Effects Of Caloric Restriction Research Articles

Targeting negative energy balance with calorie restriction and mitochondrial uncoupling in db/db mice

ObjectiveCalorie restriction is a first-line treatment for overweight individuals with metabolic impairments. However, few patients can adhere to long-term calorie restriction. An alternative approach to calorie restriction that also causes negative energy balance is mitochondrial uncoupling, which decreases the amount of energy that can be extracted from food. Herein we compare the metabolic effects of calorie restriction with the mitochondrial uncoupler BAM15 in the db/db mouse model of severe hyperglycemia, obesity, hypertriglyceridemia, and fatty liver. MethodsMale db/db mice were treated with ∼50% calorie restriction, BAM15 at two doses of 0.1% and 0.2% (w/w) admixed in diet, or 0.2% BAM15 with time-restricted feeding from 5 weeks of age. Mice were metabolically phenotyped over 4 weeks with assessment of key readouts including body weight, glucose tolerance, and liver steatosis. At termination, liver tissues were analysed by metabolomics and qPCR. ResultsCalorie restriction and high-dose 0.2% BAM15 decreased body weight to a similar extent, but mice treated with BAM15 had far better improvement in glucose control. High-dose BAM15 treatment completely normalized fasting glucose and glucose tolerance to levels similar to lean db/+ control mice. Low-dose 0.1% BAM15 did not affect body mass but partially improved glucose tolerance to a similar degree as 50% calorie restriction. Both calorie restriction and high-dose BAM15 significantly improved hyperglucagonemia and liver and serum triglyceride levels. Combining high-dose BAM15 with time-restricted feeding to match the time that calorie restricted mice were fed resulted in the best metabolic phenotype most similar to lean db/+ controls. BAM15-mediated improvements in glucose control were associated with decreased glucagon levels and decreased expression of enzymes involved in hepatic gluconeogenesis. ConclusionsBAM15 and calorie restriction treatments improved most metabolic disease phenotypes in db/db mice. However, mice fed BAM15 had superior effects on glucose control compared to the calorie restricted group that consumed half as much food. Submaximal dosing with BAM15 demonstrated that its beneficial effects on glucose control are independent of weight loss. These data highlight the potential for mitochondrial uncoupler pharmacotherapies in the treatment of metabolic disease.

The antitumour effects of caloric restriction are mediated by the gut microbiome.

Calorie restriction (CR) and intermittent fasting (IF) without malnutrition reduce the risk of cancer development. Separately, CR and IF can also lead to gut microbiota remodelling. However, whether the gut microbiota has a role in the antitumour effect related to CR or IF is still unknown. Here we show that CR, but not IF, protects against subcutaneous MC38 tumour formation through a mechanism that is dependent on the gut microbiota in female mice. After CR, we identify enrichment of Bifidobacterium through 16S rRNA sequencing of the gut microbiome. Moreover, Bifidobacterium bifidum administration is sufficient to rescue the antitumour effect of CR in microbiota-depleted mice. Mechanistically, B. bifidum mediates the CR-induced antitumour effect through acetate production and this effect is also dependent on the accumulation of interferon-γ+CD8+ T cells in the tumour microenvironment. Our results demonstrate that CR can modulate the gut taxonomic composition, which should be of oncological significance in tumour growth kinetics and cancer immunosurveillance.

No Effect of Calorie Restriction or Dietary Patterns on Spatial Working Memory During a 2-Year Intervention: A Secondary Analysis of the CALERIE Trial

BackgroundThe effect of calorie restriction (CR) on cognitive function is not well understood, and the impact of the dietary patterns consumed during CR has not been investigated. ObjectivesWe analyzed the combined association of CR and dietary quality with spatial working memory (SWM) in healthy adults without obesity. MethodsThe Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial was a 2-y, multisite clinical trial. This trial was registered at clinicaltrials.gov as NCT00427193. Participants were randomized to a 25% reduction in EI (n = 143) or an ad libitum Control (n = 76). The Dietary Inflammatory Index (DII) and the Healthy Eating Index (HEI) captured dietary quality, with a lower DII and higher HEI score indicating a healthier diet. The Cambridge Neuropsychological Test Automated Battery battery was used to assess SWM. Longitudinal associations between each dietary pattern index and SWM for CR and Control were assessed by multivariable negative binomial models that included baseline, 12-mo, and 24-mo visits. ResultsParticipants were aged 38.1 ± 7.2 y with a BMI of 25.1 ± 1.7 kg/m2. A total of 70% of the participants were female. Baseline mean DII and HEI scores were −0.15 (range: −3.77, 4.21) and 59.1 (24.1, 91.0) and did not differ between groups. Improvements in DII and HEI were significantly different between CR and Control over 2 y (both P-interaction = 0.001). In longitudinal analyses, there was no association of either index with SWM. Furthermore, though within-group improvements in SWM were observed at 12 mo, there was no statistically significant difference between CR (SWM errors: 9.0; 95% CI: 1.9, 41.6) and Control (11.7; 95% CI: 2.6, 53.5; P > 0.99), holding DII constant. Comparable results were observed at 24 mo and for the HEI. ConclusionsDietary quality during CR was not associated with measures of SWM over 2 y in healthy adults without obesity. These results suggest that, in healthy populations, dietary patterns and CR may have a limited impact on working memory. Further research is required to understand the concurrent effect of these nutritional strategies.

Fecal microbiota and inflammatory and antioxidant status of obese and lean dogs, and the effect of caloric restriction.

Obesity is the most common nutritional disease in dogs, and is generally managed by caloric restriction. Gut microbiota alteration could represent a predisposing factor for obesity development, which has been associated with a low-grade inflammatory condition and an impaired antioxidant status. Besides, weight loss has been shown to influence the gut microbiota composition and reduce the inflammatory response and oxidative stress. However, these insights in canine obesity have not been fully elucidated. The aim of this study was to assess the differences in serum and inflammatory parameters, antioxidant status, fecal microbiota and bacterial metabolites in 16 obese and 15 lean client-owned dogs and how these parameters in obese may be influenced by caloric restriction. First, for 30 days, all dogs received a high-protein, high-fiber diet in amounts to maintain their body weight; later, obese dogs were fed for 180 days the same diet in restricted amounts to promote weight loss. Before the introduction of the experimental diet (T0), small differences in fecal microbial populations were detected between obese and lean dogs, but bacterial diversity and main bacterial metabolites did not differ. The fecal Dysbiosis Index (DI) was within the reference range (< 0) in most of dogs of both groups. Compared to lean dogs, obese dogs showed higher serum concentrations of acute-phase proteins, total thyroxine (TT4), and antioxidant capacity. Compared to T0, dietary treatment affected the fecal microbiota of obese dogs, decreasing the abundance of Firmicutes and increasing Bacteroides spp. However, these changes did not significantly affect the DI. The caloric restriction failed to exert significative changes on a large scale on bacterial populations. Consequently, the DI, bacterial diversity indices and metabolites were unaffected in obese dogs. Caloric restriction was not associated with a reduction of inflammatory markers or an improvement of the antioxidant status, while an increase of TT4 has been observed. In summary, the present results underline that canine obesity is associated with chronic inflammation. This study highlights that changes on fecal microbiota of obese dogs induced by the characteristics of the diet should be differentiated from those that are the consequence of the reduced energy intake.

Akt substrate of 160kDa is essential for the calorie restriction-induced increase in insulin-stimulated glucose uptake by skeletal muscle of female rats.

We evaluated effects of calorie restriction (CR; consuming 65% of ad libitum (AL) intake) for 8 weeks on female wildtype (WT) and Akt substrate of 160kDa knockout (AS160-KO) rats. Insulin-stimulated glucose uptake (ISGU) was determined in isolated epitrochlearis muscles incubated with 0, 50, 100, or 500 µU/mL insulin. Phosphorylation of key insulin signaling proteins that control ISGU (Akt and AS160) was assessed by immunoblotting (Akt phosphorylation on Threonine-308, pAktThr308 and Serine-473, pAktSer473; AS160 phosphorylation on Serine-588, pAS160Ser588, and Threonine-642, pAS160Thr642). Abundance of proteins that regulate ISGU (GLUT4 glucose transporter protein and hexokinase II) was also determined by immunoblotting. The major results were as follows: (i) WT-CR versus WT-AL rats had greater ISGU with 100 and 500 µU/mL insulin; (ii) CR versus WT-AL rats had greater GLUT4 protein abundance; (iii) WT-CR versus WT-AL rats had greater pAktThr308 with 500 µU/mL insulin; (iv) WT-CR versus WT-AL rats did not differ for pAktSer473, pAS160Ser588, or pAS160Thr642 at any insulin concentration; (v) AS160-KO versus WT rats with each diet had lower ISGU at each insulin concentration, but not lower pAkt on either phosphosite; (vi) AS160-KO versus WT rats had lower muscle GLUT4 abundance regardless of diet; and (vii) AS160-KO-CR versus AS160-KO-AL rats did not differ for ISGU, GLUT4 abundance, pAkt on either phosphosite, or pAS160 on either phosphosite. These novel results demonstrated that AS160 expression, but not greater pAS160 on key phosphosites, was essential for the CR-induced increases in muscle ISGU and GLUT4 abundance of female rats.

3,4-Dimethoxychalcone, a caloric restriction mimetic, enhances TFEB-mediated autophagy and alleviates pyroptosis and necroptosis after spinal cord injury.

Background: Caloric restriction mimetics (CRMs) mimic the favourable effects of caloric restriction (CR) and have been shown to have therapeutic effects in neuroinflammatory disease. However, whether CRMs improve the functional recovery from spinal cord injury (SCI) and the underlying mechanism of action remain unclear. In this study, we used the CRMs 3,4-dimethoxychalcone (3,4-DC) to evaluate the therapeutic value of CRMs for SCI. Methods: HE, Masson and Nissl staining; footprint analysis; and the Basso mouse scale were used to determine the functional recovery from SCI after 3,4-DC treatment. RNA sequencing was used to identify the mechanisms of 3,4-DC in SCI. Western blotting, qPCR and immunofluorescence were used to detect the levels of pyroptosis, necroptosis, autophagy and the AMPK-TRPML1-calcineurin signalling pathway. We employed a dual-luciferase reporter assay in vitro and applied AAV vectors to inhibit TFEB in vivo to explore the mechanism of 3,4-DC. Results: 3,4-DC reduced glial scar area and motor neuron death and improved functional recovery after SCI. RNA-sequencing results indicated that oxidative stress, pyroptosis, necroptosis, and autophagy may be involved in the ability of 3,4-DC to improve functional recovery. Furthermore, 3,4-DC inhibited pyroptosis and necroptosis by enhancing autophagy. We also found that 3,4-DC enhances autophagy by promoting TFEB activity. A decrease in the TFEB level abolished the protective effect of 3,4-DC. In addition, 3,4-DC partially regulated TFEB activity through the AMPK-TRPML1-calcineurin signalling pathway. Conclusions: 3,4-DC promotes functional recovery by upregulating TFEB-mediated autophagy and inhibiting pyroptosis and necroptosis after SCI, which may have potential clinical application value.

Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: A randomized, double-blind crossover trial

Aims/hypothesisSodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment in type 2 diabetes mellitus patients results in glucosuria, causing an energy loss, and triggers beneficial metabolic adaptations. It is so far unknown if SGLT2i exerts beneficial metabolic effects in prediabetic insulin resistant individuals, yet this is of interest since SGLT2is also reduce the risk for progression of heart failure and chronic kidney disease in patients without diabetes. MethodsFourteen prediabetic insulin resistant individuals (BMI: 30.3 ± 2.1 kg/m2; age: 66.3 ± 6.2 years) underwent 2-weeks of treatment with dapagliflozin (10 mg/day) or placebo in a randomized, placebo-controlled, cross-over design. Outcome parameters include 24-hour and nocturnal substrate oxidation, and twenty-four-hour blood substrate and insulin levels. Hepatic glycogen and lipid content/composition were measured by MRS. Muscle biopsies were taken to measure mitochondrial oxidative capacity and glycogen and lipid content. ResultsDapagliflozin treatment resulted in a urinary glucose excretion of 36 g/24-h, leading to a negative energy and fat balance. Dapagliflozin treatment resulted in a higher 24-hour and nocturnal fat oxidation (p = 0.043 and p = 0.039, respectively), and a lower 24-hour carbohydrate oxidation (p = 0.048). Twenty-four-hour plasma glucose levels were lower (AUC; p = 0.016), while 24-hour free fatty acids and nocturnal β-hydroxybutyrate levels were higher (AUC; p = 0.002 and p = 0.012, respectively) after dapagliflozin compared to placebo. Maximal mitochondrial oxidative capacity was higher after dapagliflozin treatment (dapagliflozin: 87.6 ± 5.4, placebo: 78.1 ± 5.5 pmol/mg/s, p = 0.007). Hepatic glycogen and lipid content were not significantly changed by dapagliflozin compared to placebo. However, muscle glycogen levels were numerically higher in the afternoon in individuals on placebo (morning: 332.9 ± 27.9, afternoon: 368.8 ± 13.1 nmol/mg), while numerically lower in the afternoon on dapagliflozin treatment (morning: 371.7 ± 22.8, afternoon: 340.5 ± 24.3 nmol/mg). Conclusions/interpretationDapagliflozin treatment of prediabetic insulin resistant individuals for 14 days resulted in significant metabolic adaptations in whole-body and skeletal muscle substrate metabolism despite being weight neutral. Dapagliflozin improved fat oxidation and ex vivo skeletal muscle mitochondrial oxidative capacity, mimicking the effects of calorie restriction. Trial registrationClinicalTrials.gov NCT03721874.

Dieting Behavior Characterized by Caloric Restriction and Relation to Sleep: A Brief Contemporary Review.

There is sufficient evidence showing that greater sleep quality improves weight loss outcomes achieved through dietary modifications; however, the effects of dietary modifications such as caloric restriction on sleep outcomes is less established. Caloric restriction is a commonly recommended weight-loss method, yet it may result in short-term weight loss and subsequent weight regain, known as "weight cycling", which has recently been shown to be associated with both poor sleep and worse cardiovascular health. The purpose of this brief narrative review was to summarize the evidence from recent studies of the effects of caloric restriction on sleep. Six articles were identified that specifically measured effects of a caloric restriction-based intervention on aspects of sleep as primary or secondary outcomes. Most research to date indicates that caloric restriction improves sleep outcomes including sleep quality and sleep onset latency. However, the relation between caloric restriction and sleep duration is less clear. Given the mixed results and the potential for severe caloric restriction to lead to weight cycling, future studies are needed to clarify how caloric restriction affects sleep and the potential implications for weight-management efforts.

Synergetic effects of concurrent chronic exposure to a mixture of OCPs and high-fat diets on type 2 diabetes and beneficial effects of caloric restriction in female zebrafish

This study aimed to investigate the relationship among chronic exposure to a low concentration of organochlorine pesticides (OCPs), high-fat diet (HFD)-induced obesity, and caloric restriction in type 2 diabetes (T2D). Thus, female zebrafish were divided into four groups and treated for 12 weeks as follows: (i) negative control, (ii) HFD (obesity) control, (iii) obesity + a mixture of OCPs (OP), and (iv) obesity + a mixture of OCPs + caloric restriction (OPR). We then assessed T2D-related effects via hematological analysis, histopathology, mitochondrial evaluation, and multiomics analyses. The OP group showed a significant increase in glucose levels, whereas the OPR group maintained glucose at nonsignificant levels. Multiomics analyses revealed that the exacerbated metabolic effects in the OP group were associated with molecular alterations in oxidative stress, inflammation, nucleotide metabolism, and glucose/lipid homeostasis. These alterations were histologically verified by the increased numbers of hypertrophic adipocytes and inflammatory cells observed. Caloric restriction activated pathways related to antioxidant response, mitochondrial fatty acid oxidation, and energy metabolism in zebrafish, leading to preserved glucose homeostasis. In conclusion, this study identified molecular mechanisms underlying the synergistic effect of concurrent exposure to a mixture of OCPs and HFD as well as shed light on the beneficial effect of regular caloric restriction in T2D development.

Calorie Restriction Provides Kidney Ischemic Tolerance in Senescence-Accelerated OXYS Rats

Kidney diseases belong to a group of pathologies, which are most common among elderly people. With age, even outwardly healthy organisms start to exhibit some age-related changes in the renal tissue, which reduce the filtration function of kidneys and increase the susceptibility to injury. The therapy of acute kidney injury (AKI) is aggravated by the absence of targeted pharmacotherapies thus yielding high mortality of patients with AKI. In this study, we analyzed the protective effects of calorie restriction (CR) against ischemic AKI in senescence-accelerated OXYS rats. We observed that CR afforded OXYS rats with significant nephroprotection. To uncover molecular mechanisms of CR beneficial effects, we assessed the levels of anti- and proapoptotic proteins of the Bcl-2 family, COX IV, GAPDH, and mitochondrial deacetylase SIRT-3, as well as alterations in total protein acetylation and carbonylation, mitochondrial dynamics (OPA1, Fis1, Drp1) and kidney regeneration pathways (PCNA, GDF11). The activation of autophagy and mitophagy was analyzed by LC3 II/LC3 I ratio, beclin-1, PINK-1, and total mitochondrial protein ubiquitination. Among all considered protective pathways, the improvement of mitochondrial functioning may be suggested as one of the possible mechanisms for beneficial effects of CR.

Metabolic and physical function are improved with lifelong 15% calorie restriction in aging male mice

Chronic calorie restriction (CR) results in lengthened lifespan and reduced disease risk. Many previous studies have implemented 30–40% calorie restriction to investigate these benefits. The goal of our study was to investigate the effects of calorie restriction, beginning at 4 months of age, on metabolic and physical changes induced by aging. Male C57BL/6NCrl calorie restricted and ad libitum fed control mice were obtained from the National Institute on Aging (NIA) and studied at 10, 18, 26, and 28 months of age to better understand the metabolic changes that occur in response to CR in middle age and advanced age. Food intake was measured in ad libitum fed controls to assess the true degree of CR (15%) in these mice. We found that 15% CR decreased body mass and liver triglyceride content, improved oral glucose clearance, and increased all limb grip strength in 10- and 18-month-old mice. Glucose clearance in ad libitum fed 26- and 28-month-old mice is enhanced relative to younger mice but was not further improved by CR. CR decreased basal insulin concentrations in all age groups and improved insulin sensitivity and rotarod time to fall in 28-month-old mice. The results of our study demonstrate that even a modest reduction (15%) in caloric intake may improve metabolic and physical health. Thus, moderate calorie restriction may be a dietary intervention to promote healthy aging with improved likelihood for adherence in human populations.

Caloric Restriction Decreases Radiation-Induced Normal Tissue Toxicity

<h3>Purpose/Objective(s)</h3> Improvements in radiation delivery are limited by normal tissue toxicity. Studies show that the patient's metabolic state affects radiation toxicity. It has previously been shown that caloric restriction can be used to induce radiation sensitivity in treating breast and prostate tumors. Here we investigate the effect of caloric restriction on radiation induced normal tissue toxicity in two murine models. <h3>Materials/Methods</h3> To determine the role of diet on radiation induced normal tissue toxicity two toxicity models were used to assess mice fed either an ad libitum (AL), caloric restriction (CR: 30% reduction of calories) or ketogenic diet (KD: 60mg fat). A leg shortening model was used to assess acute and long-term skin toxicity by treating one leg of 9-week old Balb/c mice with a single- fraction of 30Gy of irradiation (320kV) with the rest of the body shielded and the contralateral leg serving as an unirradiated control. Measurements of leg length of irradiated compared with control leg length were performed. To assess differences in bone marrow, gastrointestinal and cardiac toxicity, total body radiation was administered to Balb/c mice using a dose of 6.5Gy (LD 50/30) with cohorts from each experimental diet. Histologic evaluation of small intestines and bone marrow was performed after tissue collection at 0, 1, 72 hours as well as 16-18 days post TBI. Small intestinal histology was reviewed by a gastrointestinal pathologist. Serum was evaluated for cardiac troponin 1 levels using ELISA at the same time points. Statistical comparisons were made using students t-test. <h3>Results</h3> The leg shortening model revealed radiation acute skin toxicity at 2 weeks post an ad libitum or ketogenic diet with skin peeling, hair loss, and moist desquamation that lasted 3 weeks compared to the mice treated with CR that had a delayed acute skin toxicity that only lasted 1 week. Long term, the irradiated leg was notably shortened and decreased by 22% and 20% relative to the contralateral leg in the AL and KD groups with 14% leg shortening and decreased fibrosis at 120 days post treatment in the CR groups (p<0.01). Gastrointestinal toxicity was decreased after TBI in mice on CR diet with less denuded villi epithelium and less obvious change in villi length at 72 hours compared to AL diet. The CR mice at 72 hours also had less variation in nuclear size within the epithelium and less changes in Paneth cells. Bone marrow was more hypocellular in the TBI mice on ad libitum diet compared with mice in the CR cohort. Acute cardiac toxicity was evaluated with serum troponin and was less elevated 72 hours post radiation in the CR group, 0.16ng/ml compared to 0.25ng/ml in the AL mice (p=0.03). <h3>Conclusion</h3> Dietary changes impact radiation induced toxicity. Our data show that caloric restriction decreases acute skin toxicity, fibrosis, gastrointestinal and cardiac toxicity. Future research is warranted to translate this strategy to decrease radiation induced normal tissue toxicity.

Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms.

Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none of the commonly studied caloric restriction mimetics actually produce a decrease in calories. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are a class of drugs which lower glucose by promoting its elimination through urine, thus inducing a net loss of calories. This effect promotes a metabolic shift at the systemic level, fostering ketones and fatty acids utilization as glucose-alternative substrates, and is accompanied by a modulation of major nutrient-sensing pathways held to drive aging, e.g., mTOR and the inflammasome, overall resembling major features of caloric restriction. In addition, preliminary experimental data suggest that SGLT-2i might also have intrinsic activities independent of their systemic effects, such as the inhibition of cellular senescence. Consistently, evidence from both preclinical and clinical studies have also suggested a marked ability of SGLT-2i to ameliorate low-grade inflammation in humans, a relevant driver of aging commonly referred to as inflammaging. Considering also the amount of data from clinical trials, observational studies, and meta-analyses suggesting a tangible effect on age-related outcomes, such as cardiovascular diseases, heart failure, kidney disease, and all-cause mortality also in patients without diabetes, here we propose a framework where at least part of the benefit provided by SGLT-2i is mediated by their ability to blunt the drivers of aging. To support this postulate, we synthesize available data relative to the effect of this class on: 1- animal models of healthspan and lifespan; 2- selected molecular pillars of aging in preclinical models; 3- biomarkers of aging and especially inflammaging in humans; and 4- COVID-19-related outcomes. The burden of evidence might prompt the design of studies testing the potential employment of this class as anti-aging drugs.

Dietary Patterns and Meal Timing to Achieve a Healthy Body Weight and Promote Cardiometabolic Health: What Is the Evidence?

Dietary Patterns and Meal Timing to Achieve a Healthy Body Weight and Promote Cardiometabolic Health: What Is the Evidence?

Calorie restriction ameliorates hyperglycemia, modulates the disordered gut microbiota, and mitigates metabolic endotoxemia and inflammation in type 2 diabetic rats.

The effects of calorie restriction (CR) on gut microbiota and the mechanism of CR ameliorating hyperglycemia in streptozotocin (STZ)-induced T2DM model rats were explored. High-fat diet and STZ injection were applied to induce T2DM model rats. Rats were divided into the following three groups: the control-diet ad libitum group, the T2DM model group fed with ad libitum diet, and the T2DM group fed with 30% restriction diet. 16S rRNA sequencing was used to determine the bacterial communities. Lipopolysaccharide (LPS)-binding protein (LBP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured. Glucose tolerance and insulin sensitivity were improved by CR, as well as the levels of fasting and random plasma glucose. Besides, CR not only modulated the overall structure of gut microbiota but also had selective enrichment in anti-inflammatory bacteria such as Lachnospiraceae_NK4A136_group, Ruminococcaceae_9, Allobaculum, Alistipes, and Oscillibacter, and decreased pro-inflammatory pathogenic bacteria such as Bacteroides, Lachnoclostridium, and Bifidobacterium. Tax4Fun indicated that CR could regulate related functional pathways such as lipopolysaccharide biosynthesis, and the plasma levels of LBP, IL-6, and TNF-α were markedly reduced by CR, suggesting the mechanism of CR ameliorating hyperglycemia may associate with the modulation of disordered gut microbiota and the reduction of metabolic endotoxemia and inflammation. CR could ameliorate hyperglycemia, the mechanism of which may associate with the alteration of the overall structure of gut microbiota, restoration of disordered microbiota function, and the downregulation of metabolic endotoxemia and inflammation in diabetic rats.

The Effect of Calorie Restriction on Body Weight, Fat Tissue Weight and the Histopathological Picture of Fat Tissue in Rats

Background : Calorie restriction is a reduction in calorie intake without malnutrition, as the main tool to improve health (Tomiyama et al.,2017). Limitation of calorie intake around 20-40% of total calorie intake, but intake remains adequate to reduce inflammation (Trepanowski et al., 2010). Obesity is one of the consequences of excessive calorie consumption which causes inflammation so that it can increase the risk of degenerative diseases (Susantiningsih, 2015). Overweight is divided into two, namely hypertrophy occurs by the accumulation of large amounts of fat in unilocular fat cells, so that the size of fat cells reaches four times larger, but the number of fat cells does not increase. And hyperplasia is a heavy obesity because in addition to growing cells also the number of cells becomes more (Sunny Wangko, 2014). One effort that can be done to reduce the increase in degenerative diseases is by limiting caloric intake or appropriate calorie restriction (Brzek et al., 2012).Purpose : This study purpose to determine changes in body weight, fat tissue and histopathological features of fat tissue in rats given calorie restriction and reviewed according to Islamic views.Methods : This type of research is an experimental laboratory for 6 weeks with research subjects male white rats (Wistar Strain) which is divided into 2 groups, namely control, and Calorie Restrictions Taking samples of body weight and fat tissue in the abdomen and supraclavicular to see the number of cells fat, fat cell size and weight of white fat tissue and brown fat tissue.Results : Calorie restriction can reduce fat cell size, and weight of white fat tissue significantly (p &lt;0.05). in brown fat there was a significant increase. but in the measurement of body weight and fat cell numbers there were no significant differences (p&gt; 0.05).Conclusion : In calorie restriction there was no significant relationship after a study of body weight and fat cell count, but found a significant relationship to the weight of white fat tissue and brown fat tissue and the size of fat cells. In Islamic view calorie restriction is the same as limiting food intake as recommended by the Prophet about 1/3 of the stomach for food.

The Effect of Calorie Restriction on The Growth of Adipose Tissue in Mice

The aging process can be slowed by reducing the calorie intake consumed by the body by calorie restriction or fasting. This study aimed to analyze the effect of calorie restriction on adipose tissue in mice. The experimental research design uses 12 months old Rattus Novergicus Strain Wistar, weighing 250–300 grams. The intervention was carried out for 14 days, then the average weight of subcutaneous and visceral fat was measured using Kruskal Wallis analysis and ANOVA. Based on the four treatment groups, the mice fasting and given a high-calorie diet (group 4) had the highest average fat weight value of 4.02 grams in the subcutaneous and 3.55 grams in the visceral area. Meanwhile, in group 1, mice that were not fasting and did not get a high-calorie diet had the lowest average fat weight values, namely 2.14 grams in the subcutaneous area and 2.72 grams in the visceral area. Based on the test results, it was found that there was no difference between subcutaneous (p=0.121) and visceral (p=0.443) fat tissue in all groups. Calorie restriction is beneficial for delaying aging and increasing mammal life span, but intermittent calorie restriction does not affect adipose tissue.

A Review of Calorie Restriction and Beneficial Health Effects

Calorie restriction has been the subject of research and studies for years. Although calorie restriction is a broad definition; the way, time, amount and situations of restriction are very important. While restricting, carbohydrate, fat and protein balances should be well evaluated. However, this restriction shows various positive effects when done under suitable conditions without causing malnutrition. With calorie restriction, the production of free radicals and the oxidative stress they cause are reduced. In addition to medical treatments applied in common chronic diseases; as an alternative method, it is seen that improvements in vital functions occur with the necessary calorie restrictions specific to the disease. Maintaining health throughout life is only possible with a balanced diet, regular and continuous exercise program. Nutrition is an issue that needs attention in every period of life. It should not be forgotten that one of the most important key points in living a long and healthy life is nutrition. Therefore, the purpose of this review; is to draw attention to some beneficial effects of calorie restriction, as a topic that is still up-to-date and researches, by giving examples from studies.

Effects of weight loss through lifestyle changes on heart rate variability in overweight and obese patients: A systematic review

The effects of calorie restriction and physical activity on autonomic regulation and cardiac vagal control in overweight and obese individuals remain inconsistent. Thus, this systematic review aimed to evaluate the weight loss effects through lifestyle changes on heart rate variability (HRV) markers in overweight and obese subjects. A systematic search for studies published up to November 2021 was conducted in MEDLINE, Embase, EBSCO host and VHL REGIONAL/LILACS. The main outcomes were changes in HRV indices from pre- and post-nutritional intervention and exercise in overweight and obese individuals. This review was registered in PROSPERO: CRD42021274467. The literature search retrieved 959 articles, of which 12 were included in this review. The intervention in nine studies was diet only, in two studies was diet and exercise, and in one study diet was compared to diet and exercise. The weight loss was greater than 10% in four studies and between 5 and 10% in three studies. Most of the studies revealed that weight loss through lifestyle changes seems to promote beneficial effects on HRV, restoring sympathovagal balance by increasing parasympathetic activity and reducing sympathetic activation. This systematic review exhibited the beneficial effects of weight loss through lifestyle changes on cardiac autonomic control in overweight and obese individuals. Future investigations need standardization of HRV indices for better interpretation of autonomic function in different clinical situations.

Effects of caloric restriction and rope-skipping exercise on cardiometabolic risk factors in overweight or obese college students

Objective: To explore the effect of three interventions including caloric restriction, rope-skipping exercise and caloric restriction combined with rope-skipping exercise on cardiometabolic risk factors in overweight or obese college students. Methods: This study was a pilot randomized controlled trial. Overweight or obese students who met the inclusion criteria were recruited at Sun Yat-sen University in September 2019 and were randomly divided into four groups: caloric restriction group (CR), rope-skipping group (RS), combined group (CR-RS) and control group (CT). The intervention in each group lasted 8 weeks, specifically: the daily energy intake of CR was 100% to 110% of the basal metabolic energy; RS was instructed to rope three times a week, and CR-RS combined caloric restriction with rope-skipping. At the baseline and end of 8-week intervention, basic information, anthropometric indicators and fasting vein blood of students were collected. Paired t test and Wilcoxon paired-samples signed rank test were used for comparison before and after intervention, and analysis of covariance was used for comparison between groups after intervention. Results: A total of 29 students completed the trial and were included in the final analysis (7, 9, 7 and 6 students in CR, RS, CR-RS and CT, respectively). The mean age of students were (19.00±1.00) years, including 11 males and 18 females. The baseline characteristics of four groups were comparable. After 8 weeks of intervention, compared with CT, there was an increase in the body fat percentage and fat mass index in CR and CR-RS (P<0.05). Insulin level decreased in CR-RS (P<0.05). Systolic blood pressure in CR and diastolic blood pressure in CR-RS were higher (P<0.05). Compared with baseline, fat mass index decreased in CR (P<0.05), while body weight, BMI, and fat mass index decreased in CR-RS (P<0.05). Conclusion: It is suggested that the caloric restriction alone and calorie restriction combined with rope-skipping exercise can benefit overweight or obese college students with cardiometabolic risk factors.