Adipose tissue autophagy and homeostasis in alcohol-induced liver injury

Li, Yuan; Ding, Wen–Xing

doi:10.1016/j.livres.2017.03.004

Cited by 18 publications

(14 citation statements)

References 134 publications

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“…Autophagosomes bring the enveloped cargoes to the lysosomes to form autolysosomes where the lysosomal enzymes consequently degrade the cargos [1,2]. Autophagy is generally induced in response to the starvation conditions to generate biomolecules for cell survival purposes [1][2][3]. Autophagic degradation is split into two categories, selective or nonselective.…”

Section: Introductionmentioning

confidence: 99%

Role and Mechanisms of Mitophagy in Liver Diseases

McKeen

Zhang

et al. 2020

Cells

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166

122

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The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is associated with both acute and chronic liver diseases with emerging evidence indicating that mitophagy, a selective form of autophagy for damaged/excessive mitochondria, plays a key role in the liver’s physiology and pathophysiology. This review will focus on mitochondrial dynamics, mitophagy regulation, and their roles in various liver diseases (alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, and cancer) with the hope that a better understanding of the molecular events and signaling pathways in mitophagy regulation will help identify promising targets for the future treatment of liver diseases.

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Section: Introductionmentioning

confidence: 99%

Role and Mechanisms of Mitophagy in Liver Diseases

McKeen

Zhang

et al. 2020

Cells

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166

122

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“…Both an increased level of the lipidated form of LC3 (LC3-II) as an autophagosome marker and a decreased level of ubiquitin-binding scaffold protein p62, also called sequestosome 1(SQSTM1), were observed in obese humans and mice, the combination of which would appear to be consistent with an increase in autophagy activity during adipogenesis (Klionsky et al, 2016; Yoshii and Mizushima, 2017). The level of autophagy activity seems to differ or at least to fluctuate depending on the adipose tissue type, external stimuli, and tissue age (Bluher, 2013; Kosacka et al, 2015; Li and Ding, 2017). Autophagy is activated when white adipocyte is undergoing differentiation to form lipid droplets.…”

Section: Introduction: Autophagy In Adipocytesmentioning

confidence: 99%

“…Adipocytes undergo three major types of autophagy: macroautophagy, macrolipophagy (generally referred as lipophagy), and mitophagy. These occur dynamically depending on browning status (Baerga et al, 2009; Singh et al, 2009b; Zhang et al, 2009; Singh and Cuervo, 2012; Li and Ding, 2017; Ghosh et al, 2018). Both autophagy malfunction and adipocyte dysfunction are clearly connected with the causes of metabolic disorders such as obesity and diabetes (Baerga et al, 2009; Singh et al, 2009b; Zhang et al, 2009; Bjorndal et al, 2011; Singh and Cuervo, 2012; Bluher, 2013; Scheele and Nielsen, 2017; Ghosh et al, 2018).…”

Section: Introduction: Autophagy In Adipocytesmentioning

confidence: 99%

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Jang

Bae

et al. 2019

Front. Physiol.

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Autophagy, lipophagy, and mitophagy are considered to be the major recycling processes for protein aggregates, excess fat, and damaged mitochondria in adipose tissues in response to nutrient status-associated stress, oxidative stress, and genotoxic stress in the human body. Obesity with increased body weight is often associated with white adipose tissue (WAT) hypertrophy and hyperplasia and/or beige/brown adipose tissue atrophy and aplasia, which significantly contribute to the imbalance in lipid metabolism, adipocytokine secretion, free fatty acid release, and mitochondria function. In recent studies, hyperactive autophagy in WAT was observed in obese and diabetic patients, and inhibition of adipose autophagy through targeted deletion of autophagy genes in mice improved anti-obesity phenotypes. In addition, active mitochondria clearance through activation of autophagy was required for beige/brown fat whitening – that is, conversion to white fat. However, inhibition of autophagy seemed detrimental in hypermetabolic conditions such as hepatic steatosis, atherosclerosis, thermal injury, sepsis, and cachexia through an increase in free fatty acid and glycerol release from WAT. The emerging concept of white fat browning–conversion to beige/brown fat–has been controversial in its anti-obesity effect through facilitation of weight loss and improving metabolic health. Thus, proper regulation of autophagy activity fit to an individual metabolic profile is necessary to ensure balance in adipose tissue metabolism and function, and to further prevent metabolic disorders such as obesity and diabetes. In this review, we summarize the effect of autophagy in adipose tissue browning in the context of obesity prevention and its potential as a promising target for the development of anti-obesity drugs.

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“…In particular, it was observed that the loss of SNX10 gene in mice determined the over-expression of autophagy markers LAMP-2A, Nrf2 and AMPK in alcohol-mediated liver steatosis (77). Furthermore, several studies noticed that alcohol consumption induce adipose tissue atrophy leading to autophagy impairment and block of tissue homeostasis, which lead to development of diseases correlated with development of pathologies affecting several tissue and organs, including liver (78).…”

Section: Autophagy In Liver Pathogenesismentioning

confidence: 99%

Targeting autophagy in liver cancer

Fazio¹,

Matrood²

2018

Transl. Gastroenterol. Hepatol.

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Autophagy is a catabolic cellular process conserved in animals. It is characterized by the main role of recycling all the non-functional products of the cells. Once, autophagy players detect non-functioning sub-cellular organelles and proteins, they start the so-called nucleation process. The organelles will be surrounded by a double membrane vesicle mainly constituted by endoplasmic reticulum (ER) membrane and autophagy proteins, e.g., MAP1LC3B, Beclin-1, VPS34, Unc-51 like autophagy activating kinase (ULK1) and ubiquitination-related proteins. Then the autophagic membrane will go through an elongation phase involving additional autophagy players. Once the autophagic vesicle is complete, the sub-cellular organelles will be isolated from the rest of the cytosol and driven to the final fusion with lysosomes. Here, the digestion process will end. Alteration and or impairment of autophagy have been shown to be correlated with development of diseases affecting the central nervous system, e.g., Alzheimer and other neurodegenerative diseases. Nonetheless, autophagy defect is responsible for tumorigenesis in blood and solid malignancies, in particular liver cancer. Malignancies of the liver are determined by several genetics and epigenetics mechanisms triggering the up-regulation of survival mechanisms and resistance to cell death. Furthermore, liver cancer could result from pathologic conditions like cirrhosis and fibrosis related to virus infection, aflatoxin, alcohol consumption and high fat diet together with insulin resistance. The role exerted by autophagy in the pathogenesis of the liver and tumor development has been evidenced in recent years. The alteration of autophagy assumes a fundamental role for liver tumorigenesis determining an accumulation of non-functional proteins and organelles that trigger oxidative stress leading to genotoxic stress and gene alterations. Furthermore, the absence of this degradation mechanism could prompt the cells to alter their metabolic status and turn into malignant cells. Interestingly, the heterozygous loss of function of Beclin-1 is able to trigger liver tumorigenesis or even the simple accumulation of proteins caused by the block of the final autolysosome fusion and degradation process is responsible for liver cancer development. This review highlights the importance of targeting the autophagy process in liver cancer in order to restore its function and to promote autophagy-mediated cell demise.

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Adipose tissue autophagy and homeostasis in alcohol-induced liver injury

Cited by 18 publications

References 134 publications

Role and Mechanisms of Mitophagy in Liver Diseases

Role and Mechanisms of Mitophagy in Liver Diseases

Autophagy in Adipocyte Browning: Emerging Drug Target for Intervention in Obesity

Targeting autophagy in liver cancer

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