The association between lifestyle and metabolic dysfunction-associated steatotic liver disease (MASLD) has been well documented. However, evidence is still limited from vulnerable populations, especially middle-aged and elderly adults with comorbid hypertension and diabetes, who are at higher risk of developing MASLD than the general population. We aimed to examine the potential causal links of a healthy lifestyle with the risk of MASLD in this vulnerable population.

A total of 41,964 middle-aged and elderly participants with comorbid hypertension and diabetes were included in a longitudinal cohort from 2010 to 2023. Weighted scores for lifestyle were evaluated by exercise frequency, alcohol consumption, smoking status and salt intake. Marginal structural models were used to estimate the single lifestyle-MASLD associations, which were further risk stratified by quartile ranges of weighted scores.

A mean follow-up period of 5.2 years (217 972 person-years) revealed that 21 697 participants developed MASLD. The hazard ratio (HR) of daily exercise, never consuming alcohol, never smoking and low salt intake for the risk of MASLD was 0.617 (95% confidence interval: 0.365 ~ 1.042), 0.237 (0.093 ~ 0.603), 0.153 (0.097 ~ 0.240) and 0.945 (0.919 ~ 0.971), respectively. Compared with weighted scores that were below the 25th percentile, the HR was 0.952 (0.902 ~ 1.005), 0.747 (0.694 ~ 0.803) and 0.097 (0.065 ~ 0.144) for the 25th, 50th and 75th percentiles, respectively.

In this vulnerable population, daily exercise, abstinence from alcohol and smoking and a low-salt diet may reduce the risk of MASLD, and the most stringent combination of healthy lifestyles could reduce the risk of MASLD by over 90%.

Metabolic-dysfunction-associated steatotic liver disease (MASLD) has emerged as a significant public health concern, attributed to its increasing prevalence and correlation with metabolic disorders, including obesity and type 2 diabetes. Recent research has highlighted that mitochondrial dysfunction can result in the accumulation of lipids in non-adipose tissues, as well as increased oxidative stress and inflammation. These factors are crucial in advancing the progression of MASLD. Despite advances in the understanding of MASLD pathophysiology, challenges remain in identifying effective therapeutic strategies targeting mitochondrial dysfunction. This review aims to consolidate current knowledge on how mitochondrial imbalance affects the development and progression of MASLD, while addressing existing research gaps and potential avenues for future research. This review was conducted after a systematic search of comprehensive academic databases such as PubMed, Embase, and Web of Science to gather information on mitochondrial dysfunction as well as mitochondrial-based treatments for MASLD.

Background: Non-alcoholic steatohepatitis (NASH) is characterized by increased production of proinflammatory cytokines, fibrosis, and hepatocyte apoptosis. This study aimed to assess the efficacy of N-acetyl cysteine (NAC), rosuvastatin (RSV), and vitamin E (VE) in patients with NASH. Methods: A double-blinded, parallel, randomized, controlled study was conducted and registered on clinicaltrials.gov (Identifier: NCT06105060), involving 135 NASH participants, who were divided into three groups: the control group (group 1), consisting of patients receiving standard therapy VE at a dosage of 400 IU twice daily. In the treated group (group 2), patients were administered NAC at a dosage of 1200 mg twice daily, while treatment (group 3) received RSV at a dosage of 20 mg once daily. FibroScan® examination of liver tissue and fibrosis scores, along with tests for liver aminotransferases, lipid profile, glycemic parameters, and renal and hepatic functions, were assessed before and after six months of treatment. Results: The analyzed groups demonstrated a significant reduction in steatosis and lipid peroxidation (p < 0.05). The NAC group demonstrated greater anti-inflammatory and anti-apoptotic effects compared to the RSV group, although this difference was not significant in the control group. NAC is conceded as the only significant antifibrotic agent in liver stiffness measurement (LSM), biological marker findings, and non-invasive liver fibrosis scores (p < 0.05), in addition to its improvement of several metabolic parameters and health-related quality of life. Conclusions: Patients receiving NAC demonstrated safety and efficacy in enhancing steatosis, fibrosis, and metabolic parameters, representing a novel strategy in the management of NASH.

To explore the knowledge-action gap regarding health behaviors and their influencing factors among patients with metabolic dysfunction-associated fatty liver disease (MAFLD), using the Health Belief Model as a theoretical framework.

A qualitative approach was adopted, involving semistructured interviews with individuals with MAFLD.

Participants were recruited from a community hospital and a tertiary hospital in Nanjing, China, between July and October 2022.

A purposive sample of 21 adults with MAFLD, who were primarily overweight or obese (86%), males (52%), and aged ≥ 60 years (52%).

This study focused on the knowledge-action gap in health behaviors among MAFLD patients.

Data were analyzed using content analysis, with the Health Belief Model guiding the identification of themes and categorization of specific domains.

This study found that perceptions of disease susceptibility and severity, perceived barriers to healthy lifestyles, and various modifying factors impeded the adoption of healthy behaviors. In contrast, perceived benefits, cues to action, and self-efficacy facilitated the implementation of these behaviors.

This research highlights the factors contributing to the knowledge-action gap in health behaviors among MAFLD patients. The findings suggest potential targets for interventions aimed at enhancing the alignment between patients' knowledge and their actions, ultimately promoting better health outcomes.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.

With the high burden of Metabolic dysfunction-associated steatotic liver disease (MASLD), (previously known as Non-Alcoholic Fatty Liver Disease - NAFLD) in the community, current models of care that require specialist review for disease risk stratification overwhelm hospital clinic capacity and create inefficiencies in care. The LOCal Assessment and Triage Evaluation of Non-Alcoholic Fatty Liver Disease (LOCATE-NAFLD) randomised trial compared usual care to a community-based nurse delivered liver risk assessment. This study evaluates the implementation strategy of the LOCATE model.

The evaluation used mixed methods (quantitative trial data and qualitative framework analysis of semi-structured interviews) to explore the general practitioner (GP) and patient perspectives of acceptability (Acceptability Framework), and factors associated with reach, effectiveness, adoption, implementation, and maintenance (RE-AIM framework) of the LOCATE model of care.

The LOCATE model was considered highly acceptable by both patients and GPs. The model of care achieved appropriate reach across the participating health services, reaching high-risk patients faster than usual care and with predominantly positive patient experiences. A notable reduction in anxiety and stress was experienced in the intervention group due to the shorter waiting times between referral and assessment. There was an overall perception of confidence in nursing staff capability to perform the community-based screening and GPs indicated confidence in managing low-risk MASLD without the need for specialist review. Challenges to implementation, adoption and maintenance included variable prioritisation of liver disease assessment in complex cases, the need for further GP training in MASLD assessment and treatment pathways, available funding and referral pathways for community screening, and accessibility of effective diet and exercise professional support.

Nurse delivered community-based liver screening is highly acceptable to GPs and patients and has shown to be an effective mechanism to identify high risk patients. Adoption and maintenance of the model of care faces significant challenges related to affordable access to screening, prioritisation of liver disease in complex patient cohorts, and unresolved difficulties in prescribing effective strategies for sustained lifestyle intervention in the primary care setting.

The trial was registered on 30 January 2020 and can be found via Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12620000158965.

The prevalence of metabolic associated fatty liver disease (MAFLD) is high. However, there are few studies on the effects of time-restricted feeding (TRF) and caloric restriction (CR) in MAFLD.

To investigate the efficacy and mechanism of 4 h TRF and 60% CR in MAFLD.

Twelve male Sprague-Dawley rats were randomly assigned to the Normal group (normal diet, 10 kcal% fat), while the remaining 38 rats were assigned to the MAFLD group (high-fat diet, 60 kcal% fat). 10 weeks later, the MAFLD group was randomly divided into the 4 h TRF, 60% CR, 4 h TRF + 60% CR, and Model groups; all rats were then given normal diet. After 4 weeks, weight, blood lipid, and other indicators were detected.

After the high-fat diet was discontinued, the liver lipid levels in the rat with MAFLD significantly reduced, while the body weight was not significantly changed. The rats in the Model group were heavier than those in the other four groups (p < 0.01). The triglyceride levels were higher in the TRF + CR group compared with the Model group (p < 0.01). Compared with the Model group, 110 metabolites were decreased in the TRF + CR group, and 83 metabolites were elevated in liver. Kyoto Encyclopedia of Genes and Genomes revealed that the mechanism involved the proliferator-activated receptor alpha signaling pathway, metabolic pathway, and so on. We observed differences in silent information regulator transcript 1 (SIRT1) mRNA levels in all five groups (p = 0.003).

4 h TRF and 60% CR significantly reduced body weight and liver lipid in rats with MAFLD. 4 h TRF can improve MAFLD, and there is no need to excessively restrict food intake.

Disruption of hepatic lipid homeostasis leads to excessive hepatic triglyceride accumulation and the development of metabolic dysfunction-associated steatotic liver disease (MASLD). Autophagy, a critical process in liver lipid metabolism, is impaired in MASLD pathogenesis. Irisin, a skeletal muscle-driven myokine, regulates lipid metabolism, but its impact on hepatic lipid metabolism is not well understood. Here, we aimed to explore the role of irisin in hepatic steatosis and the underlying mechanisms involved.

A high-fat diet (HFD)-induced MASLD mouse model was used, and the recombinant irisin protein, herein referred to as "Irisin", was intraperitoneally administered for 4 weeks to evaluate the effects of irisin on hepatic lipid accumulation. Liver tissues were stained with Oil red O (ORO), and triglyceride (TG) and total cholesterol (TC) contents were measured in serum and liver homogenates. The expression of the autophagosome marker microtubule-associated protein 1 light chain 3 (LC3), the autophagy receptor protein sequestosome-1 (SQSTM1/p62), autophagy initiation complex unc-51-like kinase 1 (ULK1) and the lysosomal functional protein cathepsin B was measured via Western blotting, and the expression of the transcription factor EB (TFEB) was analyzed via immunofluorescence to explore autophagic changes. The effect of irisin on autophagic flux was further evaluated in palmitic acid-induced HepG2 cells by measuring autophagic degradation with chloroquine (CQ), and analyzing the colocalization of LC3 and lysosome-associated protein 1 (LAMP1). The possible mechanism was examined by measuring the expression of the autophagic sirtuin 3 (SIRT3) pathway and further validated using overexpression of SIRT3 with plasmid transfection or siRNA-mediated knockdown. Student's t-test was utilized for statistical analysis.

Irisin significantly reduces hepatic lipid accumulation in mice fed with HFD, accompanied by enhanced hepatocyte autophagy and upregulation of the SIRT3 pathway. In HepG2 cells, Irisin attenuated palmitic acid-induced lipid accumulation, which was partially dependent on SIRT3 levels. Mechanistically, Irisin treatment upregulated SIRT3 and phosphorylated AMP-activated protein kinase (AMPK), inhibited mammalian target of rapamycin (mTOR) activity, promoted TFEB nucleus translocation, increased cathepsin B expression, enhanced autophagic degradation, and alleviated hepatic steatosis. No significant changes in phosphorylation of ULK1 in the hepatocytes were observed. However, when siRNA was used to knock down SIRT3, the changes of those protein were partially reversed, and hepatic steatosis was further exacerbated.

Our findings highlight irisin as a potential therapeutic for hepatic steatosis by modulating autophagy and lipid metabolism, potentially providing a novel therapeutic target for the management of MASLD. Further research is needed to elucidate the underlying mechanisms and explore the potential clinical applications of this approach in the treatment of MASLD.

The degree of perceived enjoyment of performed physical activity may be a key aspect with relevance for the effort to get people to be physically active. Spinning, or indoor cycling, is a widespread physical activity that can be performed in a group or individually. The effect of the group element on the enjoyment of spinning remains unclear. Therefore, the purpose of the present study was to test the hypothesis that enjoyment was greater during spinning exercise performed in a group session as compared to individually.

Twenty recreationally active persons (56 ± 6 years, 1.74 ± 0.09 m, 81.0 ± 14.7 kg, and BMI of 26.5 ± 3.7) performed 44-min group and individual instructor-led spinning sessions. Values of power output, heart rate, and cadence were recorded during the sessions. Perceived enjoyment of the exercise was determined by means of a questionnaire (PACES-8) after the exercise.

Values of power output, heart rate, and cadence were not different between the two sessions. Enjoyment was statistically significantly greater by 1.4 ± 2.1 points (p = 0.005) during spinning performed in a group session as compared to individually. As a reference framework, 56 points is the maximal sum score.

The difference in enjoyment between conditions was modest and clinically insignificant. In other words, the group element of the spinning session was considered to be of minor importance for the participants' perception of enjoyment.

This article comments on the work by Soresi and Giannitrapani. The authors have stated that one of the most novel and promising treatments for metabolic dysfunction-associated steatotic liver disease (MASLD) is the use of glucagon-like peptide 1 receptor agonists, especially when used in combination therapy. However, despite their notable efficacy, these drugs were not initially designed to target MASLD directly. In a groundbreaking development, the Food and Drug Administration has recently approved resmetirom, the first treatment specifically aimed at reducing liver fibrosis in metabolic-associated steatohepatitis. Resmetirom, an orally administered, liver-directed thyroid hormone beta-selective agonist, acts directly on intrahepatic pathways, enhancing its therapeutic potential and marking the beginning of a new era in the treatment of MASLD. Furthermore, the integration of lifestyle modifications into liver disease management is an essential component that should be considered and reinforced. By incorporating dietary changes and regular physical exercise into treatment, patients may achieve improved outcomes, reducing the need for pharmacological interventions and/or improving treatment efficacy. As a complement to medical therapies, lifestyle factors should not be overlooked in the broader strategy for managing MASLD.

Non-alcoholic fatty liver disease (NAFLD) management requires sustainable lifestyle modifications. This study aimed to evaluate the effectiveness of the RESET care plan, a comprehensive program that is an integrated personalized diet, exercise, and cognitive behavior therapy, delivered via MyTatva's digital health application enabled through a body composition analyzer (BCA) and smartwatch.

To evaluates the effectiveness of the comprehensive program delivered via MyTatva's digital health app enabled through internet of thing devices.

This retrospective observational study analyzed deidentified data from 22 participants enrolled in the MyTatva RESET care program. Participants were divided into three groups: Group A, diet plan; Group B, diet + exercise plan; and Group C, diet + exercise + cognitive behavioral therapy plan. Participants were provided with a BCA and smartwatch for continuous monitoring of anthropometric parameters. Statistical analysis, including one-way ANOVA and post-hoc Tukey's Honest Significant Difference test, was conducted to compare mean changes in anthropometric parameters across the groups.

All intervention groups showed significant improvement across all anthropometric parameters. Group C showed the most significant improvements, with mean weight reduction of 7% or more (6.99 ± 2.98 kg, 7.00% ± 3.39%; P = 0.002) from baseline, a benchmark associated with improved NAFLD conditions. Post-hoc analysis revealed that Group C had significantly greater improvements than Groups A and B. Weight reduction was observed in 85.7% of Group A participants, 77.8% of Group B participants, and 100% of Group C participants.

The comprehensive RESET care plan achieved a 7% weight reduction in 12 weeks, demonstrating its effectiveness in managing NAFLD. These results support adopting digitally supported, patient-centric approaches for NAFLD treatment.

Previous research has indicated that long working hours are connected to a variety of health conditions, including nonalcoholic fatty liver disease (NAFLD). However, this association which has been observed in more population is limited. Our research is designed to evaluate the association between working hours, working type, and NAFLD.

The study comprised adults with complete details on working hours, working type, and NAFLD from the NHANES 1999-2014. We employed the hepatic steatosis index (HSI) to evaluate NAFLD and examined the relationship between working hours or working type and hepatic steatosis using weighted multiple-variable regression models and restricted cubic spline (RCS) analysis. In addition, further subgroup analysis was performed based on sex, age, ratio of family income to poverty (PIR), education, and diabetes.

Long working hours were significantly linked to an elevated risk of NAFLD (OR: 1.57, 95%CI: 1.21-2.05), even after controlling for confounding factors. RCS analysis suggested that there was no nonlinear relationship between them. When weekly working hours > 50, the likelihood of NAFLD among the population heightened to 57% and this risk increased to 99% in the female population. As for working type, increasing physical intensity of work was associated with higher NAFLD risk, but only heavy manual labor continued to show significance after adjustment (OR:1.39, 95%CI: 1.06-1.81). We observed that the relationship between heavy manual labor and NAFLD was more significant in the older and male populations.

Our results indicate that long working hours and engaging in heavy physical labor are independent risk factors for NAFLD. As working hours increase and individuals engage in heavy physical labor for extended periods, the risk of developing NAFLD significantly rises.

The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), parallels the rise in sedentary lifestyles. MASLD is the most common form of steatotic liver disease (SLD), which represents the umbrella beneath which the vast majority of chronic liver diseases fall, including alcohol-related liver disease and their overlap. These conditions are the leading contributors to chronic liver disease, significantly impacting global morbidity and mortality. Despite the emergence of new pharmacotherapies, exercise represents the foundation of MASLD treatment.

This review aims to provide an updated perspective on the role of exercise in the management of SLD, highlight its molecular and clinical benefits, and explore its benefits and safety in the stage of cirrhosis.

Evidence from pre-clinical and clinical studies was reviewed to evaluate the impact of exercise on SLD (mainly MASLD), advanced chronic liver disease stages, and its relevance in the context of evolving therapies such as Resmetirom and incretin-based anti-obesity medications.

Exercise remains a cornerstone intervention in the management of MASLD, with suggested benefits even for patients who have progressed to cirrhosis. Personalized exercise regimens should be prioritized for all patients, including those receiving pharmacotherapy. Further research is needed to refine exercise protocols and investigate their impact on histologic and clinical outcomes, as well as their potential synergistic effects with emerging treatments.

Despite the abundant body of evidence linking high-intensity interval training (HIIT) to cardiometabolic markers, little is known about how HIIT affects liver enzymes, particularly in obese adolescents. This study aimed to investigate the effects of HIIT on metabolic dysfunction-associated steatotic liver disease (MASLD)-related biomarkers in overweight/obese adolescent girls.

Thirty-three overweight/obese adolescent girls (age, 17.0 ± 1.15 yr.; body mass index, 33.3 ± 4.77 kg/m2) were randomly assigned to HIIT (n = 17) or control (n = 16) groups. The HIIT group participated in a nine-week HIIT program (three times weekly) without caloric restriction. Maximal aerobic speed, body composition indexes, blood pressure, MASLD-related biomarkers [liver enzymes (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), plasma lipids, uric acid, platelet count, and homeostasis model assessment index for insulin-resistance (HOMA-IR)] were examined at baseline and after the intervention.

Significant "time × group" interactions were found for body composition indexes, systolic blood pressure, maximal aerobic speed, liver enzymes ALT and AST, plasma lipids, glucose, and HOMA-IR. The HIIT program resulted in an increase in maximal aerobic speed (p = 0.035) and a decrease in body composition and plasma lipids (p < 0.01), systolic blood pressure (p = 0.011), ALT (p = 0.013), AST (p = 0.012), and HOMA-IR (p = 0.01), but no significant changes in uric acid and platelet count. None of these markers changed in the control group.

HIIT resulted in an improvement in MASLD-related biomarkers. HIIT could be an effective exercise therapy to prevent and reverse MASLD in adolescents with obesity.

Steatotic liver disease (SLD) and Hepatocellular Carcinoma (HCC) are characterised by a substantial rewiring of lipid fluxes caused by systemic metabolic unbalances and/or disrupted intracellular metabolic pathways. SLD is a direct consequence of the interaction between genetic predisposition and a chronic positive energy balance affecting whole-body energy homeostasis and the function of metabolically-competent organs. In this review, we discuss how the impairment of the cross-talk between peripheral organs and the liver stalls glucose and lipid metabolism, leading to unbalances in hepatic lipid fluxes that promote hepatic fat accumulation. We also describe how prolonged metabolic stress builds up toxic lipid species in the liver, and how lipotoxicity and metabolic disturbances drive disease progression by promoting a chronic activation of wound healing, leading to fibrosis and HCC. Last, we provide a critical overview of current state of the art (pre-clinical and clinical evidence) regarding mechanisms of action and therapeutic efficacy of candidate SLD treatment options, and their potential to interfere with SLD/HCC pathophysiology by diverting lipids away from the liver therefore improving metabolic health.

Metformin was developed from an offshoot of Guanidine. It is known to be the first-line medication for type 2 diabetes mellitus, polycystic ovarian syndrome, and weight reduction. Metformin has also been shown to have effectiveness in the management of non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, and various carcinomas like hepatocellular, colorectal, prostate, breast, urinary bladder, blood, melanoma, bone, skin, lung and so on. This narrative review focuses on the effect of metformin on non-alcoholic fatty liver disease, liver cirrhosis, and hepatocellular carcinoma. The search platforms for the topic were PubMed, Scopus, and Google search engine. Critical words for searching included 'Metformin,' AND 'Indications of Metformin,' AND 'Non-Alcoholic Fatty Liver Disease,' AND 'Metformin mechanism of action,' AND 'NAFLD management,' AND 'NAFLD and inflammation,' AND 'Metformin and insulin,' AND 'Metformin and inflammation,' AND 'Liver cirrhosis,' AND 'Hepatocellular carcinoma.' Lifestyle modification and the use of hypoglycemic agents can help improve liver conditions. Metformin has several mechanisms that enhance liver health, including reducing reactive oxygen species, nuclear factor kappa beta (NF-κB), liver enzymes, improving insulin sensitivity, and improving hepatic cell lipophagy. Long-term use of metformin may cause some adverse effects like lactic acidosis and gastrointestinal disturbance. Metformin long-term overdose may lead to a rise in hydrogen sulfide in liver cells, which calls for pharmacovigilance. Drug regulating authorities should provide approval for further research, and national and international guidelines need to be developed for liver diseases, perhaps with the inclusion of metformin as part of the management regime.

Metabolic associated liver disease (MASLD) is the most common liver disease in the world especially in people with metabolic syndrome. First-line treatments mainly consist in lifestyle modifications for these populations. The main objective of this study is to assess the effect of a short intervention program with different exercise modalities on Fatty Liver Index (FLI) in patients with metabolic syndrome.

85 patients (40 men, 45 women) with metabolic syndrome and liver steatosis were randomized in 3 groups for a 3 weeks residential program: Re group-high-resistance-moderate-endurance; rE group-moderate-resistance with high-endurance and re group-moderate-resistance with moderate-endurance. Patients also followed a negative energy balance of 500 kcal/day. Then, a follow-up of 1 year with interviews with dieticians and exercise physicians to maintain lifestyle modification was performed. Anthropometric, cardiometabolic and hepatic outcomes were performed at baseline, at the end of the 3-week residential program, 3 months, 6 months and 12 months after baseline.

This study demonstrated that all three training programs significantly improve FLI and that this effect was lasting among the follow-up (p < 0.001). More specifically, the Re group exhibited a more pronounced decrease in FLI compared with re (p < 0.05). Finally, the decrease in FLI was associated with improvement in anthropometric and cardiometabolic outcomes at 3-weeks (p < 0.001) and 3-months (p < 0.01).

Short duration program is effective to improve FLI and cardiometabolic parameters in MASLD patients. Encourage to increase physical activity even for a short duration is relevant in this population.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition amongst females of reproductive age, leading to lifelong cardiometabolic, reproductive, psychological, and dermatologic symptoms as well as a reduced quality of life. Lifestyle interventions, which can include structured exercise programmes delivered by appropriately trained exercise professionals such as clinical exercise physiologists, are considered first-line strategies in PCOS management due to their therapeutic effects on various health outcomes and quality of life. This position statement builds on the 2023 International Evidence-based Guideline for the Assessment and Management of PCOS and describes the role of the exercise professional in the context of the multidisciplinary care team which includes physicians and allied health professionals. This position statement aims to equip exercise professionals with a broad understanding of the pathophysiology of PCOS, how it is diagnosed and managed in clinical practice, and evidence- and consensus-based recommendations for physical activity and exercise in PCOS management. In line with the physical activity recommendations for the general public, individuals with PCOS should aim to undertake between 150 to 300min of moderate-intensity or 75 to 150min of vigorous-intensity aerobic activity per week, or an equivalent combination of both spread throughout the week. Additionally, muscle-strengthening activities on two non-consecutive days per week are recommended to maintain health and prevent weight gain. For further health benefits and to achieve modest weight loss, individuals with PCOS should aim for a minimum of 250min of moderate-intensity or 150min of vigorous-intensity aerobic activity per week, or an equivalent combination of both spread throughout the week, plus muscle-strengthening activities on two non-consecutive days per week. Adolescents with PCOS should aim for a minimum of 60min moderate- to vigorous-intensity activity each day, incorporating muscle- and bone-strengthening activities three times per week. Finally, exercise professionals should consider the significant psychological burden, including weight stigma, and the high prevalence of comorbidities amongst individuals with PCOS and take appropriate measures to deliver safe and efficacious exercise interventions.

Fat is a "double-edged sword": while it is a necessary substance for the body, the long-term intake of excessive fat will cause obesity, with the liver subjected to lipotoxicity as it accumulates. It will then continue to deteriorate, eventually leading to liver failure, which is a negative impact of high-fat food intake. Research has shown that exercise can reverse the side effects of a chronic high-fat diet and help the body to mitigate the harmful effects of lipotoxicity. In our study, it was found that moderate-intensity cardio-training (MICT) and high-intensity interval exercise (HIIT) effectively protected the livers of high-fat diet (HFD) ApoE-/- mice against lipotoxicity. Previous results demonstrated that 12 weeks of HFD resulted in a significant elevation of CD36 in the livers of C57BL/6J mice, while knockdown of CD36 did not reduce the accumulation of fat in the liver. Therefore, we used ApoE-/- mice as experimental subjects. Although HFD caused the development of hyperlipidemia and atherosclerosis, it is interesting to note that, due to the knockdown of ApoE, the livers of ApoE-/- mice in the non-exercise group did not show significant lipid deposition; however, after 12 weeks of MICT and HIIT, the livers of ApoE-/- mice showed significant lipid deposition. After we analyzed the lipid metabolism in their livers, we found that this was caused by the promotion of transport of peripheral fat into the liver due to exercise. Moreover, 12 weeks of exercise effectively reduced atherosclerosis, and the livers of ApoE-/- mice in the exercise group were not damaged by lipotoxicity. The results showed that a 12-week exercise treatment activated AMPK in the livers of HFD ApoE-/- mice through the APN-AdipoR1 signaling pathway, improved hepatic lipid metabolism disorders, and promoted the nuclear translocation of TFEB to enhance autophagic-lysosomal lipid scavenging. After the peripheral lipid is input into the liver due to exercise, the energy generated through gluconeogenesis can be used to replenish the energy consumed by exercise and maintain the normal operation of various functions in the liver, based on which the high autophagic flux in the liver can be maintained and the lipid clearance rate can be enhanced to protect the liver from lipotoxicity.

Metabolic dysfunction-associated fatty liver disease is a significant risk factor for cardiovascular disease (CVD). This study assesses the association between leisure-time physical activity, sedentary behavior, and CVD risk among patients with metabolic dysfunction-associated fatty liver disease, considering genetic predisposition to CVD.

This cohort study included 157 794 participants with metabolic dysfunction-associated fatty liver disease from the UK Biobank who were free of CVD at baseline. The study measured leisure-time sedentary behaviors (watching TV, using a computer, and driving) and physical activities (walking for pleasure, light and heavy do-it-yourself activities, strenuous sports, and other exercises) in terms of frequency and duration over the 4 weeks before assessment. Both a Cox proportional hazard model and an isotemporal substitution model were utilized in the study to assess the association between leisure sedentary behavior, physical activities, and CVD risk.

During a median 12.5 years of follow-up, 26 355 CVD cases were reported, including 19 746 coronary heart disease, 4836 stroke, and 7398 heart failure cases. High physical activity levels were linked to a significantly lower risk of CVD (21%), coronary heart disease (20%), stroke (15%), and heart failure (31%). In contrast, individuals with >6.5 h/d of sedentary behavior faced a 16% to 21% higher risk of these conditions compared with those with ≤3.5 h/d. Notably, replacing 30 minutes of inactivity with physical activity reduced CVD risks by 3% to 16%, particularly with strenuous sports. A significant interaction was observed between physical activity, sedentary behavior, and genetic predisposition in relation to stroke risk.

Among patients with metabolic dysfunction-associated fatty liver disease, higher leisure-time physical activity levels correlate with reduced CVD risks, while increased sedentary behavior is linked to higher CVD risks. Replacing sedentary time with physical activity consistently shows benefits in reducing CVD outcomes, irrespective of genetic predisposition.

Metabolic dysfunction-associated steatotic liver disease management guidelines have been published worldwide; we aimed to summarize, categorize, and compare their lifestyle intervention recommendations.

We searched metabolic dysfunction-associated steatotic liver disease/NAFLD management guidelines published between January 1, 2013, and June 31, 2024, through databases including PubMed/MEDLINE, Cochrane, and CINAHL. In total, 35 qualifying guidelines were included in the final analysis. Guideline recommendations were categorized into 5 domains (ie, weight reduction goals, physical activity, nutrition, alcohol, and tobacco smoking) and were ranked based on how frequently they appeared. A recommendation was defined as widely adopted if recommended in ≥24 (≥66.6%) of the guidelines. These included increasing physical activity; reducing body weight by 7%-10% to improve steatohepatitis and/or fibrosis; restricting caloric intake; undertaking 150-300 or 75-150 minutes/week of moderate or vigorous-intensity physical activity, respectively; and decreasing consumption of commercially produced fructose. The least mentioned topics, in ≤9 of the guidelines, evaluated environmental determinants of health, mental health, referring patients for psychological or cognitive behavioral therapy, using digital health interventions, and assessing patients' social determinants of health.

Most guidelines recommend weight reduction through physical activity and improving nutrition, as these have proven positive effects on health outcomes when sustained. However, gaps regarding mental health and the social and environmental determinants of metabolic dysfunction-associated steatotic liver disease were found. To optimize behavioral modifications and treatment, we recommend carrying out studies that will provide further evidence on social support, environmental factors, and mental health, as well as further exploring digital health interventions.

Metabolic-associated fatty liver disease (MAFLD) has gradually become one of the main health concerns regarding liver diseases. Postmenopausal women represent a high-risk group for MAFLD; therefore, it is of great importance to identify and intervene with patients at risk at an early stage. This study established a predictive nomogram model of MAFLD in postmenopausal women and to enhance the clinical utility of the new model, the researchers limited variables to simple clinical and laboratory indicators that are readily obtainable.

Data of 942 postmenopausal women from January 2023 to October 2023 were retrospectively collected and divided into two groups according to the collection time: the training group (676 cases) and the validation group (226 cases). Significant indicators independently related to MAFLD were identified through univariate logistic regression and stepwise regression, and the MAFLD prediction nomogram was established. The C-index and calibration curve were used to quantify the nomogram performance, and the model was evaluated by measuring the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).

Of 37 variables, 11 predictors were identified, including occupation (worker), body mass index, waist-to-hip ratio, number of abortions, anxiety, hypertension, hyperlipidemia, diabetes, hyperuricemia, and diet (meat and processed meat). The C-index of the training group predicting the related risk factors was 0.827 (95% confidence interval [CI] 0.794-0.860). The C-index of the validation group was 0.787 (95% CI 0.728-0.846). Calibration curves 1 and 2 (BS1000 times) were close to the diagonal, showing a good agreement between the predicted probability and the actual incidence in the two groups. The AUC of the training group was 0.827, the sensitivity was 0.784, and the specificity was 0.735. The AUC of the validation group was 0.787, the sensitivity was 0.674, and the specificity was 0.772. The DCA curve showed that the nomogram had a good net benefit in predicting MAFLD in postmenopausal women.

A predictive nomogram for MAFLD in postmenopausal women was established and verified, which can assist clinicians in evaluating the risk of MAFLD at an early stage.

Non-alcoholic fatty liver disease (NAFLD) is a common long-lasting liver disease that affects millions of people around the world. It is best identified with a hepatic fat build-up that ultimately leads to inflammation and damage. The classification and nomenclature of NAFLD have long been a controversial topic, until 2020 when a group of international experts recommended substituting NAFLD with MAFLD (metabolic dysfunction-associated FLD). MAFLD was then terminologically complemented in 2023 by altering it to MASLD, i.e., metabolic dysfunction-associated steatotic liver disease (MASLD). Both the MAFLD and the MASLD terminologies comprise the metabolic element of the disorder, as they offer diagnostic benchmarks that are embedded in the metabolic risk factors that underlie the disease. MASLD (as a multisystemic disease) provides a comprehensive definition that includes a larger population of patients who are at risk of liver morbidity and mortality, as well as adverse cardiovascular and diabetes outcomes. MASLD highlights metabolic risks in lean or normal weight individuals, a factor that has not been accentuated or discussed in previous guidelines. Novel antihyperglycemic agents, anti-hyperlipidemic drugs, lifestyle modifications, nutritional interventions, and exercise therapies have not been extensively studied in MAFLD and MASLD. Nutrition plays a vital role in managing both conditions, where centralizing on a diet rich in whole vegetables, fruits, foods, healthy fats, lean proteins, and specific nutrients (e.g., omega-3 fatty acids and fibers) can improve insulin resistance and reduce inflammation. Thus, it is essential to understand the role of nutrition in managing these conditions and to work with patients to develop an individualized plan for optimal health. This review discusses prevention strategies for NAFLD/MAFLD/MASLD management, with particular attention to nutrition and lifestyle correction.

Liver diseases contribute to ~2 million deaths each year and account for 4% of all deaths globally. Despite various treatment options, the management of liver diseases remains challenging. Physical exercise is a promising nonpharmacological approach to maintain and restore homeostasis and effectively prevent and mitigate liver diseases. In this review, we delve into the mechanisms of physical exercise in preventing and treating liver diseases, highlighting its effects on improving insulin sensitivity, regulating lipid homeostasis, and modulating immune function. In addition, we evaluate the impact of physical exercise on various liver diseases, including liver ischemia/reperfusion injury, cardiogenic liver disease, metabolic dysfunction-associated steatotic liver disease, portal hypertension, cirrhosis, and liver cancer. In conclusion, the review underscores the effectiveness of physical exercise as a beneficial intervention in combating liver diseases.

The incidence of steatotic liver disease has increased in recent years. Thus, steatotic liver disease is a major public health issue in Japan. This study investigated the association between weight reduction and the remission of metabolic dysfunction-associated steatotic liver disease (MASLD)/Metabolic and alcohol related/associated liver disease (MetALD) in Japanese individuals undergoing health checkups.

This retrospective observational study included 8,707 Japanese patients with MASLD/MetALD who underwent health checkups from May 2015 to March 2023. The participants were monitored for its remission at their subsequent visit. MASLD was diagnosed on abdominal ultrasonography and based on the presence of at least one of five metabolic abnormalities. The impact of body mass index (BMI) reduction on MASLD/MetALD remission was assessed via logistic regression analysis and using receiver operating characteristic curves.

Logistic regression analysis revealed that weight loss was significantly associated with MASLD/MetALD remission. Other factors including exercise habits and reduced alcohol consumption were significant predictors of MASLD/MetALD remission in the overall cohort and in male patients. The optimal BMI reduction cutoff values for MASLD/MetALD remission were 0.9 kg/m2 and 4.0% decrease in the overall cohort, 0.85 kg/m2 and 3.9% decrease in males, and 1.2 kg/m2 and 4.5% decrease in females. In participants with a BMI of 23 kg/m2, the cutoff values were 0.75 kg/m2 and 2.7% BMI reduction.

Weight reduction plays an important role in both MASLD and MetALD remission among Japanese individuals. That is, targeting specific BMI reduction is effective. This underscores the importance of targeted weight management strategies in preventing and managing MASLD/MetALD in the Japanese population.

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain-gut-liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain-gut-liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines.

Chronic liver disease is a significant global health problem. Epidemiological trends do not show improvement in chronic liver disease incidence but rather a shift in etiologies, with steatotic liver disease (SLD) from metabolic dysfunction and alcohol becoming increasingly important causes. Consequently, there is a pressing need to develop a comprehensive public health approach for SLD. To that end, we propose a public health framework for preventing and controlling SLD. The framework is anchored on evidence linking physical inactivity, unhealthy dietary patterns, alcohol use, and obesity with both incidence and progression of SLD. Guided by the framework, we review examples of federal/state-level, community-level, and individual-level interventions with the potential to address these determinants of SLD. Ultimately, mitigating SLD's burden requires primary risk factor reduction at multiple socioecological levels, by scaling up the World Health Organization's "best buys," in addition to developing and implementing SLD-specific control interventions.