Lipophagy: A potential therapeutic target for nonalcoholic and alcoholic fatty liver disease

Biochem Biophys Res Commun. 2023 Sep 10:672:36-44. doi: 10.1016/j.bbrc.2023.06.030. Epub 2023 Jun 14.

Abstract

Lipid droplets are unique lipid storage organelles in hepatocytes. Lipophagy is a key mechanism of selective degradation of lipid droplets through lysosomes. It plays a crucial role in the prevention of metabolic liver disease, including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), and is a potential therapeutic target for treating these dysfunctions. In this review, we highlighted recent research and discussed advances in key proteins and molecular mechanisms related to lipophagy in liver disease. Reactive oxygen species (ROS) is an inevitable product of metabolism in alcohol-treated or high-fat-treated cells. Under this light, the potential role of ROS in autophagy in lipid droplet removal was initially explored to provide insights into the link between oxidative stress and metabolic liver disease. Subsequently, the current measures and drugs that treat NAFLD and AFLD through lipophagy regulation were summarized. The complexity of molecular mechanisms underlying lipophagy in hepatocytes and the need for further studies for their elucidation, as well as the status and limitations of current therapeutic measures and drugs, were also discussed.

Keywords: AFLD; Lipid droplets; Lipophagy; NAFLD; ROS; Therapeutic target.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology
  • Fatty Liver, Alcoholic* / metabolism
  • Humans
  • Lipid Droplets / metabolism
  • Lipid Metabolism / physiology
  • Liver / metabolism
  • Metabolic Diseases* / metabolism
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species