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Autophagy and Liver Diseases

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Autophagy Networks in Inflammation

Abstract

Autophagy is a mechanism involved in cellular homeostasis under basal and stressed conditions delivering cytoplasmic content to the lysosomes for degradation to macronutrients. Autophagy provides essential components (amino acids, lipids and carbohydrates) needed to meet the cell’s energy necessities, and it also regulates energy supply by controlling the number, quality, and dynamics of the mitochondria. Lastly, autophagy also modulates the levels of enzymes in metabolic pathways. It is generally recognised that autophagy plays a role in the hepatic lipid metabolism. It is not surprising that dysregulation of autophagy has been connected with liver-specific disorders such as fatty liver, non-alcoholic steatohepatitis and hepatocellular carcinoma. However, controversy of the exact role of autophagy in the lipid metabolism exists: some publications report a lipolytic function of autophagy, whereas others claim a lipogenic function. This chapter aims to give an update of the present knowledge (last 5 years) on autophagy in the hepatic lipid metabolism, hepatic insulin resistance, steatohepatitis and hepatic fibrogenesis. An improved understanding of the autophagic process should lead to potentially innovative therapies with direct relevance to surgical diseases.

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Abbreviations

A-1ATD:

Alpha-1 antitrypsin deficiency

AASLD:

American Association for the Study of Liver Diseases

ACC:

Acetyl-CoA carboxylase

ADH:

Alcohol dehydrogenase

ALD:

Alcoholic liver disease

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

ATZ:

z mutation of alpha-1-antitrypsin

CDKs:

Cyclin-dependent kinases

CDT:

Carbohydrate deficient transferrin

CKD:

Chronic kidney disease

CPT-1:

Carnitine palmitoyltransferase 1

CVD:

Cardiovascular disease

CYP2E1:

Cytochrome P450 2E1

DIC:

Disseminated intravascular coagulopathy

EC:

Endothelial cells

GGT:

Gamma glutamyl transferase

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HMGB1:

High mobility group box 1

HSPs:

Heat shock proteins

I/R:

Ischemia-reperfusion

IL-1:

Interleukin-1

IL-12:

Interleukin-12

INF-γ:

Interferon-γ

KC:

Kupffer cells

LCHAD:

Long-chain 3-hydroxyl coenzyme A dehydrogenase

LDs:

Lipid droplets

MAPK:

Mitogen-activated protein kinase

miRNAs:

MicroRNAs

MPT:

Mitochondrial permeability transition

MUFAs:

Monounsaturated fatty acids

NAE:

NEDD8-activating enzyme

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

OSA:

Obstructive sleep apnoea

PAS:

Phagophore assembly site

PL:

Phospholipid

ROS:

Reactive oxygen species

SNAREs:

NSF attachment protein receptors

Spred protein:

Sprouty-related protein with Ena/vasodilator-stimulated phosphoprotein homology-1 domain

TAG:

Triacylglycerol

TNF-α:

Tumour necrosis factor-α

TPN:

Total parenteral nutrition

TTP:

Tumor progression

VLDL:

Very low-density lipoprotein

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Esposito, E., Campolo, M., Cordaro, M., Casili, G., Cuzzocrea, S. (2016). Autophagy and Liver Diseases. In: Maiuri, M., De Stefano, D. (eds) Autophagy Networks in Inflammation. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-30079-5_17

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