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Physiology of the hormetic effect.

Beneficial (hormetic) effects of ionizing radiation have been largely ignored in developing radiobiological theory, chiefly because a suitable explanatory hypothesis is lacking. Examination of the relevant literature has revealed that food restriction effects in animals resemble those of low-level, low-LET, whole-body ionizing radiation exposure (without food restriction) in two major respects: increased longevity and change in the variance of longevity. These physiological changes can be interpreted as resulting from alteration of the "steady-state" flux of oxygen radicals which affect the endocrine balance. Oxy-radical-producing, low-level ionizing radiation exposure (whole body) is interpreted by the body as excess food intake, thus lowering the appetite and reducing caloric intake which, in turn, increases longevity. The greater variance in longevity accompanying increases in the median age at death with food restriction alters the ratio of long-lived to short-lived descendants and hastens the population's adaptation to semi-permanently diminished rates of food supply. Less variance and earlier mean ages at death result from an increased rate of food supply. Whole-body ionizing radiation exposure results in a mixed response, because it reduces caloric intake while signaling that an increase has occurred.

Adaptation, Physiological↗

Hypotheses concerning roles of dietary energy, cured meat, and serum tocopherols in adult glioma development.

We conducted a pilot study to determine whether: (1) high levels of energy intake increase glioma risk; (2) the previously observed relationship between cured meat consumption and glioma risk can be attributed to confounding by energy intake, and (3) alpha-tocopherol modifies caloric intake and gamma-tocopherol modifies cured meat consumption. We identified 40 age-sex-race matched glioma sets, and obtained serum vitamin C and alpha- and gamma-tocopherol levels for 23 of these sets. Glioma risk increased with quartile of total dietary energy adjusted for fat, protein, and nitrite-containing meat consumption (odds ratio = 1.0, 2.7, 5.8, 8.2; p value for trend test = 0.02). Although positive associations between individual cured meats and glioma risk decreased when adjusted for caloric intake, the small sample size makes it difficult to interpret the results. Serum alpha-tocopherol appeared to modify the effect of calories and serum gamma-tocopherol may modify the effect of cured meat on glioma risk. While the observed interaction is predicted by experimental research, our findings are based on small numbers. Larger studies are needed to further evaluate our preliminary findings.

Adult↗

Childhood obesity: behavioral aberration or biochemical drive? Reinterpreting the First Law of Thermodynamics.

Childhood obesity has become epidemic over the past 30 years. The First Law of Thermodynamics is routinely interpreted to imply that weight gain is secondary to increased caloric intake and/or decreased energy expenditure, two behaviors that have been documented during this interval; nonetheless, lifestyle interventions are notoriously ineffective at promoting weight loss. Obesity is characterized by hyperinsulinemia. Although hyperinsulinemia is usually thought to be secondary to obesity, it can instead be primary, due to autonomic dysfunction. Obesity is also a state of leptin resistance, in which defective leptin signal transduction promotes excess energy intake, to maintain normal energy expenditure. Insulin and leptin share a common central signaling pathway, and it seems that insulin functions as an endogenous leptin antagonist. Suppressing insulin ameliorates leptin resistance, with ensuing reduction of caloric intake, increased spontaneous activity, and improved quality of life. Hyperinsulinemia also interferes with dopamine clearance in the ventral tegmental area and nucleus accumbens, promoting increased food reward. Accordingly, the First Law of Thermodynamics can be reinterpreted, such that the behaviors of increased caloric intake and decreased energy expenditure are secondary to obligate weight gain. This weight gain is driven by the hyperinsulinemic state, through three mechanisms: energy partitioning into adipose tissue; interference with leptin signal transduction; and interference with extinction of the hedonic response to food.

Child↗

Changes in energy balance following smoking cessation and resumption of smoking in women.

Caloric intake, resting metabolic rate (RMR), leisure-time physical activity, and sensitivity and preference for sweet taste were prospectively examined in 7 female smokers across 3 weeks during periods of normal smoking (Week 1), complete cessation (Week 2), and resumption of smoking (Week 3). Energy balance changed significantly across weeks, as caloric intake increased (largely as a result of alcohol consumption) and RMR decreased during cessation, followed by decreased caloric intake and increased RMR with resumption of smoking. Activity and taste sensitivity and preference remained unchanged. Smoking cessation may thus cause rapid change in energy balance, which is quickly reversed on resumption of smoking.

Adolescent↗

The hepatic vagus mediates fat-induced inhibition of diabetic hyperphagia.

Diabetic rats both overeat high-carbohydrate diet and have altered hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF). In contrast, a high-fat diet reduces caloric intake of diabetics to normal, reflected by normal hypothalamic NPY and CRF content. How the brain senses these changes in diet is unknown. To date, no hormonal changes explain these diet-induced changes in caloric intake. We tested whether the common branch of the hepatic vagus mediates the fat signal. We presented fat in two ways. First, diabetic and vehicle-treated rats were offered a cup of lard in addition to their normal high-carbohydrate diet. Second, we switched diabetic rats from high-carbohydrate diet to high-fat diet, without choice. In streptozotocin-treated rats, both methods resulted in fat-induced inhibition of caloric intake and normalization of hypothalamic neuropeptides to nondiabetic levels. Strikingly, common branch hepatic vagotomy (unlike gastroduodenal vagotomy) entirely blocked these fat-induced changes. Although a shift in hepatic energy status did not explain the lard-induced changes in diabetic rats, the data suggested that common hepatic branch vagotomy does not interfere with hepatic energy status. Furthermore, common branch hepatic vagotomy without diabetes induced indexes of obesity. Abnormal function of the hepatic vagus, as occurs in diabetic neuropathy, may contribute to diabetic obesity.

Adenosine Triphosphate↗

Oxidative DNA damage levels in rats fed low-fat, high-fat, or calorie-restricted diets.

Increased fat and caloric content of the diet has been associated with increased mammary tumor incidence. The dietary modulation of cellular redox state may be one mechanism behind this association. We have examined the effects of changes in dietary fat and caloric intake on the levels of 5-hydroxymethyluracil in DNA from rat liver and mammary gland. Female Fischer 344 rats, 40 days old, were maintained on 3% (low-fat), 5% (control), or 20% (high-fat) corn oil diets for 2 weeks. A fourth group of rats had the same daily fat intake as the control group, but total caloric intake was restricted by 40%. As a measure of oxidative DNA damage, 5-hydroxymethyluracil levels were measured in the DNA extracted from liver and mammary gland by gas chromatography-mass spectrometry. 5-Hydroxymethyluracil levels in the liver DNA of the low-fat, high-fat, and calorie-restricted groups were decreased relative to that of control, but the only significant decrease was in the calorie-restricted group (p less than 0.01). In the mammary gland DNA, statistically significant decreases in damage were found in each group relative to control (p less than 0.05). The relationship between fat in the diet and oxidative stress is thus complex. These results show that changes in dietary intake of both fat and calories can modulate oxidative DNA damage levels, and the effect of diet was more clearly evident in the DNA from mammary gland than in DNA from liver.

Animals↗

Growth and body composition in type 1 diabetes mellitus.

Over the last 50 years the prognosis for growth and pubertal development in children with type 1 diabetes mellitus (T1DM) has improved considerably. The early reports of Mauriac's syndrome were related not only to relative deficiency of insulin but also reduced caloric intake. Improved insulin delivery and liberalisation of caloric intake has resulted in improved growth, but subtle abnormalities persist. The frequently reported increased height at diagnosis may relate to prior hyperinsulinaemia and genetic background with respect to lDDM2 the insulin gene VNTR. Subsequent growth faltering is thought to be related to impairment of the GH/IGF-1 axis but children with T1DM are also more at risk of hypothyroidism and coeliac disease. At puberty, persisting abnormalities of the GH/IGF-1 axis and our inability to reverse these totally, even with intensified insulin therapy, contribute to the blunted pubertal growth in the girls but abnormal sex steroid concentrations may also be important. Intensification of insulin therapy may result in leptin resistance and excessive gains in fat mass, particularly in girls. Although it is likely that most children with T1DM will have normal final heights, this excessive weight gain in girls may lead to problems with compliance. Furthermore, hyperinsulinaemia in these subjects may also lead to ovarian hyperandrogenism, increased early risk of microvascular complications and long-term risk of cardiovascular disease.

Body Composition↗

The effect of decreased growth rate on frequency and severity of osteochondrosis in pigs.

Rapid weight gain seems to be related to high incidence and severity of osteochondrosis. For this reason the effect of weight gain on osteochondrosis was investigated. In one experiment including 18 pigs, frequency and severity of osteochondrosis in pigs on a low caloric intake and in those on a high caloric intake (ad libitum feeding) were compared. In another experiment 8 pigs from 2 litters of pigs with a mainly wild hog ancestry were studied. These pigs had a much lower growth rate than modern domestic pigs and their constitution was different. The results of these two experiments were unequivocal. Animals with a low weight gain, nutritionally or genetically induced, had an incidence of osteochondrosis which was close to zero. It was considered that the very high growth rate in the modern domestic pig is the main reason for the high incidence of osteochondrosis. High growth rate is the result of selective breeding and intensive feeding. There are some morphologic characteristics of the modern domestic pig similar to those seen in acromegaly in man and in animals treated with growth hormone.

Animal Feed↗

Effect of caloric restriction on colonic proliferation in obese persons: implications for colon cancer prevention.

Dietary intervention to prevent colon cancer is a major health issue. At present it is not clear which dietary factors modify colon cancer risk. Caloric restriction reduces the incidence of many spontaneous and carcinogen-induced tumors in rodents, but its role in human carcinogenesis is unknown. The relationships of body mass index (BMI), body composition, and resting metabolic rate (RMR) to colon cancer risk are also undefined. In this study involving obese persons, we measured the effect of reducing caloric intake on rectal cell proliferation, a biomarker in colon carcinogenesis, and studied the relation of BMI, body composition, and RMR to rectal cell proliferation. Colonic cell proliferation was measured in rectal biopsies from persons weighing more than 130% of ideal body weight. Follow-up biopsies were performed in patients who enrolled in and completed a 16-week behavior modification weight-reduction program in which caloric intake was reduced. Baseline measurements included body composition by total body electrical conductance, RMR, and BMI. Rectal biopsies were processed for autoradiography following incubation with [3H]thymidine. Epithelial proliferation measurements were evaluable in 35 persons at baseline and in 8 persons before and after caloric restriction. Before caloric restriction, mean (+/- SD) BMI was 38 +/- 4 kg/m2 and percentage of body fat 41 +/- 2%. Subjects reduced their caloric intake by a mean of 34 +/- 4% and their weight by 8.6 +/- 1%. Caloric restriction resulted in a 39% reduction in whole-crypt labeling index (P < 0.001) and a 57% reduction in upper crypt labeling index (P < 0.05) without reduction in crypt depth. Labeling index was unrelated to BMI, RMR, or body composition. We conclude that caloric restriction reduced rectal cell proliferation measurements--intermediate biomarkers related to colon carcinogenesis. BMI, RMR, and body composition were unrelated to colonic proliferation. Caloric restriction may have a role in colon cancer prevention.

Adult↗

[Survival of patients in acute renal failure: effect of nutrition and its associated complications].

A retrospective study of 150 patients with acute renal failure (ARF) was conducted to assess the influence of both protein and caloric intake and non-renal complications on the prognosis, as well as the predictive value of plasma protein levels. The majority of ARF had occurred in medical or surgical settings (46% and 32.7%, respectively). Nutritional data were available from 94 patients, fed either by parenteral or enteral routes, or both. The mean caloric intake was higher (29 kcal/kg/day) in patients who recovered than in those who did not (24 kcal/kg/day, p less than 0.01). A caloric intake above 35 kcal/kg/day resulted in an improved survival, independently of either patients' age or non-renal complications. Serum prealbumin and transferrin levels were higher in surviving patients than in those who died, 0.25 vs 0.16 g/l (p less than 0.001) and 1.7 vs 1.4 g/l (p less than 0.01), respectively. Nutritional support in ARF could be adapted according to the variations of these serum markers. Its influence on survival should be assessed with regard to the associated prognosis factors.

Acute Kidney Injury↗

The performance of brown egg-type layers fed different protein and energy levels in the tropics.

The effects of feeding three protein levels (16, 18, and 20%), each at three metabolizable energy levels (2400, 2600, and 2800 kcal/kg diet), were studied with 990 caged Warren Studler Sex-Sal Link pullets over a 336-day laying period. Dietary protein had no significant effects on hen-day egg production, egg weight, Haugh units, feed intake, feed conversion, feed cost per dozen eggs, caloric intake, egg weights, and final body weight. Protein consumption on all levels of dietary protein was over 20 g per bird per day and increased significantly with increases in dietary protein. Mortality was lowest on the highest protein level. The highest energy level (2800 kcal/kg diet) significantly depressed egg production and feed and protein intake. The feed costs per dozen eggs increased significantly with increases in dietary energy level. Caloric intake and final body weights were similar for the medium (2600 kcal/kg diet) and highest energy levels (2800 kcal/kg diet) but significantly higher than that obtained on the lowest energy level (2400 kcal/kg diet). Egg weights, Haugh units, feed per dozen eggs, and mortality were not significantly affected by energy levels. In spite of the average maximum monthly temperatures, ranging from 26.8 to 35.2 C, annual egg production was about 71 to 73% for the best groups, figures comparable with those obtainable in temperate climates. Egg weight and Haugh units were similar to reported temperate zone values. This experiment supports the use of 16% protein and a metabolizable energy level of 2400 kcal/kg diet for brown egg-type layers.

Analysis of Variance↗

Feeding patterns in bulimia nervosa.

We characterized the naturalistic feeding patterns of 54 women with bulimia nervosa and 11 matched controls over a continuous 24-hr period in a feeding laboratory. Overall, bulimic women consumed more calories in 24 hr (4446 +/- 584 kcal) than did controls (1845 +/- 649 kcal). Bulimic women consumed a wide range of caloric intake, with 44% overeating and 19% undereating in comparison to the range of controls. In addition, bulimics showed a disruption of circadian feeding patterns. For overeating bulimic women, the majority of meals were of normal size and frequency. Increased caloric intake in the group of overeating bulimic women was mainly due to the fact that 37% of their meals were greater than 1000 calories. Large meals occurred predominantly during the afternoon and evening and consisted primarily of dessert and snack foods. Importantly, the percentage of fat, but not carbohydrates, consumed increased as meal size, and 24-hr caloric intake increased. This study is the first to describe the naturalistic feeding characteristics of a large number of bulimics by direct observation. These findings are consistent with previous self-reports and extend and replicate previous laboratory studies. We think that laboratory studies are a reasonable replica of naturalistic feeding and should facilitate further investigation of the psychological and physiological correlates of feeding behavior in eating disorders.

Adolescent↗

Modifications in dietary self-selection specifically attributable to voluntary wheel running and exercise training in the rat.

To explore the effects of physical exercise on total caloric intake, body weight gain, and dietary self-selection in rats, female rats of the Dark Agouti strain were placed on macronutrient self-selection. They had free access to running wheels during the whole experimental period. After 16 days of voluntary exercise only, they were trained on a motor-driven treadmill (16 m/min) at the beginning of the dark period. Runtime was progressively increased and reached 3 h per day (plateau). When trained, the rats decreased spontaneous wheel running. Voluntary wheel running did not modify body weight gain. However, it increased both carbohydrate and total caloric intakes. Exercise training reduced body weight gain, but did not further modify total caloric intake. Moreover it increased protein and reduced fat intakes. Most of the training-induced modifications were not side effects of fasting during exercise training.

Animals↗

Dietary fat-induced hyperphagia in rats as a function of fat type and physical form.

The influence of dietary fat on food intake and weight gain was assessed by feeding adult female rats diets that differed in the type and form of fat, as well as in the availability of other macro- and micronutrients. Compared to chow-fed controls, the various fat diets increased total food intake by 4% to 27%. Specifically, rats fed chow and a separate source of fat (fat option diet) consumed more fat and total calories, and gained more weight when the fat source was emulsified corn oil rather than pure corn oil or was vegetable shortening rather than corn oil. However, corn oil and shortening had similar effects on caloric intake and weight gain when presented as emulsified gels. Also, pure and emulsified-gel forms of shortening did not differ in their effects on caloric intake and weight gain. Supplementing the vegetable shortening with micronutrients, however, enhanced its hyperphagia-promoting effect. The results of two-choice tests revealed that the rats' preferences for the orosensory properties of the various fat sources did not account for the differential hyperphagias obtained. Rather, it appears that long-term fat selection and caloric intake are influenced primarily by postingestive factors. Fat selection and total intake were determined not only by the fat source itself, but also by the other diet options. That is, rats selected more fat and consumed more calories when chow was the alternative food than when separate sources of carbohydrate and protein were available.

Animals↗

Additive effects of mood and eating forbidden foods upon the perceptions of overeating and binging in bulimia nervosa.

We examined the relationship between actual caloric intake and subjective perceptions of amount eaten using self-monitoring data. Forty subjects participated in the study: 20 bulimia nervosa patients and 20 normal controls. All subjects monitored their eating for a 2-week period and rated each eating episode on a Likert-type scale ranging from an undereat to a binge. Estimates of actual caloric intake were compared with these subjective ratings. Bulimics were found to overrate the amount consumed, relative to controls. The effect increased as caloric intake increased. Bulimics' ratings of amount eaten and binging were found to be predicted by the estimate of the actual amount eaten, the type of foods eaten, and the subjects' mood prior to eating, while nonbulimics' ratings were predicted only by the estimated actual amount. Subjective ratings of amount were found to be the best predictor of purgative activity. The results are discussed in terms of a perceptual bias theory, treatment implications, and possible revisions to the current DSM criteria for bulimia nervosa.

Affect↗

Comparison of fat storage between Fischer 344 and obesity-resistant Lou/C rats fed different diets.

OBJECTIVE: We aimed to characterize further the Lou/C (LOU) and Fischer 344 (F344) rat strains for nutritional traits to validate their use as contrasting strains for molecular genetic studies. RESEARCH METHODS AND PROCEDURES: Five batches of LOU and F344 rats were used to measure caloric intake, weight gain, and body composition when fed a chow diet, a self-selection diet (together with the study of preferences for macronutrients), hypercaloric diets, and a chow diet in a cold environment. RESULTS: Despite a higher caloric intake when fed a chow diet, LOU rats showed a lower weight gain, final body weight, and percentage of fat tissue, together with a higher percentage of carcass weight, than F344 rats. When fed a self-selection diet, LOU males ingested less protein and more fat than F344 males, and the reverse was observed for females. In this condition, feed efficiency was reduced in LOU but increased in F344 rats compared with the chow diet. Diet-induced obesity was observed in F344 rats but not in LOU rats fed hypercaloric diets. In a cold environment, both LOU and F344 rats displayed an increased percentage of brown adipose tissue compared with control groups, together with a higher caloric intake. DISCUSSION: The study shows robust nutritional differences between the LOU rat, a lean strain with a low feed efficiency and resistant to diet-induced obesity, and the contrasting F344 rat strain. It also shows the interest in these strains for studying the genetic components of resistance to obesity.

Adipose Tissue↗

Nutrient composition: effects on appetite in monkeys with oral factors held constant.

The effects of macronutrients on appetite and total caloric intake in monkeys (Macaca mulatta) was studied using a new feeding and infusion system which yoked intragastric infusion of various nutrients to oral ad lib intake and removed the confounding factor of palatability from the assessment of nutrient effects on feeding behavior. A suction-activated liquid diet feeding system provided free access to a nutritionally complete diet, with 1 ml of diet delivered orally by pump with each discrete suck by the monkey. A second pump was yoked to the oral feeding pump and delivered various nutrients directly into the stomach via an implanted intragastric cannula. Thus, while oral diet composition remained constant, the net diet reaching the stomach varied over ranges of 28 to 77% carbohydrate, 16 to 65% fat and 7 to 36% protein. No significant differences in total caloric intake were observed between intakes of diets with net composition of high carbohydrate or high fat. When protein was increased to 36%, total caloric intake was generally reduced, and this effect was sustained for at least 3 weeks. Therefore, protein appears to have an increased specific satiating effect beyond the caloric content, when compared to carbohydrate or fat.

Animals↗

Infant and caregiving factors affecting weight-for-age and motor development of full-term and premature infants at 1 year post-term.

Guided by a theoretical process model, we examined direct and indirect effects of infants' biologic condition and experience, the caregiving environment, and caloric intake variables on two outcomes, weight-for-age and motor development, for 52 full-term and 47 premature infants at 12 months post-term age. For full-term infants, birth weight and infant expression of positive affect and behavior during feeding had predicted positive direct effects on weight-for-age. Infant regulation of negative affect and behavior had an unexpected negative effect on this outcome. For premature infants, severity of acute illness, mother's regulation of negative affect and feeding behavior, and caloric intake affected weight-for-age in unpredicted directions. Caregiving variables had indirect effects, through caloric intake, on both outcomes only for premature infants. The findings suggest the theoretical process model differs for premature infants and full-term infants, both in the contributing variables and in the processes of effects.

Adult↗