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Effect of fenfluramine on caloric intake and macronutrient selection in Lou/c rats during aging.

Previous studies have shown a shift of preferences from carbohydrate to fat and a decrease in protein intake in self-selected Lou/c rats with advancing age. This study investigated a potential neurochemical mechanism underlying age-related modifications by evaluating the effects of fenfluramine (dl-F), a drug that enhances 5-HT release and blocks its re-uptake by presynaptic terminals, on macronutrient selection. The drug dl-F (1.5 and 3mg/kg s.c.) induces a dose-related hypophagia with the oldest animals being the most sensitive. The main decrease is in fat consumption with minor changes in carbohydrate and protein consumptions. Young, but not old animals, compensate during the day the nocturnal intake decrease induced by dl-F. The plasma concentration of dexfenfluramine (d-F) was higher as the rats aged. The icv administrations of dl-F induced a caloric intake decrease in the oldest groups and a differential effect on protein intake between old and young rats. Metergoline induced a partial reversion of dl-F effect on food intake but this effect was not age related. These data suggest a possible implication of serotoninergic system in modifications of food behavior during aging. However, further studies are needed.

Aging↗

Acute effects of nicotine on hunger and caloric intake in smokers and nonsmokers.

The inverse relationship between smoking and body weight may be due in part to nicotine's effects on reducing hunger and eating. Male smokers and nonsmokers (n = 10 each), abstinent overnight from smoking and food, participated in four sessions, involving consumption of a liquid caloric load or water followed by nicotine (15 micrograms/kg) or placebo via nasal spray every 20 min for 2 h. Hunger and satiety ("fullness") ratings were obtained prior to each dose presentation. At the end of the two sessions involving the caloric load (simulating breakfast), subjects were also presented with typical lunch/snack food items varying in sweet taste and fat content for ad lib consumption. Results indicated that, for both smokers and nonsmokers, the hunger-reducing effects of nicotine occurred only following caloric load consumption, and there was no effect of nicotine on hunger afer water consumption. Smokers unexpectedly reported greater satiation than nonsmokers following the caloric load regardless of nicotine or placebo condition. Nicotine also resulted in less caloric intake during the meal, and the decrease was not specific to consumption of sweet, high-fat foods. These results indicate that nicotine reduces appetite, possibly helping to explain the influence of smoking on body weight.

Adult↗

Synergy between leptin and cholecystokinin (CCK) to control daily caloric intake.

Both cholecystokinin (CCK), a short-term meal-related satiety signal, and the ob protein leptin, a postulated long-term adiposity hormone, are thought to be important signals in the multiple interacting systems that control appetite and adiposity. We hypothesized that these hormones may synergistically interact to suppress feeding. Following IP administration of leptin (two doses of 50 micrograms each) and CCK (2, 4, 8, or 16 micrograms) total daily caloric intake was significantly reduced by leptin and CCK compared to leptin alone. These results support the hypothesis that CCK and leptin may synergistically interact to control long-term feeding.

Animals↗

[Modification of the caloric intake as a function of energy expenditure in patients with diarrhea].

UNLABELLED: We have compared, using non protein RQ method, energy expenditures of diarrheic patients with intraperitoneal or intraluminal suppuration and feed enterally (group II) or intravenously (group III). Five non suppurative diarrheic patients feed enterally were studied as control (group I). Carbohydrate, protein and fat intakes were not significantly different in the 3 groups of patients. Patients of group II metabolized significantly less of carbohydrate (p less than 0.01) and more of fat (P less than 0.01) than groups I and III patients. Carbohydrate and fat expenditures of patients of groups I and III were not significantly different. CONCLUSION: 1) There is a possible trouble of carbohydrate absorption in suppurative diarrheic patients. 2) Therefore caloric intake must be preferably parenteral in these patients.

Adolescent↗

Influence of formula concentration on caloric intake and growth of normal infants.

Fifteen fullterm female infants were enrolled in each of two feeding groups and all but one completed the proposed period of observation to age 112 days. Formulas prepared from the same ingredients (fat-free milk solids, a mixture of corn and coconut oils, lactose, vitamins and minerals) were fed ad libitum to both groups. Formula concentration was 54 kcal/100 ml for one group and 100 kcal/100 ml for the other. A limited selection of commercially prepared strained foods was permitted after 28 days of age. Weighed intakes of food were recorded for each day of study. During the internal 8 through 41 days of age, the infants fed the 54 kcal/100 ml formula consumed a considerably greater quantity of food but fewer calories than did those fed the 100 kcal/100 ml formula. Those fed the 54 kcal/100 ml formula also gained less weight. These differences between feeding groups were statistically significant. After 41 days of age, mean caloric intakes (kcal/kg/day) and rates of gain in weight were similar for the two feeding groups. The data provide a basis of speculation on the possible difference in allocation of calories to growth and non-growth in the two groups.

Age Factors↗

[Excess caloric intake induced severe hypercapnia in a patient with Duchenne muscular dystrophy on noninvansive positive pressure ventilation].

In many patients with neuromuscular diseases, respiratory failure is mainly caused by alveolar hypoventilation in their terminal stages. Malnutrition is one of the common and serious problems in patients with chronic respiratory failure. Energy consumption for breathing is remarkably high in respiratory compromised patients, causing subsequent increase of total energy expenditure. However, most patients have limited capacity of oral intake. Nutritional depletion is associated with wasting of respiratory muscles, impairment of respiratory drive, alteration of respiratory pattern, and pathological change of pulmonary parenchyma. These indicate that nutritional and ventilatory support is very important in these patients. However, overfeeding also may have detrimental influence on respiratory failure. We experienced a Duchenne muscular dystrophy (DMD) patient on noninvasive positive pressure ventilation (NIPPV) who developed hypercapnia after total parenteral nutrition (TPN). Analysis of clinical course of this patient revealed that there is a significant correlation between PaCO2 and caloric intake. Excess carbohydrate intake can precipitate fat synthesis which induces over-production of carbon dioxide (CO2). Since NIPPV doesn't have a closed circuit, there are some difficulties in respiratory management, such as air leakage to stomach and mouth, and airway obstruction. Failure to optimize NIPPV setting against increased CO2 load might cause hypercapnia in this patient. These suggest that evaluation of energy expenditure and design of nutritional program are essential to avoid hypercapnia due to nutritional support.

Adult↗

Caloric intake, stress, and menstrual function in athletes.

The cause of menstrual disturbance in athletes is still debated. Apart from the acute and chronic effects of exertion, other associated behavioral variables are suspected to play a key role. A longitudinal study with frequent blood sampling was undertaken to link information about nutrition and stress with a quantitative assessment of endocrine menstrual function in 18 endurance-trained athletes and 25 age-matched, nonathletic women. Four athletes did not show hormonal signs of follicular development. The 14 athletes with cyclic gonadal function did not differ from controls with regard to estradiol concentrations during the follicular phase and at midcycle. During the luteal phase, however, they showed significantly reduced areas under the estradiol and progesterone curves. Caloric intake, as assessed by nutritional diaries, correlated positively with the area under the progesterone curve during the luteal phase (rs = 0.70, P less than 0.01). Ratings of subjective stress in the area "partner, family, friends" correlated negatively with the luteal progesterone area (rs = 0.80; P less than 0.01). Data support the hypothesis that nutrition and stress may play a critical role in the genesis of menstrual disturbance in athletes.

Adult↗

A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer.

This double-blind, cross-over trial was designed to assess the effects of megestrol acetate (MA) on cancer-induced cachexia. Forty consecutive malnourished patients with advanced non-hormone-responsive tumors receiving no antineoplastic treatment were randomized to receive MA 480 mg/day versus placebo for 7 days. During day 8, a cross-over was made until day 15. Appetite, pain, nausea, depression, energy, and well-being were assessed with a visual analog scale (0 to 100 mm) at 9:00 AM and 4:00 PM during days 6, 7, 13, and 14. Weight (W;kg), tricep skinfold (TS; mm), arm circumference (AC; cm), and calf circumference (CC; cm) were measured at days 1, 8, and 15. Caloric intake (CI; Kcal/day) was determined during days 6, 7, 13, and 14. In 31 evaluable patients, the percentual difference in appetite at 9:00 AM, appetite at 4:00 PM, energy, and well-being after MA was +15.1, +14, +3.2, and +5.2, versus -12 (P = 0.03), -5.1 (P = 0.015), -10 (P = 0.024), and -8.3 (not significant) after placebo. Percentual difference in W, TS, AC, and CC after MA was +0.2, +1, -0.1, and +0.4 versus -0.8 (P = 0.03), -0.8 (P = 0.001), -0.3 (not significant), and -0.5 (P = 0.04) after placebo. CI during MA was 3480 +/- 1574 (48-hour intake), versus 2793 +/- 1542 (P less than 0.001) during placebo. Patients and investigators blindly chose MA in 20 (66%, P = 0.023) and 28 cases (92%, P less than 0.001), placebo in eight and two cases, and made no choice in three and one cases, respectively. Toxicity consisted of mild edema and nausea in three and two cases, respectively. After mean follow-up of 27 +/- 13 days, on an open basis, an average increase in W and AC of 4.8 +/- 1.7 kg and 2.8 +/- 1.7 cm was observed, respectively. The authors conclude that MA is a powerful appetite stimulant with subjective and objective effects on nutritional status.

Appetite↗

Long-term optional ingestion of corn oil induces excessive caloric intake and obesity in mice.

Corn oil is well tolerated by mice but tolerance may decrease with excessive ingestion. In the present study, we compared the effects of optional ingestion of excessive corn oil with ingestion of water (control) or a 20% sucrose solution in mice. During the entire study, mice consistently ingested 100% corn oil and incrementally ingested 20% sucrose. Food intake in the corn-oil group was approximately constant but that in the sucrose group was slightly decreased. Body-weight gains in the corn-oil group were higher than those in the control and sucrose groups. At the end of the study, hepatic hypertrophy and fatty liver were present, especially in the corn-oil group, and the visceral fat of mice fed corn oil increased significantly compared with the other two groups. These results suggest that mice, when given a choice, will continue to overeat corn oil over the long term, inducing excessive caloric intake and obesity.

Animals↗

Regulation of bile acid pool size and plasma lipid levels in the SHR/N-corpulent rat: influence of the level of caloric intake.

In the obese progeny of the SHR/N-cp strain of the rat the bile acid pool was at least twice as large as that in their lean littermates even when only 6 weeks old. The composition of the pool remained unchanged in the obese females, but in their male counterparts the proportion of cholic acid was significantly increased. Cholestyramine feeding reduced the pool size by 26% in the obese rats, but a similar effect also occurred in the lean animals. The obese rats consumed about 60% more food per day than their lean littermates. When obese females were pair-fed to the intake of their lean controls from 6 to 11 weeks of age, the bile acid pool remained significantly enlarged, although not to the same extent as in the obese rats fed ad lib. Plasma cholesterol levels were reduced but remained significantly higher than the levels in the lean animals. The marked hypertriglyceridemia exhibited by the obese rats fed ad libitum did not develop in their pair-fed counterparts. In contrast, there was a comparatively smaller reduction in plasma cholesterol and triglyceride levels in the obese rats fed cholestyramine. Hepatic steatosis persisted in the pair-fed animals as well as in those given cholestyramine. Restricting caloric intake significantly reduced the body weight gain of the obese rats but had little effect on the extent of their corpulence. These studies show that at least some of the characteristics of this congenic strain, including hypertriglyceridemia and hepatic and intestinal hypertrophy, are due mainly to excess dietary intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of palatable diet on growth, caloric intake and endocrine-metabolic profile in weanling rats with dorsomedial hypothalamic lesions.

Weanling male Sprague-Dawley rats received bilateral electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats); sham-operated rats served as controls. All animals were fed lab chow for 15 postoperative days. At that time they were subdivided into two groups each. One DMNL and one control group continued to be fed lab chow until the termination of the experiment on postoperative day 116. A second DMNL and control group were fed a high-fat diet and 32% sucrose solution (HF/SS diet). All DMNL rats showed reduced body weight and linear growth, but the HF/SS diet depressed these parameters further below the levels of the chow-fed groups. Both DMNL and control rats fed HF/SS had more carcass fat, heavier epididymal fat pads, more carcass fat per calories eaten, higher plasma levels of glucose, glycerol and free fatty acids but lower insulin levels than chow-fed DMNL rats and controls. This occurred in the face of lower body weights and caloric intake. Neither growth hormone nor insulin showed lesion effects. Rats with DMNL exhibited the same inverse relationship between plasma insulin and free fatty acids as controls. The data indicate that DMNL rats respond to the HF/SS diet essentially like sham-operated controls, i.e., they develop dietary obesity. Although they do show some small deficits, their lipogenic capacity is actually significantly greater than that of HF/SS-diet fed controls.

Animals↗

Protein, amino acid, and caloric intakes of selected pregnant women.

Toxemia of pregnancy is characterized by a combination of at least two of the following clinical symptoms: hypertension, edema, and proteinuria. In three successive trials over three consecutive years, the dietary intakes of a selected number of young pregnant women attending a Maternal and Infant Care Clinic at Tuskegee Institute were evaluated for protein, amino acids, and total calories. Women with toxemia were identified, and women without toxemia served as controls. The toxemic group generally consumed more protein than the controls, but values were statistically significant only in the first trial. However, all essential amino acids were consumed in significantly greater amounts by the toxemic group. Protein and essential amino acids were consumed in adequate amounts (at least two-thirds of the RDA) by both groups but in amounts smaller than the national average. Non-essential amino acids were also consumed in adequate amounts, with the toxemic group consuming larger quantities than the controls. Caloric intakes were adequate for young pregnant women. The relationships of glucosuria and of toxemia to protein and amino acid intake were similar and were opposite to the relationship of anemia to protein and amino acid intake. Meats and grains contributed the greatest quantity of protein and amino acids to the diet in all groups. Data seem to imply that any relationship of protein and amino acids with toxemia of pregnancy is a complex one involving several possibly interrelated nutritional parameters.

Adolescent↗

Rates of apoptosis and proliferation vary with caloric intake and may influence incidence of spontaneous hepatoma in C57BL/6 x C3H F1 mice.

Although the dysregulation of physiological signals and mechanisms controlling cell proliferation has been a major focus in cancer research, recent evidence suggests that explicit evaluation of apoptosis or physiological cell death may be equally important in understanding multistage carcinogenesis. Dietary restriction of rodents is well known to reproducibly retard development of spontaneous and chemically induced tumors. We reasoned that the decrease in metabolic and hormonal trophic factors induced with this intervention could promote selective cell deletion via apoptosis. To pursue this possibility, we quantified the spontaneous apoptotic rate in liver sections from diet-restricted (DR) and ad libitum-fed (AL) 12-month-old male C57BL/6 x C3H F1 mice, a murine strain known to develop a high incidence of spontaneous liver tumors by 18 months of age. The identification of hepatocyte apoptotic bodies was facilitated by in situ end-labeling immunohistochemistry. The basal rate of proliferation of hepatocytes was quantified utilizing proliferating cell nuclear antigen immunohistochemistry. The incidence of apoptotic bodies and total proliferating cell nuclear antigen-positive cells was enumerated in 14 mice/group by scoring 50,000 random hepatocytes/liver and expressed as the mean incidence/100 cells. When the comparison was made between diet groups, the apoptotic rate was significantly higher in the DR mice relative to the AL mice, while the proliferation rate was significantly lower (P < 0.01 and P < 0.05, respectively). The increase in spontaneous level of apoptosis and the decrease in proliferation rate in livers of DR mice were associated with a significantly lower rate of spontaneous hepatoma over a 36-month period. In summary, the results suggest that caloric intake may modulate the basal turnover rates of cell death and proliferation in a direction consistent with a cancer-protective effect in the DR mice and a cancer-promoting effect in AL mice.

Animals↗

Caloric intake and eating behavior in infants and toddlers with cystic fibrosis.

OBJECTIVE: Infants and toddlers with cystic fibrosis (CF) are at risk for poor growth. Controlled behavioral assessment studies have not focused on this population. This study compared calorie intake, percentage of Recommended Daily Allowance (RDA) per day and per kilogram, and percentage of calories from fat, protein, and carbohydrates between infants and toddlers with CF and healthy peers. Also, eating behaviors, such as meal duration, bites and sips per minute, percentage of meal spent eating, children's problematic eating behaviors, and parents' perceptions of mealtime behaviors were compared between infants and toddlers with CF and controls. Five hypotheses were tested. 1) Infants and toddlers with CF would be comparable to controls on the number of calories consumed per day and the percentage of calories from fat. 2) Infants and toddlers with CF would not meet the CF dietary guidelines for the percentage of RDA for calories or the percentage of calories from fat. 3) Infants and toddlers with CF would have longer meal durations than healthy peers, but would not differ on the pace of eating, the number of calories consumed during the meal, or the percentage of time spent eating during the meal. 4) Parents of infants and toddlers with CF would perceive more problematic mealtime behavior than controls. 5) Parents' perceptions of children's mealtime behavior would positively correlate with meal duration and negatively correlate with the number of calories consumed during the meal. DESIGN: A 2-group comparison study. SETTING/SAMPLE: A clinical sample of 35 infants and toddlers with CF (M = 18.6; standard deviation = 8.1 months; range = 7-35 months) and a community sample of 34 healthy peers matched for age, gender, socioeconomic status, and number of parents and siblings present during mealtimes. MEASUREMENT AND MAIN RESULTS: Children's calorie intake was measured using 3-day diet diaries. The 2 groups did not differ on the total number of calories consumed per day, the percentage of calories derived from fat, or the percentage of RDA consumed per day. Infants and toddlers with CF were not meeting the CF dietary recommendations of 120% to 150% RDA for energy with 40% of calories coming from fat. Using the Dyadic Interaction Nomenclature for Eating, a behavioral coding system, videotaped recordings of children's dinner meals were scored for meal duration, number of bites and sips per minute, number of calories per bite or sip, and the percentage of 10-second intervals with bites and sips. The CF sample had significantly longer mealtimes (20.2 minutes) than the control group (16.4 minutes), but did not differ on calories consumed at the meal, bites and sips per minute, calories per bite and sip, or time spent eating during the meal. On the Behavioral Pediatrics Feeding Assessment Scale, a measure of parental perceptions of mealtime behavior that was completed by a subset of families (39 families), parents of infants and toddlers with CF endorsed a greater number of mealtime behaviors as problems and a higher occurrence of problems than did parents of controls. Examples of these behaviors for the CF sample included problems with their child's willingness to try new foods (48%), eat vegetables (48%), and observations that their child has a poor appetite (32%) and would rather drink than eat (32%). Parents of children with CF chose a greater number of mealtime strategies and feelings as problems and reported more frequently using problematic strategies at mealtimes than did parents of controls. Examples of problematic strategies and feelings for parents of infants and toddlers with CF included feeling anxious/frustrated when feeding their children (37%), not feeling confident that their child eats enough (32%), and using coaxing to get their child to take a bite (26%). For the entire sample, a positive correlation of 0.29 was found between the number of mealtime behavior problems reported by parents and meal duration, suggesting the co-occurrence of problematic mealtime behavior with longer meal duration. No relationship was found between the number of child mealtime behavior problems reported by parents and the number of calories consumed during the filmed meal. For the CF sample, a correlation of -0.26 between children's weight percentile for age and the filmed meal duration was found, suggesting a tendency for meal duration to increase as children's weight for age decreases. Post-hoc analyses were conducted comparing infants and toddlers with previously reported samples of preschool and school-aged children on meal duration. Results demonstrated that in each group, children with CF had longer meals than age-matched controls. CONCLUSIONS: Our findings reveal significant deficits in achieving dietary recommendations for many families of infants and toddlers with CF. Only 11% of infants and toddlers with CF met the CF dietary recommendation of at least 120% of the RDA/day for energy. In addition, infants and toddlers were found to derive only 34% of their daily calories from fat, compared with the recommended 40% needed for a moderate to high fat diet. These results underscore the need for intervention in families of infants and toddlers with CF, who in addition to being at increased risk for malnutrition, may also experience a hastening in the decline of their pulmonary status because of poor nutritional status. Currently, there is limited programmatic research on nutritional and feeding interventions for toddlers and infants with CF. One study, which used a hospital-based behavioral education program to increase the caloric intake of 3 children (ages 10-20 months) who were below the fifth percentile for weight for length, found at least a 54% increase in calories for each child after treatment. Similarly, preliminary findings of 2 parent-based interventions, a nutrition education curriculum and a nutrition education plus behavior parent-training curriculum, found a 22% and 32% increase in daily calories, respectively, at treatment completion. A large-scale clinical trial is needed to evaluate the efficacy of any nutritional intervention before widespread dissemination. Additional assessment-focused research is also needed to identify patients' who may be at greatest risk for malnutrition and to guide the development of interventions to treat them.

Age Factors↗

Physiologic effects of lowering caloric intake in nonhuman primates and nonobese humans.

Caloric restriction (CR) reduces the rate of aging and increases life span in all small animal species studied to date, but the effects of CR in humans remain uncertain. This review summarizes current knowledge of the effects of CR in nonhuman primates and humans. The results suggest that CR has a range of beneficial effects in nonhuman primates studied under laboratory conditions, and short-term markers of CR seen in animal models appear to occur in humans subject to CR also. However, the overall benefit of CR in human populations remains to be established, and studies in human populations are needed.

Aging↗

Daily caloric intake of normal-weight adults: response to changes in dietary energy density of a luncheon meal.

The extent and time course of caloric compensation for surreptitious dilutions and supplements to the energy value of the diet were examined in free-living normal-weight adults. Ten subjects were provided lunches containing approximately 66% more or less calories than their customary midday meal for 2-wk periods which were interposed between 1-wk baseline or recovery periods. Diet records were kept throughout the study. Total energy intakes did not differ among the three control periods (weeks 1, 4, and 7) or between any of these periods and when subjects were provided the low-calorie meal. Total energy intake was significantly higher relative to all other periods when subjects ingested the high-calorie meal. To the extent that compensation occurred, it was apparent immediately and did not appear to change over the 2-wk study periods. The results suggest that humans compensate more readily for decreases than for increases in caloric intake.

Adult↗

Genotype and age influence the effect of caloric intake on mortality in mice.

Long-term caloric restriction (CR) has been repeatedly shown to increase life span and delay the onset of age-associated pathologies in laboratory mice and rats. The purpose of the current study was to determine whether the CR-associated increase in life span occurs in all strains of mice or only in some genotypes and whether the effects of CR and ad libitum (AL) feeding on mortality accrue gradually or are rapidly inducible and reversible. In one experiment, groups of male C57BL/6, DBA/2, and B6D2F1 mice were fed AL or CR (60% of AL) diets beginning at 4 months of age until death. In the companion study, separate groups of mice were maintained chronically on AL or CR regimens until 7, 17, or 22-24 months of age, after which, half of each AL and CR group was switched to the opposite regimen for 11 wk. This procedure yielded four experimental groups for each genotype, namely AL-->AL, AL-->CR, CR-->CR, and CR-->AL, designated according to long-term and short-term caloric regimen, respectively. Long-term CR resulted in increased median and maximum life span in C57BL/6 and B6D2F1 mice but failed to affect either parameter in the DBA/2 mice. The shift from AL-->CR increased mortality in 17- and 24-month-old mice, whereas the shift from CR-->AL did not significantly affect mortality of any age group. Such increased risk of mortality following implementation of CR at older ages was evident in all three strains but was most dramatic in DBA/2 mice. Results of this study indicate that CR does not have beneficial effects in all strains of mice, and it increases rather than decreases mortality if initiated in advanced age.

Aging↗

Role of caloric intake in the weight loss after jejunoileal bypass for obesity.

Sixty-five patients were studied prospectively after jejunoileal bypass for obesity. Dietary intake pre- and postoperatively was measured either directly by weighing food or by a research dietary history. Of 65 measurements, 59 were made at least 6 months after operation, when over 75% of weight loss had been achieved. Fat absorption was measured in 42 of the patients. The entire group ate fewer calories (mean +/- SE = 2595 +/- 135) postoperatively than preoperatively (mean +/- SE = 3261 +/- 138). This difference was highly significant (P less than 0.001). Forty-eight patients ate less after their operation. The caloric deficit calculated from the observed weight loss could be accounted for entirely by the estimated decrease in intake in 22 of the 48 patients who ate less postoperatively. Moreover, measured fat malabsorption accounted for only 31% of the observed weight loss in those who ate more postoperatively and 21% in those who ate less. We conclude that a decrease in caloric intake, along with malabsorption, is an important factor in the long term postoperative weight loss (1-9 months) after jejunoileal bypass for obesity.

Body Weight↗