Oxidative Stress in Non-alcoholic Fatty Liver Disease. An Updated Mini Review

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut–liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.

Garcinia cambogia Ameliorates Non-Alcoholic Fatty Liver Disease by Inhibiting Oxidative Stress-Mediated Steatosis and Apoptosis through NRF2-ARE Activation

“…Furthermore, a high intake of fat and carbohydrates can induce ER stress, and dysfunction of ER develops metabolically-driven NAFLD progress [ 73 , 74 ]. Although this study revealed that HCA had therapeutic effects by suppressing lipid accumulation and apoptosis in liver cells, other components may be effective to NAFLD since recent clinical trials suggest that protein oxidation/glycation and ER stress are involved in liver fibrosis in NAFLD [ 75 , 76 ]. Thus, further studies are needed to investigate additional anti-NAFLD effects and the underlying mechanism of the G. cambogia and its components.…”

Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk

“…As a result, ROS causes damage to DNA, lipids, and proteins, forming oxidative damage products [ 51 ]. Following lipotoxic liver injury, ER stress and DNA damage promote further NAFLD inflammation and fibrotic progression [ 52 ].…”

Fibroblast growth factor 21 in dairy cows: current knowledge and potential relevance

“…Based on this, the plasma FGF21 concentration has even been suggested as a surrogate marker for fatty liver in humans [105,106]. It has been recognized that the development of a non-alcoholic fatty liver disease (NAFL D) in humans, which is frequently associated with obesity, is caused by multiple pathophysiological factors including inflammation, ER stress, oxidative stress and elevated plasma concentrations of NEFA [107]. These factors are considered to act as triggers for the induction of hepatic FGF21 expression [11,35].…”