The effect of intermittent fasting on microbiota as a therapeutic approach in obesity.

Obesity, a public health challenge, arises from a complex interplay of factors such as dietary habits and genetic predisposition. Alterations in gut microbiota, characterized by an imbalance between Firmicutes and Bacteroidetes, further exacerbate metabolic dysregulation, promoting inflammation and metabolic disturbances. Intermittent fasting (IF) emerges as a promising dietary strategy showing efficacy in weight management and favoring fat utilization. Studies have used mice as animal models to demonstrate the impact of IF on gut microbiota composition, highlighting enhanced metabolism and reduced inflammation. In humans, preliminary evidence suggests that IF promotes a healthy microbiota profile, with increased richness and abundance of beneficial bacterial strains like Lactobacillus and Akkermansia. However, further clinical trials are necessary to validate these findings and elucidate the long-term effects of IF on microbiota and obesity. Future research should focus on specific tissues and cells, the use of advanced -omics techniques, and exploring the interaction of IF with other dietary patterns, to analyze microbiota composition, gene expression, and potential synergistic effects for enhanced metabolic health. While preliminary evidence supports the potential benefits of IF in obesity management and microbiota regulation, further research with diverse populations and robust methodologies is necessary to understand its implications and optimize personalized dietary interventions. This review explores the potential impact of IF on gut microbiota and its intricate relationship with obesity. Specifically, we will focus on elucidating the underlying mechanisms through which IF affects microbiota composition, as well as its subsequent effects on obesity.

Quality of Life and Its Association With Time in Range Among People With Type 2 Diabetes Mellitus Following Different Dietary Interventions: A Crossover Clinical Trial.

Background Quality of Life (QoL) is an essential consideration in healthcare. Numerous studies have examined QoL in India; however, data on QoL following different dietary interventions are lacking. Similarly, the use of technology such as continuous glucose monitoring (CGM) for diabetes care has independently demonstrated improvements in glycemic control; however, its association with QoL remains limited. Purpose The purpose was to study the role of different dietary interventions on QoL and its association with Time in Range (TIR), Time Above Range (TAR), and Time Below Range (TBR) among the Type 2 Diabetes Mellitus (T2DM) population. Methodology A crossover interventional clinical trial (CTRI/2022/07/044356) was conducted among participants with T2DM of less than 5 years' duration, aged between 25 and 55 years, with an HbA1c level of less than 8%, and who were on Metformin only. Their QoL was assessed after following two diet patterns: the Continuous Calorie Restricted Diet (CCRD) - calorie reduction with small frequent meals, and Time Restricted Intermittent Fasting (TRIF) - calorie reduction with only two meals a day, using the Modified QoL (MDQOL-17) questionnaire. The association between post-dietary interventions QoL and TIR was studied using a 14-day CGM device. Results The overall QoL of 51 participants at the end of the dietary interventions was significantly better compared to their QoL before any dietary intervention (85.6±19.0% and 63.1±13.0%, respectively, p = 0.000). Decreased TIR correlated with increased role limitations due to physical functioning (p = 0.002) and decreased energy levels (p = 0.00). As TBR increased, role limitation due to emotional well-being increased, and energy levels decreased significantly (p = 0.01). As TAR increased, energy levels decreased (p = 0.01). A simple linear regression model was statistically significant for role limitations due to physical functioning (p = 0.003) and energy fatigue (p = 0.000), suggesting that higher TIR is associated with higher scores in these domains. Conclusion Dietary interventions that improve the TIR and reduce the TAR and TBR can enhance the QoL of individuals with T2DM.

Label-free Raman spectroscopy reveals tumor microenvironmental changes induced by intermittent fasting for the prevention of breast cancer in animal model.

The development of tools that can provide a holistic picture of the evolution of the tumor microenvironment in response to intermittent fasting on the prevention of breast cancer is highly desirable. Here, we show, for the first time, the use of label-free Raman spectroscopy to reveal biomolecular alterations induced by intermittent fasting in the tumor microenvironment of breast cancer using a dimethyl-benzanthracene induced rat model. To quantify biomolecular alterations in the tumor microenvironment, chemometric analysis of Raman spectra obtained from untreated and treated tumors was performed using multivariate curve resolution-alternative least squares and support vector machines. Raman measurements revealed remarkable and robust differences in lipid, protein, and glycogen content prior to morphological manifestations in a dynamically changing tumor microenvironment, consistent with the proteomic changes observed by quantitative mass spectrometry. Taken together with its non-invasive nature, this research provides prospective evidence for the clinical translation of Raman spectroscopy to identify biomolecular variations in the microenvironment induced by intermittent fasting for the prevention of breast cancer, providing new perspectives on the specific molecular effects in the tumorigenesis of breast cancer.

A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1.

The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake. Furthermore, the IF 5:2 regimen blunted NASH-HCC transition when applied therapeutically. The timing, length, and number of fasting cycles as well as the type of NASH diet were critical parameters determining the benefits of fasting. Combined proteome, transcriptome, and metabolome analyses identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. In line with this, PPARα targets and PCK1 were reduced in human NASH. Notably, only fasting initiated during the active phase of mice robustly induced glucocorticoid signaling and free-fatty-acid-induced PPARα signaling. However, hepatocyte-specific glucocorticoid receptor deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivo abolished the beneficial outcomes of fasting against inflammation and fibrosis. Moreover, overexpression of Pck1 alone or together with Ppara in vivo lowered hepatic triglycerides and steatosis. Our data support the notion that the IF 5:2 regimen is a promising intervention against NASH and subsequent liver cancer.

Intermittent fasting influences immunity and metabolism.

Intermittent fasting (IF) modifies cell- and tissue-specific immunometabolic responses that dictate metabolic flexibility and inflammation during obesity and type 2 diabetes (T2D). Fasting forces periods of metabolic flexibility and necessitates increased use of different substrates. IF can lower metabolic inflammation and improve glucose metabolism without lowering obesity and can influence time-dependent, compartmentalized changes in immunity. Liver, adipose tissue, skeletal muscle, and immune cells communicate to relay metabolic and immune signals during fasting. Here we review the connections between metabolic and immune cells to explain the divergent effects of IF compared with classic caloric restriction (CR) strategies. We also explore how the immunometabolism of metabolic diseases dictates certain IF outcomes, where the gut microbiota triggers changes in immunity and metabolism during fasting.

Intermittent Fasting After ST-Segment-Elevation Myocardial Infarction Improves Left Ventricular Function: The Randomized Controlled INTERFAST-MI Trial.

BACKGROUND: Intermittent fasting has shown positive effects on numerous cardiovascular risk factors. The INTERFAST-MI trial (Intermittent Fasting in Myocardial Infarction) has been designed to study the effects of intermittent fasting on cardiac function after STEM (ST-segment-elevation myocardial infarction) and the feasibility of future multicenter trials. METHODS: The INTERFAST-MI study was a prospective, randomized, controlled, nonblinded, single-center investigator-initiated trial. From October 1, 2020, to July 15, 2022, 48 patients were randomized to the study groups intermittent fasting or regular diet and followed for 6 months with follow-up visits at 4 weeks and 3 months. RESULTS: In all, 22 of 24 patients in the intermittent fasting group with a mean age of 58.54±12.29 years and 20 of 24 patients in the regular diet group with a mean age of 59.60±13.11 years were included in the intention-to-treat population. The primary efficacy end point (improvement in left ventricular ejection fraction after 4 weeks) was significantly greater in the intermittent fasting group compared with the control group (mean±SD, 6.636±7.122%. versus 1.450±4.828%; P=0.038). This effect was still significant and even more pronounced after 3 and 6 months. The patients in the intermittent fasting group showed a greater reduction in diastolic blood pressure and body weight compared with the control group. The mean adherence of patients in the intermittent fasting group was a median of 83.7% (interquartile range, 69.0%-98.4%) of all days. None of the patients from either group reported dizziness, syncope, or collapse. CONCLUSIONS: Our results suggest that intermittent fasting after myocardial infarction may be safe and could improve left ventricular function after STEMI. REGISTRATION: URL: https://www.drks.de; Unique identifier: DRKS00021784.

The effect of last meal "Suhoor" timing on diurnal variations in cognitive performance during Ramadan fasting among female athletes.

The present study aimed to investigate the effect of the timing of the last meal, "Suhoor", on diurnal variation in cognitive performance during Ramadan intermittent fasting (RIF). In a randomized order, 26 adolescent female athletes (aged 15.9 ± 0.9 y) were tested in three sessions at 7:00 a.m., 12:00 p.m., and 5:00 p.m. across four different conditions: the 10 days preceding Ramadan (PR); the final 12 days of Ramadan (RO): two different conditions: Early Suhoor (SEarly), and Late Suhoor (SLate); and, ultimately, the 10 days immediately after Ramadan (AR) with an in-between recovery period of ≥24 h. During each test session, the oral temperature (OT), simple reaction time test (SRT), choice reaction time test (CRT), attention test (ATT), and mental rotation test (MRT) were evaluated. The Pittsburgh Sleep Quality Index (PSQI) and daily diary intake were assessed across the three periods. Compared to PR, the sleep parameters assessed by the PSQI were significantly lower during the RO and AR periods. However, neither total dietary intake nor OT showed any changes due to RIF. Compared to PR, the afternoon performances of SRT, CRT, ATT, and MRT significantly declined under both the SEarly and SLate conditions. Notably, midday performance decreased only during SLate, while morning performance remained unaffected in both conditions. Additionally, compared to SEarly, these performances were better during SLate in the afternoon and at midday. In summary, nutrient intake timing had a significant effect on the diurnal fluctuations in cognitive functions during Ramadan fasting, particularly around noon and in the afternoon. Our results illustrate the benefits of a late last meal (Suhoor) in preserving optimal morning cognitive abilities and preventing any impairment during the fasted state at midday or in the afternoon, which could affect overall athletic performance.

Twice-Weekly 36-Hour Intermittent Fasting Practice Attenuates Hunger, Quadruples ß-Hydroxybutyrate, and Maintains Weight Loss: A Case Report.

Intermittent fasting (IF) approach to weight loss obviates the inconvenience of calorie counting required in daily caloric restriction (DCR). A metabolic defense mechanism (MDM) obstructs weight loss and facilitates weight regain possibly by increasing hunger and efficiency of exercise energy expenditure (EEf), and by reducing resting metabolic rate (RMR) and energy expenditure (EE) including physical activity (PA). IF may test whether its paradigm can better counteract MDM than DCR. A knowledge gap exists about whether the duration of weekly uninterrupted fasts (UFs), when the IF protocols are isocaloric, affects the MDM. The aim and objective of this 82-week study were to determine whether 36 hours of near-absolute twice-weekly UF will exacerbate MDM but generate similar rates of weight and fat losses compared to four IF studies featuring 20 hours of weekly UF with both IF protocols matched for weekly hours of fast (108) and free access to food (60), a fasting-to-eating (F/E) ratio of 1.8. This case report presents results of twice-weekly fasting on non-consecutive days (5:2-NC) and compares them to results from a 4:3-NC protocol with a 20-hour UF caused by a modification of providing a 500-600 kcal meal on three fasting days (M4:3-NC). Because the large meal raises insulin concentration for four hours at the start of the fasting day, the 20-hour UF consists of the remaining eight hours on the fasting day, followed by 12 additional nocturnal hours of fasting. The hypotheses were that (1) because of their matched F/E ratio, the rates of weight and fat losses will be similar in both protocols, and (2) because of its longer UF period, hunger will be higher and RMR and EE will be lower, in 5:2-NC than in M4:3-NC protocol. The main findings were that the 5:2-NC protocol produced (1) slower rates of weight and fat losses, (2) modest reduction in the sensation of hunger and substantial decline in fullness, (3) no change in RMR and EE, and (4) fourfold post-fast increase in the circulating concentration of the ketone body ß-hydroxybutyrate (BHB), 2.5 greater than in the M4:3-NC protocol. The absence of increased hunger and changes in EE, the variability of the rate of weight loss in the 5:2-NC protocol, plus increased EEf in one M4:3-NC study, suggest that IF does not mitigate MDM, but that shortened UF period in M4:3-NC reduces the rise in BHB. Thus, the addition of a large meal on fasting days is unnecessary for the prevention of hunger and is counterproductive for increases in BHB and its potential health benefits. Continuous practice of the 5:2-NC protocol allows sustained weight loss and maintenance of lost weight with diminished hunger for as long as it is implemented.

Intermittent Metabolic Switching and Vascular Cognitive Impairment.

Intermittent fasting (IF), a dietary pattern alternating between eating and fasting periods within a 24-hour cycle, has garnered recognition for its potential to enhance both healthspan and lifespan in animal models and humans. It also shows promise in alleviating age-related diseases, including neurodegeneration. Vascular cognitive impairment (VCI) spans a severity range from mild cognitive deficits to severe cognitive deficits and loss of function in vascular dementia. Chronic cerebral hypoperfusion has emerged as a significant contributor to VCI, instigating vascular pathologies such as microbleeds, blood-brain barrier dysfunction, neuronal loss and white matter lesions. Preclinical studies in rodents strongly suggest that IF has the potential to attenuate pathological mechanisms, including excitotoxicity, oxidative stress, inflammation, and cell death pathways in VCI models. Hence, this supports evaluating IF in clinical trials for both existing and at-risk VCI patients. This review compiles existing data supporting IF's potential in treating VCI-related vascular and neuronal pathologies, emphasizing the mechanisms by which IF may mitigate these issues. Hence providing a comprehensive overview of the available data supporting IF's potential in treating VCI by emphasizing the underlying mechanisms that make IF a promising intervention for VCI.

Treatment of mice with maternal intermittent fasting to improve the fertilization rate and reproduction.

Maternal intermittent fasting (MIF) can have significant effects on several tissue and organ systems of the body, but there is a lack of research on the effects on the reproductive system. So, the aim of our study was to analyze the effects of MIF on fertility. B6C3F1Crl (C57BL/6N × C3H/HeN) male and female mice were selected for the first part of the experiments and were analyzed for body weight and fat weight after administration of the MIF intervention, followed by analysis of sperm counts and activation and embryo numbers. Subsequently, two strains of mice, C57BL/6NCrl and BALB/cJRj, were selected and administered MIF to observe the presence or absence of vaginal plugs for the purposes of mating success, sperm and oocyte quality, pregnancy outcome, fertility status and in vitro fertilization (IVF). Our results showed a significant reduction in body weight and fat content in mice receiving MIF intervention in B6C3F1Crl mice. Comparing the reproduction of the two strains of mice. However, the number of litters was increased in all MIF interventions in C57BL/6NCrl, but not statistically significant. In BALB/cJRj, there was a significant increase in the number of pregnant females as well as litter size in the MIF treatment group, as well as vaginal plugs, and IVF. There was also an increase in sperm activation and embryo number and the MIF intervention significantly increased sperm count and activation. Our results suggest that MIF interventions may be beneficial for reproduction in mice.

The Effect of a Combined Intermittent Fasting Healthy Plate Intervention on Anthropometric Outcomes and Body Composition Among Adults With Overweight and Obesity: Nonrandomized Controlled Trial.

BACKGROUND: Adult obesity and overweight pose a substantial risk to global public health and are associated with various noncommunicable diseases. Although intermittent fasting (IF) is increasingly used as a relatively new dietary strategy for weight loss, the effectiveness of 2 days per week of dry fasting remains unknown. OBJECTIVE: This study aims to evaluate the effectiveness of a combined dry IF and healthy plate (IFHP) and healthy plate (HP) intervention in improving anthropometric outcomes and body composition. METHODS: This nonrandomized controlled trial involved 177 adults who were overweight and obese. Among them, 91 (51.4%) were allocated to the IFHP group and 86 (48.6%) were allocated to the HP group. The overall study duration was 6 months (October 2020 to March 2021). The intervention was divided into 2 phases: supervised (3 months) and unsupervised (3 months). The data were collected at baseline, after the supervised phase (month 3), and after the unsupervised phase (month 6). Anthropometric (weight, height, waist circumference, and hip circumference) and body composition (body fat percentage, body fat mass, skeletal muscle mass, and visceral fat area) data were measured at all 3 data collection points. Sociodemographic data were obtained using a questionnaire at baseline. RESULTS: Most participants were female (147/177, 83.1%) and Malay (141/177, 79.7%). After 3 months, there were significant reductions in weight (difference -1.68; P<.001), BMI (difference -0.62; P<.001), body fat percentage (difference -0.921; P<.001), body fat mass (difference -1.28; P<.001), and visceral fat area (difference -4.227; P=.008) in the IFHP group, whereas no significant changes were observed in the HP group. Compared to baseline, participants in the IFHP group showed a significant decrease in weight (difference -1.428; P=.003), BMI (difference -0.522; P=.005), body fat percentage (difference -1.591; P<.001), body fat mass (difference -1.501; P<.001), visceral fat area (difference -7.130; P<.001), waist circumference (difference -2.304; P=.001), and hip circumference (difference -1.908; P=.002) at month 6. During the unsupervised phase, waist (IFHP difference -3.206; P<.001, HP difference -2.675; P=.004) and hip (IFHP difference -2.443; P<.001; HP difference -2.896; P<.001) circumferences were significantly reduced in both groups (P<.01), whereas skeletal muscle mass (difference 0.208; P=.04) and visceral fat area (difference -2.903; P=.003) were significantly improved in the IFHP group only. No significant difference in the between-group comparison was detected throughout the intervention (all P>.05). CONCLUSIONS: A combined IFHP intervention was effective in improving anthropometric outcomes and body composition in adults with overweight and obesity. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/33801.

Dietas populares y su impacto en la piel. Una revisión narrativa / Popular Diets and Skin Effects: A Narrative Review

Se han popularizado diversas dietas para perder peso, incrementar la capacidad física y para el manejo de múltiples enfermedades crónicas: cardiovasculares, neurológicas o cutáneas. Destacan la dieta cetogénica y el ayuno intermitente, con resultados prometedores en la medicina tradicional y deportiva. Además, la dieta mediterránea se ha consolidado como una forma de alimentación de impacto positivo muy significativo en la salud. Otras dietas populares son la dieta «paleo», la dieta vegana y la libre de gluten. La dieta cetogénica, el ayuno intermitente y la dieta mediterránea aportan resultados favorables en dermatosis inflamatorias como la psoriasis, dermatitis atópica, hidradenitis supurativa o acné. La dieta mediterránea podría actuar también como factor protector para el desarrollo de algunas neoplasias cutáneas. En este artículo presentamos una revisión del papel de diversas dietas populares en el manejo de dermatosis. (AU)

Numerous diets for losing weight, building strength, and managing a range of cardiovascular, neurologic, and skin diseases have become popular in recent years. The ketogenic diet and intermittent fasting in particular have shown promising results in clinical and sports medicine. The Mediterranean diet, in turn, is widely recognized for its numerous health benefits. Also popular are the paleo diet and vegan and gluten-free diets. Positive effects on inflammatory conditions, such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne, have been observed in patients who practice intermittent fasting or follow ketogenic or Mediterranean diets. This last choice may also protect against certain skin cancers. We review the role of several popular diets in the management of skin disorders. (AU)

[Translated article] Popular Diets and Skin Effects: A Narrative Review / Dietas populares y su impacto en la piel. Una revisión narrativa

Numerous diets for losing weight, building strength, and managing a range of cardiovascular, neurologic, and skin diseases have become popular in recent years. The ketogenic diet and intermittent fasting in particular have shown promising results in clinical and sports medicine. The Mediterranean diet, in turn, is widely recognized for its numerous health benefits. Also popular are the paleo diet and vegan and gluten-free diets. Positive effects on inflammatory conditions, such as psoriasis, atopic dermatitis, hidradenitis suppurativa, and acne, have been observed in patients who practice intermittent fasting or follow ketogenic or Mediterranean diets. This last choice may also protect against certain skin cancers. We review the role of several popular diets in the management of skin disorders. (AU)

Se han popularizado diversas dietas para perder peso, incrementar la capacidad física y para el manejo de múltiples enfermedades crónicas: cardiovasculares, neurológicas o cutáneas. Destacan la dieta cetogénica y el ayuno intermitente, con resultados prometedores en la medicina tradicional y deportiva. Además, la dieta mediterránea se ha consolidado como una forma de alimentación de impacto positivo muy significativo en la salud. Otras dietas populares son la dieta «paleo», la dieta vegana y la libre de gluten. La dieta cetogénica, el ayuno intermitente y la dieta mediterránea aportan resultados favorables en dermatosis inflamatorias como la psoriasis, dermatitis atópica, hidradenitis supurativa o acné. La dieta mediterránea podría actuar también como factor protector para el desarrollo de algunas neoplasias cutáneas. En este artículo presentamos una revisión del papel de diversas dietas populares en el manejo de dermatosis. (AU)

Sex-Dependent Metabolic Effects in Diet-Induced Obese Rats following Intermittent Fasting Compared with Continuous Food Restriction.

Recently, intermittent fasting has gained relevance as a strategy to lose weight and improve health as an alternative to continuous caloric restriction. However, the metabolic impact and the sex-related differences are not fully understood. The study aimed to compare the response to a continuous or intermittent caloric restriction in male and female rats following a previous induction of obesity through a cafeteria diet by assessing changes in body weight, energy intake, metabolic parameters, and gene expression in liver hepatic and adipose tissue. The continuous restriction reduced the energy available by 30% and the intermittent restriction consisted of a 75% energy reduction on two non-consecutive days per week. The interventions reduced body weight and body fat in both sexes, but the loss of WAT in females was more marked in both models of caloric restriction, continuous and intermittent. Both caloric restrictions improved insulin sensitivity, but more markedly in females, which showed a more pronounced decrease in HOMA-IR score and an upregulation of hepatic IRS2 and Sirt1 gene expression that was not observed in males. These findings suggest the fact that females are more sensitive than males to reduced caloric content in the diet.

Effects of intermittent fasting on periodontal inflammation and subgingival microbiota.

BACKGROUND: Studies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long-term intermittent fasting on periodontal health and the subgingival microbiota. METHODS: This pilot study was part of a nonrandomized controlled trial. Overweight/obese participants (n = 14) entered an intermittent fasting program, specifically the 5:2 diet, in which they restricted caloric intake to about a quarter of the normal total daily caloric expenditure for two nonconsecutive days/week. Subjects underwent a thorough clinical and laboratory examination, including an assessment of their periodontal condition, at baseline and 6 months after starting the diet. Additionally, subgingival microbiota was assessed by 16S rRNA gene sequencing. RESULTS: After 6 months of intermittent fasting, weight, body mass index, C-reactive protein, hemoglobin A1c (HbA1c), and the cholesterol profile improved significantly (p < 0.05). Moreover, significant reductions were observed in bleeding on probing (p = 0.01) and the presence of shallow periodontal pockets after fasting (p < 0.001), while no significant change was seen in plaque index (p = 0.14). While we did not observe significant changes in α- or ß-diversity of the subgingival microbiota related to dietary intervention (p > 0.05), significant differences were seen in the abundances of several taxa among individuals exhibiting ≥60% reduction (good responders) in probing pocket depth of 4-5 mm compared to those with <60% reduction (bad responders). CONCLUSION: Intermittent fasting decreased systemic and periodontal inflammation. Although the subgingival microbiota was unaltered by this intervention, apparent taxonomic variability was observed between good and bad responders.

Would Combination Be Better: Swimming Exercise and Intermittent Fasting Improve High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Obese Rats via the miR-122-5p/SREBP-1c/CPT1A Pathway.

Background: Swimming and intermittent fasting can both improve obesity-induced NAFLD, but which of the two is more effective and whether the combination of the two has a superimposed effect is inconclusive. Methods: The model of NAFLD in obese rats was established by a high-fat diet and performed swimming, intermittent fasting, and a combination of both interventions for 8 weeks. Serum lipids and enzyme activity were measured by an automatic biochemical analyzer. Liver morphostructural analysis was observed by transmission electron microscopy, and morphology was observed by HE staining. RT‒PCR was used to detect the mRNA level. Results: Morphology and microstructure of the liver of model rats were impaired, with the upregulation of miR-122-5p, SREBP-1c, FASN and ACC1. Eight weeks of swimming exercise, intermittent fasting and the combination of both attenuate these effects, manifested by the downregulation of miR-122-5p and upregulation of CPT1A mRNA levels. There was no significant stacking effect of the combination of the swimming and intermittent fasting interventions. Conclusion: NAFLD leads to pathology in model rats. Eight weeks of swimming exercise, intermittent fasting and the combination of both can inhibit miR-122-5p and improve hepatic lipid metabolism, while no significant additive effects of combining the interventions were found.

Aging as a target for the prevention and treatment of Alzheimer's disease.

Alzheimer's disease (AD), the most common etiology of dementia in older adults, is projected to double in prevalence over the next few decades. Current treatments for AD manage symptoms or slow progressive decline, but are accompanied by significant inconvenience, risk, and cost. Thus, a better understanding of the risk factors and pathophysiology of AD is needed to develop novel prevention and treatment strategies. Aging is the most important risk factor for AD. Elucidating molecular mechanisms of aging may suggest novel therapeutic targets. While aging is inevitable, it may be accelerated by caloric excess and slowed by caloric restriction (CR) or intermittent fasting. As such, CR may slow aging and reduce the risk of all diseases of aging, including dementia due to AD. The literature on CR, intermittent fasting, and treatment with polyphenols such as resveratrol-a pharmacologic CR-mimetic-supports this hypothesis based on clinical outcomes as well as biomarkers of aging and AD. More studies exploring the role of CR in regulating aging and AD progression in man are needed to fill gaps in our understanding and develop safer and more effective strategies for the prevention and treatment of AD.

It's About Timing: Contrasting the Metabolic Effects of Early vs. Late Time-Restricted Eating in Humans.

PURPOSE OF REVIEW: Time-restricted eating (TRE), a form of intermittent fasting, restricts feeding time across the day, imposing a daily 'eating window'. The time of day when the eating window occurs could result in differential metabolic effects. Here, we describe recent intervention studies in humans assessing the metabolic consequences of an early- (i.e., eating window starting in the early morning) vs. late (i.e., eating window starting after midday)-TRE protocol. RECENT FINDINGS: Well-controlled studies indicate that both TRE protocols effectively reduce body weight and improve altered glucose metabolism, lipid profile, inflammation, or blood pressure levels. An early-TRE (e-TRE) might have a further positive impact on improving blood glucose, insulin levels, and insulin resistance. However, the studies directly assessing the metabolic consequences of an early- vs. late-TRE have shown dissimilar findings, and more well-controlled clinical trials are needed on the metabolic benefits of these two types of TRE. Evidence suggests that an e-TRE might have enhanced metabolic results, particularly regarding glucose homeostasis. More long-term studies, including larger sample sizes, are needed to assess the metabolic, circadian, and adherence benefits, together with socio-cultural acceptance of both TRE approaches.

Therapeutic effects of intermittent fasting on high-fat, high-fructose diet; involvement of jejunal aquaporin 1, 3, and 7.

Background: Aquaporins (AQPs) are transmembrane channel proteins. Aquaporin 1 (AQP1), Aquaporin 3 (AQP3), and Aquaporin 7 (AQP7) are expressed in the jejunum. The purpose of this study was to ascertain how a high-fat high-fructose diet (HFFD) and intermittent fasting (IF) affect AQP1, AQP3, and AQP7 expression in the rat jejunum. Methods: Sixteen adult male rats were divided into control rats (n = 4) fed on a basal diet and water ad libitum for 12 weeks; IF control rats (n = 4) followed the IF protocol, HFFD-fed rats (n = 8) fed HFFD for eight weeks, and rats were randomized into two groups: HFFD only or HFFD and IF protocol from the beginning of the 9th week until the end of the experiment. The lipid profile values were assessed after 12 weeks. Jejunal oxidative markers (malondialdehyde and reduced glutathione) and AQP1, AQP3, and AQP7 mRNA expression were measured. Jejunal sections were used for morphometric analysis of villus length and crypt depth. Immunohistochemical evaluation of AQP1, AQP3, and AQP7 expression was also performed. Results: IF ameliorates HFFD-induced lipid profile, oxidative stress, and jejunal morphometric changes. The results of both mRNA expression using PCR and immunohistochemistry showed a significant increase in AQP1, AQP3, and AQP7 expression in HFFD, whereas IF caused a decline in this expression. Conclusion: These findings suggest that IF can reduce inflammation, and oxidative stress and restore jejunal morphology caused by HFFD.

Dietary fasting and time-restricted eating in Huntington's disease: therapeutic potential and underlying mechanisms.

Huntington's disease (HD) is a devastating neurodegenerative disorder caused by aggregation of the mutant huntingtin (mHTT) protein, resulting from a CAG repeat expansion in the huntingtin gene HTT. HD is characterized by a variety of debilitating symptoms including involuntary movements, cognitive impairment, and psychiatric disturbances. Despite considerable efforts, effective disease-modifying treatments for HD remain elusive, necessitating exploration of novel therapeutic approaches, including lifestyle modifications that could delay symptom onset and disease progression. Recent studies suggest that time-restricted eating (TRE), a form of intermittent fasting involving daily caloric intake within a limited time window, may hold promise in the treatment of neurodegenerative diseases, including HD. TRE has been shown to improve mitochondrial function, upregulate autophagy, reduce oxidative stress, regulate the sleep-wake cycle, and enhance cognitive function. In this review, we explore the potential therapeutic role of TRE in HD, focusing on its underlying physiological mechanisms. We discuss how TRE might enhance the clearance of mHTT, recover striatal brain-derived neurotrophic factor levels, improve mitochondrial function and stress-response pathways, and synchronize circadian rhythm activity. Understanding these mechanisms is critical for the development of targeted lifestyle interventions to mitigate HD pathology and improve patient outcomes. While the potential benefits of TRE in HD animal models are encouraging, future comprehensive clinical trials will be necessary to evaluate its safety, feasibility, and efficacy in persons with HD.