circuits involving alpha- and beta-adrenergic receptors located, respectively, in the ventromedial and lateral hypothalamus.

The injection of adrenergic and adrenolytic drugs directly into the brain through permanently implanted cannulas has yielded results showing that food consumption in the rat is regulated by a hypothalamic alpha-adrenergic "hunger" system. and a hypothalamic beta-adrenergic "satiety" system. The rats' differential responses to alpha-adrenergic and beta-adrenergic drugs injected into different hypothalamic sites indicate the following: (1) the lateral hypothalamic "feeding" center contains beta receptors, the activation of which produces satiation, presumably by inhibition of the lateral "feeding" cells; (2) the ventromedial hypothalamic "satiety" center contains alpha receptors, the activation of which produces eating, presumably by inhibition of the ventromedial "satiety" cells; and (3) the medio-lateral perifornical area of the hypothalamus contains both alpha and beta receptors, which lead to inhibition of the ventromedial or lateral hypothalamic centers respectively. It is suggested that the ventromedial and lateral hypothalamus are connected by reciprocal circuits, so that activation of the ventromedial center results in stimulation of the lateral beta receptors which inhibit the lateral "feeding" cells, and activation of the lateral center results in stimulation of the ventromedial alpha receptors which inhibit the ventromedial "satiety" cells.

Adrenergic alpha-Agonists↗

Increased thirst and hunger in adult rats undernourished as infants: an alternative explanation.

1. Rats were undernourished in early life by feeding their mothers a restricted quantity of a good-quality diet throughout lactation. Their undernutrition continued postweaning from 25 to 42 d of age, after which they were fed ad lib. Control rats were well nourished at all times. 2. Behavioural assessment of thirst was carried out on adult males. These were deprived of water for 23 h/d throughout the period of testing. Compared to control rats, previously-undernourished (PU) rats pressed a lever at a higher rate in a Skinner box to gain a water reward, drank more frequently during their first 5 min in an unfamiliar cage, and tended to run more quickly down an alleyway for water. PU rats also drank more (/kg body-weight 0-75) of a quinine solution (I g/l) when this was available to them ad lib. as their only source of fluid. 3. A second group of rats was growth-retarded during gestation and the suckling and early postweaning periods. The rats had free access to food from 42 d of age. In adulthood their ad lib. food and water consumption was measured. PU males ate and drank more (/kg body-weight 0-75) than control males. 4. These results indicate that adult rats which have been undernourished in early life display increased thirst. An attempt is made to explain this finding, together with their previously-demonstrated enhanced hunger drive, purely in terms of gross anatomical and physiological differences.

Animals↗

Hunger behaviour contributes to early nutritional homeostasis.

OBJECTIVES AND METHODS: Our goal was to describe nutritional homeostasis in healthy exclusively breastfed infants (n = 175) during their first 5 d, by cross-sectional measurements of body weight, blood glucose, plasma insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding-protein-1 (IGFBP-1), free fatty acids (FFA), glycerol, ketone (3-OH-butyric acid) and lactate. We also investigated whether nutrition affected feeding behaviour by timing the interval between feedings. RESULTS: A progressive loss of body weight, as percentage of birthweight, occurred up to 2 d of age, with a maximal decrease of 5.8 +/- 2.1% (mean +/- SD); this was accompanied by inhibition of anabolic hormone and metabolic pathways and an increased mobilization of stored fat and ketogenesis. The interval between feedings decreased between d 1 and 2. Weight gain occurred at 3 d and the following re-feeding phase returned fuel stores to their previous levels and established an anabolic hormonal and metabolic situation. Infants with weight loss exceeding 10% had a further accentuation in their peripheral picture of starvation and a further 7% shortening of the interval between feedings. CONCLUSIONS: breastfeeding on demand is accompanied by a balanced nutritional situation and an increased drive to eat when weight reduction is <6%. However, a weight loss of > or = 10%, probably elicits hunger sensations in response to decreased fuel availability.

Analysis of Variance↗

Appetite, hunger, and satiety in the elderly.

Food intake declines with age and the elderly frequently report a decrease in appetite. Social and physical factors as well as decreased energy expenditure may be part of the explanation for the decreased food intake; however, it is possible that changes in hunger mechanisms are also involved, but more studies similar to those conducted on thirst are needed. The consumption of a varied diet depends in part on sensory-specific satiety, that is, the decrease in the pleasantness of a food as it is consumed. We have shown that sensory-specific satiety changes with age such that it was absent in individuals over the age of 65 and this could be part of the explanation of why the elderly consume more monotonous diets. Additional basic studies on how aging affects the controls of food intake will suggest ways to improve the nutritional status of the elderly.

Aged↗

Snacks consumed in a nonhungry state have poor satiating efficiency: influence of snack composition on substrate utilization and hunger.

BACKGROUND: Several epidemiologic studies suggest that snacking may play an etiologic role in obesity. OBJECTIVE: We assessed the behavioral and metabolic consequences of a high-carbohydrate (HC) or high-protein (HP) snack consumed 215 min after lunch, thereby investigating ways that snacking in a nonhungry state could be involved in the etiology of obesity. DESIGN: Eight lean young men attended 3 sessions (basal, HP snack, and HC snack) in a counterbalanced order with 2 wk between sessions. During all sessions, subjects were time-blinded while we measured the temporal pattern of plasma glucose, insulin, and fatty acid concentrations; hunger ratings; substrate oxidation; and energy expenditure from 215 min after the beginning of lunch until the spontaneous dinner request. RESULTS: Compared with the basal (no snack) session, the HP snack delayed the spontaneous dinner request (by 38 +/- 16 min, P < 0.05) but the HC snack did not. Energy and macronutrient intakes at dinner were unaffected by both snacks. After the HP snack, plasma fatty acid concentrations were lower (P < 0.05), but glucose and insulin were unchanged compared with the basal session. After the HC snack, plasma glucose and insulin concentrations were higher and plasma fatty acid concentrations were lower than those in the basal session (P < 0.05 for both). Both snacks promoted carbohydrate utilization (P < 0.05), and the HC snack depressed fat oxidation (P < 0.05). CONCLUSION: This study showed that a snack consumed in a satiety state has poor satiating efficiency irrespective of its composition, which is evidence that snacking plays a role in obesity.

Adult↗

Learning to overeat: maternal use of restrictive feeding practices promotes girls' eating in the absence of hunger.

BACKGROUND: Experimental findings causally link restrictive child-feeding practices to overeating in children. However, longitudinal data are needed to determine the extent to which restrictive feeding practices promote overeating. OBJECTIVES: Our objectives were to determine whether restrictive feeding practices foster girls' eating in the absence of hunger (EAH) and whether girls' weight status moderates the effects of restrictive feeding practices. DESIGN: Longitudinal data were used to create a study design featuring 2 maternal restriction factors (low and high), 2 weight-status factors (nonoverweight and overweight), and 3 time factors (ages 5, 7, and 9 y). RESULTS: Mean EAH increased significantly (P < 0.0001) from 5 to 9 y of age. Higher levels of restriction at 5 y of age predicted higher EAH at 7 y of age (P < 0.001) and at 9 y of age (P < 0.01). Girls who were already overweight at 5 y of age and who received higher levels of restriction had the highest EAH scores at 9 y of age (P < 0.05) and the greatest increases in EAH from 5 to 9 y of age (P < 0.01). CONCLUSIONS: The developmental increase in EAH from 5 to 9 y of age may be especially problematic in obesigenic environments. These longitudinal data provide evidence that maternal restriction can promote overeating. Girls who are already overweight at 5 y of age may be genetically predisposed to be especially responsive to environmental cues. These findings are not expected to be generalized to boys or to other racial and ethnic groups.

Adult↗

Fermentable and nonfermentable fiber supplements did not alter hunger, satiety or body weight in a pilot study of men and women consuming self-selected diets.

Little is known about the relative effects of fermentable fiber (FF) vs. nonfermentable fiber (NFF) on energy regulation in humans. We compared 27 +/- 0.6 g/d supplements of FF (pectin, beta-glucan) and NFF (methylcellulose) for their ability to decrease ad libitum energy intake (EI) and hunger, increase satiety and cause spontaneous body weight and fat losses. Men and women (n = 11) aged 23-46 y, BMI 20.0-34.4 kg/m2, consumed first NFF and then FF for 3 wk each, with a 4-wk washout period between phases. Daily satiety assessed with analog scales was higher with NFF than FF (60.7 +/- 1.0 vs. 57.7 +/- 0.8 mm, P = 0.01). However, there were no differences in reported EI (NFF < FF by 7%, P = 0.31, NFF < baseline by 9.5%, P = 0.11), body weight (NFF 0.13 kg, P = 0.73; FF 0.13 kg, P = 0.60) or fat percentage (NFF -0.3%, P = 0.56; FF -0.1%, P = 0.66) within either phase. In contrast to findings in animals, NFF was more, rather than less satiating than FF, and use of neither NFF nor FF preparations was associated with body weight or fat loss. These pilot results suggest no role for short-term use of FF and NFF supplements in promoting weight loss in humans consuming a diet ad libitum.

Adult↗

Effects of hunger on aggression, approach, and avoidance by juncos (Junco hyemalis).

The aggressive tendencies of male dark-eyed juncos Junco hyemalis did not differ significantly following deprivation from food for 20 and 60 min. Tendencies to approach opponents at food, in contrast, increased with longer deprivation. Acute hunger and aggression are thus not competing behavioral systems. Nor do differences in rates of approach by subordinates affect aggressive tendencies of dominant birds.

Aggression↗

The effect of gut peptides on hunger, satiety, and food intake in humans.

A number of peptides synthesized and secreted by gastrointestinal cells have been shown to possess significant effects on food intake and on perceptions of hunger and satiety in humans. In this paper, we review the available literature on these effects and emphasize the current obstacles for the therapeutic application of peptides to the problem of obesity.

Appetite↗

High-glycemic index foods, hunger, and obesity: is there a connection?

The relative importance of different dietary causes of obesity remains controversial. This review examines whether consumption of high-glycemic index (GI) carbohydrates may be a contributing factor. Although data from long-term studies are lacking, short-term investigations indicate that consumption of high-GI carbohydrates may increase hunger and promote overeating relative to consumption of items with a lower GI. As long-term research on GI and weight regulation accumulates, consumption of whole grain and lower GI cereals instead of highly refined cereals is a dietary change that may help prevent overeating and is consistent with current dietary guidelines.

Blood Glucose↗

Differences between the anorexic actions of amphetamine and fenfluramine--possible effects on hunger and satiety.

The inhition of feeding in rats brought about by amphetamine and fenfluramine was continuously monitored for periods of up to 24 h using a pellet detecting eatometer. For rats tested under conditions of food deprivation the two drugs gave rise to distinctive anorexic profiles: amphetamine delayed the onset of eating whereas fenfluramine allowed eating to commence normally but brought about an early termination of the initial bout of feeding. When the drugs were administrated to rats with free access to food, analysis of the meal pattern showed that amphetamine gave rise to a small increase in the inter-meal interval while fenfluramine brought about a clear reduction tion in meal size. It is suggested that the contrasting modes of action of these drugs represent an effect of amphetamine upon hunger and an action of fenfluramine on satiety. This suggestion is in keeping with the proposed mechanisms of action of these drugs, amphetamine acting upon a hpothalamic motivational system and fenfluramine acting by means of a postulated serotoninergic satiety system. Use of the continuous monitoring technique has pointed pointed to certain limitations in the assessment of anorexic drug action by means of discrete food sampling periods.

Animals↗

Self-stimulation of the brain; its use to study local effects of hunger, sex, and drugs.

My conclusions are these: (i) The cells which mediate primary rewarding effects are located in a midline system running from the midbrain through the hypothalamus and midline thalamus and into the subcortical and cortical groups of the rhinencephalon. (ii) The cell groups which mediate primary rewarding effects are different from those which mediate primary punishing effects. (iii) Despite this relative independence, there are, undoubtedly, relationships of mutual inhibition existing between these two systems. Rewards do, among other things, tend to reduce sensitivity to pain, and punishments do tend to reduce rewarding effects. (iv) These primary reward systems of the brain are subdivided into specific drive-reward subsystems mediating the specific drives such as hunger and sex. (v) Because there are also subsystems of this set of rewarding structures sensitive to different chemical effects, it is reasonable to hope that eventually it will be possible to control the reward systems pharmacologically in cases where behavior disorders seem to result from deficits or surfeits of positive motivation.

Brain↗

Time course of effects of preloads high in fat or carbohydrate on food intake and hunger ratings in humans.

A high-carbohydrate (CHO) yogurt (81% CHO) and a high-fat yogurt (65% fat), containing similar levels of protein, were given in equal volumes as preloads to 14 normal-weight, nondieting males and 14 normal-weight, nondieting females. The yogurts were formulated to have similar energy densities and sensory properties, so that differences in responses to the preloads would depend on postingestive physiological effects. Three intervals (30, 90, and 180 min) between the preloads and a self-selection meal consisting of a variety of foods were utilized. The self-selection meal was served at the subject's normal lunchtime under all conditions. In the 30-min-delay condition, subjects accurately compensated for the calories in the preloads compared with a no-preload condition, but as the interval increased, compensation was less precise. No significant differences in subsequent food intake were found between the high-CHO and high-fat yogurts at any time interval. Also, there were no differences in ratings of hunger and fullness between the yogurts. The macronutrient composition of the preloads did not affect the types of foods, or macronutrients, consumed at lunch.

Adult↗

Combating hidden hunger: the role of international agencies.

The importance of micronutrient deficiencies or "hidden hunger" was clearly emphasized by the inclusion of specific goals on iron, vitamin A, and iodine deficiency at the 1990 World Summit for Children and other major international nutrition conferences. Significant progress has since been made toward eliminating vitamin A and iodine deficiencies, with less progress made toward reducing the burden of iron-deficiency anemia. The role of international agencies, such as the World Health Organization, United Nations Children's Fund, Food and Agricultural Organization, and World Bank in assisting countries to make progress toward the World Summit for Children goals has been very important. International agencies have played a critical role in advocating for and raising awareness of these issues at the international, regional, and national levels among policymakers and the general population. Using a rights-based approach, UNICEF and other agencies have been instrumental in elevating to the highest political level the discussion of every child's right to adequate nutrition. International agencies have also been very supportive at the national level in providing technical guidance for programs, including monitoring and evaluation. These agencies have played a critical role in engaging the cooperation of other partners, including bilateral donors, non-governmental organizations, and the private sector for micronutrient programs. Furthermore, international agencies provide financial and material support for micronutrient programs. In the future, such agencies must continue to be heavily involved in programs to achieve the newly confirmed goals for 2010. The present paper focuses on the role of international agencies in combating micronutrient deficiencies, drawing on the lessons learned over the last decade. The first section of the paper summarizes the progress achieved since 1990, and the second section describes the specific role of international agencies in contributing to that progress.

Anemia, Iron-Deficiency↗

Ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, and hunger responses to a mixed meal in anorexic, obese, and control female adolescents.

To determine whether peptide YY (PYY), ghrelin, glucose-dependent insulinotropic polypeptide (GIP), and satiety responses to food intake are impaired in anorexia or obesity, we studied 30 female adolescents with anorexia nervosa [body mass index (BMI) 16.3 kg/m2], obesity (BMI 34.3 kg/m2), or normal weight (BMI 20.2 kg/m2). PYY, ghrelin, GIP, insulin, and glucose concentrations and four markers of satiety were measured for 240 min after a mixed meal. The area under the curve for glucose was similar in obese (OB) and normal-weight control (C) subjects but was 15% lower in anorexic (AN) subjects. The area under the curve for insulin was 47% lower in AN and 87% higher in OB subjects, compared with C subjects. After the meal, PYY increased significantly in C (+41%, P < 0.05) but not in AN or OB adolescents. Ghrelin concentrations were highest in AN subjects and lowest in the OB group, compared with C subjects and fell significantly by 25% in all three groups. GIP concentrations were lower in AN subjects throughout the test and increased in all three groups after the mixed meal. AN adolescents reported being less hungry than OB and C adolescents. There was a negative correlation between fasting ghrelin (but not PYY or GIP) and BMI and insulin (r2= 0.33) and a positive correlation between the decrease in hunger 15 min after the meal and PYY concentrations at 15 min (r2= 0.20). In conclusion, the blunted PYY response to a meal in OB adolescents suggests that PYY plays a role in the pathophysiology of obesity. Ghrelin is unlikely to play a causal role in anorexia nervosa or obesity. The lower GIP observed in AN subjects despite a similar caloric intake may appropriately prevent an excessive insulin response in these patients.

Adolescent↗

Changes in body fluid and energy compartments during prolonged hunger strike.

UNLABELLED: Prolonged total food deprivation in non-obese adults is rare, and few studies have documented body composition changes in this setting. In a group of eight hunger strikers who refused alimentation for 43 days, water and energy compartments were estimated, aiming to assess the impact of progressive starvation. Measurements included body mass index (BMI), triceps skinfold (TSF), arm muscle circumference (AMC), and bioimpedance (BIA) determinations of water, fat, lean body mass (LBM), and total resistance. Indirect calorimetry was also performed in one occasion. The age of the group was 43.3+/-6.2 years (seven males, one female). Only water, intermittent vitamins and electrolytes were ingested, and average weight loss reached 17.9%. On the last two days of the fast (43rd-44th day) rapid intravenous fluid, electrolyte, and vitamin replenishment were provided before proceeding with realimentation. Body fat decreased approximately 60% (BIA and TSF), whereas BMI reduced only 18%. Initial fat was estimated by BIA as 52.2+/-5.4% of body weight, and even on the 43rd day it was still measured as 19.7+/-3.8% of weight. TSF findings were much lower and commensurate with other anthropometric results. Water was comparatively low with high total resistance, and these findings rapidly reversed upon the intravenous rapid hydration. At the end of the starvation period, BMI (21.5+/-2.6 kg/m2) and most anthropometric determinations were still acceptable, suggesting efficient energy and muscle conservation. CONCLUSIONS: 1) All compartments diminished during fasting, but body fat was by far the most affected; 2) Total water was low and total body resistance comparatively elevated, but these findings rapidly reversed upon rehydration; 3) Exaggerated fat percentage estimates from BIA tests and simultaneous increase in lean body mass estimates suggested that this method was inappropriate for assessing energy compartments in the studied population; 4) Patients were not morphologically malnourished after 43 days of fasting; however, the prognostic impact of other impairments was not considered in this analysis.

Adipose Tissue↗