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Results for “Caloric Restriction”

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PubMed1994

Chronic caloric restriction induces stress proteins in the hypothalamus of rats.

The induction of stress proteins (sps) in the hypothalamus of female Fischer 344 rats in response to caloric restriction (CR) and to heat stress was investigated. Caloric restriction was found to elicit sps 27, 34, 70, and 90 in the hypothalamus of both young and old rats while none was found in the hypothalamus of ad libitum (AL) fed controls. Heat stress initiated heat shock proteins (hsps/sps) 27, 70, and 90 in the hypothalamus of the young (AL) fed animals, the same proteins evoked by feeding stress. The same sps were induced in the old (AL) rats although the expression showed substantial decline with age. This reduction was less marked, however, with the old CR rats. Stress protein 34, an infrequently reported protein, was related to feeding and was not induced by heat shock. Recent reports point to the important role sps play in the cellular reaction to stress, as well as their involvement in the higher functions. The findings reported here suggest that sps are involved in the regulatory mechanisms allowing CR animals to tolerate stress related to metabolic substrate deprivation.

Aging↗

PubMedDate not supplied

Moderate caloric restriction increases diaphragmatic antioxidant enzyme mRNA, but not when combined with lifelong exercise.

Diaphragmatic antioxidant enzymes are upregulated following acute and long-term treadmill exercise, but the effect of lifelong voluntary exercise (E) on diaphragmatic antioxidants is unknown. Therefore, 10-week old Fisher 344 rats were assigned to either: (a) sedentary ad libitum (AL) fed (24AL; n = 6); (b) E + 8% caloric restriction (24ECR; n = 9); or (c) sedentary + 8% caloric restriction (24CR; n = 9) groups. Diaphragms were harvested from animals at 24 months of age. Heme oxygenase-1 (HO-1) mRNA in addition to catalase (CAT), glutathione peroxidase (GPX), copper-zinc superoxide dismutase (Cu-ZnSOD) and manganese superoxide dismutase (MnSOD) mRNA and protein levels were measured. Reduced glutathione (GSH) and citrate synthase (CS) activity were measured to assess antioxidant status and oxidative capacity, respectively. The 24CR group demonstrated increased GPX, HO-1, MnSOD, and CAT mRNA compared to 24AL and 24ECR. Interestingly, the increased mRNA in 24CR animals did not result in elevated protein levels. No group differences in Cu-ZnSOD mRNA, CS activity, or GSH were observed, although GSH was 30% greater in 24CR animals (p = 0.085). In summary, although CR elevated the mRNA of key antioxidant enzymes in the diaphragm, lifelong CR alone or in combination with voluntary exercise did not alter diaphragm CS activity, antioxidant protein quantity, or GSH levels.

Animals↗

PubMed1996

Effects of caloric restriction on expression of testicular cytochrome P450 enzymes associated with the metabolic activation of carcinogens.

Previous work demonstrated that microsomal cytochrome P4502A1 (CYP2A1) is expressed in rat testicular Leydig cells. The present study investigates the effects of diet, age, and strain on rat testicular CYP2A1 expression and assesses the potential role of testicular CYP2A1 in the metabolic activation of carcinogens. In ad libitum-fed 18-week-old Fischer 344 rats, testicular CYP2A1 immunoreactive protein and testosterone 7alpha-hydroxylase activity (7alpha-TOHase) exhibited a circadian variation with a daytime maximum and a night-time minimum (82.2 +/- 42.0 and 21.9 +/- 4.5 pmol 7alpha-hydroxytestosterone/min/mg protein, respectively). Caloric restriction (to 60% of ad libitum consumption), which reduces the severity of Leydig cell tumors in rats, decreased expression of both CYP2A1 and testicular 7alpha-TOHase >80% and eliminated their circadian variation. Conversely, caloric restriction induced a circadian rhythm in testicular 7-benzyloxyresorufin-O-dealkylase activity. Testicular microsomes from ad libitum-fed rats having peak diurnal 7alpha-TOHase activity had significantly greater (30%) microsome-mediated aflatoxin B1-DNA binding activity compared to microsomes prepared from nocturnal phase ad libitum-fed or calorically restricted rats which expressed low 7alpha-TOHase activity. In 12-month-old Fischer 344 rats, high CYP2A1 expression was correlated with severe Leydig cell hyperplasia (r = 0.80), whereas CYP2A immunoreactive protein and 7alpha-TOHase were expressed at lower levels in Sprague-Dawley than in Fischer 344 rats and were undetectable in pig, monkey, and human testes. These are strains/species that do not exhibit significant Leydig cell hyperplasia. This suggests that caloric intake, strain, and circadian factors may all mediate testicular CYP2A1 expression in the rat and that CYP2A1 may in turn influence carcinogen activation and pathological status in the testis.

Aflatoxin B1↗

PubMed1976

Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man.

To evaluate the effect of caloric restriction and dietary composition on circulating T3 and rT3 obese subjects were studied after 7-18 days of total fasting and while on randomized hypocaloric diets (800 kcal) in which carbohydrate content was varied to provide from 0 to 100% calories. As anticipated, total fasting resulted in a 53% reduction in serum T3 in association with reciprocal 58% increase in rT3. Subjects receiving the no-carbohydrate hypocaloric diets for two weeks demonstrated a similar 47% decline in serum T3 but there was no significant change in rT3 with time. In contrast, the same subjects receiving isocaloric diets containing at least 50 g of carbohydrate showed no significant changes in either T3 or rT3 concentration. The decline in serum T3 during the no-carbohydrate diet correlated significantly with blood glucose and ketones but there was no correlation with insulin or glucagon. We conclude that dietary carbohydrate is an important regulatory factor in T3 production in man. In contrast, rT3 concentration is not significantly affected by changes in dietary carbohydrate. Our data suggest that the rise in serum rT3 during starvation may be related to more severe caloric restriction than that caused by the 800 kcal diet.

Adult↗

PubMed1995

Effects of caloric restriction on age-related oxidative modifications of macromolecules and lymphocyte proliferation in rats.

Decreased immune function associated with aging has been demonstrated in both humans and animals. We hypothesize that reactive oxygen species (ROS)-mediated damage to biological macromolecules may contribute to compromised immune response during aging. In this study, we compared the levels of lipid peroxidation and oxidatively modified proteins in plasma and splenocytes, and the mitogen-induced T lymphocyte proliferation in ad lib-fed (AL) and caloric restricted (CR) Fischer 344 x BNF1 male rats at the ages of 5, 18, and 31 months. The results show that AL rats exhibit an age-related decrease in proliferative response of splenic lymphocytes to phytohemagglutinin (PHA) and concanavalin A (Con A). This functional decline in T-lymphocytes during aging is inversely correlated to the levels of both lipid peroxidation and protein carbonyl in the plasma and splenic lymphocytes. Caloric restriction, however, can partially reverse the age-dependent decrease in T lymphocyte proliferation and significantly reduce lipid peroxidation and protein carbonyl contents in plasma and splenocytes. The above observations support the hypothesis that the age-associated declines in immune function are related to the oxidative modification of biological macromolecules, which in turn may lead to enzyme inactivation, membrane disruption, and cell senescence. One of the mechanisms by which caloric restriction reverses declined immune function in aged rats is hypothesized to be through reduction in ROS production and thereby protection of cellular macromolecules against oxidative damage.

Aging↗

PubMed1987

Inhibition of chemically induced mammary and colon tumor promotion by caloric restriction in rats fed increased dietary fat.

Tumor promotion associated with increased dietary fat may be inhibited by reduction in total caloric intake. This hypothesis was tested in rats given either 7,12-dimethylbenz(a)anthracene to induce mammary tumors or 1,2-dimethylhydrazine to induce colon tumors. One week after dosage with either carcinogen, the rats were fed semipurified diets that provided 4% fat with ad libitum calories or 13.1% fat with a reduction of calories by 40% from ad libitum intake. Rats treated with 7,12-dimethylbenz(a)anthracene and subjected to caloric restriction weighed 40% less than those fed ad libitum; rats treated with 1,2-dimethylhydrazine were heavier at the onset of caloric restriction and lost weight and weighed approximately 40% less than animals fed ad libitum. At 20 weeks after 7,12-dimethylbenz(a)anthracene administration, rats fed ad libitum had 80% tumor incidence while in those fed restricted calories, 20% had tumors (P less than 0.001). All other measures of mammary tumor growth were significantly reduced in rats given restricted calories. Six months after 1,2-dimethylhydrazine administration, colon tumor incidence was 100% in rats fed ad libitum and 53% in those fed the calorie-restricted diet (P less than 0.001). This reduction of colonic carcinogenesis was seen despite a significant increase in mucosal labeling index following [3H]thymidine autoradiography. This paradoxical finding may be due to the increased fat content of the calorie-restricted diet. These data demonstrate that the tumor-promoting effects of dietary fat can be more than offset by a reduction in total caloric intake and that the promoting effect of fat may be due, at least in part, to its greater caloric density.

Animals↗

PubMed1978

Effects of caloric restriction on the kinetics of indocyanine green in patients with liver diseases and in the rat.

The effect of caloric restriction on the hepatic uptake and excretion of indocyanine green (ICG) was studied in man as well as in rats. It was demonstrated that following a 72-hr caloric restriction in man, the plasma clearance rate for ICG was increased significantly at the low dose of 0.5 mg/kg, and transport maximum was increased without a significant change of storage capacity. In rats, the maximal biliary excretion was significantly increased after 48-hr fast, but neither maximal hepatic uptake (Vmax) nor hepatic ICG content was altered. The evidence is consistent with the view that fasting increases the ICG plasma clearance at low doses by enhancement of excretory steps at the bile canalicular membrane.

Adult↗

PubMed1996

Effects of age and caloric restriction on cell proliferation in hepatocyte cultures from control and hepatectomized Fischer 344 rats.

The effects of age and caloric restriction on cell proliferation, measured as scheduled DNA synthesis (SDS), were evaluated in primary hepatocyte cultures from control and partially hepatectomized (PH) young to old ad libitum (AL) and caloric-restricted (CR) male Fischer 344 (F344) rats. We reported significant age- or CR-related decreases in SDS in control cultures. PH-induced cultures exhibited significant increases in SDS compared with their control counterparts. Hepatocytes from PH-induced old CR diet-fed animals exhibited significant increases in SDS compared with cultures from control old CR, PH-induced young CR and PH-induced old AL animals. Alternatively, SDS rates for PH-induced young CR animals were significantly lower at 48 h and higher at 72 h than the rates we reported for cultures from PH-induced young AL F344 rats. These data suggest that CR decreases and preserves the proliferative capacity in hepatocytes from young animals and may permit animals to respond more efficiently with induced compensatory cellular replication in old age.

Age Factors↗

PubMed2005

Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss.

The prevalence of type 2 diabetes mellitus (T2DM) and obesity in the western world is steadily increasing. Bariatric surgery is an effective treatment of T2DM in obese patients. The mechanism by which weight loss surgery improves glucose metabolism and insulin resistance remains controversial. In this review, we propose that two mechanisms participate in the improvement of glucose metabolism and insulin resistance observed following weight loss and bariatric surgery: caloric restriction and weight loss. Nutrients modulate insulin secretion through the entero-insular axis. Fat mass participates in glucose metabolism through the release of adipocytokines. T2DM improves after restrictive and bypass procedures, and combinations of restrictive and bypass procedures in morbidly obese patients. Restrictive procedures decrease caloric and nutrient intake, decreasing the stimulation of the entero-insular axis. Gastric bypass (GBP) operations may also affect the entero-insular axis by diverting nutrients away from the proximal GI tract and delivering incompletely digested nutrients to the distal GI tract. GBP and biliopancreatic diversion combine both restrictive and bypass mechanisms. All procedures lead to weight loss and decrease in the fat mass. Decrease in fat mass significantly affects circulating levels of adipocytokines, which favorably impact insulin resistance. The data reviewed here suggest that all forms of weight loss surgery lead to caloric restriction, weight loss, decrease in fat mass and improvement in T2DM. This suggests that improvements in glucose metabolism and insulin resistance following bariatric surgery result in the short-term from decreased stimulation of the entero-insular axis by decreased caloric intake and in the long-term by decreased fat mass and resulting changes in release of adipocytokines. Observed changes in glucose metabolism and insulin resistance following bariatric surgery do not require the posit of novel regulatory mechanisms.

Biomarkers↗

PubMedDate not supplied

Effects of caloric restriction on gene expression in the arcuate nucleus.

Neuroendocrine alterations that repress energy-costly physiologic processes such as reproduction and growth and induce stress responses, might underlie the antiaging effect of caloric restriction (CR). Neurons in the arcuate nucleus of the hypothalamus (ARH) might have a pivotal role in these neuroendocrine alterations. We investigated the effects of CR on gene expression of neuropeptide Y (NPY), proopiomelanocortin (POMC), growth hormone-releasing hormone (GHRH), somatostatin (SRIH), and cyclophilin (CP) in the ARH in male F344 rats at 6 months of age. Rats were fed ad libitum or a 30% caloric restricted diet with a modified alternate-days feeding regimen from 6 weeks of age. Reverse transcription-polymerase chain reaction (RT-PCR) methods were used to quantify mRNA levels over multiple time points during the 12-h/12-h dark/light cycle over a 2-days feeding cycle. The present study demonstrated that CR increased NPY-mRNA levels, but decreased POMC, GHRH, and CP mRNA levels differentially over the feeding cycle. The SRIH level was not significantly affected by CR. The present results support the neuroendocrine hypothesis of CR.

Analysis of Variance↗

PubMed2000

Metabolic mass, metabolic rate, caloric restriction, and aging in male Fischer 344 rats.

Previous investigators have found the metabolic rate to be the same in calorically-restricted and ad-libitum fed rodents, and hence concluded that the Rate of Living Theory does not help explain the longer lifespan of the calorically-restricted (CR) animal. However, these previous instigators may not have used reliable estimates of metabolic mass in their calculations of metabolic rate. Hence the present study investigated the reliability of ten different estimates of metabolic mass (MM) in 21-month-old male Fischer 344 rats fed three different diets to yield a wide range of body compositions. Two criteria were used to rank each estimate of metabolic mass: strong correlation with daily caloric intake (DCI); and zero Y-intercept on the regression curve of DCI versus the MM. The combined weight of the heart, liver, kidneys and brain (OW) was found to be the best estimate of MM. Statistical analysis of the differences in metabolic rate in the three groups of rats showed that the significance of these differences depended on the estimate of MM used. OW yielded different results than did fat-free mass (FFM), body weight (BW), BW(0.75), and BW(0.67). Therefore, because previous investigators used FFM, BW, BW(0.75), or BW(0.67), rather than a more reliable estimate such as OW, their finding that metabolic rate was not different in the CR and ad-lib groups, and their conclusion that the Rate of Living Theory does not help explain the longer lifespan of the CR animal, are called into question.

Aging↗

PubMed2000

Caloric restriction improves thermotolerance and reduces hyperthermia-induced cellular damage in old rats.

Adult-onset, long-term caloric restriction (CR) prolongs maximum life span in laboratory rodents. However, the effect of this intervention on an organism's ability to cope with a physical challenge has not been explored. We investigated the influence of CR and aging on stress tolerance in old rats exposed to an environmental heating protocol on two consecutive days. We hypothesized that CR would increase heat tolerance by reducing cellular stress and subsequent accrual of oxidative injury. All calorically restricted rats survived both heat exposures compared with only 50% of their control-fed counterparts. CR also decreased heat-induced radical generation, stress protein accumulation, and cellular injury in the liver. In addition, heat stress stimulated marked induction of the antioxidant enzymes manganese-containing superoxide dismutase and catalase, along with strong nuclear catalase expression in liver samples from rats subjected to CR. In contrast, stress-related induction of antioxidant enzymes was blunted, and nuclear catalase expression was unchanged from euthermic conditions in the control-fed group. These data suggest that CR reduces cellular injury and improves heat tolerance of old animals by lowering radical production and preserving cellular ability to adapt to stress through antioxidant enzyme induction and translocation of these proteins to the nucleus.

Adaptation, Physiological↗

PubMed2003

Effects of caloric restriction on cognition and behavior in developing mice.

The effects of caloric restriction (CR) on cognition and behavior in developing mice were investigated in this study. Male and female Kunmin mice were fed a standard rodent diet ad libitum (Control); 80% of control (20% CR) or 65% of control (35% CR) for 6 months. Body weight gain was significant reduced in CR mice relative to control. Learning and memory retention test in a Y maze demonstrated that CR increased learning but not retention in male mice, whereas CR did not affect learning or retention in females. Open field test revealed no difference in exploratory activity between CR and control mice. These findings suggest that CR produce sex-dependent effect on cognition, but not exploratory activity, in developing animals.

Aging↗

PubMed2005

Caloric restriction does not reverse aging-related changes in hippocampal BDNF.

Caloric restriction (CR) can attenuate the aging-related decline in learning and memory in rats. Understanding the mechanisms underlying this effect could lead to therapies for human memory impairment. We tested the hypotheses that aging is associated with a decline in hippocampal brain-derived neurotrophic factor (BDNF), a growth factor that enhances learning and memory, and that CR increases hippocampal BDNF. We compared BDNF protein levels in hippocampal subregions of young, middle-aged and old rats fed CR or ad libitum (AL) diets. Mean BDNF levels in the dentate gyrus and CA3 did not differ with diet but increased with age. In CA1, BDNF levels were slightly higher in CR than AL rats at middle and old age but did not change across lifespan. These data suggest that mnemonic impairments with age do not reflect a decrease in hippocampal BDNF. Furthermore, if CRs attenuation of aging-related memory changes is mediated by BDNF, then it must be through a small, CA1-specific increase and does not involve reversal of an aging-related decline in BDNF.

Age Factors↗

PubMed1994

Temporal and substrate-dependent patterns of stress protein expression in the hypothalamus of caloric restricted rats.

Stress proteins (sps) 27, 34, 70 and 90 (Mr x 10(3)) were induced in the hypothalamus of caloric restricted (CR) rats by feeding stress. A definite time pattern for sps synthesis was observed when their induction was examined at several time points after the rats were fed, and the level of sps expression was found to vary significantly at different times of the day. The same group of proteins was induced in ad libitum fed rats when they were subjected to food deprivation for 48 h. Stress protein 34 expression in the hypothalamus of old caloric restricted rats was found to be dependent on blood glucose levels, and was substantially reduced when insulin was added to the glucose infusion. The expression of sps 27, 70 and 90, however, was little changed with glucose and/or insulin infusion.

Aging↗

PubMed1992

Caloric restriction in pregnant diabetic women: a review of maternal obesity, glucose and insulin relationships as investigated at the University of California, San Diego.

Caloric restriction during pregnancy is contraindicated for women with a normal body mass index (BMI) of 19.8-26 kg/m2. Reduction of caloric intake in obese pregnant normal and diabetic women has been a controversial topic for many years. This paper reviews several clinical studies initiated in 1978 at the University of California, San Diego. One focus of this review concerns modest caloric reduction in obese women with gestational diabetes mellitus (GDM). Metabolic observations of diabetes during pregnancy in the past decade include extensive use of a 400 kcal isocaloric breakfast meal tolerance test to assess maternal glucose:insulin relationships and the degree of insulin resistance in obese pregnant subjects. We have previously reported that maternal hyperinsulinemia with or without maternal hyperglycemia is an important factor in fetal macrosomia. We suggest for obese pregnant diabetic women implementation of nutritional recommendations of the 1990 Committee on Nutritional Status During Pregnancy and Lactation, Food and Nutrition Board, Institute of Medicine, National Academy of Sciences that advise a lower caloric intake for obese normal pregnant women with BMIs greater than 26. In obese noninsulin-dependent diabetic women and those with GDM, we urge that a large prospective epidemiologic study be undertaken to assess the respective roles of modest maternal caloric restriction and maternal glucose:insulin relationships on neonatal and long-term longitudinal measurements of growth and development of children of diabetic mothers.

Adult↗

PubMed1986

Effects of caloric restriction and exercise on insulin receptors in obesity: association with changes in membrane lipids.

We have studied the effects of supervised caloric restriction and exercise on mononuclear leukocyte lipid composition, membrane fluidity, and insulin receptors in ten nondiabetic obese adults, (175 +/- 9.3% of ideal body weight) and ten normal adult subjects. In a second study, we examined the effects of caloric restriction alone using a very low calorie liquid diet in the treatment of another ten obese adults. In both groups of obese adults, fasting insulin levels were elevated and fell to normal levels following treatment. Insulin binding to monocytes, which was reduced in obese subjects, increased toward normal after short-term treatment; this was due to the restoration of total insulin binding capacity to levels one half of that seen in the normal adult group. Obese subjects undergoing either treatment had elevated membrane cholesterol/phospholipid ratios prior to treatment (0.499 +/- 0.050 and 0.446 +/- 0.011 v 0.400 +/- 0.025 mol/mol in normal adults P less than 0.005 by ANOVA). Prior to treatment, for all subjects there was a significant inverse correlation between insulin tracer binding and membrane cholesterol/phospholipid ratios (r = .484, n = 34, P less than 0.005). This relationship did not change significantly in obese subjects in either treatment group. Cell membrane microviscosity was determined by fluorescence polarization (FP) using DPH (2 X 10(-6) mol/L). Prior to weight loss, obese subjects had significantly higher FP values than controls (0.304 +/- 0.006 and 0.319 v 0.259 +/- 0.009, P less than 0.005, by ANOVA) indicating greater microviscosity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Effect of caloric restriction on the induction of hepatic cytochrome P-450 and Ah receptor binding in C57BL/6N and DBA/2J mice.

While it is known that caloric restriction alters activities of certain xenobiotic metabolizing enzymes, the mechanism(s) by which this occurs have not been determined. In this study, caloric restriction (CR) increases activities of liver cytochrome P450IA1 dependent ethoxyresorufin-O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) and cytochrome P450IIB1 dependent pentoxyresorufin-O- dealkylase (PROD) in DBA/2J or C57BL/6N mice. However, the cytosolic Ah receptor binding in both strains of mice was not increased. The hepatic cytochrome P450IA1 activity was increased by CR in DBA/2J mice (a strain lacking normal Ah receptor binding), indicating that this induction need not be mediated by the Ah receptor. The effects of CR, sex and strain on P450IA1 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were also determined. Specific induction of cytochrome P450IA1 by TCDD was greater in females than in males of both strains, whereas the P450 isozymes induced in male DBA/2J mice had less specificity toward 7-ethoxyresorufin than those induced in C57BL/6N mice. Moreover, P450IA1 induction by TCDD was significantly potentiated by CR in the DBA/2 strain, indicating the interactive involvement of different regulatory mechanisms.

Animals↗