Bisphenols, epigenetic aging, and metabolic liver disease: Effects of a BP-free diet

Methods

Summary

Specific objectives: 1. Examine the association between hepatic epigenetic aging and MASLD progression across different disease stages, genders, and age groups. 1.1. Assess correlations between epigenetic aging markers, steatosis, and steatohepatitis, considering the potential use of the epigenetic clock in peripheral blood mononuclear cells (PBMCs) as a non-invasive biomarker. 1.2. Analyze the relationship between hepatic epigenetic aging and metabolic disorders such as obesity, diabetes, and metabolic syndrome. 2. Assess the impact of bisphenols (BPs) exposure and its accumulation in adipose tissue on liver epigenetic ageing and MASLD progression, considering variations across age groups, genders, and disease severity. 3. Evaluate the relationship between hepatic epigenetic aging and intestinal dysfunction, considering the intestine as the primary entry route for BPs and its impact on metabolic health. 4. Integrate body levels of BPs with hepatic epigenetic aging markers and MASLD progression, identifying interactions between environmental exposure, epigenetic regulation, gut health, and metabolic dysfunction. 5. Whether a BP-free diet can reduce MASLD severity and improve metabolic function.

Methodology: The project consists of two studies: A prospective observational study (OB1-4) with 80 patients undergoing bariatric surgery. Liver, visceral adipose tissue, and jejunum samples will be collected, along with blood and urine samples. Histological classification will divide patients into normal liver, simple steatosis, or MASH. A longitudinal intervention study (OB5) with 40 non-obese, overweight or grade 1 obesity patients recruited from a MASLD consultation. BP levels, liver damage, and inflammatory markers will be evaluated before and after a BP-free diet for six months. Comprehensive analyses will be conducted, including BP quantification, epigenomic, transcriptomic, histological, and immunohistochemical studies, as well as surveys on dietary habits and daily plastic use, along with clinical and biochemical assessments.