Physiopathology of nonalcoholic fatty liver disease: from diet to nutrigenomics

Abstract

Purpose of review Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and is strongly associated with metabolic disorders, such as obesity, type 2 diabetes mellitus, and metabolic syndrome, to the extent that a new definition of metabolic associated fatty liver disease has been proposed. Recent findings Insulin resistance, worsened by a high-fat and high-carbohydrate diet, is the key to the physiopathology of hepatic steatosis. This is driven by several mechanisms that are mostly activated at a genetic level, such as de-novo lipogenesis and triglyceride synthesis. Therefore, many diet regimens have been studied, although significant controversies remain regarding their metabolic effects and long-term sustainability. Summary In this review, we summarized the role and effects of the main macronutrients on the development of NAFLD and discussed the molecular mechanisms involved. We also discussed the importance of genetic polymorphisms, epigenetic alterations, and dysbiosis to determine if lifestyle modification and a specific dietary regimen could be an essential part of NAFLD treatment.

A review of experimental and clinical studies on the therapeutic effects of pomegranate (Punica granatum) on non‐alcoholic fatty liver disease: Focus on oxidative stress and inflammation

“…These include IR, the buildup of harmful lipids, and the release of pro‐inflammatory cytokines that can damage the liver and activate hepatic stellate cells, leading to fibrosis (Kuchay et al, 2020 ). Consuming a diet high in carbohydrates and fat can worsen IR, which is a key factor in the development of NAFLD (Meneghel et al, 2022 ). OS is a risk factor for NAFLD because it can cause lipid peroxidation in the membranes of liver cells.…”

Nutritional Genomics in Nonalcoholic Fatty Liver Disease

“…Several environmental factors, such as obesity, type 2 diabetes, hyperlipidemia, and metabolic syndrome, have been linked to the development of NAFLD [4,6,7]. Lifestyle habits, such as physical inactivity and an unbalanced diet, particularly in cases of sedentarism and excessive caloric intake, are major risk factors for the development of NAFLD, as they contribute to insulin resistance, dyslipidemia, and adiposity, which are key factors in the pathogenesis of the disease [2, 3,7,8]. High fructose diets may also potentially increase the risk of NAFLD, although the evidence in the context of a normocaloric diet is not yet conclusive [3].…”

Combination of a Glucagon-Like Peptide 1 Analog and a Sodium-Glucose Cotransporter 2 Inhibitor Improves Lipid Metabolism Compared to the Monotherapies in Experimental Metabolic Syndrome

“…Metabolic syndrome encompasses various features (hyperglycemia, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, hypertension, central obesity, and fatty liver) that together increase the risk of cardiovascular disease and diabetes mellitus [2,3]. Intraabdominal adiposity has a well-known association with an increased risk of insulin resistance and fatty liver disease [3,4]. Furthermore, high-fat diets (HFDs) are consistently associated with metabolic alterations, central obesity, and negative changes in lipid profile and glucose metabolism, contributing to insulin resistance and obesity [4,5].…”

“…Intraabdominal adiposity has a well-known association with an increased risk of insulin resistance and fatty liver disease [3,4]. Furthermore, high-fat diets (HFDs) are consistently associated with metabolic alterations, central obesity, and negative changes in lipid profile and glucose metabolism, contributing to insulin resistance and obesity [4,5].…”