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) is strongly correlated with the severity of obesity, and the extent of liver fibrosis is associated with a higher risk of liver-related complications, cardiovascular events, and overall mortality. Leptin circulating levels are directly correlated with the amount of adipose tissue. Aims: In the present study, we investigated the association between circulating leptin levels and liver steatosis and fibrosis. Methods: Eighty-six patients (41.7 ± 12.6 yrs, 35 men, 41%), naïve to medications, who attended the Nutrition Center for the Research and Care of Obesity and Metabolic Diseases at the National Institute of Gastroenterology “Saverio de Bellis” for weight management, were cross-sectionally evaluated. Demographic, anthropometric, clinical, and laboratory data were collected and analyzed. All patients underwent liver ultrasonographic assessment by FibroScan to diagnose liver steatosis (controlled attenuation parameter, CAP > 275 dBm) and fibrosis (liver stiffness measurement, LSM > 8.2 kPa). Results: Sixty-three individuals (73.3%) had liver steatosis, and 17 (19.8%) had liver fibrosis. The mean leptin levels were 22.3 ± 14.1 ng/mL, while the BMI and waist circumference were 36.7 ± 7.2 kg/m² and 114.5 ± 16.4 cm, respectively. CAP values exhibited no correlation with leptin (r = 0.09, p = 0.436), while a significant connection was seen between leptin and LSM (β = 0.065; p = 0.038). Specifically, for each unit increase in leptin, LSM values were varied by +0.065 units (p = 0.038). This association was independent of gender, age, insulin resistance, adiponectin, RBP4, and visfatin. This is the first study showing these results by using FibroScan assessment in patients naïve to medications. Conclusions: Circulating leptin concentrations are independently correlated with hepatic fibrosis in individuals with a BMI ≥ 25 kg/m². These findings indicate a function for leptin in promoting liver fibrosis; however, longitudinal studies are required to elucidate the causal nature of this interaction.

Inorganic polyphosphate (iPolyP) is a ubiquitous molecule composed of a variable number of orthophosphate units. Recent studies have highlighted its involvement in colorectal cancer (CRC) cell proliferation. However, further investigations are needed to elucidate its role in CRC cell progression and migration, as well as its influence on the tumor microenvironment. This study focuses on the inorganic polyphosphate (iPolyP)/transient receptor potential cation channel subfamily M member 8 (TRPM8) axis and its impact on CRC progression. To investigate these issues, western blotting, fixed and live cells immunofluorescence, 2D and 3D cell culture on CRC-patient derived tissues, ELISA, and wound healing assays were performed. Our results show that inorganic polyphosphate induces the expression of epithelial-to-mesenchymal transition (EMT) markers in CRC cells. Furthermore, the iPolyP/TRPM8 axis indirectly promotes tumor growth through activation of the Nucleotide-binding oligomerization domain, Leucine-rich Repeat and Pyrin domain-containing protein 3 (NLRP3) inflammasome in immune cells, leading to increased levels of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the tumor microenvironment (TME), thereby advancing CRC. These findings suggest that targeting the iPolyP/TRPM8 pathway may be a promising strategy to inhibit CRC progression and metastasis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of steatotic liver disease and has major implications on cardiovascular safety. As the precise role linking MASLD to cardiovascular diseases is still unclear, the present study aims to investigate the association between liver steatosis and fibrosis and circulating plasminogen activator inhibitor-1 (PAI-1) levels. Eighty-two patients (41.6 ± 12.4 yrs, 34 men, 41%), naïve to medications, who attended the Nutrition Center for the Research and Care of Obesity and Metabolic Diseases at the National Institute of Gastroenterology “Saverio de Bellis” for weight management, were cross-sectionally evaluated. Demographic, anthropometric, clinic, and laboratory data were collected and analyzed. All patients underwent liver ultrasonographic assessment by FibroScan to diagnose liver steatosis (controlled attenuation parameter or CAP > 275 dBm) and fibrosis (liver stiffness > 8.2 kPa). Sixty-one individuals (74.4%) had liver steatosis, and 17 (20.7%) had liver fibrosis. PAI-1 mean levels were 3,261 ± 1,270 pg/mL, mean body mass index (BMI) and waist circumference (WC) values were 36.6 ± 7.1 kg/m2 and 114.1 ± 16.5 cm, respectively. Mild systolic and diastolic arterial pressure elevation and significantly high values of fasting plasma insulin (19.6 ± 12.6 IU/mL) and homeostatic model assessment of insulin resistance or HOMA-IR (4.8 ± 3.5) were also found. CAP values were correlated with several anthropometric, clinical, and laboratory parameters of insulin resistance. We found a significant association between PAI-1 and CAP (β = 1.605; p = 0.004), and noteworthily, when PAI-1 increased by 100 units, the expected variation of CAP values was by + 1.6 units (p = 0.004). Notably, the association was independent of gender, age, and insulin resistance. Circulating PAI-1 levels are correlated with liver steatosis and, to a lesser extent, fibrosis in apparently healthy patients with a BMI ≥ 25 kg/m2. This is the first study to show these results in patients naïve to medications, using FibroScan assessment. The bidirectional relationship between circulating PAI-1 levels and CAP measurement highlights the relevance of our research from a diagnostic and pathophysiological-prognostic viewpoint. Longitudinal trials are needed to clarify the cause-effect association between MASLD and PAI-1 levels.

This Italian cohort study found that PLHIV using fixed-dose 2-drug ART were younger, had fewer comorbidities, and less resistance than those on free combinations.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide. Its prevalence is constantly increasing, particularly among obese individuals. Lifestyle modifications remain the first-line intervention for the management and treatment of MASLD. The most widely recommended dietary regime for MASLD is the Mediterranean Diet (MedDiet). Despite its countless benefits, this dietary regimen is difficult to follow in some cases. This study aimed to assess the effects of an 8-week Very Low-Calorie Ketogenic Diet (VLCKD) in obese patients with MASLD. Methods: The study included 55 obese adults aged 18–64 years, recruited from the Center of Nutrition for Obesity and Metabolic Diseases, National Institute of Gastroenterology “Saverio de Bellis” Research Hospital (Castellana Grotte, Bari, Italy). Anthropometry, body composition (BIA), liver status (FibroScan^®), serum biochemistry and circulating biomarkers of adipose dysfunction were assessed at baseline (T0) and post-intervention (T1). Results: Significant improvements in liver steatosis (CAP p < 0.0001), liver stiffness (p = 0.0005), anthropometric parameters (waist p < 0.0001), and body composition (FM p <0.0001) were observed. A significant reduction in leptin levels and an increase in sex hormone-binding globulin (SHBG p < 0.0001) were also observed. Conclusions: In this uncontrolled pre-post analysis, the 8-week VLCKD intervention was associated with improvements in hepatic steatosis, body weight, and fat mass, and selected circulating biomarkers of adipose tissue dysfunction in adults with obesity and MASLD.