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Results for “Caloric Restriction”

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At least 811 records · Page 45Linked to original sources

PubMed2007

The interaction between the renin-angiotensin system and peroxisome proliferator activated receptors: a hypothesis including the participation of mitochondria in aging.

The objective of improving health is intimately associated with preventing and delaying age-related diseases. Nutritional and pharmacological approaches aimed at retarding aging are uncovering mechanisms, whose definitive roles in cell and tissue physiology need to be defined. In this article we hypothesize that peroxisome proliferator activated receptor (PPAR)-modulation is a pivotal process that underlies the association between mitochondria and the renin-angiotensin system (RAS) in aging. This hypothesis is based on several lines of evidence suggesting that: a) mitochondrial function and oxidant production are active participants in the aging process; b) PPARs, by regulating mitochondrial function and uncoupling proteins (UCP), seem to play a major role in the age-retarding effects of caloric restriction; c) RAS inhibition delays the deleterious effects of aging and also upregulates PPARs; and d) a number of physiological and molecular events that occur in experimental caloric restriction, and experimental and clinical RAS inhibition, involve changes in mitochondrial functions.

Aging↗

PubMed2004

Lack of direct effect of moderate hyperleptinemia to improve endothelial function in lean rat aorta: role of calorie restriction.

Leptin stimulates vascular sympathetic activity and NO release. The resulting effect of hyperleptinemia on endothelial function is unknown. Reduction of food intake associated with hyperleptinemia may mediate some of the vascular effects of leptin. This study was designed to assess the relative effects of short-term moderate caloric restriction and hyperleptinemia on vascular function in lean rat. Endothelium-dependent and -independent vasorelaxation, nitric oxide synthase (eNOS) expression and nitrite production were measured in lean rats receiving leptin subcutaneous infusion (-26% caloric intake, -4% body weight versus control) or moderate caloric restriction (pair-feeding) for one week. Plasma leptin was increased (P < = 0.05) by approximately 300% in the leptin-infused group, while it decreased (P < or = 0.05) by approximately 40% in calorie-restricted animals. Both leptin infusion and calorie restriction resulted in improved (P < 0.05) endothelium-dependent vasorelaxation to acetylcholine (EC50: -6.1 +/- 0.2 and -6.2 +/- 0.2 versus -5.4 +/- 0.2 in control) and unaltered endothelium-independent vasodilation to DEA-NONOate. Furthermore, in aortas from leptin-infused and calorie-restricted rats, expression of eNOS and nitrite production were increased (P < = 0.05) to similar extent compared to control animals. These findings suggest that moderate short-term calorie restriction with adaptive hypoleptinemia has independent beneficial effects on endothelial function in lean animals by enhancing eNOS expression and function. In addition, physiological hyperleptinemia does not independently contribute to improved vascular function above and beyond the effect of calorie restriction.

Animals↗

PubMed2006

Effects of age and caloric intake on glutathione redox state in different brain regions of C57BL/6 and DBA/2 mice.

The main purpose of the present study was to determine whether specific regions of the mouse brain exhibit different age-related changes in oxidative stress, as indicated by glutathione redox state and the level of protein-glutathionyl mixed disulfides. Comparison of 3- and 21-month-old mice indicated an age-related decrease in the ratio of reduced to oxidized glutathione (GSH/GSSG) as well as a pro-oxidizing shift in the calculated redox potential (ranging from 6 to 15 mV) in the cortex, hippocampus, striatum and cerebellum, whereas there was little change in the brainstem. This pro-oxidizing shift in redox state was due to a modest decrease in GSH content occurring in all the brain regions examined, and elevations in GSSG amount that were most pronounced in the striatum and cerebellum. The regional changes in glutathione redox state were paralleled by increases in the amounts of protein-mixed disulfides. A reduction of caloric intake by 40% for a short period (7 weeks), implemented in relatively old mice (17 months), increased the GSH/GSSG ratio and redox potential at 19 months in the same brain regions that exhibited age-related decreases. The effects of age and caloric restriction were qualitatively similar in C57BL/6 and DBA/2 mice. However, young DBA/2 mice, which do not show extension of life span in response to long-term caloric restriction, had lower GSH/GSSG ratios and higher protein-mixed disulfides than age-matched C57BL/6 mice. The current findings demonstrate that oxidative stress, as reflected by glutathione redox state, increases in the aging brain in regions linked to age-associated losses of function and neurodegenerative diseases.

Aging↗

PubMed1999

Adjusted and unadjusted energy usage rates both determine body fat and plasma leptin in male Fischer 344 rats.

Previous studies of the relationship between plasma leptin and energy usage have yielded contradictory findings. The present study was therefore conducted to clearly distinguish and measure the energy usage rate and the energy usage rate adjusted for a surrogate of metabolically active tissue mass. We investigated the simultaneous relationships between these two measures of energy usage, leptin, and body fat in 21-month-old adult male Fischer 344 rats on three different long-term dietary regimens: (1) continuous ad libitum feeding (Ad-lib); (2) ad libitum feeding until early adulthood, and then continuous 60% caloric restriction (CR); and (3) ad libitum feeding until early adulthood, then 60% caloric restriction until 16 months, and then ad libitum feeding for 5 months (CR/Ad-lib). Two versions of the daily usage rate were measured: daily dietary caloric intake (DCI), and daily energy expenditure (EE) based on indirect calorimetry. Two versions of the metabolically active tissue mass were also measured: fat-free mass (FFM), and the sum of the weight of the heart, brain, liver, and kidneys. Energy usage rates were adjusted for these measures of metabolically active tissue mass to yield measures of the energy metabolic rate. Correlation, regression, and path analyses showed that both the energy usage rate and adjusted energy usage rate played important independent roles in determining body fat and plasma leptin, but only after multivariate techniques were used to account for the simultaneous interactions between variables. Increases in the energy usage rate were associated with increases in body fat and the adjusted energy usage rate. Increases in the adjusted energy usage rate were associated with decreases in body fat and plasma leptin. These findings suggest that differences in subjects adjusted energy usage rate could explain some of the apparently contradictory findings concerning the relationship between energy usage and plasma leptin in previously published studies. In conclusion, this appears to be the first study to clearly separate and quantify the effects of the energy usage rate and adjusted energy usage rate on body fat and plasma leptin. The findings suggest that under conditions of long-term stable body weight, both of these measures of energy usage play independent simultaneous roles in determining body fat and plasma leptin.

Adipose Tissue↗

PubMed1990

Effect of prolonged modified fasting in obese persons on in vitro markers of immunity: lymphocyte function and serum effects on normal neutrophils.

The effects of nutritional manipulation on immune function have been extensively studied in animals, but few studies have examined dietary restriction in humans. Obese patients enrolled in a protein-sparing, calorically restricted diet were monitored over a 3-month period with in vitro examination of mitogen- and antigen-induced lymphocyte blastogenesis. The sera from these patients were evaluated for effects on neutrophil chemotaxis, phagocytosis and microbial killing. Significant changes in body weight, triglycerides and glucose occurred during the diet, and most patients exhibited urinary ketosis. The diet was associated with increased blastogenesis in unstimulated cultures and in varicella and candida antigen-stimulated cultures, but blastogenesis was unchanged for phytohemagglutinin, concanavalin A, SK-SD and histoplasma. In assays of serum effects on neutrophil function, patients with urinary ketosis had depression of chemotaxis and microbial killing but not phagocytosis when compared to baseline or nonketotic patients. This study indicates that long-term caloric restriction is associated with significant effects on in vitro lymphocyte stimulation and with significant serum effects on normal neutrophil function.

Blood Glucose↗

PubMed2005

Central and peripheral effects of insulin/IGF-1 signaling in aging and cancer: antidiabetic drugs as geroprotectors and anticarcinogens.

Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules linked to longevity include DAF-2 and insulin receptor (InR) and their homologues in mammals and to inactivation of the corresponding genes followed by increased life span in nematodes, fruit flies, and mice. It is possible that the life-prolonging effect of caloric restriction are due to decreasing IGF-1 levels. A search of pharmacological modulators of life span-extending mutations in the insulin/IGF-1 signaling pathway and mimetics of effects of caloric restriction could be a direction in the regulation of longevity. Some literature and our own observations suggest that antidiabetic drugs could be promising candidates for both life span extension and prevention of cancer.

Aging↗

PubMed2007

Effect of calorie restriction with or without exercise on body composition and fat distribution.

CONTEXT: There is debate over the independent and combined effects of dieting and increased physical activity on improving metabolic risk factors (body composition and fat distribution). OBJECTIVE: The objective of the study was to conduct a randomized, controlled trial (CALERIE) to test the effect of a 25% energy deficit by diet alone or diet plus exercise for 6 months on body composition and fat distribution. DESIGN: This was a randomized, controlled trial. SETTING: The study was conducted at an institutional research center. PARTICIPANTS: Thirty-five of 36 overweight but otherwise healthy participants (16 males, 19 females) completed the study. INTERVENTION: Participants were randomized to either control (healthy weight maintenance diet, n = 11), caloric restriction (CR; 25% reduction in energy intake, n = 12), or caloric restriction plus exercise (CR+EX; 12.5% reduction in energy intake + 12.5% increase in exercise energy expenditure, n = 12) for 6 months. MAIN OUTCOME MEASURES: Changes in body composition by dual-energy x-ray absorptiometry and changes in abdominal fat distribution by multislice computed tomography were measured. RESULTS: The calculated energy deficit across the intervention was not different between CR and CR+EX. Participants lost approximately 10% of body weight (CR: - 8.3 +/- 0.8, CR+EX: - 8.1 +/- 0.8 kg, P = 1.00), approximately 24% of fat mass (CR: - 5.8 +/- 0.6, CR+EX: - 6.4 +/- 0.6 kg, P = 0.99), and 27% of abdominal visceral fat (CR: 0.9 +/- 0.2, CR+EX: 0.8 +/- 0.2 kg, P = 1.00). Both whole-body and abdominal fat distribution were not altered by the intervention. CONCLUSION: Exercise plays an equivalent role to CR in terms of energy balance; however, it can also improve aerobic fitness, which has other important cardiovascular and metabolic implications.

Abdominal Fat↗

PubMed2004

Calorie restriction counteracts the impairment of adipocyte insulin-stimulated lipogenesis in aging rats, but not that induced by dexamethasone treatment.

In order to detect metabolic derangements that could be implicated in the pathogenesis of age-related insulin resistance, insulin-stimulated lipogenesis was investigated in isolated adipocytes from 24-month-old Sprague-Dawley rats, and the protective influence of caloric restriction was assessed. For comparison, the effects of glucocorticoid administration, used as a pharmacological tool to alter insulin sensitivity, were also studied. Caloric restriction consisted in a 40% reduction of the daily food intake of controls starting at 3 months of age. Dexamethasone (0.13 mg/kg/day) was administered for 14 days prior to sacrifice to both ad libitum-fed and dietary-restricted aging rats. Three-month-old animals, treated or untreated with dexamethasone, served as young controls. The results showed a significant age-related decrease of insulin-stimulated lipogenesis, which was fully prevented by a lifelong regimen of dietary restriction. Dexamethasone treatment markedly reduced insulin-stimulated lipogenesis in adipocytes isolated from all groups of rats, including those submitted to calorie restriction. In conclusion, our data indicate that the mechanism by which aging alters adipose tissue insulin-induced lipogenesis is reversed by dietary intervention and appears to be different from that triggered by dexamethasone. This particular defect might contribute to an imbalance of fat distribution among tissues that could induce or aggravate peripheral insulin resistance in old age.

Adipocytes↗

PubMed1998

The effect of dehydroepiandrosterone combined with a low-fat diet in spontaneously obese dogs: a clinical trial.

Dehydroepiandrosterone (DHEA) has been shown to have antiobesity activity in rodents and spontaneously obese dogs. This study evaluated the effect of DHEA or placebo combined with a low-fat/high-fiber diet in spontaneously obese dogs in a clinical trial. Spontaneously obese, euthyroid dogs, referred to the University of Wisconsin School of Veterinary Medicine for treatment of their obesity, were evaluated for percent overweight, rate of weight loss, serum cholesterol, plasma lipoprotein and serum biochemistry profiles, complete blood count, and endocrine profiles (T4, T3, cortisol, insulin, and DHEA-sulfate). DHEA-treated dogs had a significantly increased rate of actual and percent excess weight loss compared with placebo-treated dogs. Serum cholesterol decreased in both treatment groups; however, DHEA-treated dogs had a significantly greater reduction than placebo-treated dogs. DHEA-treated dogs had a significant 32% reduction in total plasma cholesterol, which was due to a 27% reduction in the lipoprotein fraction containing the high-density lipoprotein (HDL) and a 50% reduction in the lipoprotein fraction containing the low-density lipoprotein (LDL). Placebo-treated dogs did not have a significant reduction in total plasma cholesterol or in the fraction containing LDL; however, they did have a significant 11% reduction in the fraction containing HDL. Significant decreases in serum T4 and T3 observed in dogs receiving DHEA were not noted in dogs receiving placebo. DHEA in combination with caloric restriction results in a faster rate of weight loss than does caloric restriction alone. In addition, DHEA has hypocholesterolemic activity, particularly affecting the lipoprotein fraction containing the LDL cholesterol.

Animals↗

PubMed2004

Effects of undernutrition on serum and testicular testosterone levels and sexual function in adult rats.

The aim of this study was to evaluate testosterone concentrations, sexual behavior, and androgen receptor protein level in the testes of rats submitted to protein- and energy-restricted diets during 30 days. Adult male Wistar rats were assigned to one of the following groups: (C) control, diet with 23% of protein; (PR) protein-restricted, diet with 8% of protein; (ER) energy-restricted, diet with 23% of protein in restricted quantities. Mount number, ejaculation latencies and copulatory efficiency were evaluated to determine sexual behavior. At the end of the experiment, the animals were sacrificed to determine serum and testicular testosterone concentrations as well as testicular androgen receptor protein level. Compared to the C group, the ER group presented a significant decrease in body (36%), testis (20%) and epididymis (14%) weights in serum (78%) and testicular (68%) testosterone concentrations as well as in copulatory efficiency (26%). On the other hand, the ER group presented a significant increase in mount number (114%) and ejaculatory latency (62%). The androgen receptor protein levels were significantly reduced in both PR and ER groups (41% and 74%, respectively). This is the first paper to demonstrate that the effect of undernutrition on reproduction is not related to reduced protein intake but caloric restriction. Also, in caloric restriction, there is a relationship between sex behavior, androgen receptors, and testosterone concentration.

Animals↗

PubMed1988

Effects of a chronic wasting infection on skeletal muscle size and contractile properties.

To evaluate the effects of chronic infection on skeletal muscle dimensions and contractile properties, we used a hamster model of visceral leishmaniasis, a parasitic infection of the reticuloendothelial system produced by Leishmania donovani (LD). To distinguish between effects of reduced caloric intake and infection per se, we also studied healthy control animals and noninfected animals subjected to caloric restriction. Three muscles were tested in vitro: plantaris, soleus, and diaphragm. Both caloric restriction and LD infection caused loss of body weight and reduced muscle cross-sectional areas and wet weights. The interventions had variable effects on in vitro contractile properties, the most pronounced being reduction in peak tension in response to tetanic stimulation. Tension loss was 35-45%, except for a loss of 65% in plantaris of LD-infected animals. We conclude that chronic LD infection affects skeletal muscles in both indirect and direct ways. 1) Reduced caloric intake due to anorexia decreases muscle size and active tension. Disuse probably enhances this effect in limb muscles. 2) Infection produces profound weakness of inactive fast-twitch muscle by unknown mechanisms.

Animals↗

PubMed2004

Mechanisms underlying the impaired regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in aged rat liver.

As the main risk factor for cardiovascular disease, hypercholesterolemia is one of the most studied age-related metabolic alterations. In the liver, cholesterol homeostasis is strictly regulated through the modulation of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the key enzyme of cholesterol biosynthesis. With ageing, hepatic HMG-CoA reductase becomes completely activated and cholesterol content increases in the blood. The research reported in this paper uses the regulatory enzymes of reductase (i.e., the AMP-dependent kinase (AMPK) and the protein phosphatase 2A (PP2A)), the HMG-CoA reductase thermodependent activity and the "in vitro" enzyme degradation to elucidate the role played by the HMG-CoA reductase regulation and its membrane interaction. Related experiments were performed on 3 and 24 months "ad libitum" (AL) fed rats and 24 months caloric-restricted rats. The results show no changes in the PP2A level and the activation state of AMP dependent kinase in aged "ad libitum" fed rats. By contrast, the activation state of the kinase is enhanced in the aged caloric-restricted animals. With respect to the adult, the thermodependent activity of reductase remains unchanged, while the degradation rate of the HMG-CoA reductase is slower and independent on proteasome. These findings support the hypothesis that a different arrangement of the HMG-CoA reductase membrane domain in aged rats is a cause of reductase deregulation.

AMP-Activated Protein Kinases↗

PubMed1992

Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats.

To study the effect of a sudden loss of body weight on the beta-cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum.

Aging↗

PubMed2002

Age-related changes of cholesterol and dolichol biosynthesis in rat liver.

Ageing has been defined as a gradually decreased ability to maintain homeostatic potential and increased risk to die, associated with a tissue accumulation of altered proteins and lipids. Among other, increased concentration of an isoprenoid compound, dolichol (Dol), in mammalian tissues during ageing has been reported and it has been considered as a new biomarker of ageing. However, the mechanism and the role of this accumulation is still unknown. Aim of this work was to study the mechanism of age-dependent Dol accumulation in the liver analysing the activity of the hepatic rate-limiting enzyme of isoprenoid biosynthesis, the 3-hydroxy 3-methylglutaryl CoA reductase (HMGCoA reductase), the Dol synthesis by mevalonate (MVA), the Dol level in the plasma, and the cholesterol (Chol) synthesis and content of ageing rat fed ad libitum (AL) or subjected to the effect of food restriction. Since the caloric restrictions are the most reproducible way to slow ageing and to extend life span, animals on these nutritional regimens were used to study ageing related mechanisms. The data show that during ageing the hepatic Dol accumulation is associated with an increase of HMGCoA reductase activity, which is affected by diet restriction, and with an increase of MVA incorporation in Dol and Chol, which is not. In addition, the liver of aged rats maintains the capability to regulate its Chol content and to modify Chol delivery into the blood.

Aging↗

PubMed1991

The correlation of body growth with diethylnitrosamine-induced hepatocarcinogenesis in relation to serum insulin and somatomedin-C.

Caloric restriction depresses the development of several types of tumours, yet the mechanisms involved are poorly understood. In the present experiment we investigated the development of diethylnitrosamine (DEN)-induced liver tumours in mice treated with caffeine. The latter was found to reduce body growth, possibly due to increased energy expenditure, without reducing food consumption. Newborn mice received an i.p. injection of DEN. At weaning they were either fed lab chow ad libitum, with the same diet containing 0.2% (w/w) of caffeine, or their access to food was restricted to 70% of that consumed by the ad libitum group. Diet caloric restriction starting at weaning in male Swiss mice decreased the rate of development of glucose-6-phosphatase-deficient (G6Pd) preneoplastic foci. At the age of 24 weeks, 10% of the surface of a standardized liver section of ad libitum fed mice was G6Pase negative, compared to only 1% in the restricted mice due to a reduction of the number and size of these preneoplastic foci. The number and size of G6Pd foci decreased to the same extent with the ingestion of a lab chow supplemented with 0.2% of caffeine as with the diet restriction. This finding suggests that restriction slows down hepatic tumour growth by modifying body growth rather than by limited nutrient supply. In parallel, somatomedin-C (Sm-C) and insulin secretion following glucose challenge were decreased in diet restricted mice and those treated with 0.2% caffeine. The serum Sm-C and insulin levels were respectively 480 and 4.6 ng/ml in the restricted mice, 519 and 16.6 ng/ml in the caffeine-fed mice and 664 and 25.7 ng/ml in the ad libitum fed mice. Our results suggest that the decrease of secretion of these two hormones that are known mitogens for hepatocytes in vitro may be responsible at least in part for the reduction in the growth of liver tumours.

Animals↗

PubMed2003

Minireview: The adipocyte--at the crossroads of energy homeostasis, inflammation, and atherosclerosis.

Adipose tissue evolved to efficiently store energy for times of caloric restriction. The large caloric excess common in many Western diets has negated the need for this thrifty function, leaving adipose tissue ill-equipped to handle this increased load. An excess of adipose tissue increases risk for a number of conditions including coronary artery disease, hypertension, dyslipidemias, type 2 diabetes, and even cancer. Indeed, the ability of the adipocyte to function properly when engorged with lipid can lead to lipid accumulation in other tissues, reducing their ability to function and respond normally. The role of adipose tissue as an endocrine organ capable of secreting a number of adipose tissue-specific or enriched hormones, known as adipokines, is gaining appreciation. The normal balance of these adipose tissue secretory proteins is perturbed in obesity. Paradoxically, the lack of normal adipose tissue, as seen in cases of lipodystrophy and lipoatrophy, is also associated with pathologic sequelae similar to what is seen with obesity. The pathologic findings associated with lack of adipose tissue, largely due to inability to properly store lipids, may also be due to a lack of adipokines. In this review, we highlight the role of adipose tissue as an endocrine organ focusing on some of the recent advances in the identification and pharmacological characterization of adipokines as well as their regulation in the context of obesity and insulin-resistant states.

Adipocytes↗

PubMed2001

Antiaging therapy: an overview.

Today's researchers are exploring caloric restriction, cell-based therapies, hormonal therapies, and genetic manipulations. So far, caloric restriction has the soundest basis, and estrogen replacement is among the interventions most widely used. As the human genome is studied, treatments with genetic mechanisms move all the closer to becoming reality.

Aging↗

PubMed2002

Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats.

Ischemic preconditioning (PC) has been proposed as an endogenous form of protection against-ischemia reperfusion injury. We have shown that PC does not prevent postischemic dysfunction in the aging heart. This phenomenon could be due to the reduction of cardiac norepinephrine release, and it has also been previously demonstrated that age-related decrease of norepinephrine release from cardiac adrenergic nerves may be restored by caloric restriction. We investigated the effects on mechanical parameters of PC against 20 min of global ischemia followed by 40 min of reperfusion in isolated hearts from adult (6 mo) and "ad libitum"-fed and food-restricted senescent (24 mo) rats. Norepinephrine release in coronary effluent was determined by high-performance liquid chromatography. Final recovery of percent developed pressure was significantly improved after PC in adult hearts versus unconditioned controls (85.2 +/- 19% vs. 51.5 +/- 10%, P < 0.01). The effect of PC on developed pressure recovery was absent in ad libitum-fed rats, but it was restored in food-restricted senescent hearts (66.6 +/- 13% vs. 38.3 +/- 11%, P < 0.05). Accordingly, norepinephrine release significantly increased after PC in both adult and in food-restricted senescent hearts, and depletion of myocardial norepinephrine stores by reserpine abolished the PC effect in both adult and in food-restricted senescent hearts. We conclude that PC reduces postischemic dysfunction in the hearts from adult and food-restricted but not in ad libitum-fed senescent rats. Despite the possibility of multiple age-related mechanisms, the protection afforded by PC was correlated with increased norepinephrine release, and it was blocked by reserpine in both adult and food-restricted senescent hearts. Thus caloric restriction may restore PC in the aging heart probably via increased norepinephrine release.

Adrenergic Uptake Inhibitors↗