Autophagy in Non-Alcoholic Fatty Liver Disease (NAFLD)

Abstract

Abstract"utophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients. The potential role of autophagy in disease is increasingly recognised and investigated. To date, a key role of autophagy in hepatic lipid metabolism is recognised and dysfunctional autophagy might be an underlying cause of non-alcoholic faty liver disease N"FLD . Nevertheless, the exact role of autophagy in lipid metabolism remains controversial, with both a lipolytic function of autophagy and lipogenic function reported. This chapter aims to review the current knowledge on autophagy in N"FLD, with a special focus on its role in hepatic lipid metabolism, hepatic glucose metabolism and insulin resistance, steatohepatitis, hepatocellular injury and hepatic ibrogenesis. Finally, interaction with another cellular homeostatic process, the unfolded protein response UPR , will be briely discussed.

Mitochondrial Energy-Regulating Effect of Atractyloside Inhibits Hepatocellular Steatosis Through the Activation of Autophagy

“…The key role of autophagy in hepatic lipid degradation in various cell types, including adipocytes and hepatocytes, and in dysfunctional autophagy might lead to the accumulation of lipids and TGs (Kwanten et al, 2016). The upregulation of AMPK and downregulation of mTOR observed in the present study may have induced autophagy.…”

Osteocalcin prevents insulin resistance, hepatic inflammation, and activates autophagy associated with high-fat diet–induced fatty liver hemorrhagic syndrome in aged laying hens

“…Ultramicrostructural analysis also revealed that HFD inhibits hepatic autophagy but OCN reversed the effect. Autophagy, a self-degradative process, is a critical biological function for the degradation of damaged intracellular components by lysosomes ( Amir and Czaja, 2011 ; Ni et al., 2012 ; Kwanten et al., 2016 ; Mao et al., 2016 ). Hepatocytes' autophagic function is affected by hepatocytic lipid accumulation by which it reduces the infusion efficiency between autophagosomes and lysosomes, leading to suppressed autophagy ( Singh et al., 2009 ).…”

“…Hepatocytes' autophagic function is affected by hepatocytic lipid accumulation by which it reduces the infusion efficiency between autophagosomes and lysosomes, leading to suppressed autophagy ( Singh et al., 2009 ). The hepatocytes' autophagy is also inhibited by insulin resistance-associated hepatocyte oxidative stress, inflammatory reaction, and apoptosis ( Amir and Czaja, 2011 ; Kwanten et al., 2016 ; Wu et al., 2018 ). Autophagy has been potentially linked to fibrogenesis ( Amir and Czaja, 2011 ).…”

A New Possible Mechanism by Which Punicalagin Protects against Liver Injury Induced by Type 2 Diabetes Mellitus: Upregulation of Autophagy via the Akt/FoxO3a Signaling Pathway

“…In recent years, with in-depth study of autophagy, several studies have found that abnormality of autophagy function is closely related to diabetic liver injury. 4,35,36 Autophagy may be involved in the occurrence and development of diabetic liver injury through degradation of lipid droplets, 37−39 attenuation of insulin resistance, 40,41 and maintenance of pancreatic islet beta cell structure and function. 42,43 Furthermore, increased autophagy can improve NAFLD animal models of hepatic steatosis and reduce chronic liver injury.…”