Association between individual phenotypic features and lifestyle factors on the risk of non-alcoholic fatty liver disease in older subjects with metabolic syndrome

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, whose prevalence is growing worldwide in parallel with obesity and type 2 diabetes mellitus (T2DM) rates. This trend spreads the global burden of NAFLD due to an increase in health-care costs and a negative impact on wellbeing and the quality of life. The prevalence of NAFLD is higher in men than women in adulthood. However, this tendency changes in ageing because postmenopausal status is associated with a higher risk to develop NAFLD. Also, body fat redistribution characterized by enlarged visceral adipose tissue (VAT) leads to insulin resistance, playing a crucial role in NAFLD pathogenesis. Unhealthy lifestyle behaviours, including poor eating habits and physical inactivity, cause harmful effects on health outcomes. The associations between sex-differences, metabolic phenotype, lifestyle factors and specific bioactive compounds on risk factors and predisposition to develop NAFLD in the elderly population with a high risk of cardiovascular disease and MetS features are scarcely known. Hence, the aims of the present thesis were: 1) to evaluate sex-related differences in risk factors of NAFLD in elderly individuals; 2) to assess the relationship between VAT and insulin resistance on NAFLD risk factors; 3) to study the associations between lifestyle factors focused on adherence to the Mediterranean diet (MedDiet), dietary components, and physical activity on factors linked to NAFLD; 4) to investigate the interrelationships between some urinary metabolites associated to MedDiet with cardiometabolic and liver markers involved in NAFLD development. In Chapter 1, we found that women had an increased risk to develop NAFLD measured by the hepatic steatosis index (HSI) compared to men, suggesting the potential role of sex differences on risk factors related to NAFLD in elderly individuals. In Chapter 2, increased amounts of visceral adipose tissue (VAT) and triglyceride Glucose Index (TyG) values were associated with worsened liver status and exacerbated cardiometabolic risk factors. Besides, the TyG index could be a proxy indicator of increased deposition of VAT in women diagnosed with MetS. In Chapter 3, those individuals with greater adherence to the MedDiet and higher levels of physical activity were inversely associated with HSI related to liver steatosis state. Furthermore, higher consumption of legumes was associated with a lower risk to have increased HSI values. In Chapter 4, a healthier lipid profile and liver enzymes levels were linked to higher concentrations of urinary resveratrol metabolites, where total urine resveratrol concentration was inversely associated with the risk of having elevated liver enzymes. In summary, the findings presented in this thesis show the implications of potential sex-related differences and individual phenotype on the predisposition of NAFLD. This relationship was even more marked in individuals with an adiposopathy VAT and insulin resistance features. Notably, the TyG index could be proposed as a reliable marker of enlarged VAT deposition in women with MetS features. Another point of interest is that lifestyle modifications focused on greater adherence to the MedDiet, especially promoting the consumption of some dietary components (legumes) and bioactive compounds (resveratrol) as well as increased levels of physical activity might be considered a relevant part of a liver-healthy lifestyle in elderly individuals at high cardiovascular risk diagnosed with MetS.