This Obesity Medicine Association (OMA) Expert Joint Perspective examines steatotic liver disease (SLD), which is composed of metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH) in children with obesity. The prevalence of obesity is increasing, rates have tripled since 1963 from 5 % to now 19 % of US children affected in 2018. MASLD, is the most common liver disease seen in children, can be a precursor to the development of Type 2 Diabetes (T2DM) and is the primary reason for liver transplant listing in young adults. We must be vigilant in prevention and treatment of MASLD in childhood to prevent further progression.

This joint clinical perspective is based upon scientific evidence, peer and clinical expertise. The medical literature was reviewed via PubMed search and appropriate articles were included in this review. This work was formulated from the collaboration of eight hepatologists/gastroenterologists with MASLD expertise and two physicians from the OMA.

The authors who are experts in the field, determined sentinel questions often asked by clinicians regarding MASLD in children with obesity. They created a consensus and clinical guideline for clinicians on the screening, diagnosis, and treatment of MASLD associated with obesity in children.

Obesity and the comorbidity of MASLD is increasing in children, and this is a medical problem that needs to be addressed urgently. It is well known that children with metabolic associated chronic disease often continue to have these chronic diseases as adults, which leads to reduced life expectancy, quality of life, and increasing healthcare needs and financial burden. The authors of this paper recommend healthy weight reduction not only through lifestyle modification but through obesity pharmacotherapy and bariatric surgery. Therefore, this guidance reviews available therapies to achieve healthy weight reduction and reverse MASLD to prevent progressive liver fibrosis, and metabolic disease.

Lifestyle interventions, such as diet and exercise, are currently the main therapies against metabolic dysfunction-associated steatotic liver disease (MASLD). However, not much is known about the combined impact of fiber and exercise on the modulation of gut-liver axis and MASLD amelioration. Here, we studied the impact of the combination of exercise training and a fiber-rich diet on the amelioration of MASLD. Male APOE*3-Leiden.CETP mice were fed a high-fat high-cholesterol diet with or without the addition of fiber (10% inulin) and exercise trained on a treadmill, or remained sedentary. Exercise training and fiber supplementation reduced fat mass gain and lowered plasma glucose levels. Only the combination treatment, however, induced fat loss and decreased plasma triglyceride and cholesterol levels compared with sedentary control mice. Exercise training with and without the addition of fiber had a similar ameliorating effect on the MASLD score. Only exercise without fiber decreased the hepatic expression of inflammatory markers. Fiber diet was mainly responsible for remodeling the gut microbial composition, with an increase in the relative abundance of the short-chain fatty acid (SCFA)-producing genera Anaerostipes and Muribaculaceae, whereas, surprisingly, exercise training alone and with fiber resulted in the highest increase of SCFA production. Overall, the combination of exercise training and dietary fiber decreases fat mass and improves glucose and lipid homeostasis but does not have an additional synergistic positive effect on liver health compared with exercise training alone.NEW & NOTEWORTHY The combination of dietary fiber intake and exercise training has a synergetic beneficial effect on the metabolic health, resulting in fat loss, lowered blood glucose, and lowered plasma lipid levels in mice with steatotic liver disease. However, fiber supplementation, despite a positive remodulation of the gut-liver axis, does not have an additional positive effect on liver health compared with exercise training alone.

Resistance training, as a modality of physical exercise, has been recognized as a fundamental pillar in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). Current reviews, however, have not given due priority to the specific effects of this type of training on hepatic and clinical markers in individuals with MASLD. This study aimed to compile the available evidence on the impact of resistance training on hepatic and clinical parameters in individuals diagnosed with MASLD. To this end, a systematic search was conducted in the PubMed, Lilacs, Embase, Cochrane, SciELO, and Pedro databases, as well as a manual search, covering the period from January 2011 to December 2023. Randomized clinical trials that evaluated liver fat, insulin resistance, and liver enzymes in individuals with MASLD who were exclusively subjected to resistance training interventions were selected. This study is registered with International Prospective Register of Systematic Reviews (PROSPERO) (CRD4202236638) and the risk of bias in the eligible studies was assessed using ROB 2. Six studies were included, totaling 232 adult participants. Resistance training resulted in a significant reduction in liver fat ( P  < 0.001), liver enzymes ( P  < 0.05), and insulin resistance ( P  < 0.05) in individuals in the strength training group. Furthermore, greater adherence to resistance training (>90%) was observed compared to aerobic training. It is concluded that resistance training can be an easily accepted and consistent option for adults with MASLD, playing an important role in improving the clinical and hepatic markers of these individuals.

In this study, our objective was to provide practice recommendations by thoroughly examining lifestyle interventions for adults diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD). This was achieved through a systematic review of the literature, specifically focusing on lifestyle modification interventions in adults with MASLD.

The PIPOST (Population, Intervention, Professional, Outcome, Setting, and Type of evidence) framework was used to identify the questions for summarizing evidence. Utilizing the 6S model for the hierarchy of evidence, a computerized search was conducted to retrieve articles pertaining to lifestyle interventions for adults with MASLD from websites such as the UpToDate Clinical Advisor, BMJ Best Practice, JBI Library, Cochrane Library, International Guidelines Library, and PubMed, among others. The available research included clinical decisions, clinical practice guidelines, evidence summaries, systematic evaluation, expert consensus, and expert opinions. Two researchers independently evaluated the methodology of the studies, and evidence was subsequently extracted and grouped thematically. Our review encompassed publications from January 2018 to March 2023.

A total of 26 publications were identified for the final review, consisting of seven guidelines, nine systematic evaluations, and 10 expert consensuses/opinions. From these sources, we derived six themes, 28 pieces of evidence: intervention modalities, diet management, exercise management, weight loss management, personalized management, and multidisciplinary collaboration.

In the management of adults with MASLD, healthcare professionals should embrace a multidisciplinary team approach, adhere to the best available evidence, and develop structured and personalized interventions based on the best evidence for lifestyle modifications.

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.

The Plants for Joints (PFJ) intervention significantly improved pain, stiffness, and physical function, and metabolic outcomes, in people with metabolic syndrome-associated osteoarthritis (MSOA). This secondary analysis investigated its effects on body composition.

In the randomized PFJ study, people with MSOA followed a 16-week intervention based on a whole-food plant-based diet, physical activity, and stress management, or usual care. For this secondary analysis, fat mass, muscle mass, and bone mineral density were measured using dual-energy X-ray absorptiometry (DEXA) for all participants. Additionally, in a subgroup (n ​= ​32), hepatocellular lipid (HCL) content and composition of visceral adipose tissue (VAT) were measured using magnetic resonance spectroscopy (MRS). An intention-to-treat analysis with a linear-mixed model adjusted for baseline values was used to analyse between-group differences.

Of 66 people randomized, 64 (97%) completed the study. The PFJ group experienced significant weight loss (-5.2 ​kg; 95% CI -6.9, -3.6) compared to controls, primarily from fat mass reduction (-3.9 ​kg; 95% CI -5.3 to -2.5). No significant differences were found in lean mass, muscle strength, or bone mineral density between groups. In the subgroup who underwent MRI scans, the PFJ group had a greater reduction in HCL (-6.5%; 95% CI -9.9, 3.0) compared to controls, with no observed differences in VAT composition.

The PFJ multidisciplinary intervention positively impacted clinical and metabolic outcomes, and appears to significantly reduce body fat, including liver fat, while preserving muscle mass and strength.

Senescence impairs liver physiology, mitochondrial function and circadian regulation, resulting in systemic metabolic dysregulation. Given the limited research on the effects of combined exercise on an ageing liver, this study aimed to evaluate its impact on liver metabolism, circadian rhythms and mitochondrial function in senescence-accelerated mouse-prone 8 (SAMP8) and senescence-accelerated mouse-resistant 1 (SAMR1) mice. Histological, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunoblotting analyses were conducted, supplemented by transcriptomic data sets and AML12 hepatocyte studies. Sedentary SAMP8 mice exhibited decreased muscle strength, reduced mitochondrial complex I levels and increased lipid droplet accumulation. In contrast, combined exercise mitigated muscle strength loss, upregulated proteins involved in mitochondrial complexes (CIII, CIV, CV) and increased Bmal1 messenger RNA (mRNA) expression in the liver. These molecular adaptations are associated with healthier liver phenotypes and may influence metabolic function and cellular longevity. Notably, elevated lipid content in aged mice was reduced post-exercise, indicating liver benefits even after a relatively short intervention. The combined exercise regimen did not improve aerobic capacity, likely due to the low volume and brief duration of running. Moreover, no significant effects were observed in SAMR1 mice, possibly because the training intensity was insufficient for younger, healthier animals. These findings underscore the potential of combined strength and endurance exercise to attenuate age-related liver dysfunction, particularly in ageing populations.

The effects of excessive alcohol consumption on the prognosis of metabolic dysfunction-associated fatty liver disease (MAFLD) remain unclear. We investigated all-cause and cause-specific mortality according to the amount of alcohol consumed by Asian individuals with MAFLD.

This nationwide retrospective study included 996,508 adults aged 40-79 years who underwent health check-ups between 2009 and 2012. Participants were categorized by the alcohol consumption-non-alcohol, moderate alcohol, and heavy alcohol group (≥ 30 g/day for men, ≥ 20 g/day for women) and by the combination of the presence or absence of MAFLD. Hepatic steatosis was defined as the fatty liver index ≥ 30. Cox analyses were used to analyze the association between alcohol consumption and MAFLD and all-cause and cause-specific mortality.

MAFLD significantly increased all-cause, liver-, and cancer-related mortality. Individuals with both MAFLD and heavy alcohol consumption expressed the highest mortality risk in liver-related mortality compared to non-MAFLD and non-alcohol group (adjusted hazard ratio (HR), 9.8; 95% confidence interval (CI), 8.20-12.29). Regardless of MAFLD, heavy alcohol consumption increased the risk of liver- and cancer-related mortality.

MAFLD and heavy alcohol consumption increased all-cause, liver-, and cancer-related mortality. Heavy alcohol consumption and MAFLD synergistically increase liver-related mortality.

To identify factors associated with non-alcoholic fatty liver disease over a 5-year period.

Three hundred seven participants, including 165 women, with a mean age of 55.6 ± 12.0 years underwent continuous quantitative MRI of the liver using the proton-density fat fraction (PDFF). The liver's fat fractions were determined at baseline and 5 years later, and the frequency of participants who developed fatty liver disease and potential influencing factors were explored. Based on significant factors, a model was generated to predict the development of fatty liver disease.

After excluding participants with pre-existing fatty liver, the baseline PDFF of 3.1 ± 0.9% (n = 190) significantly increased to 7.67 ± 3.39% within 5 years (p < 0.001). At baseline, age (OR = 1.04, p = 0.006, CI = 1.01-1.07), BMI (OR = 1.11, p = 0.041, CI = 1.01-1.23), and waist circumference (OR = 1.05, p = 0.020, CI = 1.01-1.09) were identified as risk factors. Physical activity was negatively associated (OR = 0.43, p = 0.049, CI = 0.18-0.99). In the prediction model, age, physical activity, diabetes mellitus, diastolic blood pressure, and HDL-cholesterol remained as independent variables. Combining these risk factors to predict the development of fatty liver disease revealed an AUC of 0.7434.

Within a five-year follow-up, one-quarter of participants developed fatty liver disease influenced by the triggering factors of age, diabetes mellitus, low HDL-cholesterol, and diastolic blood pressure. Increased physical activity has a protective effect on the development of fatty liver.

Steatotic liver disease (SLD) is a prevalent metabolic disease. While single component movement behaviors have been related to its development, comprehensive assessments of their joint associations are scarce.

To investigate the single-component and multi-component associations of moderate and vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep with prevalent SLD in Brazilian adults.

A cross-sectional analysis using data from the third wave of the ELSA-Brasil cohort (2017-2019). Participants wore an ActiGraph wGT3X-BT in the waist for seven days and completed a sleep diary. SLD was defined by a Fatty Liver Index ≥ 60. To investigate single-component and multi-component associations, we used three exposure modeling approaches based on Poisson models: multivariable-adjusted regression, restricted cubic splines, and compositional data analysis.

Among 8569 participants (55.7% women, mean age 59.2 ± 8.60), 43.9% had SLD. Total activity volume adjusted for covariates was inversely associated with prevalent SLD. Every 1 mg/day increase in total activity volume was associated with a PR of 0.95 in individuals sleeping < 7 h/day (95% CI 0.94-0.97) and 0.95 (95% CI 0.93-0.96) in those sleeping ≥ 7 h/day. Increasing 30 min/day of MVPA was associated with decreasing prevalence of SLD (sleep ≥ 7 h/day [PR 0.83; 95% CI 0.77-0.89]; sleep ≥ 7 h/day [PR 0.78; 95% CI 0.74-0.83]). Sleep, SB, and LPA were not associated with SLD. Associations of total activity volume and MVPA were more pronounced among females. Adjustment with adiposity markers attenuated the associations.

In adults, total activity volume and MVPA were inversely associated with SLD in a dose-response fashion. Substituting lower-intensity behaviors with MVPA was associated with a lower prevalence of SLD independent of sleep duration, sex, and age.

Current guidelines for nonalcoholic fatty liver disease (NAFLD) recommend high volumes and/or intensities of physical activity (PA), the achievement of which generally requires participation in supervised exercise training programs that however are difficult to implement in routine clinical practice. Conversely, counselling interventions may be more suitable, but result in only modest increases in moderate-to-vigorous-intensity PA (MVPA). This study assessed whether a counseling intervention for increasing PA and decreasing sedentary time (SED-time) is effective in improving NAFLD markers in people with type 2 diabetes.

Three-hundred physically inactive and sedentary patients were randomized 1:1 to receive one-month theoretical and practical counseling once-a-year (intervention group) or standard care (control group) for 3 years. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γGT) levels were measured and fatty liver index (FLI), hepatic steatosis index (HSI), and visceral adiposity index (VAI) were calculated. Total PA volume, light-intensity PA (LPA), moderate-to-vigorous-intensity PA (MVPA), and SED-time were objectively measured by an accelerometer.

Throughout the 3-year period, NAFLD markers did not change in the control group, whereas ALT, γGT, FLI, and HSI decreased in the intervention group, with significant between-group differences, despite modest MVPA increases, which however were associated with larger decrements in SED-time and reciprocal increments in LPA. Mean changes in NAFLD markers varied according to quartiles of (and correlated with) changes in MVPA (all markers) and SED-time, LPA, and PA volume (ALT, γGT, and HSI). Mean changes in MVPA or PA volume were independent predictors of changes in NAFLD markers. When included in the models, change in cardiorespiratory fitness and lower body muscle strength were independently associated with some NAFLD markers.

A behavior change involving all domains of PA lifestyle, even if insufficient to achieve the recommended MVPA target, may provide beneficial effects on NAFLD markers in people with type 2 diabetes.

The prevalence and incidence of NAFLD is rising due to the obesity pandemic, caused by the widespread availability of ultra-processed foods and the decrease of physical activity. Factors such as socioeconomic status (SES), ethnicity and geographical location are associated with NAFLD, with lower SES correlating with higher incidence, particularly in regions like America or Europe. Beside the quality of food, the quantity also plays a crucial role. The World Health Organization (WHO) recommends a Mediterranean diet with a balanced energy intake. Since no hard medical treatment is available for NAFLD, lifestyle adjustments are key. Patient empowerment by providing relevant information and co-ownership of the therapy will increase the implementation rate and enhance the quality of medical follow-up and medication adherence, as studies report a good adherence to medication among patients who are well-aware of the severity of their disease. Regarding sustainability, patients with NAFLD have a high load of ambulatory follow-up, which, since the COVID-19 pandemic, can be partially provided by teleconsulting. Both patients' lifestyle modifications and healthcare practitioners' therapeutical strategy can decrease the carbon footprint.

While hypertension is a well-recognized risk factor for non-alcoholic fatty liver disease (NAFLD), the specific roles of various common blood pressure measurements [diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse pressure (PP), mean arterial pressure (MAP)] in detecting NAFLD and evaluating the associated risk in adults remain unclear.

A retrospective analysis was conducted on 14,251 adult participants undergoing health screenings in the NAfld in the Gifu Area, Longitudinal Analysis project (NAGALA). Following the Z-transformation of the independent variables, we evaluated the relationships between the four blood pressure indices and NAFLD through multivariable logistic regression models. This analysis documented the odds ratio (OR) and 95% confidence interval (CI) for each standard deviation (SD) increase. Additionally, the effectiveness of these indices in identifying NAFLD was comparatively analyzed using receiver operating characteristic (ROC) curves.

After adequately adjusting for confounders, all blood pressure indices except PP showed a positive correlation with NAFLD. For each SD increment, MAP had the strongest association with NAFLD compared to SBP and DBP. This finding was confirmed in populations without exercise habits, under 60 years of age, with normal blood pressure, and in non-obese groups. Furthermore, based on ROC analysis, MAP was found to have the highest accuracy in identifying NAFLD compared to the other three blood pressure indices.

Among the four blood pressure indices evaluated, MAP demonstrates the greatest efficacy in identifying NAFLD and assessing its associated risk. These findings underscore the potential of MAP as the most promising blood pressure index for screening NAFLD.

Plants are a natural treasure trove; their secondary metabolites participate in several pharmacological processes, making them a crucial component in the synthesis of novel pharmaceuticals and serving as a reserve resource foundation in this process. Nonalcoholic fatty liver disease (NAFLD) is associated with the risk of progression to hepatitis and liver cancer. The "Treatise on Febrile Diseases," "Compendium of Materia Medica," and "Thousand Golden Prescriptions" have listed herbal remedies to treat liver diseases.

Chinese herbal medicines have been widely used for the prevention and treatment of NAFLD owing to their efficacy and low side effects. The production of reactive oxygen species (ROS) during NAFLD, and the impact and potential mechanism of ROS on the pathogenesis of NAFLD are discussed in this review. Furthermore, common foods and herbs that can be used to prevent NAFLD, as well as the structure-activity relationships and potential mechanisms, are discussed.

Web of Science, PubMed, CNKI database, Google Scholar, and WanFang database were searched for natural products that have been used to treat or prevent NAFLD in the past five years. The primary search was performed using the following keywords in different combinations in full articles: NAFLD, herb, natural products, medicine, and ROS. More than 400 research papers and review articles were found and analyzed in this review.

By classifying and discussing the literature, we obtained 86 herbaceous plants, 28 of which were derived from food and 58 from Chinese herbal medicines. The mechanism of NAFLD was proposed through experimental studies on thirteen natural compounds (quercetin, hesperidin, rutin, curcumin, resveratrol, epigallocatechin-3-gallate, salvianolic acid B, paeoniflorin, ginsenoside Rg1, ursolic acid, berberine, honokiol, emodin). The occurrence and progression of NAFLD could be prevented by natural antioxidants through several pathways to prevent ROS accumulation and reduce hepatic cell injuries caused by excessive ROS.

This review summarizes the natural products and routinely used herbs (prescription) in the prevention and treatment of NAFLD. Firstly, the mechanisms by which natural products improve NAFLD through antioxidant pathways are elucidated. Secondly, the potential of traditional Chinese medicine theory in improving NAFLD is discussed, highlighting the safety of food-medicine homology and the broader clinical potential of multi-component formulations in improving NAFLD. Aiming to provide theoretical basis for the prevention and treatment of NAFLD.

The effect of exercise on clinical parameters in patients with non-alcoholic fatty liver disease (NAFLD) combined with type 2 diabetes mellitus (T2DM) is unknown. In this meta-analysis, we identified and evaluated the effect of exercise on clinical parameters (BMI, ALT, lipid metabolism, glucose metabolism) in patients with NAFLD combined with T2DM. We conducted a comprehensive search of Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, and CNKI in December 2022. Data from relevant randomized controlled trials were collected according to inclusion and exclusion criteria. 6 eligible studies with 238 subjects were finally included. We used Review Manager 5.3 for meta-analysis. The study found that exercise improved BMI, ALT, TC, LDL-C, HbA1c, and HOMA-IR, TG, but did not significantly improve HDL-C. Subgroup analysis showed that high-intensity interval training significantly improved BMI (SMD: -0.43, 95% CI: -0.80, -0.06), ALT (SMD: -4.63, 95% CI: -8.42, -0.83), TC (SMD: -0.94, 95% CI: -1.82, -0.07), LDL-C (SMD: -0. 87, 95% CI: -1.26, -0.49), HbA1c (SMD: -1.12, 95% CI: -1.75, -0.48), HOMA-IR (SMD: -0.59, 95% CI: -0.94, -0.25); moderate-intensity continuous training improved ALT (SMD: -3.96, 95% CI: -7.71, -0.21), TG (SMD: -1.59, 95% CI: -2.58, -0.61), HbA1c (SMD: -0.71, 95% CI: -1.37, -0.05), HOMA-IR (SMD: -1.73, 95% CI: -3.40, -0. 06), and to some extent HDL-C levels (SMD: 0.53, 95% CI: 0.04, 1.02); resistance training improved LDL-C (SMD: -2.06, 95% CI: -3.14, -0.98). In conclusion, exercise improved indicators in patients with NAFLD combined with T2DM, but the improvement indicators varied by type of exercise.

The incidence and remission of nonalcoholic fatty liver disease (NAFLD) are sparsely studied outside Asia.

This prospective study aimed to investigate NAFLD incidence and remission, and their predictors among a general Finnish population.

The applied cohort included 1260 repeatedly studied middle-aged participants with data on liver ultrasound and no excessive alcohol intake. Hepatic steatosis was assessed by liver ultrasound with a 7.2-year study interval. Comprehensive data on health parameters and lifestyle factors were available.

At baseline, 1079 participants did not have NAFLD, and during the study period 198 of them developed NAFLD. Of the 181 participants with NAFLD at baseline, 40 achieved NAFLD remission. Taking multicollinearity into account, key predictors for incident NAFLD were baseline age (odds ratio 1.07; 95% CI, 1.02-1.13; P = .009), waist circumference (WC) (2.77, 1.91-4.01 per 1 SD; P < .001), and triglycerides (2.31, 1.53-3.51 per 1 SD; P < .001) and alanine aminotransferase (ALAT) (1.90, 1.20-3.00 per 1 SD; P = .006) concentrations as well as body mass index (BMI) change (4.12, 3.02-5.63 per 1 SD; P < .001). Predictors of NAFLD remission were baseline aspartate aminotransferase (ASAT) concentration (0.23, 0.08-0.67 per 1 SD; P = .007) and WC change (0.38, 0.25-0.59 per 1 SD; P < .001).

During follow-up, NAFLD developed for every fifth participant without NAFLD at baseline, and one-fifth of those with NAFLD at baseline had achieved NAFLD remission. NAFLD became more prevalent during the follow-up period. From a clinical perspective, key factors predicting NAFLD incidence and remission were BMI and WC change independent of their baseline level.

Forkhead box a2 (Foxa2) is proven to be an insulin-sensitive transcriptional regulator and affects hepatic steatosis. This study aims to investigate the mechanism by which Foxa2 affects nonalcoholic fatty liver disease (NAFLD).

Animal and cellular models of NAFLD were constructed using high-fat diet (HFD) feeding and oleic acid (OA) stimulation, respectively. NAFLD mice received tail vein injections of either an overexpressing negative control (oe-NC) or Foxa2 (oe-Foxa2) for four weeks. HepG2 cells were transfected with oe-NC and oe-Foxa2 for 48 h before OA stimulation. Histological changes and lipid accumulation were assessed using hematoxylin-eosin staining and oil red O staining, respectively. Expression of Foxa2, NF-κB/IKK pathway proteins, lipid synthesis proteins, and fatty acid β-oxidation protein in HFD mice and OA-induced HepG2 cells was detected using western blot.

Foxa2 expression was downregulated in HFD mice and OA-induced HepG2 cells. Foxa2 overexpression attenuated lipid accumulation and liver injury, and reduced the levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol, or triglyceride in HFD mice and OA-induced HepG2 cells. Moreover, Foxa2 overexpression decreased the expression of lipid synthesis proteins and increased fatty acid β-oxidation protein expression in the liver tissues. Furthermore, overexpression of Foxa2 downregulated the expression of p-NF-κB/NF-κB and p-IKK/IKK in OA-induced HepG2 cells. Additionally, lipopolysaccharide (NF-κB/IKK pathway activator) administration reversed the downregulation of lipid synthesis proteins and the upregulation of fatty acid β-oxidation protein.

Foxa2 expression is downregulated in NAFLD. Foxa2 ameliorated hepatic steatosis and inhibited the activation of the NF-κB/IKK signaling pathway.

Metabolic-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide, affecting 25% of people globally and up to 80% of people with obesity. MAFLD is characterised by fat accumulation in the liver (hepatic steatosis) with varying degrees of inflammation and fibrosis. MAFLD is strongly linked with cardiometabolic disease and lifestyle-related cancers, in addition to heightened liver-related morbidity and mortality. This position statement examines evidence for exercise in the management of MAFLD and describes the role of the exercise professional in the context of the multi-disciplinary care team. The purpose of these guidelines is to equip the exercise professional with a broad understanding of the pathophysiological underpinnings of MAFLD, how it is diagnosed and managed in clinical practice, and to provide evidence- and consensus-based recommendations for exercise therapy in MAFLD management. The majority of research evidence indicates that 150-240 min per week of at least moderate-intensity aerobic exercise can reduce hepatic steatosis by ~ 2-4% (absolute reduction), but as little as 135 min/week has been shown to be effective. While emerging evidence shows that high-intensity interval training (HIIT) approaches may provide comparable benefit on hepatic steatosis, there does not appear to be an intensity-dependent benefit, as long as the recommended exercise volume is achieved. This dose of exercise is likely to also reduce central adiposity, increase cardiorespiratory fitness and improve cardiometabolic health, irrespective of weight loss. Resistance training should be considered in addition to, and not instead of, aerobic exercise targets. The information in this statement is relevant and appropriate for people living with the condition historically termed non-alcoholic fatty liver disease (NAFLD), regardless of terminology.

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming a significant global health concern, representing the leading cause of chronic liver disease and posing a substantial public health challenge. NAFLD is associated with higher insulin resistance (IR) levels, a key pathophysiological mechanism contributing to its development and progression. To counter this growing trend, it is crucial to raise awareness about NAFLD and promote healthy lifestyles to mitigate the impact of this disease.

Relevant studies regarding IR and NAFLD published until May 30, 2023, were extracted from Google PubMed, Scopus, and Web Of Science web databases. The following keywords were used: IR, diabetes mellitus, Non-alcoholic fatty liver disease, and metabolic syndrome.

IR leads to an accumulation of fatty acids within liver cells, resulting from increased glycolysis and decreased apolipoprotein B-100. Furthermore, the manifestations of NAFLD extend beyond liver-related morbidity and mortality, affecting multiple organs and giving rise to various non-communicable disorders such as diabetes mellitus, metabolic syndrome, polycystic ovary syndrome, obstructive sleep apnea, and cardiovascular disease. Although lifestyle modification remains the primary treatment approach for NAFLD, alternative therapies, including pharmacological, herbal, and surgical interventions, may be considered. By implementing early and simple measures, cirrhosis, end-stage liver disease, and hepatocellular carcinoma can be prevented.

There is a clear association between NAFLD and elevated levels of IR. Several metabolic conditions, such as obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome, are closely interrelated with NAFLD and IR. Raising awareness about NAFLD and promoting a healthy lifestyle are crucial steps to reverse the impact of this disease.

Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of cirrhosis and other chronic liver diseases (COCLDs).

To conduct a comprehensive and comparable updated analysis of the global, regional, and national burden of COCLDs due to NAFLD in 204 countries and territories from 1990 and 2019 by age, sex, and sociodemographic index.

Data on COCLDs due to NAFLD were collected from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Numbers and age-standardized prevalence, death, and disability-adjusted life years (DALYs) were estimated through a systematic analysis of modelled data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. The estimated annual percentage change was used to determine the burden trend.

In 2019, the global age-standardized prevalence rate of COCLDs due to NAFLD was 15022.90 per 100000 population [95% uncertainty interval (UI): 13493.19-16764.24], which increased by 24.51% (22.63% to 26.08%) from 1990, with an estimated annual percentage change of 0.78 (95% confidence interval: 0.74-0.82). In the same year, however, the age-standardized death rate and age-standardized DALYs per 100000 population were 1.66 (95%UI: 1.20-2.17) and 43.69 (95%UI: 31.28-58.38), respectively. North Africa and the Middle East had the highest prevalence rates of COCLDs due to NAFLD. The death rate increased with age up to the 95+ age group for both sexes. Males had higher numbers of prevalence, death rate, and DALYs than females across all age groups before the 65-69 age group. The sociodemographic index was negatively correlated with the age-standardized DALYs.

Globally, the age-standardized prevalence rate has increased during the past three decades. However, the age-standardized death rate and age-standardized DALYs decreased. There is geographical variation in the burden of COCLDs due to NAFLD. It is strongly recommended to improve the data quality of COCLDs due to NAFLD across all countries and regions to facilitate better monitoring of the burden of COCLDs due to NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is a dynamic chronic liver disease that develops in close association with metabolic irregularities. Between 2016 and 2019, the global prevalence among adults was reported as 38% and among children and adolescents it was about 10%. NAFLD can be progressive and is associated with increased mortality from cardiovascular disease, extrahepatic cancers and liver complications. Despite these numerous adverse outcomes, no pharmacological treatments currently exist to treat nonalcoholic steatohepatitis, the progressive form of NAFLD. Therefore, the main treatment is the pursuit of a healthy lifestyle for both children and adults, which includes a diet rich in fruits, nuts, seeds, whole grains, fish and chicken and avoiding overconsumption of ultra-processed food, red meat, sugar-sweetened beverages and foods cooked at high heat. Physical activity at a level where one can talk but not sing is also recommended, including leisure-time activities and structured exercise. Avoidance of smoking and alcohol is also recommended. Policy-makers, community and school leaders need to work together to make their environments healthy by developing walkable and safe spaces with food stores stocked with culturally appropriate and healthy food items at affordable prices as well as providing age-appropriate and safe play areas in both schools and neighbourhoods.

Our study is applying a community-based approach to examine the influence of exercise on gut microbiota (GM) and discover GM structures linked with NAFLD improvements during exercise. The majority of microbiome research has focused on finding specific species that may contribute to the development of human diseases. However, we believe that complex diseases, such as NAFLD, would be more efficiently treated using consortia of species, given that bacterial functionality is based not only on its own genetic information but also on the interaction with other microorganisms. Our results revealed that exercise significantly changes the GM interaction and that structural alterations can be linked with improvements in intrahepatic lipid content and metabolic functions. We believe that the identification of these characteristics in the GM enhances the development of exercise treatment for NAFLD and will attract general interest in this field.

Non-alcoholic fatty liver disease (NAFLD) is a very common liver disease associated with obesity, unhealthy diet, and lack of physical exercise. Short-term aerobic or resistance exercise has been shown to result in reduced liver fat in patients with NAFLD; however, the impact of the combination of these types of exercise has received less attention. This study investigated the effect of a short-term (7 days) concurrent exercise training program performed daily on liver steatosis indices, as well as the glycemic and lipidemic profile of overweight/obese sedentary volunteers. Twenty adult patients (age: 47.3 ± 12.3 yrs, body mass index: 32.4 ± 3.4 kg/m2) with NAFLD, detected by ultrasound and hematological indices, participated in the study. Pre- and post-exercise intervention assessment included body weight (BW), waist circumference (WC), hip/waist ratio (H/W), Homeostasis Model Assessment Insulin Resistance (HOMA-IR), blood lipids, and steatosis indices. Fatty Liver Index, Lipid Accumulation Index, WC, H/W, triglycerides, and total cholesterol were improved (p < 0.05) post-exercise, while no differences (p > 0.05) were observed in BW, HOMA-IR, HDL, LDL, Hepatic Steatosis Index, and Framingham Steatosis Index compared to pre-exercise values. It is concluded that a 7-day combined exercise program can have beneficial effects on hepatic steatosis and central adiposity indices, independently of weight loss, in patients with NAFLD.

Obesity is a heterogenous disease accompanied by a broad spectrum of cardiometabolic risk profiles. Traditional paradigms for dietary weight management do not address biological heterogeneity between individuals and have catastrophically failed to combat the global pandemic of obesity-related diseases. Nutritional strategies that extend beyond basic weight management to instead target patient-specific pathophysiology are warranted. In this narrative review, we provide an overview of the tissue-level pathophysiological processes that drive patient heterogeneity to shape distinct cardiometabolic phenotypes in obesity. Specifically, we discuss how divergent physiology and postprandial phenotypes can reveal key metabolic defects within adipose, liver, or skeletal muscle, as well as the integrative involvement of the gut microbiome and the innate immune system. Finally, we highlight potential precision nutritional approaches to target these pathways and discuss recent translational evidence concerning the efficacy of such tailored dietary interventions for different obesity phenotypes, to optimise cardiometabolic benefits.

Advances in the development of noninvasive imaging techniques have spurred investigations into ectopic lipid deposition in the liver and muscle and its implications in the development of metabolic diseases such as type 2 diabetes. Computed tomography and ultrasound have been applied in the past, though magnetic resonance-based methods are currently considered the gold standard as they allow more accurate quantitative detection of ectopic lipid stores. This review focuses on methodological considerations of magnetic resonance-based methods to image hepatic and muscle fat fractions, and it emphasizes anatomical and morphological aspects and how these may influence data acquisition, analysis, and interpretation.

Diagnosing and managing metabolic dysfunction-associated steatotic liver disease (MASLD) remains a major challenge in primary care due to lack of agreement on diagnostic tools, difficulty in identifying symptoms and determining their cause, absence of approved pharmacological treatments, and limited awareness of the disease. However, prompt diagnosis and management are critical to preventing MASLD from progressing to more severe forms of liver disease. This highlights the need to raise awareness and improve understanding of MASLD among both patients and physicians. The patient perspective is invaluable to advancing our knowledge of this disease and how to manage it, as their perspectives have led to the growing recognition that patients experience subtle symptoms and that patient-reported outcomes should be incorporated into drug development. This review and expert opinion examine MASLD and metabolic dysfunction-associated steatohepatitis from the patient and physician perspective from pre-diagnosis to diagnosis and early care, through to progression to advanced liver damage. Specifically, the paper dives into the issues patients and physicians experience, and, in turn, what is required to improve diagnosis and management, including tips and tools to empower patients and physicians dealing with MASLD.

Although physical activity (PA) is crucial in the prevention and clinical management of nonalcoholic fatty liver disease, most individuals with this chronic disease are inactive and do not achieve recommended amounts of PA. There is a robust and consistent body of evidence highlighting the benefit of participating in regular PA, including a reduction in liver fat and improvement in body composition, cardiorespiratory fitness, vascular biology, and health-related quality of life. Importantly, the benefits of regular PA can be seen without clinically significant weight loss. At least 150 min of moderate or 75 min of vigorous intensity PA are recommended weekly for all patients with nonalcoholic fatty liver disease, including those with compensated cirrhosis. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. In this roundtable document, the benefits of PA are discussed, along with recommendations for 1) PA assessment and screening; 2) how best to advise, counsel, and prescribe regular PA; and 3) when to refer to an exercise specialist.

The prevalence of non-alcoholic fatty liver disease (NAFLD) in U.S. adults is over 30%, yet the role of lifestyle factors in the etiology of NAFLD remains understudied. We examined the associations of physical activity, by intensity and type, and television viewing with prevalent NAFLD.

Cross-sectional analysis of a population-based sample of 2726 Black (49%) and White (51%) adults (Mean (SD) age, 50 (3.6) years; 57.3% female) from the CARDIA study. Exposures were aerobic activity by intensity (moderate, vigorous; hours/week); activity type (aerobic, muscle-strengthening; hours/week); and television viewing (hours/week), examined concurrently in all models and assessed by validated questionnaires. Our outcome was NAFLD (liver attenuation < 51 Hounsfield Units), measured by non-contrast computed tomography, after exclusions for other causes of liver fat. Covariates were sex, age, race, study center, education, diet quality, smoking status, alcohol consumption, and body mass index or waist circumference.

648 participants had NAFLD. In the fully adjusted modified Poisson regression model, the risk ratios per interquartile range of each exposure were moderate-intensity aerobic activity, 1.10 (95% CI, 0.97-1.26); vigorous-intensity aerobic activity, 0.72 (0.63-0.82); muscle-strengthening activity, 0.89 (0.80-1.01); and television viewing, 1.20 (1.10-1.32). Relative to less active participants with higher levels of television viewing, those who participated in ≥2 h/week of both vigorous-intensity aerobic and muscle-strengthening activity and <7 h/week of television viewing had 65% lower risk of NAFLD (risk ratio = 0.35, 95% CI = 0.23-0.51).

Adults who follow public health recommendations for vigorous-aerobic and muscle-strengthening activity, as well as minimize television viewing, are considerably less likely to have NAFLD than those who do not follow the recommendations and who have relatively high levels of television viewing.

Many abdominal obesity indices such as waist circumference (WC), lipid accumulation product (LAP), visceral obesity index (VAI), and Chinese VAI (CVAI) have been considered to be associated with the risk of non-alcoholic fatty liver disease (NAFLD), but the association between abdominal obesity indices and the pathological features of NAFLD is uncertain. This study aims to explore the associations between these indices and the pathological features of NAFLD.

A total of 147 patients with biopsy-confirmed NAFLD were enrolled in the final analysis. General information, biochemical tests, and pathological information of patients were collected. VAI, LAP, and CVAI were calculated. Spearman's correlation analysis and logistics regression analysis were applied to assess the relationship between abdominal obesity indices and the pathological features of NAFLD. Receiver operating characteristic curve analyses were used to assess the value of abdominal obesity indices in predicting liver fibrosis and non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease activity score (NAS) ≥ 5 significantly correlated with WC, LAP, VAI, and CVAI both in univariate and multivariate analyses (P < 0.05). Fibrosis was significantly and positively correlated with WC, LAP, and CVAI (P < 0.05). After adjustment for potential confounders, fibrosis remained associated with CVAI (P < 0.05).

CVAI is significantly associated with the pathological features of NAFLD, and CVAI shows the most superior efficacy in diagnosing fibrosis among these indices.

Exercise training is crucial in the management of nonalcoholic fatty liver disease (NAFLD); however, whether it can achieve clinically meaningful improvement in liver fat is unclear. We investigated the association between exercise training and the achievement of validated thresholds of MRI-measured treatment response.

Randomized controlled trials in adults with NAFLD were identified through March 2022. Exercise training was compared with no exercise training. The primary outcome was ≥30% relative reduction in MRI-measured liver fat (threshold required for histologic improvement in nonalcoholic steatohepatitis activity, nonalcoholic steatohepatitis resolution, and liver fibrosis stage). Different exercise doses were compared.

Fourteen studies (551 subjects) met inclusion criteria (mean age 53.3 yrs; body mass index 31.1 kg/m 2 ). Exercise training subjects were more likely to achieve ≥30% relative reduction in MRI-measured liver fat (odds ratio 3.51, 95% confidence interval 1.49-8.23, P = 0.004) than those in the control condition. An exercise dose of ≥750 metabolic equivalents of task min/wk (e.g., 150 min/wk of brisk walking) resulted in significant treatment response (MRI response odds ratio 3.73, 95% confidence interval 1.34-10.41, P = 0.010), but lesser doses of exercise did not. Treatment response was independent of clinically significant body weight loss (>5%).

Independent of weight loss, exercise training is 3 and a half times more likely to achieve clinically meaningful treatment response in MRI-measured liver fat compared with standard clinical care. An exercise dose of at least 750 metabolic equivalents of task-min/wk seems required to achieve treatment response. These results further support the weight-neutral benefit of exercise in all patients with NAFLD.

Despite its increasing prevalence, nonalcoholic fatty liver disease (NAFLD) remains under-diagnosed in primary care. Timely diagnosis is critical, as NAFLD can progress to nonalcoholic steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and death; furthermore, NAFLD is also a risk factor linked to cardiometabolic outcomes. Identifying patients with NAFLD, and particularly those at risk of advanced fibrosis, is important so that healthcare practitioners can optimize care delivery in an effort to prevent disease progression. This review debates the practical issues that primary care physicians encounter when managing NAFLD, using a patient case study to illustrate the challenges and decisions that physicians face. It explores the pros and cons of different diagnostic strategies and tools that physicians can adopt in primary care settings, depending on how NAFLD presents and progresses. We discuss the importance of prescribing lifestyle changes to achieve weight loss and mitigate disease progression. A diagnostic and management flow chart is provided, showing the key points of assessment for primary care physicians. The advantages and disadvantages of advanced fibrosis risk assessments in primary care settings and the factors that influence patient referral to a hepatologist are also reviewed.

Nonalcoholic fatty liver disease (NAFLD) is a range of pathologies arising from fat accumulation in the liver in the absence of excess alcohol use or other causes of liver disease. Its complications include cirrhosis and liver failure, hepatocellular carcinoma, and eventual death. NAFLD is the most common cause of liver disease globally and is estimated to affect nearly one-third of individuals in the United States. Despite knowledge that the incidence and prevalence of NAFLD are increasing, the pathophysiology of the disease and its progression to cirrhosis remain insufficiently understood. The molecular pathogenesis of NAFLD involves insulin resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. Better insight into these molecular pathways would allow for therapies that target specific stages of NAFLD. Preclinical animal models have aided in defining these mechanisms and have served as platforms for screening and testing of potential therapeutic approaches. In this review, we will discuss the cellular and molecular mechanisms thought to contribute to NAFLD, with a focus on the role of animal models in elucidating these mechanisms and in developing therapies.

This study investigated the impact of exercise training on major pulmonary vasomotor mediators and receptors including endothelial nitric oxide synthase (eNOS) inducible NOS (iNOS), endothelin-1 (ET-1), ET-1 receptors A (ET_A) and-B (ET_B) in high-fat-high-carbohydrate (HFHC) induced non-alcoholic fatty liver disease (NAFLD). NAFLD increased iNOS, ET-1 and ET_A (p<0.05)_, but not ET_B (p>0.05). Exercise attenuated iNOS, ET-1 and ET_A (p<0.05)_., but not ET_B (p>0.05) and eNOS (p>0.05). Exercise training is beneficial for pulmonary vasculature in NAFLD. DATA AVAILABILITY: The data analyzed in the present study will be available from the corresponding author upon reasonable request.

Non-Alcoholic Fatty Liver Disease (NAFLD) and Type 2 Diabetes (T2D) are highly prevalent diseases worldwide. Insulin Resistance (IR) is the common denominator of the two conditions even if the precise timing of onset is unknown. Lifestyle change remains the most effective treatment to manage NAFLD. This study aimed to estimate the effect of the Low Glycemic Index Mediterranean Diet (LGIMD) and exercise (aerobic and resistance) over a one-year period on the longitudinal trajectories of glucose metabolism regulatory pathways.

In this observational study, 58 subjects (aged 18-65) with different degrees of NAFLD severity were enrolled by the National Institute of Gastroenterology-IRCCS "S. de Bellis", to follow a 12-month program of combined exercise and diet.

The mean age was 55 ± 7 years old. Gender was equally distributed among NAFLD categories. There was a statistically significant main effect of time for glycosylated hemoglobin (Hb1Ac) over the whole period (-5.41, 95% CI: -7.51; -3.32). There was a steady, statistically significant decrease of HbA1c in participants with moderate and severe NAFLD whereas this effect was observed after the 9th month in those with mild NAFLD.

The proposed program significantly improves glucose metabolism parameters, especially HbA1c.

Lifestyle modifications, including increased physical activity and exercise, are recommended for non-alcoholic fatty liver disease (NAFLD). Inflamed adipose tissue (AT) contributes to the progression and development of NAFLD and oxylipins such as hydroxyeicosatetraenoic acids (HETE), hydroxydocosahexanenoic acids (HDHA), prostaglandins (PEG₂), and isoprostanoids (IsoP), which all may play a role in AT homeostasis and inflammation. To investigate the role of exercise without weight loss on AT and plasma oxylipin concentrations in NAFLD subjects, we conducted a 12-week randomized controlled exercise intervention. Plasma samples from 39 subjects and abdominal subcutaneous AT biopsy samples from 19 subjects were collected both at the beginning and the end of the exercise intervention. In the AT of women, a significant reduction of gene expression of hemoglobin subunits (HBB, HBA1, HBA2) was observed within the intervention group during the 12-week intervention. Their expression levels were negatively associated with VO₂max and maxW. In addition, pathways involved in adipocyte morphology alterations significantly increased, whereas pathways in fat metabolism, branched-chain amino acids degradation, and oxidative phosphorylation were suppressed in the intervention group (p < 0.05). Compared to the control group, in the intervention group, the ribosome pathway was activated, but lysosome, oxidative phosphorylation, and pathways of AT modification were suppressed (p < 0.05). Most of the oxylipins (HETE, HDHA, PEG₂, and IsoP) in plasma did not change during the intervention compared to the control group. 15-F_2t-IsoP significantly increased in the intervention group compared to the control group (p = 0.014). However, this oxylipin could not be detected in all samples. Exercise intervention without weight loss may influence the AT morphology and fat metabolism at the gene expression level in female NAFLD subjects.

The association between nonalcoholic fatty liver disease (NAFLD) and sarcopenia is known. We aimed to determine the association between skeletal muscle mass changes and NAFLD status. This retrospective single-center study analyzed patients who underwent health screening twice between November 2009 and December 2017, with a temporal gap of 6 ± 0.5 years. The degree of sarcopenia was assessed using appendicular skeletal muscle mass (ASM) adjusted for weight and body mass index (BMI). Changes in hepatic steatosis and fibrosis status were evaluated using noninvasive serum markers. Patients with a decrease in ASM/BMI (n = 353) had increased hepatic steatosis index (HSI) and fatty liver index (FLI) scores during 6 years (p < 0.05). The baseline sarcopenia group had a greater elevation in NAFLD fibrosis score (NFS) over 6 years than those without baseline sarcopenia. ASM changes over 6 years showed a negative correlation with variations in HSI (β = - 0.96 in ASM/Weight and -28.93 in ASM/BMI) and FLI (β = - 5.44 in ASM/Weight and - 167.12 in ASM/BMI). Subgroup analyses showed similar results according to sex and age. Sarcopenia may worsen steatosis and vice versa. Skeletal muscle status can be used to predict the course of NAFLD and establish individualized treatment strategies.

Structured exercise as part of lifestyle modification plays an important role in the improvement of non-alcoholic fatty liver disease (NAFLD); however, its effectiveness has been shown to vary. This systematic review with meta-analysis investigated the effects of exercise on liver function and insulin resistance markers in patients with NAFLD.

Six electronic databases were searched using terms related to exercise and NAFLD up to March 2022. Data were analyzed using a random-effects model to estimate the standardized mean difference (SMD) and 95% confidence interval.

The systematic search identified 2583 articles, of which a total of 26 studies met the inclusion criteria and were eligible. Exercise training had a moderate effect on reducing ALT (SMD: -0.59, p = 0.01) and small effects on reducing AST (SMD: -0.40, p = 0.01) and insulin (SMD: -0.43, p = 0.02). Significant reductions in ALT were found following aerobic training (SMD: -0.63, p < 0.01) and resistance training (SMD: -0.45, p < 0.001). Moreover, reductions in AST were found following resistance training (SMD: -0.54, p = 0.001), but not after aerobic training and combined training. However, reductions in insulin were found following aerobic training (SMD: -0.55, p = 0.03). Exercise interventions for <12 weeks compared to ≥12 weeks were more effective in reducing FBG and HOMA-IR, while interventions for ≥12 weeks compared to <12 weeks were more effective in reducing ALT and AST levels.

Our findings support the effectiveness of exercise in improving liver function markers but not in blood glucose control in NAFLD patients. Additional studies are needed to determine the exercise prescription to maximize health in these patients.