Metabolic dysfunction-associated steatotic liver disease (MASLD) is intrinsically linked with widespread metabolic perturbations, including within skeletal muscle. Indeed, MASLD is associated with a range of skeletal muscle abnormalities, including insulin resistance, myosteatosis, and sarcopenia, which all converge on the liver to drive disease progression and adverse patient outcomes. This review explores the mechanistic links between skeletal muscle and MASLD, including the role of abnormal glycemic control, systemic inflammation, and disordered myokine signaling. In turn, we discuss how intrinsic liver pathology can feed back to further exacerbate poor skeletal muscle health. Given the central importance of skeletal muscle in MASLD pathogenesis, it offers clinicians an opportunity to intervene for therapeutic benefit. We, therefore, summarize the role of nutrition and physical activity on skeletal muscle mass, quality, and metabolic function and discuss the knock-on effect this has on the liver. An awareness of these treatment strategies is particularly important in the era of effective pharmacological and surgical weight loss interventions, which can be associated with the development of sarcopenia. Finally, we highlight a number of promising drug agents in the clinical trial pipeline that specifically target skeletal muscle in an attempt to improve metabolic and physical functioning.

Data on tirzepatide in Asian patients with obesity are limited. This study aimed to gain a better understanding of tirzepatide for treatment of Japanese patients with obesity disease (BMI ≥25 kg/m2 with excessive fat accumulation) as defined by the Japanese Society for the Study of Obesity.

This was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of tirzepatide as an adjunct to lifestyle modifications. Japanese adults with obesity disease (BMI ≥27 kg/m2 accompanied by ≥2 obesity-related health disorders or ≥35 kg/m2 accompanied by ≥1 obesity-related health disorders), excluding diabetes, were assigned 1:1:1 via computer-generated random sequence to receive once weekly subcutaneous tirzepatide (10 mg or 15 mg) or placebo. Coprimary endpoints were the mean percent change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction at week 72, using the efficacy estimand. Efficacy and safety were assessed in the modified intention-to-treat (mITT) population. This study is registered with ClinicalTrials.gov, NCT04844918.

Between May 10, 2021, and June 24, 2023, 413 participants were screened, and 267 were randomly assigned. Due to exclusion of one study site, the mITT population was 225 participants (133 [59%] men and 92 [41%] women, mean age 50·8 [SD 10·7] years), with 73 in the tirzepatide 10 mg group, 77 in the tirzepatide 15 mg group, and 75 in the placebo group, of whom 192 (85%) completed both study and treatment. Estimated treatment differences relative to placebo in change in bodyweight at week 72 were -16·1% (95% CI -18·7 to -13·5; p<0·0001) and -21·1% (95% CI -23·6 to -18·5; p<0·0001) following tirzepatide 10 mg and 15 mg, respectively. At week 72, a higher proportion of participants achieved at least 5% bodyweight reduction with tirzepatide 10 mg (67 [94%] of 71) and 15 mg (73 [96%] of 76) compared with placebo (15 [20%] of 75; both p<0·0001). Cardiometabolic and body composition indices were also improved with tirzepatide. Participants treated with tirzepatide experienced treatment-emergent adverse events more frequently (10 mg: n=61 [84%]; 15 mg: n=66 [86%]) than those who received placebo (52 [69%]), most commonly gastrointestinal symptoms. Study discontinuations due to adverse events were infrequent (placebo: n=3 [4%]; tirzepatide 10 mg: n=1 [1%]; tirzepatide 15 mg: n=0).

In Japanese adults with obesity disease, tirzepatide provided clinically a meaningful reduction in bodyweight compared with placebo over 72 weeks, with a safety profile consistent with that observed in global populations.

Eli Lilly and Company.

For the Japanese translation of the abstract see Supplementary Materials section.

Notch1 protein plays a significant role in hepatic metabolism, as evidenced by its correlation with insulin resistance in the livers of obese individuals, making it an intriguing research target. Therefore, this study aims to investigate the impact of aerobic exercise on Notch1 pathways in the hepatic tissue of obese mice and its role in controlling hepatic metabolism.

Therefore, we conducted a cross-sectional study utilising liver biopsies from lean and obese humans, as well as an intervention study involving mice subjected to a high-fat diet. The obese-trained mice group underwent a treadmill-running protocol for 4 weeks.

Our findings revealed that obese individuals exhibited increased NOTCH1 mRNA levels compared to lean subjects. The detrimental effects of Notch1 signalling were confirmed by Notch1-overexpressed HepG2 cell lines. Obese mice with higher hepatic Notch1 signalling demonstrated a reduction in this pathway when subjected to a 4-week treadmill running. Another benefit noticed in this trained group was the amelioration of insulin resistance, as well as a reduction in pyruvate intolerance and gluconeogenic enzymes. Additionally, we observed that these protective findings were accompanied by a decrease in mTORC1 pathway activity and lipid accumulation in the liver. Pharmacological inhibition of Notch1 in obese mice led to an increase in mitochondrial respiration in the liver.

We conclude that Notch1 signalling may be a potentially useful therapeutic target in obesity, while aerobic exercise training suppresses the Notch1 pathway in the liver, contributing to the regulation of hepatic glucose and lipid metabolism in obese mice.

Nonalcoholic fatty liver disease (NAFLD) is a global health concern, and despite its high prevalence, lifestyle modifications such as exercise play a pivotal role in resolving this condition. This study aims to identify factors associated with NAFLD resolution, with a focus on the role of exercise, in different age groups.

Longitudinal data from Korean military officers, during the period 2019-2021, were obtained from the National Health Information Database. NAFLD was defined as a hepatic steatosis index ≥36, and NAFLD resolution was defined as individuals achieving hepatic steatosis index <36 in the subsequent year of diagnosis. Information on alcohol consumption, exercise frequency, and family history of diabetes was collected through self-reported questionnaires.

The analysis included a total of 163,728 individuals, with a mean age of 36.87, predominantly male (91.62%). The prevalence of NAFLD was 27.04%. Favorable factors for NAFLD resolution encompassed moderate-intensity exercise for more than 180 minutes per week, vigorous-intensity exercise for more than 90 minutes per week, female sex, age, and resistance exercise for more than 3 days per week. Hypertension, family history of diabetes, and smoking were identified as factors against NAFLD resolution. The exercise requirements for NAFLD resolution varied among age groups, with those <30 years old requiring more than 180 minutes per week of moderate- or vigorous-intensity exercise and those >50 years old needing only 90 minutes per week of such exercise.

The exercise requirements for NAFLD resolution exhibit age-related differences. Individualized guidance for NAFLD management should consider these variations and be tailored to specific age groups.

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.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and it is not only the keystone precursor of eventual liver-related morbidity, but it also places patients at considerably higher cardiovascular risk, which is still a leading cause of death in these patients. The most important common underlying pathophysiological mechanisms in these diseases are primarily related to insulin resistance, chronic inflammation and oxidative stress. The presence of MASLD with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) elevates the risk for poor outcomes, thus this review highlights a method to the therapeutic approaches. Given the intertwined nature of MASLD, T2DM, and CVD, there is an urgent need for therapeutic strategies that address all three conditions. Although lifestyle changes are important as treatment, medication plays a crucial role in managing hyperglycemia, enhancing liver function and lowering cardiovascular risk. The onset and progression of MASLD should be addressed through a multifaceted therapeutic approach, targeting inflammatory, immune, metabolic, oxidative stress, hormonal and gutaxis pathways, alongside the treatment strategies for T2DM. In this review, we discuss the effects of antidiabetic drugs with an impact on both liver outcomes and cardiovascular risk in patients affected by MASLD, T2DM and CDV.

The worldwide prevalence of diabetes is increasing, particularly among older adults. Understanding the association between muscle strength and mortality in this population is crucial for developing targeted exercise recommendations.

To assess the prospective association of muscle strength with mortality in older adults with diabetes.

From the Survey of Health, Ageing and Retirement in Europe (SHARE) study, spanning 28 countries, we included 16 149 diabetic adults aged 50 years and older (mean age 68.2 [standard deviation, SD, 9.2] years). Participants fulfilled two criteria: (1) diabetes diagnosis (ever) and (2) current use of diabetes medication. Muscle strength was assessed using handgrip dynamometry (unit: kg). Using time-varying Cox regression with restricted cubic splines, we determined the prospective association of muscle strength with all-cause and cause-specific mortality, controlling for various confounders.

Over a mean follow-up of 5.9 years (SD 3.8), 2754 participants died (17%). Using the median level of muscle strength as reference (30 kg), lower and higher levels were associated in a curvilinear fashion with higher and lower all-cause mortality risk, respectively. The 10th percentile of muscle strength (17 kg) showed a hazard ratio (HR) of 1.65 (95% confidence interval (CI) 1.53-1.79). The 90th percentile (47 kg) of muscle strength showed a HR of 0.55 (95% CI 0.49-0.63). A somewhat similar pattern, with varying strength of associations, was seen for mortality due to cardiovascular disease (CVD), respiratory disease, severe infectious disease, digestive system disease and cancer.

Muscle strength is gradually and inversely associated with all-cause and cause-specific mortality risk in older adults with diabetes. As muscle strength is highly adaptable to resistance training at all ages, the present findings highlight the importance of improving muscle strength in older adults with diabetes.

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.

Chronic diseases linked with sedentary lifestyles and poor dietary habits are increasingly common in modern society. Exercise is widely acknowledged to have a plethora of health benefits, including its role in primary prevention of various chronic conditions like type 2 diabetes mellitus, obesity, cardiovascular disease, and several musculoskeletal as well as degenerative disorders. Regular physical activity induces numerous physiological adaptations that contribute to these positive effects, primarily observed in skeletal muscle but also impacting other tissues. There is a growing interest among researchers in developing pharmaceutical interventions that mimic the beneficial effects of exercise for therapeutic applications. Exercise mimetic medications have the potential to be helpful aids in enhancing functional outcomes for patients with metabolic dysfunction, neuromuscular and musculoskeletal disorders. Some of the potential targets for exercise mimetics include pathways involved in metabolism, mitochondrial function, inflammation, and tissue regeneration. The present review aims to provide an exhaustive overview of the current understanding of exercise physiology, the role of exerkines and biomolecular pathways, and the potential applications of exercise mimetic drugs for the treatment of several diseases.

The aim was to investigate the effects of different volumes of strength training (ST) in association with photobiomodulation (PBMt) in mice fed a high-fat diet (HFD) on insulin resistance (IR). Male Swiss albino mice were fed HFD and performed high- or low-volume (one-third) ST (3 days/week), associated with PBMt (660 nm + 850 nm; ~42 J delivered) or not (lights off). ST improved IR, lowered visceral adiposity and circulating cytokines, and increased skeletal muscle hypertrophy and mitochondrial activity. The smaller volume of ST did not interfere with the improvement in IR, mitochondrial activity, or inflammatory profile, but exerted a smaller effect on visceral adiposity and skeletal muscle hypertrophy. Association with PBMt further improved IR, regardless of ST volume, although it did not affect adiposity, mitochondrial activity, and the inflammatory profile. Interestingly, PBMt positively affected quadriceps, but attenuated gluteus maximus hypertrophy. The association with PBMt induced greater improvement than ST alone.

This study aimed to evaluate the effects of a novel, low-volume combined high-intensity interval training (HIIT) and progressive resistance training (PRT) in overweight/obese adults.

This randomised control trial compared the effect of regular supervised HIIT combined with PRT (Exercise) with an unsupervised stretching intervention (Control), in previously inactive adults with either normal glucose (NG), pre-diabetes or type 2 diabetes (T2DM) with body mass index of >25 kg/m2. Participants were randomly allocated (1:1) to receive low-volume exercise or control by an online randomisation tool. The primary outcome was the difference in change of hepatic steatosis between Exercise and Control. A prespecified sensitivity analysis was undertaken for weight stable participants (<5% change in bodyweight from baseline). Secondary outcomes were change in hepatic steatosis within the glucose groups, glycaemic control, cardiorespiratory fitness, muscle strength and body composition.

Between June 2018 and May 2021, 162 participants were randomly assigned (NG: 76, pre-diabetes: 60, T2DM: 26) and 144 were included in the final analysis. Mean absolute change in hepatic steatosis was -1.4% (4.9) in Exercise (n=73) and -0.1% (7.2) in Control (n=71)(p=0.25). By preplanned sensitivity analysis, the mean change in hepatic steatosis with Exercise (n=70) was -1.5% (5) compared with 0.7% (4.6) with Control (n=61) (p=0.017). Subgroup analysis within the glucose groups showed that exercise reduced hepatic steatosis in those with pre-diabetes but not NG or T2DM (pre-diabetes: -1.2% (4.4) in Exercise and 1.75% (5.7) in Control, p=0.019).

These findings show that low-volume HIIT with PRT yields improvements in muscle strength and cardiorespiratory fitness and may have a small effect on hepatic steatosis.

The trial was prospectively registered with the ANZCTR (ACTRN12617000552381).

Exercise has multiple beneficial effects on human metabolic health and is regarded as a "polypill" for various diseases. At present, the lack of physical activity usually causes an epidemic of chronic metabolic syndromes, including obesity, cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD). Remarkably, NAFLD is emerging as a serious public health issue and is associated with the development of cirrhosis and hepatocellular carcinoma. Unfortunately, specific drug therapies for NAFLD and its more severe form, non-alcoholic steatohepatitis (NASH), are currently unavailable. Lifestyle modification is the foundation of treatment recommendations for NAFLD and NASH, especially for exercise. There are under-appreciated organs that crosstalk to the liver during exercise such as muscle-liver crosstalk. Previous studies have reported that certain exerkines, such as FGF21, GDF15, irisin, and adiponectin, are beneficial for liver metabolism and have the potential to be targeted for NAFLD treatment. In addition, some of exerkines can be modified for the new proteins and get enhanced functions, like IL-6/IC7Fc. Another importance of exercise is the physiological adaptation that combats metabolic diseases. Thus, this review aims to summarize the known exerkines and utilize a multi-omics mining tool to identify more exerkines for the future research. Overall, understanding the mechanisms by which exercise-induced exerkines exert their beneficial effects on metabolic health holds promise for the development of novel therapeutic strategies for NAFLD and related diseases.

Nonalcoholic fatty liver disease (NAFLD) involves excessive liver fat accumulation and is closely linked to oxidative stress, which contributes to liver inflammation and damage. This study aimed to evaluate how interventions such as resistance training (RT) and vitamin E supplementation (VES) can modulate markers of NAFLD and key proteins regulating glucose and lipid metabolism, such as C1Q/TNF-related proteins (CTRPs).

Forty participants with NAFLD (mean age: 32.4 ± 8.2 years) were randomly assigned to one of four groups for 12 weeks: placebo (PLB), VES, PLB + RT, and VES + RT. VES was administered at 800 IU/day in a double-blind manner. The RT regimen included eight exercises at 60-80% of one-repetition maximum (1RM), with three sets of 8-12 repetitions, performed three times per week. Pre- and post-intervention assessments included body composition, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lipid profile, glycemic control, CTRP-2, CTRP-9, and 1RM evaluations.

Following the interventions, there was a significant improvement in body composition, lipid profile, glycemic control, and 1RM indices in the exercise groups compared to non-exercise groups (p < 0.05). AST and ALT levels decreased in all groups (p < 0.05) compared to the PLB group. There was also a significant difference between the VES + RT group and both the VES and PLB + RT groups (p < 0.05). CTRP-2 and CTRP-9 levels decreased in the exercise groups compared to non-exercise groups (p < 0.05), and their changes showed a marked correlation with body composition, lipid profile, and glycemic control indices (p < 0.05).

This study highlights the benefits of RT on various health parameters among NAFLD patients. While adding VES to RT resulted in greater decreases in aminotransferases, it did not provide further improvements in other variables. Additionally, enhancements in body composition, lipid profile, and glycemic control indices were possibly associated with decreased levels of CTRPs.

Registered retrospectively in the Iranian Registry of Clinical Trials (IRCT20220601055056N1) on December 21, 2023. Access at https://irct.behdasht.gov.ir/trial/69231 .

In this issue, Burke et al. discuss the utility of the rodent synergist ablation (SA) model for examining mechanisms associated with skeletal muscle hypertrophy. In this invited perspective, we aim to complement their original perspective by discussing limitations to the model along with alternative mechanical overload models that have strengths and limitations.

Metabolic diseases, notably obesity and type 2 diabetes (T2D), have reached alarming proportions and constitute a significant global health challenge, emphasizing the urgent need for effective preventive and therapeutic strategies. In contrast, exercise training emerges as a potent intervention, exerting numerous positive effects on metabolic health through adaptations to the metabolic tissues. Here, we reviewed the major features of our current understanding with respect to the intricate interplay between metabolic diseases and key metabolic tissues, including adipose tissue, skeletal muscle, and liver, describing some of the main underlying mechanisms driving pathogenesis, as well as the role of exercise to combat and treat obesity and metabolic disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), is the main cause of chronic liver disease in children and adolescents. Indeed, epidemiological studies have shown that MASLD affects up to 40% of children with obesity. Despite the recent approval of medications that target weight loss in adolescents that could have benefits on pediatric MASLD, lifestyle interventions, such as diet and exercise, remain the mainstay of our therapeutic approach. More specifically, studies on diet alone have focused on the possible role of carbohydrate or fat restriction, albeit without a definite answer on the best approach. Weight loss after dietary intervention in children with obesity and MASLD has a beneficial effect, regardless of the diet used. In relation to the role of exercise in MASLD reversal, indirect evidence comes from studies showing that a sedentary lifestyle leading to poor fitness, and low muscle mass is associated with MASLD. However, research on the direct effect of exercise on MASLD in children is scarce. A combination of diet and exercise seems to be beneficial with several studies showing improvement in surrogate markers of MASLD, such as serum alanine aminotransferase and hepatic fat fraction, the latter evaluated with imaging studies. Several dietary supplements, such as vitamin E, probiotics, and omega-3 fatty acid supplements have also been studied in children and adolescents with MASLD, but with equivocal results. This review aims to critically present available data on the effects of lifestyle interventions, including diet, exercise, and dietary supplements, on pediatric MASLD, thus suggesting a frame for future research that could enhance our knowledge on pediatric MASLD management and optimize clinicians' approach to this vexing medical condition.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has emerged as a prevalent health concern, encompassing a wide spectrum of liver-related disorders. Insulin resistance, a key pathophysiological feature of MASLD, can be effectively ameliorated through dietary interventions. The Mediterranean diet, rich in whole grains, fruits, vegetables, legumes, and healthy fats, has shown promising results in improving insulin sensitivity. Several components of the Mediterranean diet, such as monounsaturated fats and polyphenols, exert anti-inflammatory and antioxidant effects, thereby reducing hepatic steatosis and inflammation. Furthermore, this dietary pattern has been associated with a higher likelihood of achieving MASLD remission. In addition to dietary modifications, physical exercise, particularly resistance exercise, plays a crucial role in enhancing metabolic flexibility. Resistance exercise training promotes the utilization of fatty acids as an energy source. It enhances muscle glucose uptake and glycogen storage, thus reducing the burden on the liver to uptake excess blood glucose. Furthermore, resistance exercise stimulates muscle protein synthesis, contributing to an improved muscle-to-fat ratio and overall metabolic health. When implemented synergistically, the Mediterranean diet and resistance exercise can elicit complementary effects in combating MASLD. Combined interventions have demonstrated additive benefits, including greater improvements in insulin resistance, increased metabolic flexibility, and enhanced potential for MASLD remission. This underscores the importance of adopting a multifaceted approach encompassing dietary modifications and regular physical exercise to effectively manage MASLD. This narrative review explores the biological mechanisms of diet and physical exercise in addressing MASLD by targeting insulin resistance and decreased metabolic flexibility.

Emerging treatment methods, including exercise, diet, and drugs, for nonalcoholic fatty liver disease have been proposed. However, the differences in their efficacy have not been determined. We aimed to compare the effects of these treatments excluding surgery via a systematic review and network meta-analysis of randomized controlled trials.

The data sources included PubMed, Embase, Web of Science and Cochrane up to February 1st, 2023. The endpoints consisted of body mass index (BMI), serum markers of metabolism and liver injury markers, liver fat content, and stiffness.

A total of 174 studies with 10,183 patients were included in this meta-analysis. In terms of improving BMI, Pan-agonist of peroxisome proliferator-activated receptors (PPAR) is the best treatment with the highest SUCRA (surface under the cumulative ranking) of 84.8% (mean = -3.40, 95% CI -5.55, -1.24) by the comparative effectiveness ranking. GLP-1 (glucagon-like peptide-1) has the best effect in improving the liver fat content based on the MRI-PDFF, steatosis score (SUCRA 99.7%, mean = -2.19, 95% CI -2.90, -1.48) and ballooning score (SUCRA 61.2%, mean = -0.82, 95% CI -4.46, 2.83).

Pan-agonist of PPAR was the most efficacious regimen in lowering BMIs, whereas GLP-1R agonists achieved the highest efficacy of steatosis improvement in this network meta-analysis.

Lifestyle modification represents the first-line strategy for the prevention and treatment of type 2 diabetes mellitus (T2DM), which is frequently associated with obesity and characterized by defective pancreatic insulin secretion and/or insulin resistance. Exercise training is an essential component of lifestyle modification and has been shown to ameliorate insulin resistance by reducing body fat mass and by enhancing skeletal muscle mitochondrial biogenesis and insulin-independent glucose uptake. Additionally, exercising stimulates the release of exerkines such as metabolites or cytokines, but also long non-coding RNA, microRNAs, cell-free DNA (cf-DNA), and extracellular vesicles (EVs), which contribute to inter-tissue communication. There is emerging evidence that EV number and content are altered in obesity and T2DM and may be involved in several metabolic processes, specifically either worsening or improving insulin resistance. This review summarizes the current knowledge on the metabolic effects of exercise training and on the potential role of humoral factors and EV as new biomarkers for early diagnosis and tailored treatment of T2DM.

This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD).

The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry.

After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group ( P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group ( P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group ( P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92).

Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease, is a steatotic liver disease associated with metabolic syndrome (MetS), especially obesity, hypertension, diabetes, hyperlipidemia, and hypertriglyceridemia. MASLD in 43-44% of patients can progress to metabolic dysfunction-associated steatohepatitis (MASH), and 7-30% of these cases will progress to liver scarring (cirrhosis). To date, the mechanism of MASLD and its progression is not completely understood and there were no therapeutic strategies specifically tailored for MASLD/MASH until March 2024. The conventional antiobesity and antidiabetic pharmacological approaches used to reduce the progression of MASLD demonstrated favorable peripheral outcomes but insignificant effects on liver histology. Alternatively, phyto-synthesized metal-based nanoparticles (MNPs) are now being explored in the treatment of various liver diseases due to their unique bioactivities and reduced bystander effects. Although phytonanotherapy has not been explored in the clinical treatment of MASLD/MASH, MNPs such as gold NPs (AuNPs) and silver NPs (AgNPs) have been reported to improve metabolic processes by reducing blood glucose levels, body fat, and inflammation. Therefore, these actions suggest that MNPs can potentially be used in the treatment of MASLD/MASH and related metabolic diseases. Further studies are warranted to investigate the feasibility and efficacy of phytonanomedicine before clinical application.

The risk associated with multiple cancers, cardiovascular disease, diabetes, and all-cause mortality is decreased in individuals who meet the current recommendations for physical activity. Therefore, regular exercise remains a cornerstone in the prevention and treatment of non-communicable diseases. An acute bout of exercise results in the coordinated interaction between multiple tissues to meet the increased energy demand of exercise. Over time, the associated metabolic stress of each individual exercise bout provides the basis for long-term adaptations across tissues, including the cardiovascular system, skeletal muscle, adipose tissue, liver, pancreas, gut, and brain. Therefore, regular exercise is associated with a plethora of benefits throughout the whole body, including improved cardiorespiratory fitness, physical function, and glycemic control. Overall, we summarize the exercise-induced adaptations that occur within multiple tissues and how they converge to ultimately improve cardiometabolic health.

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects many populations, and screening out the high-risk populations at an early stage is a challenge. As a sarcopenia index, the relationship between creatinine to cystatin C ratio (CCR) and MASLD remains unclear. This cross-sectional, prospective study aimed to explore the relationship between CCR and MASLD. Design Firstly, explored the correlation between CCR and MASLD in cross-sectional analyses. Then excluded the population with baseeline diagnosis of MASLD and analyzed the association with baseline CCR levels and the onset of MASLD in the population with available follow-up data. Univariate and multivariate logistic regression analyses were used to calculate odds ratios (ORs) to evaluate the association between CCR levels and MASLD.

This study included 368,634 participants from the UK Biobank for cross-sectional and prospective analyses. The demographic characteristics and laboratory measurements of all participants were obtained from the UK Biobank. MASLD was diagnosed according to the multi-society consensus nomenclature. Hepatic steatosis was defined as FLI  ≥60.

We grouped the study participants according to CCR tertiles. In cross-sectional analyses, participants in CCR tertile 1 had the highest MASLD risk (OR: 1.070, 95% CI: 1.053-1.088, p < .001). And the similar association was observed in the prospective analyses (CCR tertile 1 OR: 1.340, 95% CI: 1.077-1.660, p = .009; CCR tertile 2 OR: 1.217, 95% CI: 1.021-1.450, p = .029, respectively). After stratification by gender, the significant association between CCR and the onset of MASLD was only observed in males (CCR tertile 1 OR: 1.639, 95% CI: 1.160-2.317, p = .005; CCR tertile 2 OR: 1.322, 95% CI: 1.073-1.628, p = .005, respectively).

Our results indicated that lower CCR was significantly associated with higher risk of MASLD, based on which predictive models can be developed to screen populations at high risk of developing MASLD.

Metabolic associated fatty liver disease (MAFLD) is a novel terminology introduced in 2020 to provide a more accurate description of fatty liver disease associated with metabolic dysfunction. It replaces the outdated term nonalcoholic fatty liver disease (NAFLD) and aims to improve diagnostic criteria and tailored treatment strategies for the disease. NAFLD, the most prevalent liver disease in western industrialized nations, has been steadily increasing in prevalence and is associated with serious complications such as cirrhosis and hepatocellular carcinoma. It is also linked to insulin resistance syndrome and cardiovascular diseases. However, current studies on NAFLD have limitations in meeting necessary histological endpoints.

This literature review aims to consolidate recent knowledge and discoveries concerning MAFLD, integrating the diverse aspects of the disease. Specifically, it focuses on analyzing the diagnostic criteria for MAFLD, differentiating it from NAFLD and alcoholic fatty liver disease (AFLD), and exploring the epidemiology, clinical manifestations, pathogenesis, and management approaches associated with MAFLD. The review also explores the associations between MAFLD and other conditions. It discusses the heightened mortality risk associated with MAFLD and its link to chronic kidney disease (CKD), showing that MAFLD exhibits enhanced diagnostic accuracy for identifying patients with CKD compared to NAFLD. The association between MAFLD and incident/prevalent CKD is supported by cohort studies and meta-analyses.

This literature review highlights the importance of MAFLD as a distinct terminology for fatty liver disease associated with metabolic dysfunction. The review provides insights into the diagnostic criteria, associations with CKD, and management approaches for MAFLD. Further research is needed to develop more accurate diagnostic tools for advanced fibrosis in MAFLD and to explore the underlying mechanisms linking MAFLD with other conditions. This review serves as a valuable resource for researchers and healthcare professionals seeking a comprehensive understanding of MAFLD.

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.

Cross-sectional studies have demonstrated the association of skeletal muscle mass with metabolic-associated fatty liver disease (MAFLD), while longitudinal data are scarce. We aimed to explore the impact of changes in relative skeletal muscle mass on the MAFLD treatment response.

MAFLD patients undergoing magnetic resonance imaging-based proton density fat fraction for liver fat content (LFC) assessments and bioelectrical impedance analysis before and after treatment (orlistat, meal replacement, lifestyle modifications) were enrolled. Appendicular muscle mass (ASM) was adjusted by weight (ASM/W).

Overall, 256 participants were recruited and divided into two groups: with an ASM/W increase (n=166) and without an ASM/W increase (n=90). There was a great reduction in LFC in the group with an ASM/W increase (16.9% versus 8.2%, P < 0.001). However, the change in LFC in the group without an ASM/W increase showed no significant difference (12.5% versus 15.0%, P > 0.05). △ASM/W Follow-up-Baseline [odds ratio (OR)=1.48, 95% confidence interval (CI) 1.05-2.07, P = 0.024] and △total fat mass (OR=1.45, 95% CI 1.12-1.87, P = 0.004) were independent predictors for steatosis improvement (relative reduction of LFC ≥ 30%). The subgroup analysis showed that, despite without weight loss, decrease in HOMA-IR (OR=6.21, 95% CI 1.28-30.13, P=0.023), △total fat mass Baseline -Follow-up (OR=3.48, 95% CI 1.95-6.21, P <0.001 and △ASM/W Follow-up-Baseline (OR=2.13, 95% CI 1.12-4.05, P=0.022) independently predicted steatosis improvement.

ASM/W increase and loss of total fat mass benefit the resolution of liver steatosis, independent of weight loss for MAFLD.

Women with Polycystic Ovary Syndrome (PCOS) have a higher prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) than the general population. PCOS and NAFLD have common metabolic risk factors, however, the role of diet in NAFLD development is still uncertain in PCOS women.

To evaluate and compare the dietary patterns and nutritional intake in patients with PCOS with and without NAFLD.

Cross-sectional study that included patients with PCOS diagnosed according to Rotterdam criteria. All participants were submitted to abdominal ultrasound to investigate liver steatosis. Dietary profile was assessed by 24-hour food recall (24hR), and Food Frequency Questionnaire (FFQ). Diet quality was assessed by the Healthy Eating Index (HEI) adapted for the Brazilian population. Physical activity practice was also assessed.

87 participants were included (average age 35.2 ± 5.7 years), among whom, 67 (77%) had NAFLD. The group with PCOS and NAFLD presented higher body mass index (BMI) (34.9 ± 4.5 vs. 30.4 ± 4.9 kg/m2; p = 0.001), Waist Circumference (WC) (103 [97‒113] vs. 95 [87.5‒100] cm; p < 0.001) and were considered physically active less frequently than those without NAFLD (34.3% vs. 60%; p = 0.04). Food intake and dietary patterns assessed by 24hR, FFQ and HEI presented no difference between the groups.

PCOS women with coexistent NAFLD had higher BMI, WC and were less physically active than those without NAFLD. Dietary evaluation showed that PCOS women with NAFLD had no significant difference in macro and micronutrients or food group intake and diet quality in comparison to those without NAFLD.

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.

Proper nutrition and exercise are effective strategies to improve overall metabolic health in diabetic patients.

This study evaluated the effects of Nigella sativa (NS) supplementation during resistance training (RT) on some biochemical variables in type 2 diabetes patients.

Forty patients were assigned to groups: RT + NS (RN), NS, RT + placebo (RP), and control (CO). RT was performed and NS was consumed for 8 weeks. Blood samples were collected at rest immediately before and after the 8 week intervention.

RT or NS by themselves reduced HOMA-IR, insulin, glucose, TG, TC, LDL, ESR, CRP, AST, ALT and ALP, and increased HDL and HOMA-S. The combination of RT and NS, rather than each intervention alone, had significant effects on reduction of HOMA-IR, insulin, ESR and CRP as well as increases in HDL, HOMA-β/S.

RT combined with NS is sometimes a better strategy compared to single interventions for improving diabetes related biomarkers in type 2 diabetic patients.

Nonalcoholic fatty liver disease (NAFLD), a condition characterized by the accumulation of fat in the liver, is estimated to be the most common liver disease worldwide. Obesity is a major risk factor and contributor, and, accordingly, weight loss can improve NAFLD. Previous studies in preclinical models of diet-induced obesity and fatty liver disease have shown the independent benefits of resistance exercise training (RT) and time-restricted feeding (TRF) in preventing weight gain and hepatic build-up of fat. Here, we tested the combined effect of TRF and RT on obesity and NAFLD in mice fed a high-fat diet. Our results showed that both TRF-8-h food access in the active phase-and RT-consisting of three weekly sessions of ladder climbing-attenuated body weight gain, improved glycemic homeostasis, and decreased the accumulation of lipids in the liver. TRF combined with RT improved the respiratory exchange rate, energy expenditure, and mitochondrial respiration in the liver. Furthermore, gene expression analysis in the liver revealed lower mRNA expression of lipogenesis and inflammation genes along with increased mRNA of fatty acid oxidation genes in the TRF + RT group. Importantly, combined TRF + RT was shown to be more efficient in preventing obesity and metabolic disorders. In conclusion, TRF and RT exert complementary actions compared with isolated interventions, with significant effects on metabolic disorders and NAFLD in mice.NEW & NOTEWORTHY Whether time-restricted feeding (TRF) combined with resistance exercise training (RT) may be more efficient compared with these interventions alone is still unclear. We show that when combined with RT, TRF provided additional benefits, being more effective in increasing energy expenditure, preventing weight gain, and regulating glycemic homeostasis than each intervention alone. Thus, our results demonstrate that TRF and RT have complementary actions on some synergistic pathways that prevented obesity and hepatic liver accumulation.

Prior to this study, it is known that type 2 diabetes is linked to obesity and a sedentary lifestyle, leading to inadequate β-cell function and insulin resistance. Limited research has explored the metabolic effects of combining exercise training with antidiabetic medications, particularly focusing on insulin secretion in patients with type 2 diabetes and moderately preserved β-cell function.

The effect of the interaction of semaglutide and physical training on pancreatic β-cell secretory function is unknown in patients with type 2 diabetes.

Thirty-one patients with type 2 diabetes underwent 12 weeks of aerobic training alone or concurrent to treatment with semaglutide. Patients randomly allocated to concurrent semaglutide and training were treated with semaglutide for 20 weeks before the training and evaluated at inclusion and again before and after the training intervention. Patients randomized to training were evaluated before and after training. The primary outcome was a change in insulin secretory capacity with training, evaluated by a 2-stepped hyperglycemic (20 and 30 mM) clamp.

Training increased the incremental area under the curve for insulin from 21 to 27 nM × 2 hours (ratio 1.28, 95% CI 1.02-1.60) during clamp step 1 and from 40 to 64 nM × 2 hours (ratio 1.61, 95% CI 1.25-2.07) during step 2. Semaglutide treatment increased insulin secretion from 16 to 111 nM × 2 hours (ratio 7.10, 95% CI 3.68-13.71), and from 35 to 447 nM × 2 hours (ratio 12.74, 95% CI 5.65-28.71), correspondingly. Semaglutide and training increased insulin secretion from 130 to 171 nM × 2 hours (ratio 1.31, 95% CI 1.06-1.63), and from 525 to 697 nM × 2 hours (ratio 1.33, 95% CI 1.02-1.72), correspondingly. The median increase in total insulin secretion with the combination was 134 nM × 2 hours greater (95% CI 108-232) than with training.

The combination of aerobic training and semaglutide treatment synergistically improved β-cell secretory function. (ClinicalTrials.gov number, ID NCT04383197).

To evaluate the effects of pragmatic home-based resistance exercise training on glycated haemoglobin (HbA1c) as well as muscle strength and body composition in people with type 2 diabetes.

People with type 2 diabetes were randomized (1:1) to usual care or usual care plus home-based resistance exercise for 32 weeks. The changes in HbA1c, body composition, physical function, quality of life, continuous glucose monitoring and liver fat were compared by randomized group using linear regression.

This study recruited 120 participants (female: n = 46 [38%], age 60.2 (9.4) years, BMI 31.1 (5.4) kg.m-2 ), 64 to intervention and 56 to usual care. Intention to treat analysis revealed no effect on HbA1c (difference in difference: -0.4 mmol/mol, 95% confidence interval [CI]: -3.26, 2.47; p = 0.78) but the intervention increased the number of push-ups (3.6 push-ups, 95% CI: 0.8, 6.4), arm lean mass (116 g, 95% CI: 6, 227) and leg lean mass (438 g, 95% CI 65, 810) and decreased liver fat (-1.27%, 95% CI -2.17, -0.38), with no differences in other outcomes. Per-protocol analysis revealed similar results.

Home-based resistance exercise is unlikely to lower HbA1c in people with type 2 diabetes but may be of benefit for maintaining muscle mass and function and reducing liver fat.

Exercise training is an encouraging approach to treat cardiac dysfunction in type 2 diabetes (T2DM), but the impact of its intensity is not understood. We aim to investigate whether and, if so, how moderate-intensity training (MIT) and high-intensity interval training (HIIT) alleviate adverse cardiac remodeling and dysfunction in rats with T2DM. Male rats received standard chow (n = 10) or Western diet (WD) to induce T2DM. Hereafter, WD rats were subjected to a 12-week sedentary lifestyle (n = 8), running MIT (n = 7) or HIIT (n = 7). Insulin resistance and glucose tolerance were assessed during the oral glucose tolerance test. Plasma advanced glycation end-products (AGEs) were evaluated. Echocardiography and hemodynamic measurements evaluated cardiac function. Underlying cardiac mechanisms were investigated by histology, western blot and colorimetry. We found that MIT and HIIT lowered insulin resistance and blood glucose levels compared to sedentary WD rats. MIT decreased harmful plasma AGE levels. In the heart, MIT and HIIT lowered end-diastolic pressure, left ventricular wall thickness and interstitial collagen deposition. Cardiac citrate synthase activity, mitochondrial oxidative capacity marker, raised after both exercise training modalities. We conclude that MIT and HIIT are effective in alleviating diastolic dysfunction and pathological cardiac remodeling in T2DM, by lowering fibrosis and optimizing mitochondrial capacity.

Lifestyle modification comprising calorie restriction (CR) and increased physical activity enabling weight loss is the first-line of treatment for non-alcoholic fatty liver disease (NAFLD). However, CR alone is not optimal and evidence suggests that dietary pattern and composition are also critical in NAFLD management. Accordingly, high consumption of red and processed meat, saturated fat, added sugar, and sweetened beverages are associated with an increased risk of developing NAFLD and hepatocellular carcinoma, while other foods and compounds such as fish, olive oil, and polyphenols are, in contrast, beneficial for metabolic disorders. Therefore, several dietary interventions have been studied in order to determine which strategy would be the most beneficial for NAFLD. The evidence regarding the effectiveness of different dietary interventions such as low carbohydrate/low-fat diet, time-restricted eating diet, CR, and the well-studied Mediterranean diet is summarized.

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 global burden of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing.

This study aimed to evaluate the effect of exercise on intrahepatic lipid (IHL), serum alanine aminotransferase (ALT), body mass index (BMI), and insulin resistance in NAFLD patients.

We searched MEDLINE, Embase, Cochrane CENTRAL, KMbase, and the Korean Studies Information Service System through April 2022. The included studies were randomised control trials (RCTs) of exercise, in which IHL was measured using magnetic resonance imaging in adult NAFLD patients.

Eleven RCTs with 577 participants were included in this meta-analysis. Exercise was significantly associated with a reduction in IHL (mean difference (MD), -2.03; 95% CI, -3.26 to -0.79; P = 0.001) and a decrease in ALT (MD, -4.17; 95% CI, -6.60 to -1.73; P = 0.0008). Regarding the duration of exercise, maintaining exercise for more than 3 months significantly improved IHL (MD, -3.62; 95% CI, -5.76 to -1.48; P = 0.0009), while exercise for less than 3 months did not (MD, -1.23; 95% CI, -2.74 to 0.29; P = 0.11). BMI and insulin resistance did not improve significantly with exercise.

We found that exercise improved IHL and ALT levels in NAFLD patients. The effect of exercise is particularly increased when one engages in exercises that last longer than 3 months.

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.