Cell-type specific role of autophagy in the liver and its implications in non-alcoholic fatty liver disease

Abstract

Autophagy, a cellular degradative process, has emerged as a key regulator of cellular energy production and stress mitigation. Dysregulated autophagy is a common phenomenon observed in several human diseases, and its restoration offers curative advantage. Non-alcoholic fatty liver disease (NAFLD), more recently renamed metabolic dysfunction-associated steatotic liver disease, is a major metabolic liver disease affecting almost 30% of the world population. Unfortunately, NAFLD has no pharmacological therapies available to date. Autophagy regulates several hepatic processes including lipid metabolism, inflammation, cellular integrity and cellular plasticity in both parenchymal (hepatocytes) and non-parenchymal cells (Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells) with a profound impact on NAFLD progression. Understanding cell type-specific autophagy in the liver is essential in order to develop targeted treatments for liver diseases such as NAFLD. Modulating autophagy in specific cell types can have varying effects on liver function and pathology, making it a promising area of research for liver-related disorders. This review aims to summarize our present understanding of cell-type specific effects of autophagy and their implications in developing autophagy centric therapies for NAFLD.

Keywords: Autophagy, Non-alcoholic fatty liver disease, Hepatocytes, Macrophages, Hepatic stellate cells

Core Tip: This review presents a succinct overview of the cell-specific distinct effects of autophagy modulation on hepatic pathophysiology and its implication on the progression of non-alcoholic fatty liver disease (NAFLD). The effects of autophagy alteration on hepatocyte lipid metabolism, macrophage polarization and hepatic stellate cell plasticity are reviewed and discussed with reference to NAFLD pathobiology.