Autophagy: a new target for nonalcoholic fatty liver disease therapy

Mao, Yuqing; Yu, Fang; Wang, Jianbo; Guo, Chuanyong; Fan, Xiaoming

doi:10.2147/hmer.s98120

Cited by 97 publications

(71 citation statements)

References 97 publications

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“…Autophagy plays a pivotal role not only in normal liver physiology, but also in the pathogenesis of many liver diseases including nonalcoholic and alcoholic fatty liver and viral hepatitis (Mao et al 2016; Tang et al 2012). Acute T. cruzi infection may adapt lipophagic pathway to survive energy starvation by increasing autophagic sequestration of lipid droplets and their degradation in hepatic lysosomes.…”

Section: Resultsmentioning

confidence: 99%

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection

et al. 2016

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Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi, which affects about 10 million people in its endemic regions of Latin America. After the initial acute stage of infection, 60-80% of infected individuals remain asymptomatic for several years to a lifetime; however, the rest develop the debilitating symptomatic stage, which affects the nervous system, digestive system and heart. The challenges of Chagas disease have become global due to immigration. Despite well documented dietary changes accompanying immigration, as well as a transition to a western style diet in the Chagas endemic regions, the role of host metabolism in the pathogenesis of Chagas disease remains underexplored. We have previously used a mouse model to show that host diet is a key factor regulating cardiomyopathy in Chagas disease. In this study we investigated the effect of a high fat diet on liver morphology and physiology, lipid metabolism, immune signaling, energy homeostasis, and stress responses in the murine model of acute T. cruzi infection. Our results indicate that in T. cruzi infected mice diet differentially regulates several liver processes, including autophagy, a stress response mechanism, with corresponding implications for human Chagas disease patients.

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Section: Resultsmentioning

confidence: 99%

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection

et al. 2016

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“…Recent studies have revealed that autophagy, a cell survival mechanism for disposing of excess or defective organelles, is linked to the development of NAFLD and the regulation of autophagy has potential therapeutic effects. Autophagy reduces intracellular lipid droplets by enclosing them and fusing with lysosomes for degradation and is involved in attenuating inflammation and liver injury . To investigate whether EGCG regulates autophagy and then improves the lipid clearance in the liver, Zhou et al .…”

Section: Basic Researchmentioning

confidence: 99%

“…EGCG treatment was also shown to reduce hepatosteatosis and concomitantly increases autophagy in the livers of mice fed with a high‐fat/Western‐style (HFW) diet. Nevertheless, autophagy is regarded as a double‐edged sword, its potential effects on adipogenesis, adipocyte differentiation, as well as the association between autophagy and NAFLD remain controversial …”

Section: Basic Researchmentioning

confidence: 99%

Potential Biological Effects of (‐)‐Epigallocatechin‐3‐gallate on the Treatment of Nonalcoholic Fatty Liver Disease

Cheng

Liu

et al. 2017

Molecular Nutrition Food Res

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Nonalcoholic fatty liver disease (NAFLD) is a major health issue throughout the world. However, no validated treatments for NAFLD are currently available. In‐depth studies have demonstrated the efficacy of (‐)‐epigallocatechin‐3‐gallate (EGCG), a main bioactive chemical extracted from green tea, in treating NAFLD. EGCG exhibits multi‐pronged preventive and therapeutic activities, including promoting lipid and glucose metabolism, anti‐lipid peroxidation and anti‐inflammation activities, anti‐fibrosis, and anti‐NAFLD related tumor, thus contributing to the mitigation of NAFLD occurrence and progression. The objectives of this paper are to review and discuss the currently known targets, signaling pathways and roles of EGCG that interfere with NAFLD pathogenesis, then providing additional experimental evidence and the foundation for the further studies and clinical applications of EGCG in the prevention and treatment of NAFLD.

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“…Autophagy is considered of crucial importance in liver metabolism. Autophagy degrades and recycles protein and cell organelles supplying amino acids to cellular processes, delivers glycogen to vacuoles during starvation, and breaks down lipid droplets, providing free fatty acids and intracellular triglycerides 1‐3 . Several studies have shown that hepatic autophagy is dysregulated in metabolic liver diseases such as nonalcoholic fatty liver disease and obesity 4 …”

Section: Introductionmentioning

confidence: 99%

Absence of Atg7 in the liver disturbed hepatic regeneration after liver injury

Römermann

Ansari

Schultz‐Moreira

et al. 2020

Liver International

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Background and aims Autophagy is a critical process in cell survival and the maintenance of homeostasis. However, the implementation of therapeutic approaches based on autophagy mechanisms after liver damage is still challenging. Methods We used a hepatospecific Atg7‐deficient murine model to address this question. Results We showed that the proliferation and regeneration capacity of Atg7‐deficient hepatocytes was impaired. On the one hand, Atg7‐deficient hepatocytes showed steady‐state hyperproliferation. On the other hand, external triggers such as partial hepatectomy (PHx) or cell transplantation did not induce hepatocellular proliferation or liver repopulation. After PHx, hepatocyte proliferation was strongly decreased, accompanied by high mortality. This increase in mortality could be overcome by pharmacological mTOR inhibition. In accordance with hepatocyte hypoproliferation after damage, Atg7‐deficient hepatocytes failed to repopulate the liver in a hepatic injury model. Atg7‐deficient mice showed hepatic hypertrophy, transient cellular hypertrophy, and high transaminase levels followed by strong perisinusoidal/pericellular fibrosis with age. Their elevated modified hepatic activity index (mHAI) was almost exclusively due to apoptosis without any inflammation. These parameters were associated with variations in the triglyceride content and compromised lipid droplet formation after PHx. Mechanistically, we also observed a modulation of HGF, PAK4, NOTCH3 and YES1, which are proteins involved in cell cycle regulation. Conclusion We demonstrated the important role of autophagy in the regeneration capacity of hepatocytes. We showed the causative relationship between autophagy and triglycerides that is essential for promoting liver recovery. Finally, pharmacological mTOR inhibition overcame the impact of autophagy deficiency after liver damage and prevented mortality.

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Autophagy: a new target for nonalcoholic fatty liver disease therapy

Cited by 97 publications

References 97 publications

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection

Potential Biological Effects of (‐)‐Epigallocatechin‐3‐gallate on the Treatment of Nonalcoholic Fatty Liver Disease

Absence of Atg7 in the liver disturbed hepatic regeneration after liver injury

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