NRF-2 and nonalcoholic fatty liver disease

Solano-Urrusquieta, Arturo; Morales-González, José A.; Castro-Narro, Graciela; Cerda-Reyes, Eira; Flores-Rangel, Perla Denice; Fierros-Oceguera, Raul

doi:10.1016/j.aohep.2019.11.010

Cited by 28 publications

(26 citation statements)

References 96 publications

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“…Expression of genes encoding antioxidant enzymes and regulators of the glutathione pathway (glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, GPX2) is regulated by the transcription factor erythroid2-like 2 (Nrf2) [ 239 ]. Upon oxidative stress, Nrf2, which is anchored in the cytoplasm via binding to Keap1, dissociates from it and translocates into the nucleus, where it interacts with specific DNA sequences called antioxidant response elements in the promoter of its target antioxidant enzyme genes [ 240 ]. Nrf2 expression is increased in the first stage of NAFLD in preclinical models [ 241 ], and pharmacological activation of Nrf2 in mice fed a high-fat and high fructose diet decreases NASH parameters (insulin resistance, weight gain, TG, ALT) via the transcriptional regulation of genes involved in inflammation, apoptosis, fibrosis, ER stress, and oxidative stress [ 239 ].…”

Section: Role Of Oxidative Stress In Nafld Pathogenesismentioning

confidence: 99%

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) is often the hepatic expression of metabolic syndrome and its comorbidities that comprise, among others, obesity and insulin-resistance. NAFLD involves a large spectrum of clinical conditions. These range from steatosis, a benign liver disorder characterized by the accumulation of fat in hepatocytes, to non-alcoholic steatohepatitis (NASH), which is characterized by inflammation, hepatocyte damage, and liver fibrosis. NASH can further progress to cirrhosis and hepatocellular carcinoma. The etiology of NAFLD involves both genetic and environmental factors, including an unhealthy lifestyle. Of note, unhealthy eating is clearly associated with NAFLD development and progression to NASH. Both macronutrients (sugars, lipids, proteins) and micronutrients (vitamins, phytoingredients, antioxidants) affect NAFLD pathogenesis. Furthermore, some evidence indicates disruption of metabolic homeostasis by food contaminants, some of which are risk factor candidates in NAFLD. At the molecular level, several models have been proposed for the pathogenesis of NAFLD. Most importantly, oxidative stress and mitochondrial damage have been reported to be causative in NAFLD initiation and progression. The aim of this review is to provide an overview of the contribution of nutrients and food contaminants, especially pesticides, to oxidative stress and how they may influence NAFLD pathogenesis.

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Section: Role Of Oxidative Stress In Nafld Pathogenesismentioning

confidence: 99%

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

et al. 2020

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“…Oxidative stress, lipotoxicity, and local inflammation induce the progression from hepatic steatosis to steatohepatitis and cirrhosis. To fight against cellular stress and inflammation, the UPR is a vital mechanism in patients with non-alcoholic steatohepatitis, especially in the mitochondria, because factors, such as mitochondrial UPR and mitohormesis, prevent the evolution of fatty liver to fibrosis ( Solano-Urrusquieta et al, 2020 ). Previous studies showed that the PPAR signaling pathway (through PPARα receptor) can assist ER stress by regulating fatty acid β-oxidation pathways in peroxisomes and mitochondria, and also by inhibiting the inflammatory response in the liver ( Wang et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Liver proteome alterations in psychologically distressed rats and a nootropic drug

González-Fernández

Grigoruta

Chávez-Martínez

et al. 2021

PeerJ

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Background Chronic psychological distress is considered today a pandemic due to the modern lifestyle and has been associated with various neurodegenerative, autoimmune, or systemic inflammation-related diseases. Stress is closely related to liver disease exacerbation through the high activity of the endocrine and autonomic nervous systems, and the connection between the development of these pathologies and the physiological effects induced by oxidative stress is not yet completely understood. The use of nootropics, as the cognitive enhancer and antioxidant piracetam, is attractive to repair the oxidative damage. A proteomic approach provides the possibility to obtain an in-depth comprehension of the affected cellular processes and the possible consequences for the body. Therefore, we considered to describe the effect of distress and piracetam on the liver proteome. Methods We used a murine model of psychological stress by predatory odor as a distress paradigm. Female Sprague-Dawley rats were distributed into four experimental groups (n = 6 − 7/group) and were exposed or not to the stressor for five days and treated or not with piracetam (600 mg/kg) for six days. We evaluated the liver proteome by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D-SDS-PAGE) followed by liquid chromatography-tandem mass spectrometry (GeLC-MS/MS). Besides, we analyzed the activity of liver antioxidant enzymes, the biochemical parameters in plasma and rat behavior. Results Our results showed that distress altered a wide range of proteins involved in amino acids metabolism, glucose, and fatty acid mobilization and degradation on the way to produce energy, protein folding, trafficking and degradation, redox metabolism, and its implications in the development of the non-alcoholic fatty liver disease (NAFLD). Piracetam reverted the changes in metabolism caused by distress exposure, and, under physiological conditions, it increased catabolism rate directed towards energy production. These results confirm the possible relationship between chronic psychological stress and the progression of NAFLD, as well as we newly evidenced the controversial beneficial effects of piracetam. Finally, we propose new distress biomarkers in the liver as the protein DJ-1 (PARK7), glutathione peroxidase 1 (GPX), peroxiredoxin-5 (PRDX5), glutaredoxin 5 (GLRX5), and thioredoxin reductase 1 (TXNDR1), and in plasma as biochemical parameters related to kidney function such as urea and blood urea nitrogen (BUN) levels.

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“…In contrast, C57BL/6J mice with hepatic steatosis showed decreased mRNA expression of AMPK-PGC-1α signaling components, as well as Nrf2 and β-ATP synthase [ 51 ]. In rats fed an HFD, Lactobacillus mali APS1 reduced the levels of hepatic lipids by regulating the expression of sirtuin-1 (SIRT-1)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)/SREBP-1, and it also increased the hepatic antioxidant activity via induction of Nrf2 and HO-1 [ 51 ]. Nrf2-KO mice fed an HFD showed a downregulation of lipid metabolic genes, preventing hepatic steatosis [ 52 ].…”

Section: Nrf2 Connection With Liver Diseasesmentioning

confidence: 99%

“…Regarding lipid peroxidation, nucleotide and protein synthesis are impaired, thus inducing apoptosis, inflammation, and liver fibrosis [ 60 ]. The unfolded protein responses (UPR) plays an important role in cellular stress and inflammation in NASH [ 51 ].…”

Section: Nrf2 Connection With Liver Diseasesmentioning

confidence: 99%

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Roles of Nrf2 in Liver Diseases: Molecular, Pharmacological, and Epigenetic Aspects

et al. 2020

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Liver diseases represent a critical health problem with 2 million deaths worldwide per year, mainly due to cirrhosis and its complications. Oxidative stress plays an important role in the development of liver diseases. In order to maintain an adequate homeostasis, there must be a balance between free radicals and antioxidant mediators. Nuclear factor erythroid 2-related factor (Nrf2) and its negative regulator Kelch-like ECH-associated protein 1 (Keap1) comprise a defense mechanism against oxidative stress damage, and growing evidence considers this signaling pathway as a key pharmacological target for the treatment of liver diseases. In this review, we provide detailed and updated evidence regarding Nrf2 and its involvement in the development of the main liver diseases such as alcoholic liver damage, viral hepatitis, steatosis, steatohepatitis, cholestatic damage, and liver cancer. The molecular and cellular mechanisms of Nrf2 cellular signaling are elaborated, along with key and relevant antioxidant drugs, and mechanisms on how Keap1/Nrf2 modulation can positively affect the therapeutic response are described. Finally, exciting recent findings about epigenetic modifications and their link with regulation of Keap1/Nrf2 signaling are outlined.

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NRF-2 and nonalcoholic fatty liver disease

Cited by 28 publications

References 96 publications

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

Liver proteome alterations in psychologically distressed rats and a nootropic drug

Roles of Nrf2 in Liver Diseases: Molecular, Pharmacological, and Epigenetic Aspects

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