Short-term Fasting Research Articles

Group differences in binge eating, impulsivity, and intuitive and mindful eating among intermittent fasters and non-fasters

Intermittent fasting (IF) is an increasingly popular diet involving short-term fasting and/or caloric restriction. While published research highlights physiological effects (e.g., weight, body fat) of IF, hardly any research has examined its associations with psychological factors. This study aimed to investigate the relationship between IF and binge eating, impulsivity, intuitive eating, and mindful eating. An undergraduate sample (N = 298) was recruited through a large southwestern university psychology subject pool. The sample was divided into three groups based on IF status: Current IF (n = 70), Past IF (n = 48), and No IF (n = 182). Current IF was negatively associated with lack of perseverance (e.g., “I generally like to see things through to the end”; p < .01) and intuitive eating (p < .05), varying by subscale, compared to the other groups. Notably, Past-IF, but not Current IF, participants were more likely to binge eat than individuals who reported never fasting (p = .03). These findings add credence to the rapidly developing area of research suggesting IF is associated with increased disordered eating behaviors. Notably, the findings from this study are limited due to the lack of diversity sample, such that generalizations can only be made toward White, middle-to-high income, college students. Future longitudinal studies are needed to test the directionality of these relationships.

The circadian rhythm regulates branched-chain amino acids metabolism in fast muscle of Chinese perch (Siniperca chuatsi) during short-term fasting by Clock-KLF15-Bcat2 pathway.

As an internal time keeping mechanism, circadian rhythm plays crucial role in maintaining homeostasis when in response to nutrition change, meanwhile, branched-chain amino acids (BCAAs) in skeletal muscle play an important role in preserving energy homeostasis during fasting. Previous results from our lab suggested that fasting can influence peripheral circadian rhythm and BCAAs metabolism in fish, but the relationship between circadian rhythm and BCAAs metabolism, and whether circadian rhythm regulates BCAAs metabolism to maintain physiological homeostasis during fasting remains unclear. This study shows that the expression of 15 core clock genes, as well as KLF15 and Bcat2 is highly responsive to short-term fasting in fast muscle of Siniperca chuatsi, and the correlation coefficient between Clock and KLF15 expression is enhanced after fasting treatment. Furthermore, we demonstrate that the transcriptional expression of KLF15 is regulated by Clock, and the transcriptional expression of Bcat2 is regulated by KLF15 by using dual-luciferase reporter gene assay and Vivo-Morpholinos mediated gene knockdown technique. Therefore, fasting imposes a dynamic coordination of transcription between the circadian rhythm and BCAAs metabolic pathways. The findings highlight the interaction between circadian rhythm and BCAAs metabolism, and suggest that fasting induces a switch in KLF15 expression through affecting the rhythmic expression of Clock, and then KLF15 promotes the transcription of Bcat2 to enhance the metabolism of BCAAs, thus maintaining energy homeostasis and providing energy for skeletal muscle as well as other tissues.

Galanin, a central appetite factor, affects appetite signals in the hypothalamus and promotes feeding in Siberian sturgeon (Acipenser baerii Brandt)

Galanin is a strong appetite promoting factor in mammals, but information about the mechanism of galanin in feeding regulation is very limited in fish. This study investigated the effects of galanin on food intake and explored the feeding regulation mechanism in Siberian sturgeon. Galanin and galanin receptor-3 (galr3) cDNA sequences of 557 bp and 710 bp were obtained respectively, and they were both abundantly expressed in the hypothalamus. Four experiments were performed to determine whether galanin affects food intake in Siberian sturgeon, including short-term fasting, intraperitoneal (i.p.) injection, and intraventricular (i.c.v.) injection. The results showed that galanin mRNA expression increased significantly after fasting for 1 (P < 0.05) and 3 h (P < 0.01). The galanin (0.50, 1.00, and 1.50 μg/g BW) i.p. injection did not significantly change food intake within 1, 3, or 6 h, but the galanin i.c.v. injection concentrations of 0.01, 0.05, and 0.10 μg/g BW significantly increased food intake within 3 h (P < 0.01, P < 0.05, P < 0.001, respectively). An i.c.v. co-injection experiment with galanin and spexin was carried out to further explore the mechanism of galanin on the feeding regulation and to clarify the relationship between galanin and spexin. The results showed that 0.20 μg/g BW spexin significantly reversed the appetite promoting effect of 0.10 μg/g BW galanin (P < 0.05). Moreover, galanin did not affect the expression of galr3, while spexin significantly decreased the transcriptional level of galr3 (P < 0.05). The expression of nine appetite factors (cart, ucn3, apelin, nucb2, npy, cck, galanin, spexin, and pyy), significantly changed among the four groups (saline, galanin, spexin, and galanin + spexin). These results indicate that central galanin promotes food intake, which may have been mediated by the detected down-regulating anorexic signals including cart, ucn3, and pyy in the hypothalamus. Spexin reduced appetite, probably related to the upregulation of cart and ucn3 transcript expression and down-regulation of npy. This investigation provides a theoretical basis for an in-depth analysis of the feeding regulation mechanism in teleost.

ODP248 The Effects of Insulin-like Growth Factor-binding Protein-3 on Metabolism During Short Term Fasting in Mice in Vivo

Abstract IGFBP-3 is the main abundant circulating IGFBP and plays an important role in the metabolic effect of IGF-1. We investigated the effects of IGFBP-3 on metabolism in short-term fasting and found that when IGFBP-3 was added to mice, serum triglyceride concentration were significantly enhanced. Fasting also significantly enhanced triglyceride concentration in liver and serum to the same degree as IGFBP-3. IGFBP-3 transfection suppressed the expression of ketogenesis and beta oxidation genes in liver after 24 h fasting. Also, they were shown significantly increase oflipolysis related protein expression in peripheral adipocyte and decrease the adipocyte size. Additionally, fat accumulation was more increased in the liver transfected with IGFBP-3 after fasting than controls. These in vivo findings demonstrate that IGFBP-3 has potent lipid metabolism and fasting-antagonizing capability and suggest a role for IGFBP-3 in the pathogenesis and homeostasis control of metabolism. Presentation: No date and time listed

Hypothalamic insulin expression remains unaltered after short-term fasting in female rats.

Our previous study showed that 6-h fasting increased insulin expression in the hypothalamus of male rats. We, therefore, wanted to examine if this phenomenon occurs in female rats and whether it depended on the estrus cycle phase. Female rats in proestrus or diestrus were either exposed to 6-h fasting or had ad libitum access to food. The serum, cerebrospinal fluid, and hypothalamic insulin levels were determined using radioimmunoassay. The hypothalamic insulin mRNA expression was measured by RT-qPCR, while the hypothalamic insulin distribution was assessed immunohistochemically. Albeit the short-term fasting lowered circulating insulin, both hypothalamic insulin mRNA expression and hypothalamic insulin content remained unaltered. As for the hypothalamic insulin distribution, strong insulin immunopositivity was noted primarily in ependymal cells lining the upper part of the third ventricle and some neurons mainly located within the periventricular nucleus. The pattern of insulin distribution was similar between the controls and the females exposed to fasting regardless of the estrous cycle phase. The findings of this study indicate that the control of insulin expression in the hypothalamus differs from that in the pancreatic beta cells during short-term fasting. Furthermore, they also imply that the regulation of insulin expression in the female hypothalamus is different from males but independent of the estrus cycle phase.

Dietary Interventions in Cancer Treatment and Response: A Comprehensive Review.

Simple SummaryChemotherapy and radiotherapy are essential components to the management of most solid malignancies. These modalities exert their effects primarily by mediating the DNA damage of malignant cells; however, healthy cells are also damaged by the same mechanisms and can incur acute and late side effects resulting in both morbidity and mortality. Dietary interventions have been shown to reduce cancer growth, progression, and metastasis in many different solid tumor models and they show promise for improving cancer outcomes in early phase clinical studies. Here, we review preclinical and clinical studies that examine how dietary interventions can impact cancer treatment toxicity and efficacy in patients who were undergoing chemotherapy and/or radiotherapy. This information can help clinicians tailor the dietary regimens to patients based on their treatment methods and promote larger clinical trials to test the dietary effects on cancer treatment safety and efficacy.Chemotherapy and radiotherapy are first-line treatments in the management of advanced solid tumors. Whereas these treatments are directed at eliminating cancer cells, they cause significant adverse effects that can be detrimental to a patient’s quality of life and even life-threatening. Diet is a modifiable risk factor that has been shown to affect cancer risk, recurrence, and treatment toxicity, but little information is known how diet interacts with cancer treatment modalities. Although dietary interventions, such as intermittent fasting and ketogenic diets, have shown promise in pre-clinical studies by reducing the toxicity and increasing the efficacy of chemotherapeutics, there remains a limited number of clinical studies in this space. This review surveys the impact of dietary interventions (caloric restriction, intermittent and short-term fasting, and ketogenic diet) on cancer treatment outcomes in both pre-clinical and clinical studies. Early studies support a complementary role for these dietary interventions in improving patient quality of life across multiple cancer types by reducing toxicity and perhaps a benefit in treatment efficacy. Larger, phase III, randomized clinical trials are ultimately necessary to evaluate the efficacy of these dietary interventions in improving oncologic or quality of life outcomes for patients that are undergoing chemotherapy or radiotherapy.

Behavioral and Transcriptional Effects of Short or Prolonged Fasting on the Memory Performances of Lymnaea stagnalis

Introduction: The Garcia effect, a solid learning paradigm, was used to investigate the molecular and behavioral effects induced by different lengths of fasting on the cognitive functions in the pond snail Lymnaea stagnalis, a valid model system. Methods: Three experimental groups were used: moderately hungry snails, food-deprived for 1 day (D1 snails), severely hungry snails (D5 snails), fasting for 5 days, and satiated snails with ad libitum access to food (AL snails). In the Garcia effect, a single pairing of an appetitive stimulus with a heat stressor results in a learned taste-specific negative hedonic shift. D5 snails were injected with bovine insulin and D1 snails with the insulin receptor antibody (Ab). As a control group, AL snails were injected with saline. Gene expression analyses were performed by real-time PCR in snails’ central nervous system (CNS). Results: AL snails are “average learners,” D1 snails are the best performers, whereas the D5 ones do not show the Garcia effect. Severely fasting snails injected with insulin 3 h before the training procedure show the Garcia effect, whereas injecting 1-day fasting snails with insulin receptor Ab blocks their ability to express memory. The differences in memory performances are associated with changes in the expression levels of selected targets involved in neuronal plasticity, energy homeostasis, and stress response. Discussion: Our results suggest that short-term fasting creates an optimal internal state in L. stagnalis’ CNS, allowing a spike in insulin release and an upregulation of genes involved in neuroplasticity. Long-term fasting, instead, upregulates genes involved in energy homeostasis and animal survival.

Hepatic metabolite responses to 4-day complete fasting and subsequent refeeding in rats.

BackgroundFasting has been widely used to improve various metabolic diseases in humans. Adaptive fasting is necessary for metabolic adaptation during prolonged fasting, which could overcome the great advantages of short-term fasting. The liver is the main organ responsible for energy metabolism and metabolic homeostasis. To date, we lack literature that describes the physiologically relevant adaptations of the liver during prolonged fasting and refeeding. For that reason, this study aims to evaluate the response of the liver of Sprague-Dawley (SD) rats to prolonged fasting and refeeding.MethodsSixty-six male SD rats were divided into the fasting groups, which were fasted for 0, 4, 8, 12, 24, 48, 72, or 96 h, and the refeeding groups, which were refed for 1, 3, or 6 days after 96 h of fasting. Serum glucose, TG, FFA, β-hydroxybutyrate, insulin, glucagon, leptin, adiponectin and FGF21 levels were assessed. The glucose content, PEPCK activity, TG concentration and FFA content were measured in liver tissue, and the expression of genes involved in gluconeogenesis (PEPCK and G6Pase), ketogenesis (PPARα, CPT-1a and HMGCS2) and the protein expression of nutrient-sensing signaling molecules (AMPK, mTOR and SIRT1) were determined by RT-qPCR and western blotting, respectively.ResultsFasting significantly decreased the body weight, which was totally recovered to baseline after 3 days of refeeding. A 4-day fast triggered an energy metabolic substrate shift from glucose to ketones and caused serum hormone changes and changes in the protein expression levels of nutrient-sensing signaling molecules. Glycogenolysis served as the primary fuel source during the first 24 h of fasting, while gluconeogenesis supplied the most glucose thereafter. Serum FFA concentrations increased significantly with 48 h of fasting. Serum FFAs partly caused high serum β-hydroxybutyrate levels, which became an important energy source with the prolongation of the fasting duration. One day of refeeding quickly reversed the energy substrate switch. Nutrient-sensing signaling molecules (AMPK and SIRT1 but not mTOR signaling) were highly expressed at the beginning of fasting (in the first 4 h). Serum insulin and leptin decreased with fasting initiation, and serum glucagon increased, but adiponectin and FGF21 showed no significant changes. Herein, we depicted in detail the timing of the metabolic response and adaptation of the liver to a 4-day water-only fast and subsequent refeeding in rats, which provides helpful support for the design of safe prolonged and intermittent fasting regimens.

Intermittent fasting during adjuvant chemotherapy may promote differential stress resistance in breast cancer patients

BackgroundPreclinical studies prove that short-term fasting secures healthy cells against chemotherapy side effects and makes malignant cells more vulnerable to them. This study aimed to examine the effects of intermittent fasting (IF) during adjuvant chemotherapy AC (doxorubicin, cyclophosphamide) protocol in breast cancer (BC) patients.MethodsForty-eight newly diagnosed human epidermal growth factor receptor 2-negative (HER2 negative) BC patients were divided equally into two groups (24 each). The first group was recruited to fast intermittently for three consecutive days around chemotherapy for 18 h a day from 12 am to 6 pm and eats through 6 h a day from 6 pm to 12 am with permission of drinking water during fasting hours (IF group). This IF was repeated every 3 weeks for four cycles. The second group is a non-fasting (NF) group that was allowed to eat regularly. Toxicity in the two groups was compared. Hematologic, metabolic, and inflammatory parameters were measured and compared.ResultsToxicity related to the gastrointestinal tract (GIT) was reduced in the IF group. Hematologic parameters showed no significant variations between the two studied groups after cycle 4. There was a significant increase in median glucose and median insulin levels (P < 0.001 and P = 0.001, respectively) in the NF group between baseline and after cycle 4. In addition, there was a significant decrease in the median insulin level (P = 0.002) in the IF group between the two time points.ConclusionIF throughout chemotherapy was well tolerated and decreased the toxicity of chemotherapy. Additionally, IF-improved metabolic profiles of patients may have a positive impact on the clinical efficacy of chemotherapy.

Day-to-day fasting plasma glucose variability on the short-term prognosis of ST-segment elevation myocardial infarction: A retrospective cohort study.

Glycemic variability in one fact that explain the differences in cardiovascular outcomes. The short-term fasting plasma glucose (FPG) variability may have an on major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients with ST-segment elevation myocardial infarction (STEMI). This study retrospectively analyzed T2DM patients who underwent emergent percutaneous coronary intervention (PCI) due to STEMI in Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, between January 2016 and March 2020. All patients underwent at least 5 FPG measurements during the perioperative period. FPG variability score (FPG-VS) was defined as the percentage of the number of FPG variations > 1 mmol/L between two adjacent FPG measurements. The Cox proportional-hazards model was used to estimate the relationship between FPG-VS and MACE. A validation set was utilized to further evaluate the prognostic value of FPG-VS in a standardized STEMI diabetic diet cohort following PCI intervention. A total of 612 patients were included in the retrospective cohort study. In comparison to the minimum quintile, FPG-VS > 60% was associated with an increased risk of 30-day MACE. Moreover, compared to FPG-VS ≤ 20%, the FPG-VS > 80% group had a higher risk of MACE (odd ratio [OR] = 4.87, 95% confidence interval [CI]: 2.55-5.28), recurrent angina pectoris (OR = 5.43, 95%CI: 2.27-8.27), nonfatal myocardial infarction (OR = 5.00, 95%CI: 2.47-7.69), heart failure (OR = 3.70, 95%CI: 1.92-5.54), malignant arrhythmia (OR = 4.63, 95%CI: 1.12-6.25) and cardiac death (OR = 1.41, 95%CI: 0.17-1.97). Consistent results were obtained after adjustment for HbA1c, demonstrating the robustness of FPGFPG-VS. Moreover, the standard diet intervention group had a lower FPG-VS index as well as a lower incidence of MACE. Higher FPG variability is associated with an increased risk of MACE within 30 days in diabetes patients receiving PCI for STEMI. A standardized diet may improve the prognosis of STEMI patients by reducing the FPG-VS.

The metabolome of Mexican cavefish shows a convergent signature highlighting sugar, antioxidant, and Ageing-Related metabolites.

Insights from organisms, which have evolved natural strategies for promoting survivability under extreme environmental pressures, may help guide future research into novel approaches for enhancing human longevity. The cave-adapted Mexican tetra, Astyanax mexicanus, has attracted interest as a model system for metabolic resilience, a term we use to denote the property of maintaining health and longevity under conditions that would be highly deleterious in other organisms (Figure 1). Cave-dwelling populations of Mexican tetra exhibit elevated blood glucose, insulin resistance and hypertrophic visceral adipocytes compared to surface-dwelling counterparts. However, cavefish appear to avoid pathologies typically associated with these conditions, such as accumulation of advanced-glycation-end-products (AGEs) and chronic tissue inflammation. The metabolic strategies underlying the resilience properties of A. mexicanus cavefish, and how they relate to environmental challenges of the cave environment, are poorly understood. Here, we provide an untargeted metabolomics study of long- and short-term fasting in two A. mexicanus cave populations and one surface population. We find that, although the metabolome of cavefish bears many similarities with pathological conditions such as metabolic syndrome, cavefish also exhibit features not commonly associated with a pathological condition, and in some cases considered indicative of an overall robust metabolic condition. These include a reduction in cholesteryl esters and intermediates of protein glycation, and an increase in antioxidants and metabolites associated with hypoxia and longevity. This work suggests that certain metabolic features associated with human pathologies are either not intrinsically harmful, or can be counteracted by reciprocal adaptations. We provide a transparent pipeline for reproducing our analysis and a Shiny app for other researchers to explore and visualize our dataset.

Effects of Short-term Fasting on Ghrelin/GH/IGF-1 Axis in Healthy Humans: The Role of Ghrelin in the Thrifty Phenotype.

A greater decrease in 24-hour energy expenditure (24hEE) during short-term fasting is indicative of a thrifty phenotype. As ghrelin and the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis are implicated in the regulation of energy intake and metabolism, we investigated whether ghrelin, GH, and IGF-1 concentrations mediate the fasting-induced decrease in 24hEE that characterizes thriftiness. In 47 healthy individuals, 24hEE was measured in a whole-room indirect calorimeter both during 24-hour eucaloric and fasting conditions. Plasma total ghrelin, GH, and IGF-1 concentrations were measured by enzyme-linked immunosorbent assay after an overnight fast the morning before and after each 24-hour session. During 24-hour fasting, on average 24hEE decreased by 8.0% (P < .001), GH increased by ~5-fold (P < .001), whereas ghrelin (mean +23 pg/mL) and IGF-1 were unchanged (both P ≥ .19) despite a large interindividual variability in ghrelin change (SD 150 pg/mL). Greater fasting-induced increase in ghrelin was associated with a greater decrease in 24hEE during 24-hour fasting (r = -0.42, P = .003), such that individuals who increased ghrelin by 200 pg/mL showed an average decrease in 24hEE by 55 kcal/day. Short-term fasting induced selective changes in the ghrelin/GH/IGF-1 axis, specifically a ghrelin-independent GH hypersecretion that did not translate into increased IGF-1 concentrations. Greater increase in ghrelin after 24-hour fasting was associated with greater decrease in 24hEE, indicating ghrelin as a novel biomarker of increased energy efficiency of the thrifty phenotype.

Fasting induces a highly resilient deep quiescent state in muscle stem cells via ketone body signaling

Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here, we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Furthermore, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a nonmetabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs, leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.

Short-Term Fasting Attenuates Overall Steroid Hormone Biosynthesis in Healthy Young Women.

ContextFasting is stressful for the human body. It is managed by metabolic adaptations maintaining energy homeostasis and involves steroid hormone biosynthesis, but the exact interplay between energy and steroid metabolism remains elusive. Women with polycystic ovary syndrome (PCOS) suffer from disturbed metabolism and androgen excess, while in women with anorexia nervosa, cortisol and androgen production are decreased. By contrast, starvation of steroidogenic cells shifts adrenal steroid biosynthesis toward enhanced androgen production.AimThis study investigated the effect of fasting on steroid production in healthy women.MethodsTwenty healthy young women fasted for 48 hours; steroid profiles from plasma and urine samples were assessed at baseline, after 24 hours, and 48 hours by liquid and gas chromatography–mass spectrometry.ResultsFasting did not change overall steroidogenesis, although it increased progestogen production and lowered relative mineralocorticoid, glucocorticoid, and androgen production. The largest decrease in urine metabolites was seen for β-cortol, dehydroepiandrosterone, and androstenediol; higher levels were found for pregnanediol in urine and progesterone and aldosterone in serum. Activity of 17α-hydroxylase/17,20-lyase (CYP17A1), essential for androgen biosynthesis, was decreased after fasting in healthy women as were 21-hydroxylase (CYP21A2) and 5α-reductase activities. By contrast, hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) activity for cortisol inactivation seemed to increase with fasting.ConclusionSignificant changes in steroid metabolism occurred after 48 hours of fasting in healthy women. In contrast to metabolic changes seen at baseline in PCOS women compared to healthy women, and after starving of steroidogenic cells, no androgen excess was observed after short-term fasting in healthy young women.

Short-term Fasting Induces Alternate Activation of Orexin and Melanin-concentrating Hormone Neurons in Rats

Orexin and melanin-concentrating hormone (MCH) neurons constitute the energy balance circuitry that coordinates the fasting response. Orexin neurons mediate food foraging at the expense of energy storage, while MCH neurons promote energy storage by reducing energy expenditure and increasing food intake. It is unknown if these cell groups undergo plastic changes as hunger and metabolic changes escalate over time during fasting. To address this, we performed in vitro electrophysiological recording on orexin and MCH neurons in the lateral hypothalamus and perifornical area from rats fasted for 12 or 24 h or fed ad-libitum. Orexin neurons showed a transient decrease in presynaptic glutamate release at 12 h. This turned to an increase at 24 h of fasting, while membrane potential depolarized and AMPA receptor conductance increased. In contrast, MCH neurons were transiently depolarized at 12 h fasting along with increased presynaptic glutamate release. These changes reversed at 24 h, while the number of AMPA receptors decreased. Our results indicate that MCH neurons are preferentially activated during the early phase of fasting (12 h), which would protect against weight loss. With a longer fast, orexin neurons become activated, which would promote arousal and exploratory activity required for foraging behaviors. This alternating activation of these cell groups may reflect a dynamic balance of energy conservation and foraging behaviors to optimize energy balance during ongoing fasting.

Sulfur Amino Acid Supplementation Abrogates Protective Effects of Caloric Restriction for Enhancing Bone Marrow Regrowth Following Ionizing Radiation.

Radiation therapy damages and depletes total bone marrow (BM) cellularity, compromising safety and limiting effective dosing. Aging also strains total BM and BM hematopoietic stem and progenitor cell (HSPC) renewal and function, resulting in multi-system defects. Interventions that preserve BM and BM HSPC homeostasis thus have potential clinical significance. Here, we report that 50% calorie restriction (CR) for 7-days or fasting for 3-days prior to irradiation improved mouse BM regrowth in the days and weeks post irradiation. Specifically, one week of 50% CR ameliorated loss of total BM cellularity post irradiation compared to ad libitum-fed controls. CR-mediated BM protection was abrogated by dietary sulfur amino acid (i.e., cysteine, methionine) supplementation or pharmacological inhibition of sulfur amino acid metabolizing and hydrogen sulfide (H2S) producing enzymes. Up to 2-fold increased proliferative capacity of ex vivo-irradiated BM isolated from food restricted mice relative to control mice indicates cell autonomy of the protective effect. Pretreatment with H2S in vitro was sufficient to preserve proliferative capacity by over 50% compared to non-treated cells in ex vivo-irradiated BM and BM HSPCs. The exogenous addition of H2S inhibited Ten eleven translocation 2 (TET2) activity in vitro, thus providing a potential mechanism of action. Short-term CR or fasting therefore offers BM radioprotection and promotes regrowth in part via altered sulfur amino acid metabolism and H2S generation, with translational implications for radiation treatment and aging.

The Complementary Role of Exercise and Fasting in the Treatment of Cancer: A Narrative Review of Mechanisms Related to Metabolic Stress Elements

Background: Complementary methods such as physical activity (PA) and fasting are particularly important for cancer patients. The present study reviewed the effects of regular PA and fasting on cancer patients and attempted to explain the relevant mechanisms. Methods: Several electronic databases such as PubMed, Elsevier, and Google Scholar were searched for keywords. After reviewing, 412 articles were identified until February 1, 2021. The inclusion criteria included meta-analysis, clinical intervention studies that considered different effects of fasting and various types of exercise on health indicators. After carefully reviewing and eliminating duplicates, 68 articles were identified based on the PICO format (participants, intervention, comparison, and results). Results: The short-term fasting (STF) before chemotherapy (48-72 hours) or rehabilitation exercise could be modulating fasting blood sugar, growth factors, oxidative stress (OS), and inflammatory pathways. In addition, physiological metabolic stress induced by STF or rehabilitation exercise could regulate sex hormone-binding globulin, fat oxidation, leptin secretion, hyperinsulinemia, maintaining mass muscle, and bone density, boosting the immune system, and improving the therapeutic index of cancer. Conclusion: Metabolic stress in cancer cells leads to the intake of high doses of chemotherapy. The rehabilitation exercise prevents the complications of the disease and improves the patient’s quality of life. Thus, these interventions can be used to improve the cancer-based therapeutic index on individual differences.

Case report: successful treatment of a rare large jejunal gastrointestinal stromal tumour with surgery and using principle of short-term fasting

Small intestinal gastrointestinal stromal tumours (GISTs) are rare mesenchymal tumours of gastrointestinal tract comprise 0.04% of small intestinal neoplasms. We presented a case of 61 years female presenting in emergency with pain in epigastrium, multiple episodes of vomiting, raised total leucocyte counts. CECT abdomen showed a large non-enhancing jejunal lesion. The patient had emergency small bowel resection and anastomosis. Postoperative patient started on imatinib and kept on short-term fasting. This case report highlights the rare presentation of jejunal GISTs, successful surgical outcome and good enhancing effect of short-term fasting on chemotherapy.

Hepatic PPARα Is Destabilized by SIRT1 Deacetylase in Undernourished Male Mice.

The nutrient sensing nuclear receptor peroxisome proliferator-activated receptor-α (PPARα) regulates the host response to short-term fasting by inducing hepatic transcriptional programming of ketogenesis, fatty acid oxidation and transport, and autophagy. This adaptation is ineffective in chronically undernourished individuals, among whom dyslipidemia and hepatic steatosis are common. We recently reported that hepatic PPARα protein is profoundly depleted in male mice undernourished by a low-protein, low-fat diet. Here, we identify PPARα as a deacetylation target of the NAD-dependent deacetylase sirtuin-1 (SIRT1) and link this to the decrease in PPARα protein levels in undernourished liver. Livers from undernourished male mice expressed high levels of SIRT1, with decreased PPARα acetylation and strongly decreased hepatic PPARα protein. In cultured hepatocytes, PPARα protein levels were decreased by transiently transfecting constitutively active SIRT1 or by treating cells with the potent SIRT1 activator resveratrol, while silencing SIRT1 increased PPARα protein levels. SIRT1 expression is correlated with increased PPARα ubiquitination, suggesting that protein loss is due to proteasomal degradation. In accord with these findings, the dramatic loss of hepatic PPARα in undernourished male mice was completely restored by treating mice with the proteasome inhibitor bortezomib. Similarly, treating undernourished mice with the SIRT1 inhibitor selisistat/EX-527 completely restored hepatic PPARα protein. These data suggest that induction of SIRT1 in undernutrition results in hepatic PPARα deacetylation, ubiquitination, and degradation, highlighting a new mechanism that mediates the liver's failed adaptive metabolic responses in chronic undernutrition.

Short-Term Fasting Synergizes with Solid Cancer Therapy by Boosting Antitumor Immunity.

Simple SummaryStimulating our body’s own immune response to fight cancer is important for the success of cancer treatment in general. To further improve current cancer therapy, preclinical research shows that short-term fasting diets enhance cancer therapy efficacy, such as chemotherapy. Short-term fasting diets are low-caloric and low in protein for 3–5 days; they are usually done every couple of weeks. This review summarizes preclinical and clinical evidence of fasting diets synergizing with cancer therapy by boosting antitumor immunity.Short-term fasting (STF), using a low caloric, low protein fasting mimicking diet (FMD), appears to be a promising strategy to enhance chemotherapy-based cancer efficacy, while potentially alleviating toxicity. Preclinical results suggest that enhanced tumor immunity and decreased growth signaling, via lowering of circulating insulin and insulin growth factor 1 (IGF-1) levels form the potential underlying mechanisms. STF may boost anti-tumor responses by promoting tumor immunogenicity and decreasing local immunosuppression. These findings warrant further studies focused on the combination of STF, not only with chemotherapy, but also with immunotherapy to evaluate the full range of benefits of STF in cancer treatment. Here, we delineate the underlying anticancer mechanisms of fasting. We summarize preclinical evidence of STF boosting antitumor immunity and alleviating immunosuppression, as well as the clinical findings reporting the immunomodulatory effects of STF during various cancer treatments, including immunotherapy.