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.

Immunomodulation in non-alcoholic fatty liver disease: exploring mechanisms and applications

“…It is important to note that impaired mitochondrial metabolism is widely associated with NAFLD by mediating dysregulation of lipid metabolic homeostasis. The deeper understanding of the molecular structure of mitochondrial plasticity is still in its infancy, but it may provide new doors for the development of future physiological compounds with potential for clinical NAFLD therapy ( 106 , 107 ).…”

Autophagy and inflammation an intricate affair in the management of obesity and metabolic disorders: evidence for novel pharmacological strategies?

“…As an evolutionarily preserved process, autophagy can be found in all the eukaryotic cells including the hepatocytes, where, as a catabolic process, it contributes to the preservation of liver tissue homeostasis in both parenchymal (hepatocytes) and non-parenchymal (Kupffer cells, hepatic stellate cells, and sinusoidal endothelial cells) hepatic cells ( Raza et al, 2023 ). The understanding of cell type-specific autophagy in the liver is important to develop novel focused pharmacological targets for the treatment of liver diseases.…”

“…Indeed, it has been demonstrated that defects in autophagy homeostasis (an enhancement or a suppression) facilitate the onset and the development of metabolic disorders, including obesity, diabetes, and metabolic liver diseases ( Kim and Lee, 2014 ; Zhang et al, 2018 ; Raza et al, 2023 ).…”