Celecoxib alleviates nonalcoholic fatty liver disease by restoring autophagic flux

Liu, Cong; Liu, Lian; Zhu, Haidan; Sheng, Jiaqi; Wu, Xiaoli; He, Xingxing; Tian, Dean; Liao, Jiazhi; Li, Peiyuan

doi:10.1038/s41598-018-22339-0

Cited by 31 publications

(19 citation statements)

References 37 publications

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“…Inefficient autophagy has been found also in both mice fed with HFD, and melatonin recovered autophagy and triggered mitophagy in WT mice only. Novel evidence indicates that melatonin can be a strong modulator of autophagy and survival in diseases and activation of autophagy was an effective therapy in NAFLD and NASH [78,79,80]. According to our findings in WT mice, melatonin protected fatty liver, regulating mitophagy and p62 protein that is necessary to drive dysfunctional mitochondria to autophagosomes for dismantling [81,82].…”

Section: Discussionmentioning

confidence: 77%

Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Stacchiotti

Grossi

García-Gómez

et al. 2019

Cells

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Melatonin, an indole produced by pineal and extrapineal tissues, but also taken with a vegetarian diet, has strong anti-oxidant, anti-inflammatory and anti-obesogenic potentials. Non-alcoholic fatty liver disease (NAFLD) is the hepatic side of the metabolic syndrome. NAFLD is a still reversible phase but may evolve into steatohepatitis (NASH), cirrhosis and carcinoma. Currently, an effective therapy for blocking NAFLD staging is lacking. Silent information regulator 1 (SIRT1), a NAD+ dependent histone deacetylase, modulates the energetic metabolism in the liver. Micro-RNA-34a-5p, a direct inhibitor of SIRT1, is an emerging indicator of NAFLD grading. Thus, here we analyzed the effects of oral melatonin against NAFLD and underlying molecular mechanisms, focusing on steatosis, ER stress, mitochondrial shape and autophagy. Male C57BL/6J (WT) and SIRT1 heterozygous (HET) mice were placed either on a high-fat diet (58.4% energy from lard) (HFD) or on a standard maintenance diet (8.4% energy from lipids) for 16 weeks, drinking melatonin (10 mg/kg) or not. Indirect calorimetry, glucose tolerance, steatosis, inflammation, ER stress, mitochondrial changes, autophagy and microRNA-34a-5p expression were estimated. Melatonin improved hepatic metabolism and steatosis, influenced ER stress and mitochondrial shape, and promoted autophagy in WT HFD mice. Conversely, melatonin was ineffective in HET HFD mice, maintaining NASH changes. Indeed, autophagy was inconsistent in HET HFD or starved mice, as indicated by LC3II/LC3I ratio, p62/SQSTM1 and autophagosomes estimation. The beneficial role of melatonin in dietary induced NAFLD/NASH in mice was related to reduced expression of microRNA-34a-5p and sterol regulatory element-binding protein (SREBP1) but only in the presence of full SIRT1 availability.

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Section: Discussionmentioning

confidence: 77%

Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Stacchiotti

Grossi

García-Gómez

et al. 2019

Cells

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“…Reverse-transcribed complementary DNA was synthesized using the Prime Script RT Reagent Kit (Takara, Japan). Real-time PCR was performed as we have described before [39]. The sequences of the primers used for RT-qPCR are listed in Supplementary .…”

Section: Methodsmentioning

confidence: 99%

Primary Cilia Blockage Promotes the Malignant Behaviors of Hepatocellular Carcinoma via Induction of Autophagy

Sheng

Wang

Gan

et al. 2019

BioMed Research International

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Primary cilia are organelles protruding from cell surface into environment that function in regulating cell cycle and modulating cilia-related signal. Primary ciliogenesis and autophagy play important roles in tumorigenesis. However, the functions and interactions between primary cilia and autophagy in hepatocellular carcinoma (HCC) have not been reported yet. Here, we aimed to investigate the relationship and function of primary cilia and autophagy in HCC. In vitro, we showed that serum starvation stimuli could trigger primary ciliogenesis in HCC cells. Blockage of primary ciliogenesis by IFT88 silencing enhanced the proliferation, migration, and invasion ability of HCC cells. In addition, inhibition of primary cilia could positively regulate autophagy. However, the proliferation, migration, and invasion ability which were promoted by IFT88 silencing could be partly reversed by inhibition of autophagy. In vivo, interference of primary cilia led to acceleration of tumor growth and increase of autophagic flux in xenograft HCC mouse models. Moreover, IFT88 high expression or ATG7 low expression in HCC tissues was correlated with longer survival time indicated by the Cancer Genome Atlas (TCGA) analysis. In conclusion, our study demonstrated that blockage of primary ciliogenesis by IFT88 silencing had protumor effects through induction of autophagy in HCC. These findings define a newly recognized role of primary cilia and autophagy in HCC.

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“…(Deng et al, 2017;Gonzalez-Rodriguez et al, 2014). Partially restoring autophagic flux by celecoxib can alleviate steatosis (Liu et al, 2018).…”

Section: Studied Parameters In Interventional Groupsmentioning

confidence: 99%

Role of anti‐inflammatory interventions in high‐fat‐diet‐induced obesity

Ghazala

Medney

Meleis

et al. 2020

Biomedical Chromatography

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Lipotoxicity is defined as deposition of excess fat associated with an inflammatory response. Metabolomic analysis of fatty acids (FAs) can be a marker of silent inflammation. ω3‐Enriched diet, celecoxib, and safranal may have a protective anti‐inflammatory role. In this work, total FAs extracted from red blood cells and arachidonic acid‐to‐eicosapentaenoic acid (AA‐to‐EPA) ratios were assessed using GC–MS assay in single‐ion monitoring mode. The study was conducted on 64 male rats divided into eight groups: I, controls; II, rats received high‐fat diet (HFD), III, rats received ω‐6‐enriched HFD; IV, rats received ω‐3‐enriched HFD; V, rats received celecoxib with HFD; VI, rats received safranal with HFD; VII and VIII, rats received celecoxib and safranal with ω‐3 HFD, respectively. GC–MS Gas chromatography Mass spectrometry was performed for analysis of fatty acid methyl ester. Enzyme‐linked immunosorbent assay was used to analyze serum interleukin‐6 (IL‐6) and transforming growth factor‐beta 1 (TGF‐β1) concentrations. A statistically significant decrease of AA‐to‐EPA ratio was observed in group VII when compared with the groups receiving HFDs. This group also showed the lowest serum IL‐6 level and highest TGF‐β1 level. In conclusion, ω3‐enriched diet along with drugs (e.g. celecoxib) and herbal medications (e.g. safranal) may have an anti‐inflammatory effect in lipotoxicity. GC–MS with single‐ion monitoring is valid for the analysis of FAs.

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Celecoxib alleviates nonalcoholic fatty liver disease by restoring autophagic flux

Cited by 31 publications

References 37 publications

Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p/Sirt1 Axis and Autophagy

Primary Cilia Blockage Promotes the Malignant Behaviors of Hepatocellular Carcinoma via Induction of Autophagy

Role of anti‐inflammatory interventions in high‐fat‐diet‐induced obesity

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