Targeting Mitochondria for the Prevention and Treatment of Nonalcoholic Fatty Liver Disease: Polyphenols as a Non-pharmacological Approach

Abstract

Scope: Nonalcoholic fatty liver disease (NAFLD) has a high and growing prevalence globally. Mitochondria are fundamental in regulating cell energy homeostasis. Nevertheless, mitochondria control mechanisms can be exceeded in this context of energy overload. Damaged mitochondria worsen NAFLD progression. Diet and lifestyle changes are the main recommendations for NAFLD prevention and treatment. Some polyphenols have improved mitochondrial function in different NAFLD and obesity models. Objective: To discuss the potential role of polyphenols as a non-pharmacological approach targeting mitochondria to prevent and treat NAFLD, analyzing the influence of polyphenols' chemical structure, limitations and clinical projections. Methods: In vivo and in vitro NAFLD models were considered. Study searches were performed using the following keywords: nonalcoholic fatty liver disease, liver steatosis, mitochondria, mitochondrial activity, mitochondrial dynamics, mitochondrial dysfunction, mitochondrial morphology, mitochondrial cristae, fusion, fission, polyphenols, flavonoids, anthocyanins, AND/OR bioactive compounds. Conclusion: Polyphenols are a group of diverse bioactive molecules whose bioactive effects are highly determined by their chemical structure. These bioactive compounds could offer an interesting non-pharmacological approach to preventing and treating NAFLD, regulating mitochondrial dynamics and function. Nevertheless, the mitochondria' role in subjects with NAFLD treatment is not fully elucidated. The dosage and bioavailability of these compounds should be addressed when studied.

Contributing roles of mitochondrial dysfunction and hepatocyte apoptosis in liver diseases through oxidative stress, post-translational modifications, inflammation, and intestinal barrier dysfunction

“…These events may inactivate mitophagy and autophagy or cause mitochondrial dysfunction, leading to fat accumulation, caspase-mediated apoptosis, and NF-κB-mediated inflammation. These events collectively activate Kupffer and stellate cells in the liver, leading to further damage and dysfunction of liver physiology capsaicin [140], are excellent liver disease preventions that target mitochondrial dysfunction [379,380] and CYP2E1-induced oxidative stress [381]. N-acetylcysteine [141], naturally occurring terpenoid polyphenols, and phenolic acids [368] were reported to minimize oxidative stress and hepatotoxicity by targeting antioxidant enzymes [299].…”