Autophagy in non-alcoholic fatty liver disease and alcoholic liver disease

Khambu, Bilon; Yan, Shengmin; Huda, Nazmul; Liu, Gang; Yin, Xiao‐Ming

doi:10.1016/j.livres.2018.09.004

Cited by 77 publications

(63 citation statements)

References 70 publications

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“…37 Autophagy has been implicated as a key regulatory factor in the pathogenesis of NAFLD. 21 Autophagy activation is considered one of the pathways in lipid clearance (lipophagy) and is associated with blocking of NASH. 38,39 The expression of LC3-II and the autophagic adaptors p62 are commonly used to monitor autophagy influx.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies reported that autophagy enhancement might be responsible for the protective role during NAFLD/NASH. 21 As a result, we measured autophagy in hepatic cells after Sal treatment. LC3B, an autophagy indicator, which correlates with the content of autophagosomes reflects the activity of autophagosomes.…”

Section: Sal Enhanced Autophagy In L02 Cells Treated With Pamentioning

confidence: 99%

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<p>Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation</p>

Qi¹,

Liu²,

Gao³

et al. 2019

DMSO

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Purpose: Oxidative stress plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). TRPM2 ion channel functions as a molecular sensor for oxidative stress. The aim of this study was to examine the protective effects of Salidroside, a powerful antioxidative plant, on TRPM2 in an established in vitro model of NAFLD. Methods: NAFLD model was established by palmitic acid (PA) in hepatic L02 cell lines and was added to the media at a final concentration of 400 μM. Cells were used as normal group, PA group and PA receiving varied concentrations of Salidroside (75μg/mL, 150μg/ mL, 300μg/mL). After treating 24 hrs, MTT assay was used to detect cell viability, and ALT level was measured using an appropriate kit assay. Intracellular lipid accumulation was observed by Oil red O staining. Cytosolic Ca 2+ concentrations were evaluated by flow cytometer with Fluo-3/AM. Quantitative RT-PCR was used to measure the mRNA expression of TRPM2, IL-1β and IL-6, and the protein expressions of TRPM2, p-CaMKII and autophagy (LC3B, p62) were determined using Western blot. Results: Treatment with Salidroside effectively restored liver injury and alleviated lipid droplet deposition in a dose-dependent manner, which was associated with inhibition of TRPM2/Ca 2+ /CaMKII pathway. Additionally, autophagic clearance was enhanced by intervention with Salidroside in a dose-dependent manner. Further investigation indicated that Salidroside down-regulated the mRNA expression of IL-1β and IL-6-pro-inflammatory cytokines. Conclusion: These results suggest that Salidroside could alleviate inflammatory injury and steatosis via autophagy activation mediated by downregulation of the TRPM2/Ca 2+ /CaMKII pathway. Targeting the TRPM2 ion channel is a novel treatment strategy for oxidative stressinduced liver in NAFLD.

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Section: Discussionmentioning

confidence: 99%

Section: Sal Enhanced Autophagy In L02 Cells Treated With Pamentioning

confidence: 99%

<p>Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation</p>

Qi¹,

Liu²,

Gao³

et al. 2019

DMSO

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“…[1][2][3] The overlap in the pathophysiology of NASH and muscle wasting make it challenging to determine whether muscle wasting is a risk factor for NASH or whether it is a complication of NASH. [4][5][6][7][8][9][10] Hepatic expression of SIRT1 is downregulated in NASH animals. 5 In transgenic mice, activation of SIRT1 protects against high-fat (HF)-induced hepatic oxidative stress and fatty liver.…”

Section: Introductionmentioning

confidence: 99%

SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice

Huang

Hsu

et al. 2020

BMJ Open Gastroenterol

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BackgroundIn non-alcoholic steatohepatitis (NASH), muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice.MethodsIn vivo and in vitro study, we evaluate the SIRT1-dependent mechanisms and effects of resveratrol administration for 6 weeks with high-fat-methionine and choline deficient diet-induced NASH mice and palmitate-pretreated C2C12 myoblast cells.ResultsResveratrol treatment improved grip strength and muscle mass of limbs, increased running distance and time on exercise wheels in NASH mice. There is a negative correlation between muscular SIRT1 activity and 3-nitrotyrosine levels of NASH and NASH-resv mice. The SIRT1-dependent effect of muscle wasting was associated with the suppression of oxidative stress, upregulation of antioxidants, inhibition of protein degradation, activation of autophagy, suppression of apoptotic activity, upregulation of lipolytic genes and the reduction of fatty infiltration in limb muscles of NASH mice. In vitro, resveratrol alleviated palmitate acid-induced oxidative stress, lipid deposition, autophagy dysfunction, apoptotic signals, and subsequently reduced fusion index and myotube formation of C2C12 cells. The beneficial effects of resveratrol were abolished by EX527.ConclusionsOur study suggests that chronic resveratrol treatment is a potential strategy for amelioration of hepatic steatosis and muscle wasting in NASH mouse model.

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“…Past studies have shown that autophagy is harmed in patients with NAFLD [46,47]. Many factors involved in endoplasmic reticulum stress, insulin resistance, and mitochondrial dysfunction have been demonstrated to conduce to the exacerbation of NAFLD and are related to the disability of autophagy in the context of NAFLD [47].…”

Section: Discussionmentioning

confidence: 99%

Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes

et al. 2019

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Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, including hepatic lipid accumulation and lipotoxicity. Plant-derived polyphenols have attracted considerable attention in the prevention of NAFLD. Lotus seedpod, rich in polyphenols, is a traditional Chinese herbal medicine. Previous studies have showed that lotus seedpod possess radioprotective, antioxidant, anti-cancer, and anti-inflammatory activities. In this study, the in vitro hepatoprotective effect of lotus seedpod extract (LSE) and its main component epigallocatechin (EGC) was examined. Firstly, oleic acid (OA), an unsaturated fatty acid, was used to induce the phenotype of NAFLD in human hepatocytes, HepG2 cells. LSE dose-dependently improved the OA-induced viability loss of HepG2 cells. Non-cytotoxic concentrations of LSE or EGC abolished intracellular lipid accumulation and oxidative stress in the OA-treated cells. In addition, LSE and EGC showed a minor effect on autophagy, and potential in reducing OA-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the formation of apoptotic bodies, the exposure of phosphatidylserine, and activation of caspases. Molecular data showed the anti-apoptotic effect of LSE might be mediated via downregulation of the mitochondrial pathway. Our data imply that EGC-enriched LSE potentially could be developed as an anti-NAFLD agent.

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Autophagy in non-alcoholic fatty liver disease and alcoholic liver disease

Cited by 77 publications

References 70 publications

<p>Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation</p>

<p>Salidroside-Mitigated Inflammatory Injury of Hepatocytes with Non-Alcoholic Fatty Liver Disease via Inhibition TRPM2 Ion Channel Activation</p>

SIRT1-dependent mechanisms and effects of resveratrol for amelioration of muscle wasting in NASH mice

Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes

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