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An overfed rat model that reproduces acetaminophen disposition in obese humans.

This disposition of acetaminophen was examined in an overfed rat model of human obesity following iv administration of a subtoxic 303 +/- 5 mg/kg dose based upon ideal body weight. Weanling Sprague-Dawley rats were maintained on a nutritionally complete semisynthetic diet containing 60% vegetable shortening and were compared to animals given a standard laboratory diet over the same 22-week period. At the time of study obese rats outweighed controls by 42% (637 +/- 32 g vs. 450 +/- 7 g, respectively). The absolute clearance of acetaminophen from plasma increased by 27% in obese rats. Higher partial formation clearance to acetaminophen glucuronide and sulfate conjugates accounted for most of this increase. Clearance by sulfhydryl conjugation was also substantially increased (56%), indicating that metabolism via toxic oxidation also occurred at a greater rate in obese animals. Absolute renal clearance of the glucuronide and sulfate conjugates but not acetaminophen increased with obesity, whereas parent volume of distribution remained unchanged. Some rats raised on the energy-dense diet remained lean and were examined separately as a dietary control group. Acetaminophen disposition in these animals was indistinguishable from pellet-fed controls, suggesting that acetaminophen elimination changes in overweight animals resulted from obesity itself and not from the obesity inducing energy-dense diet. Although animals placed on the energy-dense diet ate fewer grams of food per day, their caloric intake was similar to that of pellet-fed animals when adjusted for differences in body weight and caloric content of the diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

Energy and nutrient intake of children with cancer.

Two hundred seventy-seven pediatric cancer patients received a nutritional assessment. Initial dietary intakes of patients with no prior treatment indicated a diet similar to that of the general population. The caloric intake was 75% of the RDA in a group of patients with non-malignant diseases and 80% of the RDA in the groups of patients with solid tumors and hematopoietic malignancies. Protein intake was greater than 100% of the RDA for all groups. Dietary iron was the nutrient lowest in intake, with a range of 70% to 78% of the RDA. At six-month evaluations, no significant changes occurred except for an increase in iron, niacin, riboflavin, and protein intakes in the group with solid tumors.

Adolescent↗

Protein sparing on very low calorie diets: ground squirrels succeed where obese people fail.

During seasonal cycles in ground squirrels, as in many other species, there are periods of spontaneous loss of appetite, very low calorie intake and a 30% loss in body mass. Measurements of nitrogen balance during early and later stages of the mass loss phase of the cycle (-1.2 +/- 6.7 and +13.1 +/- 8.8 mg/24 h, respectively) showed a total sparing of protein, indicating a selective use of fat. However, when no food at all was available, nitrogen balance was negative (-45 +/- 5 mg/24 h). Provided that they have access to some food, ground squirrels are therefore able to compensate for any protein utilization, while at the same time selectively losing large amounts of fat. It appears that a factor related to spontaneous reduction in food intake enables these animals to achieve the total sparing of protein that eludes dieting humans on comparably low caloric intakes.

Animals↗

Evaluation and management of dietary habits in Japanese renal stone formers.

To elucidate the relationship between the formation of kidney stones and diet, we carried out a dietary investigation in patients with urinary tract stones. Dietary intakes were estimated for 36 patients (24 men, 12 women) with calcium stones, and compared with the official dietary requirements for the Japanese. Total protein intake, animal protein intake and animal protein ratio were significantly higher for patients with stones in both men and women. Dietary salt intake was significantly higher for male patients and the total group. Dietary calcium and carbohydrate intakes were significantly lower for patients with stones in men and the total group, and tended to be lower for female patients. As a result of dietary guidance, the intakes of total protein, animal protein and salt were markedly reduced. The animal protein ratio was also lowered. Caloric intake and the dietary intakes of carbohydrate, fat and salt were reduced, too. However, the dietary calcium intake did not change. Chemical analysis of 24 hour-urine revealed that the excretion of urea nitrogen was reduced, which reflected the decrease in protein intake produced by the dietary regimen. The excretions of urate and oxalate also tended to decrease.

Adult↗

Intake of sugars in relation to fatness and micronutrient adequacy.

Dietary sugars have frequently been linked with excess body weight and poor quality diets. A review of the recent research in this area reveals no basis for a causative association between sugar intake and obesity. Rather, a diet which contains a high percentage of energy from carbohydrate (starch and sugars) may assist in weight loss if the proportion of energy from fat is low. Nutrient inadequacies tend to occur in susceptible groups (generally women and children) who have a low total energy intake, and this is compounded by a relatively high contribution from sugars. For general populations with an adequate caloric intake nutrient adequacy can be achieved across a wide range of dietary sugar (4-20% energy). In this respect, intakes at either extreme are sub-optimal.

Adult↗

Premenstrual tension syndrome with periodic bulimia nervosa: report of a case and review of the literature.

Premenstrual tension syndrome (PMS) is well known in its epidemiology, etiology, symptomatology and treatment. However, PMS characterized by bulimic episodes is rare. We report a case of a 20-year-old university student who suffered from uncontrollable binge eating premenstrually for six months before visiting our clinic. She was obese without any other notable family or medical history except the PMS noted for two years. A daily food diary for two consecutive menstrual cycles showed that the mean differences in caloric intake between premenstrual and postmenstrual days of two menstrual cycles were 679 and 703 calories, respectively. The greater peaks in caloric level were noted within the third to fifth days prior to the onset of menstruation. All binge episodes occurred in the premenstrual period, especially within five days prior to menstruation. In this report, we will also review the literature on the relationship between PMS and dietary intake, as well as bulimia nervosa.

Adult↗

Protein selection, food intake, and body composition in response to the amount of dietary protein.

Though not universally observed, moderately low-protein diets have been found to increase caloric intake and body fat. It appears that animals overeat in calories in order to obtain more dietary protein. For animals to control protein intake, they must be able to distinguish between two isocaloric diets containing different percentages of protein and make the appropriate dietary selection on the basis of their previous history of protein intake. Experiment 1 examined the 24-h diet selection (5 vs. 35% casein) of Sprague-Dawley rats that had been previously fed diets containing various percentages of dietary protein (5, 10, 20, 35, or 60% casein). Animals fed 5, 10, or 20% dietary protein showed a preference for the higher protein selection diet. In contrast, no significant diet preference was found in animals pre-fed the two higher levels of dietary protein (35 or 60% casein). In this study, daily food intake and body fat of rats fed the low-protein diets (5 and 10% casein) were similar to rats fed the 20% casein diet. Experiment 2 examined the effects of the level of methionine supplementation on rats fed 10% casein. In this study, food intake and body fat were increased by approximately 20% in rats fed 10% casein diets, regardless of the level of methionine supplementation (0.3 vs. 0.15%). Together, the results suggest that the presence of low-protein-induced hyperphagia helps maintain body protein levels in the face of moderately low dietary protein and promotes an increase in the amount of body fat and energy.

Adipose Tissue↗

Protection against chronic cadmium toxicity by caloric restriction.

Exposure to cadmium (Cd) can result in nephrotoxicity and osteotoxicity. Because Cd-induced nephrotoxicity involves oxidative stress and caloric restriction decreases oxidative stress, we examined whether reduced caloric intake will protect against Cd-induced nephrotoxicity. In addition, the protection against the osteotoxicity was also examined. Male and female Sprague-Dawley rats were provided drinking water containing 100 mg Cd/l. Since fluid intake relative to the body weight was higher in females as compared to the males, the Cd concentration in their water was reduced to 80 mg/l after 3 months and 65 mg/l after 6.5 months. During the 27 month exposure period the males and females consumed a total of about 5 g Cd/kg body weight. Food was restricted to 20 g/day after the first 3 months. During the unrestricted food intake period Cd exposure reduced the bone density in females by 23%, with a partial recovery and stabilization during the caloric restriction phase. Hepatic and renal Cd accumulation and corresponding metallothionein (MT) levels were very similar in both sexes. The reported critical Cd concentration for nephrotoxicity was reached by 9 months. Renal MT levels were maximum at this time. Despite a 1.5-fold increase in renal Cd concentration over the next 18 months, there was no significant increase in renal MT levels. In spite of high renal Cd levels and lack of availability of sufficient MT, there was no sign of nephrotoxicity, as measured by urinary protein and glucose excretion. It is concluded that caloric restriction prevents Cd-induced nephrotoxicity and also appears to control the osteotoxicity of Cd.

Animals↗

Regulation of adiposity and obesity risk by dietary calcium: mechanisms and implications.

Dietary calcium plays a pivotal role in the regulation of energy metabolism; high calcium diets attenuate adipocyte lipid accretion and weight gain during periods of overconsumption of an energy-dense diet and increase lipolysis and preserve thermogenesis during caloric restriction, thereby markedly accelerating weight loss. Intracellular Ca2+ has a key role in regulating adipocyte lipid metabolism and triglyceride storage, with increased intracellular Ca2+ resulting in stimulation of lipogenic gene expression and lipogenesis, suppression of lipolysis, and increased lipid filling and adiposity. Moreover, we have recently demonstrated that the increased calcitriol released in response to low calcium diets stimulates Ca2+ influx in human adipocytes and thereby promotes adiposity. Accordingly, suppressing calcitriol levels by increasing dietary calcium is an attractive target for the prevention and management of obesity. In support of this concept, transgenic mice expressing the agouti gene specifically in adipocytes (a human-like pattern) respond to low calcium diets with accelerated weight gain and fat accretion, while high calcium diets markedly inhibit lipogenesis, accelerate lipolysis, increase thermogenesis and suppress fat accretion and weight gain in animals maintained at identical caloric intakes. Further, low calcium diets impede body fat loss, while high calcium diets markedly accelerate fat loss in transgenic mice subjected to caloric restriction. These findings are further supported by clinical and epidemiological data demonstrating a profound reduction in the odds of being obese associated with increasing dietary calcium intake. Notably, dairy sources of calcium exert a significantly greater anti-obesity effect than supplemental sources in each of these studies, possibly due to the effects of other bioactive compounds, such as the angiotensin converting enzyme inhibitor found in milk, on adipocyte metabolism, indicating an important role for dairy products in the control of obesity.

Adipocytes↗

Impact of fat substitutes on fat intake.

Dietary fat is the number one nutrition concern of Americans. In response to rising consumer demand for reduced-fat foods, the food industry has developed a multitude of nonfat, lowfat, and reduced-fat versions of regular food products. To generate reduced-fat or fat-free products that have the same organoleptic characteristics of the regular fat version, food manufacturers frequently employ fat substitutes in the formulation of these foods. Fat substitutes are made from either carbohydrate, protein, or fat, or a combination of these components. Researchers have questioned the impact of fat substitutes on both fat and caloric intake. The majority of research studies in which fat substitutes were either covertly or overtly substituted for dietary fat indicate that in short-term, carefully-controlled conditions, fat substitutes can decrease both dietary fat intake and percentage of calorie intake from fat. However, individuals compensate for the caloric deficit created by the fat substitutes by increasing their consumption of other macronutrients, primarily carbohydrate. The long-term effect of fat substitutes on the fat intake of free-living individuals and weight control are unknown. People tend to eat more of a food when they know that food is reduced in fat. Fat substitutes should not be considered a substitute for sound nutrition education and a healthy lifestyle which includes regular exercise.

Anticholesteremic Agents↗

Sucrose intake as a function of its cost and the cost of chow.

The avid consumption of pure carbohydrate solutions, which often results in a distortion of nutrient balance, is generally presumed to be driven by their taste. In the first of two experiments, we examined the effect of consumption cost on rats' intake of three concentrations of sucrose solution (8%, 16%, and 32%) when a nutritionally complete chow was concurrently freely available. In the second experiment, we examined the intake of 24% sucrose solution and chow as the consumption costs of both were varied. Increasing the cost of sucrose resulted in a reduction in the percent calories taken from sucrose; the steepness of the decline in intake with price was inversely related to the sucrose concentration and to the cost of chow. Chow calories were substituted for relatively expensive sucrose calories. An increase in the cost of chow resulted in a reduction in the percent of calories taken from chow and a protein-poor diet. The cost of sucrose did not affect the slope of the chow intake curve, presumably because, despite its sweet taste, sucrose was not a substitute for the protein, fat, and micronutrients in chow. Total caloric intake was conserved in all cases.Thus, the avid consumption of sucrose solution is curtailed when it is costly; but the degree of change in intake with cost depends on the cost of an alternative food. These results suggest that diet selection involves a comparison not only of the taste and post-ingestive consequences of available foods, but also of the cost of calories and nutrients in the foods. Selection appears to be guided first by caloric requirements and the relative cost of calories, then by nutrient requirements and the relative cost of nutrients, and finally by taste.

Animals↗

Nutrition and the aging animal.

The surge in current thinking and research on aging, replete with causes and/or effects, has greatly stimulated serious biologists concerned with giving counsel for the feeding and management of animals to reevaluate present practices. This is particularly true for the feeding of dogs. If we are indeed concerned with the feeding of the geriatric dog, we must begin to emphasize changes in nutritional practices that go back to the period preceding birth. Unrestricted caloric intake of dogs during periods of growth and development, even when in proper balance with intake of essential nutrients, has been shown to accelerate somatic processes, resulting in delayed maturation of cartilage and excessive bone apposition. This was followed by reduced bone resorption and remodeling. These processes were associated with the development of either earlier or more severe degenerative diseases of the skeletal system. Studies with rodents have demonstrated damaging effects of unrestricted dietary intake on longevity itself. Most damaging have been the decreasing efficiency of cellular immunity and corresponding increases in autoimmune responses during later life. Judicious caloric restriction beginning even in adult life can have a rejuvenating effect on immune response capacity. Regardless of age, a controlled nutrient intake seems the order of the day. Returning to Lucretius, the graves are indeed being dug with teeth.

Aging↗

A mathematical model that accounts for the effects of caloric restriction on body weight and longevity.

Several aspects of energy dynamics, such as energy expenditure and caloric intake, are known to affect the aging process. In this article we therefore model the aging process within a mathematical framework describing the energy dynamics of an organism. The resulting model comprises food intake, body growth and survival. The equation for the mortality rate accounts for food consumption and is suited to describe caloric restriction data. For non-growing animals, the expression for the mortality rate reduces to the well-known Gompertz equation. We successfully applied our model to growth and survival data on mice exposed to different food levels.

Animals↗

Reduced serum cholecystokinin response to food intake in female athletes.

Strenuous training in women has been shown to cause menstrual dysfunction and decreased bone mineral density. These endocrine and metabolic complications are associated with an insufficient dietary intake and decreased body fat content in female athletes. The present investigation was undertaken to study serum levels of cholecystokinin (CCK), insulin, gastrin, and cortisol in 14 female long-distance runners and 15 sex- and age-matched control subjects during intake of a standardized meal (500 kcal). The athletes showed a decreased response of the "satiety peptide" CCK to the meal and reported increased hunger compared with the control group. Meal-related insulin response was also decreased in the athletes, whereas gastrin levels were comparable to those of controls. Basal levels of glucose were increased in the athletes, but there was no difference in postprandial levels between the groups. Cortisol levels were clearly elevated in the female runners. We conclude that insufficient food intake in female athletes cannot be explained by increased CCK secretion and satiety. Since the athletes reported a larger caloric intake of a normal daily breakfast than the control subjects, the decreased CCK response may instead be explained by an adaptation to increased food intake. The decreased meal-related insulin response may be a reflection of increased insulin sensitivity as an adaptation to physical exercise. However, an impaired peptide secretion cannot be excluded. The role of elevated cortisol levels in the gastrointestinal hormone response needs further investigation.

Adult↗

Is fiber satiating? Effects of a high fiber preload on subsequent food intake of normal-weight and obese young men.

This study was designed to test whether a high fiber preload can suppress food intake at a subsequent test meal. Fifty male undergraduates, 31 of normal body weight and 19 at least 15 per cent overweight, participated as paid volunteers. So as not to inhibit spontaneous food intake, they were told that the investigators were studying the effects of the parasympathetic nervous system on cognitive processes and they were given a picture rating task to perform. The stated rationale for having the subjects eat the preload between two sets of pictures was to alter the state of parasympathetic activation. The preload consisted of two roast beef sandwich halves containing a total of 400 kcal and either 5.2 or 0.2 g of crude fiber in the bread. The preload was eaten by the subjects, their meal was intentionally interrupted and then they were allowed to finish eating 30-45 minutes later (test meal). Obese subjects ate significantly fewer sandwich halves after the high than after the low fiber preload. Obese subjects ate significantly more than non-obese subjects in the low fiber treatment so that the effect of the high fiber was to normalize their intake. Although both obese and normal-weight subjects reported feeling fuller after the high fiber preload, the non-obese subjects ate virtually the same amount in both treatments. Obese subjects reported liking the high fiber bread less well than the low fiber bread but additional statistical analyses showed an intake-suppressing effect of fiber even after controlling for bread rating. These results support the hypothesis that fiber reduces caloric intake in obese people.

Adult↗

Old as mature LOU/c/jall rats enhance protein selection in response to a protein deprivation.

Previous experiments have shown a strong decrease in protein consumption as rats grow old. This result could be induced by an impaired regulation of feeding behaviour. Present study investigated the ability of ageing rats to adapt their protein intake to protein requirements. Four groups of self-selecting LOU/c/jall male and female rats (4, 16, 22, 28 months at the beginning of the experiments) were submitted to 4-days of protein deprivation periods while their macronutrient intakes were monitored. Moreover, they were submitted to a 4-day fasting period. After reintroduction of proteins, old and senescent rats were able to increase their protein intake in response to the specific protein need created by the protein deprivation. They were also able to increase caloric intake after the fasting period. These results led to the conclusion that the loss of appetite for protein observed with ageing reflects rather an adaptation than an impairment of the regulation of macronutrient choice. Another important observation was that older animals did not recover initial body weight after a body weight loss even if they ate as many calories as younger animals. This data supports a decrease in the efficacious utilization of body fuels in old and senescent rats.

Adaptation, Physiological↗

Association between fruit and vegetable intake and change in body mass index among a large sample of children and adolescents in the United States.

OBJECTIVE: To assess whether intake of fruits and vegetables was associated with change in body mass index (BMI) among a large sample of children and adolescents in the United States. DESIGN: Prospective cohort study of children and adolescent who were 9-14 y of age in 1996, when the study began. SUBJECTS: The subjects included 8203 girls and 6715 boys in an ongoing cohort study who completed at least two questionnaires between 1996 and 1999. MEASUREMENTS: Fruit and vegetable intake was assessed in 1996-1998 with a validated food frequency questionnaire designed specifically for children and adolescents. The outcome measure was change in age- and gender-specific z-score of BMI (kg/m(2)). Self-reported weight and height, which were used to calculate BMI, were collected annually from 1996 to 1999. RESULTS: During 3 years of follow-up, annual changes in BMI were slightly greater among the boys than the girls. After controlling for Tanner stage of development, age, height change, activity and inactivity, which are known or suspected predictors of change in BMI, among the girls there was no relation between intake of fruits, fruit juice, or vegetables (alone or combined) and subsequent changes in BMI z-score. Among the boys, intake of fruit and fruit juice was not predictive of changes in BMI, however, vegetables intake was inversely related to changes in BMI z-score (beta per serving=-0.003). However, after adjusting for caloric intake, the magnitude of the effect was diminished and no longer significant. CONCLUSION: Our results suggest that the recommendation for consumption of fruits and vegetables may be well founded, but should not be based on a beneficial effect on weight regulation.

Adolescent↗

Senescent terminal weight loss in the male F344 rat.

Loss of weight, often of unknown cause and culminating in death, commonly occurs in humans at advanced ages. Rats that live to old ages, such as the Fischer 344 (F344) strain, also exhibit a terminal loss in body weight. A presently held hypothesis is that the terminal weight loss in the F344 rat model is due to reduced food intake because of an alteration in hypothalamic function resulting in early satiation. We report findings on terminal weight loss and food intake in male F344 rats fed ad libitum (AL group) or a life-prolonging dietary regimen in which caloric intake was restricted (DR group). Rats in both dietary groups that did not exhibit a terminal weight loss died at younger ages than those exhibiting the loss. Terminal weight loss in the AL group was not associated with decreased food intake; indeed, half of the rats in this group had an increased food intake during the period of terminal weight loss. This finding is not in accord with the presently held hypothesis. In the DR group, terminal weight loss was associated with reduced food intake. Pathology (renal disease and neoplasms) did not explain the presence or absence of the association between reduced food intake and weight loss in either dietary group. The duration of the period of terminal weight loss was similar for the AL and DR groups. Apparently, restricting calories delays the occurrence but does not affect the duration of senescent terminal weight loss.

Aging↗