Background: Steatotic liver disease associated with metabolic dysfunction (MASLD) affects up to about 30% of the general adult population and is closely related to obesity and the metabolic syndrome. Cortisol, a stress-related hormone contributing to hepatic fat accumulation and insulin resistance, also promotes progression of the disease. The study aims to investigate the impact of lifestyle modifications on cortisol levels and hepatic steatosis in patients with MASLD. Methods: In a 16-week three-arm randomized trial, 42 patients were randomly assigned to three groups who received dietary advice (CG), dietary advice combined with aerobic exercise (AE + DA), or dietary advice with high-intensity interval training (HIIT + DA). Before the start, after 2 months of intervention, and at the end of the project, medical evaluations, routine biochemical assessments, and psychological questionnaires were analyzed. At baseline and at the end of 4 months, hepatic steatosis was evaluated by Fibroscan^®. Results: In the study population, severe hepatic steatosis (74%) and obesity (98%) were prevalent at the beginning of the study. A statistically significant (p-value = 0.001) reduction in circulating cortisol levels was observed over time in the two groups doing exercise, especially in HIIT + DA (p-value = 0.006). Hepatic steatosis, assessed by Fibroscan^®, disappeared in 10 participants (CAP value < 248, p-value = 0.003). CAP values and waist circumference decreased in all groups, statistically significantly in the AE + DA group (p-value = 0.005; p-value = 0.04, respectively). Conclusions: The study emphasizes the benefits of combining diet and exercise in managing MASLD. HIIT + DA significantly decreased cortisol levels, while AE + DA was the most potent intervention for reducing hepatic steatosis.

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) affects 30% of adults worldwide and is associated with obesity and cardiovascular risk factors. If left untreated, it can progress to severe liver disease. Lifestyle changes such as physical activity and weight loss help to reduce the severity and risk of mortality. This study estimated the impact of MASLD and leisure-time physical activity (LTPA) on mortality and examined how gender mediates this effect in a Southern Italian population. Methods: This work is a population-based prospective cohort study of inhabitants of Castellana Grotte (>30 years old) in Southern Italy, which began in 1985. Participants provided general health information, underwent anthropometric measurements and ultrasonography, and completed a validated questionnaire on their food intake and LTPA. The vital status was tracked through local municipalities Results: In total, 1826 participants (39% with MASLD) were enrolled in this study, drawn from 2970 eligible subjects; the mean age was 51.91 (±14.76) years and 56.2% were men. Subjects with MASLD who practiced low LTPA had a significantly higher risk of death than those who did not have MASLD and practiced high LTPA. In addition, subjects with MASLD who practiced low LTPA were about 19% less likely to survive to the age of 82 years. As regards gender, both men and women with MASLD and low LTPA showed a significant risk of death, but this was higher in women. Conclusions: The presence of MASLD, especially in women, increases the risk of death from all causes. LTPA plays a key role in the disease and reduces mortality in these individuals.

Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.

Background: Metabolic dysfunction-associated fatty liver disease (MASLD) affects nearly 20% of the Italian population, with an annual economic burden of € 7.94 billion on the National Health Service, largely due to advanced liver disease and metabolic comorbidities. Progressive liver fibrosis remains the strongest predictor of adverse outcomes. Early diagnosis is crucial, as fibrosis is potentially reversible in its early stages. Sedentary behavior (SB) is one of many modifiable risk factors for several chronic diseases; however, most evidence is based on self-reported data. This study investigates the association between objectively measured daily energy expenditure and liver stiffness in adults with MASLD. Methods: We conducted a cross-sectional analysis of 104 adults (18–65 years) with obesity and moderate-to-severe steatosis (CAP ≥ 248 dB/m) from the Obesity-AF study. Daily energy expenditure (METs/day) was assessed via 7-day wrist-worn actigraphy. Liver stiffness (LSM, kPa) was measured non-invasively using transient elastography (FibroScan^®). Results: Lower daily energy expenditure was independently associated with higher liver stiffness. Each 1-MET increase correlated with a −1.239 kPa reduction in LSM (95% CI: −2.012, −0.466; p = 0.002). Sedentary individuals (≤1.5 METs) exhibited significantly higher LSM (+0.73 kPa, p = 0.03) versus non-sedentary peers, even after full adjustment. Findings were robust across sensitivity analyses. Conclusions: Our study shows that SB, objectively measured by actigraphy, is independently associated with increased liver stiffness in patients with MASLD and obesity. Reducing sedentary time may represent a simple, low-cost, and scalable strategy to mitigate fibrosis progression. However, given the cross-sectional design and the specificity of our sample, longitudinal studies are needed to confirm the causal role of SB and to evaluate the effectiveness of targeted interventions in broader MASLD populations.

Background: Irritable bowel syndrome (IBS) and obesity are associated with intestinal barrier alterations that result in low-grade inflammation. Zonulin and intestinal fatty acid-binding protein (I-FABP) assess gut barrier health, while urinary indican concentrations reflect dysbiosis in the small intestine. Physical activity, such as Fitwalking, aids weight management and improves intestinal permeability. This study assesses the impact of a 12-week Fitwalking program on intestinal barrier health in IBS patients categorized by body mass index (BMI). Methods: Fifty-seven mild IBS patients were categorized as obese (OB = 18), overweight (OW = 24), or normal weight (NW = 15) and assigned to a walking group. Participants walked thrice weekly at moderate intensity for 60 min per session, using the specific Fitwalking technique, supervised by staff. Results: No significant changes in biochemical or anthropometric variables were observed. However, Fitwalking improved the Global Physical Capacity Score (GPCS) by 46%, 48%, and 24% in the NW, OW, and OB groups. Post-intervention, serum zonulin levels notably decreased in OB individuals, suggesting reduced inflammation. OW patients unexpectedly showed increased fecal zonulin levels. OB participants experienced decreased urinary indican levels. Zonulin levels positively correlated with BMI and inversely with GPCS. Conclusions: Regular exercise benefits the intestinal barrier, especially in obese IBS patients. Monitoring zonulin and I-FABP may offer insights into gut barrier integrity and GI injury severity. Future studies should explore longer intervention durations, larger populations, and advanced diagnostic tools to validate findings and investigate the mechanisms behind exercise-induced changes in intestinal permeability and gut health markers.

Background & Aims: Fatty liver disease with metabolic dysfunction (MAFLD) is a new concept proposed to replace the previous concept of Non-Alcoholic Hepatic Steatosis (NAFLD). We developed and internally validated a prognostic model to predict the likelihood of death in a cohort of subjects with MAFLD. Methods: Our work involved two steps: the first was the construction of a bootstrapped multivariable Cox model for mortality risk prognosis and the second was its validation. Results: The study cohort included 1506 subjects, of which 907 were used for internal validation. Discriminant measures for the final model were R²_D 0.6845 and Harrell’s C 0.8422 in the development and R²_D 0.6930 and Harrell’s C 0.8465 in the validation. We used the nine independent prognostic factors selected by the LASSO Cox procedure and fitted by the bootstrap Cox survival model, and observed β were: Gender 0.356 1.42 (p < 0.008), Age 0.146 (p < 0.001), Glycemia 0.004 (p < 0.002), Total Cholesterol −0.0040 (p < 0.009), Gamma Glutamyl Transpeptidase 0.009 (p < 0.001), SBP 0.009 (p < 0.036), DBP −0.016 (p < 0.041), ALP 0.008 (p < 0.071) and Widowhood 0.550 (p < 0.001). Conclusions: We produced and validated a model to estimate the probability of death in subjects with MAFLD. The instruments we used showed satisfactory predictive capabilities.