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Caloric restriction.

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Adaptation, Physiological↗

Calorie restriction reduces the incidence of myeloid leukemia induced by a single whole-body radiation in C3H/He mice.

Dietary restriction, especially caloric restriction, is a major modifier in experimental carcinogenesis and is known to decrease significantly the incidence of neoplasms. Gross and Dreyfuss [Gross, L. & Dreyfuss, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 7596-7598; Gross, L. & Dreyfuss, Y. (1986) Proc. Natl. Acad. Sci. USA 83, 7928-7931] reported that a 36% restriction in caloric intake dramatically decreased the radiation-induced solid tumors and/or leukemias. Their protocol predominantly produced lymphatic neoplasms. It is of interest to observe the effect of caloric restriction on radiation-induced myeloid leukemia, because the disease was observed to have been increased in the survivors of the atomic bombs in Hiroshima and Nagasaki. The spontaneous incidence of myeloid leukemia in C3H/He male mice is 1%, and the incidence increased to 23.3% when 3 Gy of whole-body x-ray irradiation was given. However, the incidence of myeloid leukemia was found to be significantly decreased by caloric restriction; it was reduced to 7.9% and 10.7% when restriction was started before (6 weeks old) and after (10 weeks old) irradiation, respectively. In addition, the onset of the myeloid leukemia in both restricted groups was prolonged to a greater extent as compared with the control diet group. Caloric restriction demonstrated a significant prolongation of the life span in the groups on a restricted diet after having been exposed to irradiation, either before or after dietary restriction, in comparison with mice that were only irradiated.

Aging↗

Effect of dieting on plasma leptin, soluble leptin receptor, adiponectin and resistin levels in healthy volunteers.

OBJECTIVE: Recent findings demonstrating important effects of the adipokines on metabolism, energy homeostasis and body weight regulation have prompted research on the possible role of negative energy balance in altering adipocytokine regulation. The goal of this study was to evaluate the effects of a hypocaloric diet in healthy normal-weight volunteers. An additional goal was to help clarify the contribution of restricted caloric intake to altered plasma adipokine levels in the eating disorders anorexia nervosa and bulimia nervosa. DESIGN: Participants were studied before and after a 4-week reduced-calorie diet (1000-12000 kcal/day). patients Subjects included 15 healthy, normal-weight women (age 22 +/- 3 years). MEASUREMENTS: Plasma concentrations of leptin, soluble leptin receptor protein (sOB-R), adiponectin, resistin, thyroid hormones and beta-hydroxybutyrate were determined following overnight fast before and after the 4-week reduced-calorie diet. RESULTS: Subjects lost a mean of 3.4 +/- 2.1 kg in response to the reduced-calorie diet. The weight loss phase was associated with a 60.3% decrease in plasma leptin levels (P < 0.001), a 43.5% increase in sOB-R levels (P < 0.002) and a 16.2% decrease in plasma adiponectin levels (P < 0.04). There was no significant change in plasma resistin levels. CONCLUSIONS: These results demonstrate that a modest decrease in energy intake sustained over several weeks may play an important role in altering levels of plasma leptin and sOB-R. The findings also provide preliminary evidence that, in contrast to previous results in obese subjects, caloric restriction with accompanying weight loss in healthy, normal-weight volunteers may lead to decreased circulating adiponectin levels. Additional studies will be needed to clarify the contribution of altered energy intake to abnormalities in cytokine levels in the eating disorders.

3-Hydroxybutyric Acid↗

Dependence of rates of lipolysis, esterification, and free fatty acid release in isolated fat cells on age, cell size, and nutritional state.

Rates of lipolysis, esterification, and free fatty acid release were estimated in isolated epididymal fat cells prepared from rats fed either ad lib. or with a restricted caloric intake. Basal and epinephrine- or theophylline-stimulated rates of lipolysis correlated positively with cell size in the ad lib.-fed group only. Rates of esterification, both basal and epinephrine-stimulated, correlated positively with cell size in the ad lib.-fed group but negatively in the caloric-restricted group. These findings indicate that nutritional factors can modify any possible influence of adipose cell size on lipolysis and esterification. On the other hand, in both groups of rats, epinephrine- and theophylline-stimulated rates of lipolysis correlated positively with the basal rates of lipolysis. Also, rates of esterification in the presence of epinephrine correlated positively with the basal rates of esterification, suggesting that stimulated rates of lipolysis and esterification are at least partly determined by the basal rates regardless of nutritional status. The activity of glycerokinase measured in homogenates of isolated fat cells, if applicable to intact fat cells, was sufficient to cause considerable underestimations of the basal rates of lipolysis (using glycerol production as an index). When lipolysis was stimulated, the potential errors of estimating lipolysis by glycerol production alone were negligible.

Adipocytes↗

Nutritional influences on aging of Fischer 344 rats: II. Pathology.

The aim of this study was to explore the effects of nutritional manipulations on the occurrence and progression of age-related pathologic lesions in male Fischer 344 rats. The following nutritional regimens were studied: (a) ad libitum feeding, (b) food restriction initiated at 6 weeks of age, (c) food restriction initiated at 6 months of age, (d) food restriction limited to a period of early life (6 weeks to 6 months of age), (e) protein restriction without caloric restriction. The major age-related lesions observed were chronic nephropathy, cardiomyopathy, and neoplasia. Food restriction initiated at 6 months of age was as effective as food restriction initiated at 6 weeks of age in slowing the progression of chronic nephropathy and cardiomyopathy and in delaying the occurrence of neoplasia. Food restriction limited to early life was much less effective. Protein restriction in the absence of caloric restriction did not delay the occurrence of neoplasia, but it did retard chronic nephropathy and cardiomyopathy, although much less effectively than caloric restriction involving a similar level of protein restriction.

Aging↗

Abdominal fat deposition and sudden death syndrome in broilers: the effects of restricted intake, early life caloric (fat) restriction, and calorie: protein ratio.

The effects of feed restriction, early life fat restriction, and calorie:protein ratio on abdominal fat pad development and sudden death syndrome (SDS) in the broiler chicken were studied in two experiments. In Experiment 1, restricting feed intake to 90% of ad libitum intake was found to reduce significantly (P less than .01) both 49-day body weights and abdominal fat pad size while feed efficiency was significantly (P less than .01) improved compared to groups fed a wheat diet ad libitum. Corn-fed birds tended to outperform wheat fed groups. Reduced growth rate or supplementation of the diet with additional vitamins and minerals did not effect the incidence of SDS. In Experiment 2, fat restriction in the diet from 0 to 7 days initially reduced growth rate and increased feed:gain ratios. By 49 days, no effect of fat restriction on these parameters was observed. Dietary fat restriction tended to increase abdominal fat measured at 49 days of age. Lowering the calorie: protein ratio of the finishing diet significantly (P less than .05) improved feed:gain ratios measured from 29 to 49 days and tended to reduce fat pad size. Incidence of SDS was significantly (P less than .05) lower from 29 to 56 days in groups fed the 24% protein finisher diet as compared to birds fed a 19% finisher diet.

Abdomen↗

Caloric and carbohydrate restriction in the kidney: effects on free radical metabolism.

Carbohydrate restriction and caloric restriction (60% restriction of calories in relation to controls in both cases) were imposed on OF1 mice during 8 weeks in their growing phase. The three groups of animals ingested the same amount of vitamins and minerals. Kidney ascorbate strongly decreased in both restriction groups. Nevertheless, global caloric restriction significantly increased kidney antioxidant glutathione (GSH)/oxidized glutathione (GSSG) ratio, a sign of a reduced kidney oxidative stress. Increased glutathione peroxidase and cytochrome oxidase activities and decreased in vivo peroxidation were found in the kidney when the restriction was performed by substituting carbohydrates by nonnutritive bulk. No significant changes were observed for superoxide dismutase, catalase, glutathione reductase, glutathione, uric acid, malondialdehyde (HPLC), or in vitro sensitivity to peroxidation in the kidney. The results, reported for the first time in this tissue, show that short-term caloric restriction can increase the capacity for enzymatic decomposition of hydroperoxides and can decrease oxidative stress in the kidney, thus suggesting a role for free radical metabolism in the caloric restriction phenomenon.

Animals↗

Influence of sucrose polyester on plasma lipoproteins, and cholesterol metabolism in obese patients with and without diabetes mellitus.

Sucrose polyester (SPE) is a nonabsorbable substitute for fat. This study examined its effects in 10 obese patients, 6 with diabetes mellitus. Three diabetics had hypertriglyceridemia. Most patients were studied in three periods: weight maintenance, caloric restriction + SPE, and caloric restriction without SPE. Nondiabetics generally tolerated SPE better than diabetics. In nondiabetic patients caloric restriction + SPE produced a decrease in total cholesterol and in LDL-cholesterol of 20% and 26%, respectively. In normotriglyceridemic diabetic patients caloric restriction + SPE had an effect on plasma lipoproteins similar to that of nondiabetics. In diabetics with hypertriglyceridemia caloric restriction (with or without SPE) caused a marked reduction in plasma triglycerides. In all patients caloric restriction reduced cholesterol balance and presumably cholesterol synthesis. The feeding of SPE caused increased outputs of fecal neutral steroids suggestive of decreased absorption of cholesterol; SPE also frequently caused a mild increase in fecal acidic steroids (bile acids).

Aged↗

The sexual experience of women diagnosed with anorexia nervosa or bulimia nervosa.

OBJECTIVE: Women with bulimia nervosa generally have reported greater sexual activity and experience relative to women with anorexia nervosa. However, past research has been based on small samples and has not controlled for potential confounding variables or symptom severity. We further investigated sexual experience among women diagnosed with an eating disorder. METHODS: Women evaluated in an outpatient eating disorders program, and subsequently diagnosed with either anorexia nervosa (n = 131) or bulimia nervosa (n = 319), completed the Diagnostic Survey for Eating Disorders-Revised (DSED-R) at intake. Sexual experience variables (masturbation, coitus, sexual satisfaction), as well as control variables (age, weight, and menarche) and measures of symptom severity, were derived from the DSED-R. Logistic regression analyses were used to predict sexual experience. RESULTS: After controlling for relevant covariates, bulimics were more likely than anorexics to have engaged in sexual intercourse. Masturbation experience, as well as self-ratings of current sexual satisfaction, were inversely related to degree of restriction of caloric intake, particularly among women with anorexia nervosa. When compared to anorexics, bulimics reported greater sexual interest and earlier age of first coitus. DISCUSSION: Coitus (sexual activity involving a partner) was related to eating disorder diagnosis independent of symptoms, whereas masturbation (self-focused sexual activity) was related to caloric restriction for the sample as a whole and anorexia nervosa patients in particular. These relationships between sexual experience and eating disorder symptoms and diagnosis may illuminate the personality features of women with anorexia nervosa versus bulimia nervosa as well as the functional role of caloric restriction.

Adolescent↗

[Carcinogenesis: influence of caloric intake restriction].

In experimental animals, restriction of caloric intake is associated to a decreased incidence in the number and size of both spontaneous and induced tumors. Epidemiologic evidence of a similar effect in humans is not conclusive. However, some dietary recommendations regarding calories, protein and fiber content may be made in order to help prevent cancer development in human subjects.

Animals↗

Use of growth hormone and insulin-like growth factor I in catabolism that is induced by negative energy balance.

Both GH and insulin-like growth factor I (IGF-I) have been shown to promote anabolism in human volunteers that are made catabolic by caloric restriction. We have used caloric restriction as a model of controlled catabolism to test the efficacy of these agents in reversing negative nitrogen balance. Six normal volunteers underwent caloric restriction for 2-week intervals. This restriction induced negative nitrogen balance (e.g. -239 mmol/day). During the second week either IGF-I (16 micrograms/kg h) was administered by intravenous infusion for 16 h, or GH (0.05 mg/kg) was given subcutaneously daily. GH alone improved nitrogen balance by 180 mmol/day, and IGF-I improved it by 175 mmol. The two hormones had opposite effects on carbohydrate metabolism. Mean blood glucose rose approximately 26% with GH whereas it fell 37% with IGF-I and the subjects had frequent hypoglycemic episodes during the infusion. Minimal complications were observed during the 6 days of IGF-I infusion and consisted primarily of edema and jaw pain. It appeared that IGF-I was as efficacious as GH in reversing the negative nitrogen balance induced by caloric restriction and that hypoglycemia induced by IGF-I was the major limiting factor. In a second study 7 volunteers underwent the identical caloric restriction. In contrast to the first study one treatment group received the combination of GH plus IGF-I given in exactly the same doses as in the first study. A second group received IGF-I alone. The combination of GH/IGF-I was much more potent in improving nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Attenuated allergic responses to house dust mite antigen in feed-restricted rats.

Caloric restriction has been shown to alter a broad range of immunological end points in both experimental animals and humans. The objective of this study was to investigate the effect of short-term moderate feed restriction (25% reduction) on allergic immune responses in Brown Norway rats. After 3 weeks of acclimation to their feed regimens, rats were sensitized and 2 weeks later challenged with house dust mite (HDM) antigen via intratracheal instillation. Feed restriction resulted in lower levels of antigen-specific IgE in serum and reduced antigen specific lymphoproliferative activity in pulmonary lymph nodes. Feed restriction also attenuated pulmonary inflammation, as evidenced by lower levels of lactate dehydrogenase and total protein, decreased infiltration of neutrophils and eosinophils, and reduced secretion of pro-inflammatory cytokine tumor necrosis factor (TNF)-[alpha] in bronchoalveolar lavage fluid. In addition, feed restriction decreased TNF-[alpha] secretion in serum and decreased mRNA expression of TNF-[alpha] and interleukin-6 in pulmonary lymph nodes. We conclude that feed restriction strongly dampened the allergic immune responses to HDM in rats and that this attenuation was associated with decreased expression and secretion of pro-inflammatory cytokines.

Animals↗

Effect of age and diet on stratum corneum barrier function in the Fischer 344 female rat.

Stratum corneum barrier function in the female Fischer 344 rat was assessed in animals ranging from 11 to 144 weeks of age, which were either fed ad libitum or a caloric-restricted diet at 60% ad libitum. Caloric restriction has been shown to increase the life span of rodents and delay age-associated degenerative diseases. The penetration of water, lidocaine, and hydrocortisone were measured in vitro using the finite-dose technique in Franz diffusion chambers. Water permeability did not significantly change with either age or diet condition (with the single exception of the ad libitum 144-week animals). However, between 11 and 44 weeks, both lidocaine and hydrocortisone permeability increased with age in both diet groups. By 44 weeks the caloric restriction animals had significantly greater permeability to lidocaine and hydrocortisone then their ad libitum age cohorts. Between 44 and 144 weeks, skin permeability in the ad libitum animals continued to increase with age, whereas permeability in the caloric restriction animals declined. By 144 weeks the caloric restriction skin was less permeable than the age-matched ad libitum animals but still more permeable than the 11-week animals. The data show that the barrier properties of stratum corneum change with age in the female rat and that this change can be modulated by caloric restriction.

Aging↗

Calorie restriction and spontaneous hepatic tumors in C3H/He mice.

Caloric restriction started at the young adult (YA) stage and the full adult (FA) stage in mice was compared, specifically focussing on whether there would be a delay in the onset time of spontaneous hepatoma or a reduction in its frequency. Caloric restriction lengthened the life spans of both groups, the YA, and FA. Both groups showed striking reductions of spontaneous hepatomas, from 70.9 +/- 3.5% for non-restricted controls down to 35.7 +/- 5.7 and 30.4 +/- 4.0%, for mice restricted from young adult, and from full adult stages, respectively; further, the numbers of tumor-free mice in the restricted groups increased by 45.7% and 38.5%, respectively, from 11.5%, in the non-restricted control. The cumulative incidences of hepatoma in the caloric restricted groups showed a delayed and lower incidence compared with those of the non-restricted group; a parallel delay might result from a weakened activity in tumor-promotion, whereas a lower frequency, might reflect a possible reduction of target cells for hepatomata development. Both effects can be assumed to have resulted from caloric restriction. When cumulative incidences of small hepatomas were compared between the two restricted groups, restriction started at the young adult stage is assumed to have caused fewer initiation stresses, as well as to have delayed promotion, as clearly evidenced by a flatter curve of incidence with a lower total incidence. Thus, the time at which caloric restriction is started plays a critical role in its subsequent effects.

Aging↗