Caloric Restriction Research Articles

Dapagliflozin targets SGLT2/SIRT1 signaling to attenuate the osteogenic transdifferentiation of vascular smooth muscle cells

Vascular calcification is a complication that is frequently encountered in patients affected by atherosclerosis, diabetes, and chronic kidney disease (CKD), and that is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). At present, there remains a pressing lack of any effective therapies that can treat this condition. The sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin (DAPA) has shown beneficial effects in cardiovascular disease. The role of this inhibitor in the context of vascular calcification, however, remains largely uncharacterized. Our findings revealed that DAPA treatment was sufficient to alleviate in vitro and in vivo osteogenic transdifferentiation and vascular calcification. Interestingly, our study demonstrated that DAPA exerts its anti-calcification effects on VSMCs by directly targeting SGLT2, with the overexpression of SGLT2 being sufficient to attenuate these beneficial effects. DAPA was also able to limit the glucose levels and NAD+/NADH ratio in calcified VSMCs, upregulating sirtuin 1 (SIRT1) in a caloric restriction (CR)-dependent manner. The SIRT1-specific siRNA and the SIRT1 inhibitor EX527 attenuated the anti-calcification effects of DAPA treatment. DAPA was also to drive SIRT1-mediated deacetylation and consequent degradation of hypoxia-inducible factor-1α (HIF-1α). The use of cobalt chloride and proteasome inhibitor MG132 to preserve HIF-1α stability mitigated the anti-calcification activity of DAPA. These analyses revealed that the DAPA/SGLT2/SIRT1 axis may therefore represent a viable novel approach to treating vascular calcification, offering new insights into how SGLT2 inhibitors may help prevent and treat vascular calcification.Graphical abstractDapagliflozin attenuated vascular smooth muscle cells osteogenic transdifferentiation and vascular calcification through the SIRT1-mediated deacetylation and degradation of HIF-1α in a manner dependent on caloric restriction.

Daily GDF15 treatment has sex‐specific effects on body weight and food intake and does not enhance the effects of voluntary physical activity in mice

AbstractGrowth differentiation factor 15 (GDF15) is a stress‐induced cytokine that suppresses food intake and causes weight loss. GDF15 also reduces voluntary physical activity and, thus, it is not clear whether combining GDF15 with exercise will be beneficial or if reductions in food intake would be offset by decreases in physical activity. We investigated how GDF15 treatment combined with voluntary wheel running (VWR) would impact weight gain, food intake, adiposity and indices of metabolic health in mice. High‐fat fed male and female mice underwent daily GDF15 treatments and were given access to voluntary running wheels, or not, for 11 days. In both sexes, VWR prevented weight gain. In males, GDF15 reduced food intake, as well as attenuated weight gain and the accumulation of adipose tissue, with no additional effect of VWR. In female mice, GDF15 did not impact body weight gain or body composition. GDF15 acutely reduced food intake in female mice but this was followed by a period of rebound hyperphagia and consequently GDF15 did not reduce total food intake in female mice. GDF15 treatment reduced wheel running distance in both sexes. There were main effects of VWR to improve glucose tolerance in female but not male mice. These findings show that GDF15 has sex‐specific effects on food intake and consequently weight gain and adiposity. There is no added benefit of combining GDF15 and voluntary physical activity for weight loss. Adaptive responses to acute caloric restriction induced by GDF15 might limit its effectiveness as a weight loss tool in females. imageKey points GDF15 is a stress‐induced signalling factor that reduces food intake and voluntary physical activity. It is not known whether combining GDF15 treatment with voluntary wheel running would impart beneficial combined effects in attenuating weight gain and the accumulation of adipose tissue. In the present study, we demonstrate that GDF15 reduces food intake and prevents weight gain in male but not female mice consuming a high‐fat diet and also that combining GDF15 with voluntary wheel running (VWR) does not lead to a greater dampening of weight gain. In female mice, GDF15 acutely reduced food intake, but this was followed by a period of rebound hyperphagia resulting in no differences in total food intake. In both sexes, VWR was equivalent, or superior to GDF15 in preventing weight gain.

Energy metabolism dysregulation, cerebrovascular aging, and time-restricted eating: Current evidence and proof-of-concept findings

Abstract Dysregulated energy metabolism is a hallmark of aging, including brain aging; thus, strategies to restore normal metabolic regulation are at the forefront of aging research. Intermittent fasting, particularly time-restricted eating (TRE), is one of these strategies. Despite its well-established effectiveness in improving metabolic outcomes in older adults, the effect of TRE on preserving or improving cerebrovascular health during aging remains underexplored. We explored how aging itself affects energy metabolism and contextualized these age-related changes to cerebrovascular health. We also conducted a literature search on PubMed and Scopus to identify and summarize current studies on TRE in older adults. Finally, we provided preliminary data from our proof-of-concept pilot trial on the effect of 6-month TRE on cerebrovascular health in older adults. Current evidence shows the potential of TRE to improve energy metabolism and physiological outcomes in older adults. TRE may improve cerebrovascular function indirectly due to its effect on glucose homeostasis. However, to date, direct evidence of the effect of TRE on cerebrovascular parameters is lacking. TRE is a well-tolerated and promising dietary intervention for promoting and maintaining cerebrovascular health in older adults. Further studies on TRE in older adults must be better controlled for energy balance to elucidate its independent effects from those of caloric restriction.

Longer-term effects of intermittent fasting on body composition and cardiometabolic health in adults with overweight and obesity: A systematic review and meta-analysis.

The aim of the present study was to investigate the effects of long-term intermittent fasting (IF) on body composition and cardiometabolic health in adults with overweight and obesity. PubMed, Web of Science, and Scopus were searched from inception to March 2024 to identify original randomized trials that investigated the effects of IF versus either a control diet (CON) and/or continuous caloric restriction (CR). Participants were adults with overweight and obesity and intervention durations were ≥ 6 months. Overall, a total of 24 studies involving 2032 participants were included in the meta-analysis. Compared with CON, IF significantly reduced body weight [WMD: -2.84 kg], BMI [WMD: -1.41 kg.m2], fat mass [WMD: -3.06 kg], fat-free mass [WMD: -0.81 kg], waist circumference [WMD: -3.85 cm], visceral fat [SMD: -0.37], fasting glucose [WMD: -0.14 mmol/l], triglycerides [WMD: -0.12 mmol/l], and diastolic blood pressure [WMD: -2.24 mmHg]. Conversely, IF significantly increased high-density lipoproteins [WMD: 0.04 mmol/l] when compared with CON, but had no effects on insulin, hemoglobin A1c%, total cholesterol, low-density lipoprotein, or systolic blood pressure. Compared with CR, IF significantly reduced fat mass [WMD: -0.70 kg], body fat percentage [WMD: -0.59%], and DBP [WMD: -0.91 mmHg], and increased HDL [WMD: 0.03 mmol/l], with no other significant effects. Subgroup analyses showed that the mode of IF and intervention duration were the primary moderators of IF effects on the markers. In adults with overweight or obesity, IF and CR are comparably effective for reducing body weight and adiposity, as well as for improving cardiometabolic health markers.

Cafeteria diet and caloric restriction affect metabolic but not behavioral characteristics in male Wistar rats

This study aimed to evaluate the effects of a cafeteria diet and caloric restriction on behavioral and metabolic profiles of adult male Wistar rats. The rats were randomly divided into three groups (n = 12/group) and from 10 weeks of age fed either ad libitum standard rat chow (control group), ad libitum cafeteria diet in addition to standard chow (diet-induced obesity (DIO) group) or kept on caloric restriction (at 85% weight of controls; restricted group) for a period of 12 weeks. Body weight was assessed twice per week and glucose levels were measured at three times during the 12-week period. At week 11 the animals were behaviorally profiled using the multivariate concentric square field™ (MCSF) test. After 12 weeks of diet the animals were euthanized, blood collected, relative organ weights were assessed and plasma or serum levels of insulin, glucose, and lipid profile were measured. The DIO group gained 23% more weight than the control group (p < 0.001) and increased adipose tissue weight in comparison to the control (p < 0.001) and restricted groups (p < 0.001). Glucose was significantly increased (p < 0.001) only during the second measurement at week 7 and insulin levels were elevated in the DIO group compared to controls and restricted groups (p < 0.01; p < 0.001, respectively). Plasma cholesterol levels were reduced for both DIO (p < 0.01) and restricted (p < 0.001) groups relative to controls. Adiponectin and leptin levels were higher for the DIO group in comparison to both the control (p < 0.001; p < 0.05) and restricted (p < 0.001; p < 0.001) groups. Thus, the two diets led to significant changes in body weight gain, adiposity, and metabolism. However, they did not alter the behavioral profiles in the MCSF test, suggesting that activity, exploration, risk assessment, risk taking or shelter seeking remained unaffected by the dietary interventions. The current findings suggest that an increase or reduction in energy intake resulted in no behavioral effects, despite the accompanying glycemic alterations potentially related to diabetes development.

Calcineurin inhibition enhances Caenorhabditis elegans lifespan by defecation defects-mediated calorie restriction and nuclear hormone signaling.

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of Caenorhabditis elegans through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in C. elegans. Calcineurin inhibition leads to defects in the DMP, resulting in intestinal bloating, rapid colonization of the gut by bacteria, and increased susceptibility to bacterial infection. We demonstrate that intestinal bloating caused by calcineurin inhibition mimics the effects of calorie restriction, resulting in enhanced lifespan. The TFEB ortholog, HLH-30, is required for lifespan extension mediated by calcineurin inhibition. Finally, we show that the nuclear hormone receptor, NHR-8, is upregulated by calcineurin inhibition and is necessary for the increased lifespan. Our studies uncover a role for calcineurin in the C. elegans DMP and provide a new mechanism for calcineurin inhibition-mediated longevity extension.

Dietary Supplements and the Gut–Brain Axis: A Focus on Lemon, Glycerin, and Their Combinations

Dietary supplements are products taken orally, and they contain an ingredient intended to augment the diet. Many studies demonstrate clear alterations in microbe abundances and the production of microbiota-derived metabolites, such as short-chain fatty acids, following dietary changes. This review comprehensively explores the possible interactions among gut microbiota, lemon extracts, glycerin, and their mixture products. Lemon extracts/components are associated with a vast array of health benefits, including anti-inflammation, antioxidant, anti-atherosclerotic, and anti-diabetic effects. They are also associated with increased memory and decreased depression. Glycerin can reduce serum free fatty acids and mimic caloric restriction; its metabolites can function as a broad-spectrum antimicrobial. Additionally, glycerin has a dehydrating effect on the central nervous system and can reduce focal cerebral edema and improve performance by expanding plasma volume. However, it may also have side effects, such as hyperglycemia. Therefore, combined consumption of lemon extracts and glycerin may, in part, mitigate each other’s side effects while exerting their benefits. There is growing evidence that both lemon components and glycerin are metabolized by the gut microbiota and may modulate the intestinal microbiome composition. Therefore, gut microbiome alterations are also explored as an important mechanism in the gut–brain axis regulating various effects of these dietary supplements and their application in various noncommunicable neurological disorders.

Black goji berry anthocyanins extend lifespan and enhance the antioxidant defenses in Caenorhabditis elegans via the JNK-1 and DAF-16/FOXO pathways.

The black goji berry (Lycium ruthenicum Murr.) is known for its abundance of high-quality natural antioxidants, particularly anthocyanins. Black goji berry anthocyanins (BGA) are receiving increasing attention because of their high safety and beneficial biological activities. Studies have shown that oxidative stress is a key factor affecting aging, whereas antioxidants are critical preventive and delaying strategies. In the present study, we investigated the potential anti-aging effects and mechanism of BGA using the Caenorhabditis elegans model. We found that BGA prolonged the mean lifespan of nematodes and improve their healthspan, including locomotion, pharyngeal pumping rate and stress resistance. Subsequently, we observed a significant decrease in reactive oxygen species and malondialdehyde levels in nematodes after administering BGA. Moreover, BGA enhanced the activities of the antioxidant enzymes superoxide dismutase and catalase, and elevated the glutathione disulfide/glutathione ratio. We confirmed that BGA exerted excellent antioxidative stress activity in nematodes, which may contribute substantially to its anti-aging effects. The health benefits of BGA in C. elegans might be closely related to petunidin-3-O-glucoside, the most abundant anthocyanin in BGA. Further mechanistic investigation revealed that the JNK-1 and DAF-16/FOXO pathways, rather than the calorie restriction pathway, were responsible for the antioxidant stress and life-prolonging effects of BGA in nematodes. Our research provides a theoretical foundation for studying the anti-aging effect of BGA and a basis for developing black goji berry and its anthocyanins as functional foods with anti-aging and antioxidative stress benefits. © 2024 Society of Chemical Industry.

The distinct mechanism regulating taurine homeostasis in mice: Nutrient availability affects taurine levels in the liver and energy restriction influences it in the intestine

AimsOur previous findings indicate that caloric restriction (CR) stimulates the production and secretion of taurine-conjugated bile acids in mice. Subsequent processing by gut microbiota leads to increased levels of deconjugated bile acids, taurine, and various taurine conjugates in the intestine. Furthermore, we demonstrated that carbohydrate restriction and protein restriction, to a smaller extent, mirror the impact of CR in terms of hepatic production of bile acids but not their secretion. We hypothesized that modulating dietary macronutrient levels would influence taurine homeostasis in the liver and intestine of ad libitum-fed and CR animals. Materials and methodsAd libitum-fed male mice were allocated to receive either a control, low-protein (LP), low-fat (LF), or low-carbohydrate (LC) diet. Meanwhile, CR groups were given 80 % of their regular voluntary food intake as a control, high-protein (HP), high-fat (HF), or high-carbohydrate (HC) diet. Key findingsWhile CR did not affect the taurine levels and its conjugates in the liver, alteration in carbohydrates and protein intake impacted it. Conversely, in the intestine, CR increased the amount of free and conjugated taurine, whereas the various diets did not affect it or disrupt the CR-specific phenotype. Notably, variations in diet composition impacted the expression of the taurine transporter (Slc6a6) and glutathione-S transferases (GST) in the intestine as well as cysteine dioxygenase (Cdo) in the liver. SignificanceThe liver and the intestine show distinct responses to dietary interventions, with hepatic taurine being affected by the diet composition, while intestinal taurine is governed by energy availability.

From weight loss to cancer treatment: Fasting as an adjuvant anticancer therapy

The number of studies that have been conducted on the possible benefits of different types of fasting or calorie restriction on cancer therapy, including the likelihood that these treatments lessen side effects, has been limited. However, the results are nevertheless promising. Chemotherapy’s adverse effects have led to a quest for options that reduce reliance on it. The susceptibility of tumorous cells to specific metabolites and nutrient deficiency is increasingly recognized as a key characteristic of the disease. This review delves into the data on various fasting methods and calorie restriction in rodents and humans, with a focus on biological adaptations that could potentially lower cancer risk or enhance cancer treatment results. We also emphasize recent scientific developments regarding the use of prolonged fasting and fasting-mimicking diets as a possible additional treatment for patients receiving immunotherapy or other treatments. This approach shows promise in enhancing treatment effectiveness, preventing resistance, and minimizing side effects. This study proposes that combining fasting and calorie restriction with chemotherapy, immunotherapy, or other therapies might be a potential technique to improve treatment efficacy, avoid resistance, and reduce adverse effects.

Reversal of Diabetic Nephropathy with Intensive Lifestyle Intervention: A Case Report

Background: Diabetic nephropathy is a leading cause of chronic kidney disease, and early intervention is very important to prevent the progression of the disease .Case Presentation: A 45-year-old male patient who is a known case of type 2 diabetes mellitus from 10 years and nephropathy from 1 year underwent intensive lifestyle modification, including caloric restriction, high-intensity interval training, and stress management, alongside medication. Results: After 6 months of following the advice , significant improvements were observed:HbA1c decreased from 10.5% to 6.5%, eGFR increased from 45 to 60 ml/min/1.73m, proteinuria reduced from 2.5 to 0.5 g/day, and blood pressure normalized. Conclusion: This case demonstrates the potential for intensive lifestyle intervention to reverse diabetic nephropathy, highlighting the importance of a multidisciplinary approach in managing diabetes and preventing renal complications.

The response of grey mouse lemurs to acute caloric restriction before reproduction supports the 'thrifty female hypothesis'.

The 'thrifty female hypothesis' states that females preserve more of their energy reserves during winter than males because of the sex-specific time frame of energy allocation for reproduction. As males reactivate their reproductive axis before the mating period, while females mainly allocate energy during gestation and lactation, we hypothesized that males would have to use shorter torpor bouts and longer periods of normothermic activity to promote spermatogenesis during winter, a period of low food availability. Here, we applied an acute 2week 80% caloric restriction in male and female grey mouse lemurs shortly before the mating period. We found evidence of thriftier phenotypes in wintering females, which performed deeper and longer torpor bouts than males and ultimately lost less body mass. Our results thus support the 'thrifty female hypothesis' in a seasonally breeding primate and reinforce the concept of a sex-biased trade-off in using torpor, which might ultimately benefit reproduction and survival.

Protective Effects of Chlorogenic Acid Against Amyloid-Beta-Induced Oxidative Stress and Ion Transport Dysfunction in SH-SY5Y Cells.

Caloric restriction mimetics mimic the beneficial effects of dietary restriction approaches, such as caloric restriction approaches, without limiting the dietary intake. Chlorogenic acid (CGA) acts as a caloric restriction mimetic; however, its neuroprotective mechanisms remain ambiguous. Therefore, in this study, we aimed to elucidate the neuroprotective effects of CGA on SH-SY5Y cells treated with amyloid-beta (Aβ)1-42. Aβ1-42 (1.25 μM) induced oxidative stress by significantly increasing the pro-oxidant levels and decreasing the antioxidant levels in the cells. Additionally, it decreased the Na+/K+-ATPase and Ca2+-ATPase ion transporter activities and enhanced the acetylcholinesterase activity. However, CGA (100 μM) reversed these Aβ1-42-induced changes in SH-SY5Y cells. Overall, CGA exerted neuroprotective effects against Aβ1-42-induced oxidative stress and impaired ion transporter and acetylcholinesterase activities, serving as a promising therapeutic candidate for neurodegenerative diseases, such as Alzheimer's disease.

The Effect of Time-Restricted Eating on Cardiometabolic Risk Factors: A Systematic Review and Meta-Analysis

Background/Objectives: Endogenous metabolic pathways periodically adjust with fluctuations in day and night, a biological process known as circadian rhythm. Time-restricted eating (TRE) aligns the time of food intake with the circadian rhythm. This study aims to investigate the effects of TRE on body weight, body composition and cardiometabolic risk factors. Methods: We reviewed articles from PubMed and Cochrane libraries for clinical trials that compare TRE with regular diet without calorie restriction. We conducted a meta-analysis of 26 studies. Results: Participants who followed TRE demonstrated reduction in body weight [mean-MD: −1.622 kg, (95% confidence interval (CI −2.302 to −0.941)], body mass index (BMI) [MD: −0.919 kg/m2 (95% CI: −1.189 to −0.650)], waist circumference [MD: −2.015 cm (95% CI: −3.212 to −0.819] and whole-body fat mass (WBFM) [MD: −0.662 kg (95% CI: −0.795 to −0.530)]. Improvements in cardiometabolic risk factors such as a decrease in insulin concentrations [MD: −0.458 mIU/L, (95% CI: −0.843 to −0.073)], total cholesterol [MD: −2.889 mg/dL (95% CI: −5.447 to −0.330) and LDL concentrations [MD: −2.717 mg/dL (95% CI: −4.412 to −1.021)] were observed. Conclusions: TRE is beneficial for weight loss and improvements in cardiometabolic risk factors. Further large-scale clinical trials are needed to confirm these findings.

Pharmacological Manipulation of the Aging Pathways to Effect Health Span and Lifespan with Special Reference to SGLT2 Inhibitors as Powerful Anti-aging Agents in Humans

Calorie restriction has been shown to slow the aging process in numerous organisms including primates. Caloric excess states, such as type 2 diabetes, are associated with accelerated aging and the incidence and severity of chronic diseases. The nutrient-sensing pathways and intestinal microbiome are important systems that affect aging and chronic disease development. This manuscript reviews the various pathways involved with aging and chronic disease development and examines the pharmacological manipulation of these systems which appear to slow aging and the chronic diseases of aging in experimental model organisms and collaborating human data when available. Finally, the abundance of experimental and human data suggesting the newer diabetic medications, the sodium-glucose transport inhibitors, are potent anti-aging agents is provided.

Effects of Intermittent Fasting on Human Metabolism and Evaluation of Its Effectiveness in Weight Loss

Intermittent Fasting (IF), a dietary modification through time-restricted feeding, has gained significant attention in the past few years owing to its advantages in metabolic health and weight management. Available evidence suggests that IF can improve insulin sensitivity; lower the levels of blood glucose and fat; prevent body fat accumulation; and reduce the risk of obesity-related chronic disease by mitigating oxidative damage and affecting the activity of antioxidant enzymes. However, a number of gaps in knowledge remain regarding IF, especially its long-term safety and the generalisability of IF. This paper discussed the effects of IF on metabolism and body health through the mechanism of high-intensity, nutrient-strong IF. It mentioned that IF led to improved insulin sensitivity, lower blood lipid levels and inhibition of body fat accumulation, and was easier to stick to than daily calorie restriction. Other clinical studies with longer intervals and durations also reported significant effects of IF on weight loss and body health. Long term strict IF is unfavorable for some patients – in particular the elderly and the chronically ill – due to the potential for nutritional and metabolic problems. This study serves as an important reference for the use of IF in health and weight loss management, and offers potential directions for future research. Even though IF showed clear benefits, its safety in the long term and applicability across different populations still need to be validated. Future investigations may look into the long-term effects of IF in different populations, and its potential application in various health conditions.

Assessing the Impact of Wheat Flour and Baker's Yeast Restricted Diet vs. Calorie Restriction in NAFLD Patients

IntroductionNon-alcoholic fatty liver disease (NAFLD) is a prevalent and nonalcoholic progressive liver disorder associated with metabolic disturbance. This study aimed to compare the efficacy of wheat flour or baker's yeast-restricted diet with traditional calorie restriction in NAFLD patients.Material and methodsAnalyzed data was obtained from 243 individuals with NAFLD who completed the study. Of these patients, 54 belonged to Group (1) (Standard Diet, SD); 104 belonged to Group (2) (Wheat Flour-Free Diet, WFFD); and 85 belonged to Group (3) (Yeast-Free Diet, YFD). The intervention period lasted 6 months, during which participants' dietary compliance was closely monitored.ResultsAt the end of the six-month trial, both the WFFD and HFD groups exhibited a noteworthy reduction in body mass index (BMI) and triglyceride (TG) levels when compared to a standard diet that only involved calorie restriction. Furthermore, a notable reduction in the severity of liver steatosis was seen in these groups (p&lt;0.05). The SD group did not exhibit any significant changes in these metrics. The WFFD group experienced a notable reduction in HSI values (p&lt;0.05). Cluster analysis revealed that the obese group had higher HSI, weight, and BMI values throughout the study period, indicating a more advanced stage of NAFLD.ConclusionsTo summarize, this study highlights the significance of food constituents and dietary strategies in the treatment of NAFLD. It suggests that limiting the intake of wheat flour and baker's yeast specifically could have positive effects on liver well-being.

Late-onset caloric restriction improves cognitive performance and restores circadian patterns of neurotrophic, clock and epigenetic factors in the hippocampus of male old rats.

Aging is a complex multifactorial process that results in a general functional decline, including cognitive impairment. Caloric restriction (CR) can positively influence the aging processes and delay cognitive decline. There is a rhythmic variation in memory and learning processes throughout the day, indicating the involvement of the circadian clock in the regulation of these processes. Despite growing evidence on the efficacy of CR, it has not yet been fully determined whether starting this strategy at an advanced age is beneficial for improving quality of life and eventually, for protection against age-related diseases. Here, we investigated the effect of late-onset CR on the temporal organization of the molecular clock machinery, molecules related to cognitive processes and epigenetic regulation, in the hippocampus of male old rats maintained under constant darkness conditions. Our results evidenced the existence of a highly coordinated temporal organization of Bmal1, Clock, Bdnf, Trkb, Dnmts, Sirt1, and Pgc-1α in the hippocampus of young adult rats. We observed that aging led to cognitive deficits and loss of circadian oscillations of all the above variables. Interestingly, CR restored circadian rhythmicity in all cases and, in addition, improved the cognitive performance of the old animals. This work would highlight the importance of the circadian clock and its synchronization with feeding signals, as the basis of the beneficial effects of CR. Thus, lifestyle modifications, such as CR, might be a powerful intervention to preserve hippocampal circadian organization and cognitive health during aging.

Expression of PGC-1α, PPAR-α and UCP1 genes, metabolic and anthropometric factors in response to sodium butyrate supplementation in patients with obesity: a triple-blind, randomized placebo-controlled clinical trial.

There is increasing evidence that gut metabolites have a role in the etiology of obesity. This study aimed to investigate the effects of sodium butyrate (NaB) supplementation on the expression of peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1α (PGC-1α), PPAR-α, and uncoupling protein-1 (UCP-1) genes, as well as on the metabolic parameters and anthropometric indices in persons with obesity. In this triple-blind placebo-controlled randomized clinical trial, 50 individuals with obesity were randomly assigned to NaB (600 mg/day) + hypo-caloric diet or placebo group + hypo-caloric diet for 8 weeks. The study measured the participants' anthropometric characteristics, food consumption, and feelings of hunger in addition to the serum levels of metabolic indices and the mRNA expression of the PGC-1α, PPAR-α, and UCP-1 genes in peripheral blood mononuclear cells (PBMCs). PGC-1α and UCP-1 genes expression significantly increased in NaB group compared to the placebo at the endpoint. A significant decrease in weight, BMI, and waist circumference (WC) was observed in NaB group. Among the metabolic factors, NaB significantly decreased fasting blood sugar (FBS) (P = 0.04), low-density lipoprotein cholesterol (LDL-C) (P = 0.038) and increased high-density lipoprotein cholesterol (HDL-C) (P = 0.016). NaB could not significantly change serum GLP-1 level. This study unveiled NaB supplementation alone cannot have significant beneficial effects on anthropometric, and biochemical factors. NaB could affect anthropometric and metabolic risk variables associated with obesity only when prescribed, along with calorie restriction. This study was registered in the Iranian Registry of Clinical Trials ( https://en.irct.ir/trial/53968 ) on 31 January 2021 (registry number IRCT20190303042905N2).

Narrative Review of Lifestyle Interventions in Breast Cancer Survivors: Current Evidence and Future Directions.

One in eight females will be diagnosed with breast cancer in their lifetime. While medical advances have increased the likelihood of survival, up to 90% of females will gain weight during and after treatment increasing the risk of breast cancer recurrence and obesity related co-morbidities in survivorship. Behavioral lifestyle interventions focused on diet with or without physical activity can provide breast cancer survivors non-pharmacological options to decrease weight gain and cardiometabolic risk. A PubMed search was conducted to identify all behavioral lifestyle interventions focused on diet or diet combined with physical activity longer than 4 weeks of duration in breast cancer survivors that included body weight as an outcome. This review aims to summarize the effects on body weight, body composition and cardiometabolic risk markers are summarized. Based on the review, there is high heterogeneity in type and duration of the intervention to affect weight and cardiometabolic risk in survivorship. Calorie restriction with and without physical activity appears to promote weight loss among breast cancer survivors. However, the effects on cardiometabolic factors are less clear. Future studies should be powered for both body weight and cardiometabolic effects. Researchers should also consider interventions that are: 1) less complex, 2) recruit a more racially and ethnically diverse sample, 3) integrate resistance training, 4) implement the intervention in closer proximity to diagnosis, 5) target weight management in this population before it occurs and 6) analyze body composition in addition to body weight measurements.