Endogenous liver protections against lipotoxicity and oxidative stress to avoid the progression of non-alcoholic fatty liver to more serious disease

: Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by an ectopic accumulation of lipids in at least 5% of hepatocytes. The first phase of the disease, called hepatic steatosis, progresses over time to chronic conditions such as steatohepatitis, cirrhosis, and hepatic insufficiency and cancer. The accumulation of free fatty acids in hepatocytes, particularly saturated fatty acids, is a key process in the development and progression of NAFLD. Furthermore, the accumulation of oxidative stress markers in NAFLD is closely linked to lipotoxicity due to impaired lipid metabolism and increased generation of reactive oxygen species (ROS). However, endogenous mechanisms are activated early in the liver to protect against lipotoxicity and oxidative stress, thus preventing liver mass loss and disease progression. Thus, in order to develop appropriate therapies, the purpose of this review is to discuss recent data from the literature regarding the importance of intrinsic mechanisms deployed by the liver in protecting itself against the adverse effects related to chronic lipid accumulation and ROS generation.

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Ameliorative Effect of Spinach on Non-Alcoholic Fatty Liver Disease Induced in Rats by a High-Fat Diet

International Journal of Molecular Sciences ◽

10.3390/ijms20071662 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1662 ◽

Cited By ~ 6

Author(s):

Laura Elvira-Torales ◽

Gala Martín-Pozuelo ◽

Rocío González-Barrio ◽

Inmaculada Navarro-González ◽

Francisco-José Pallarés ◽

...

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Fatty Liver ◽

High Fat Diet ◽

High Fat ◽

Oxidative Stress Biomarkers ◽

Alcoholic Fatty Liver ◽

Stress Biomarkers ◽

Expression Of Genes ◽

And Oxidative Stress

The purpose of this work was to evaluate the effect of dietary carotenoids from spinach on the inflammation and oxidative stress biomarkers, liver lipid profile, and liver transcriptomic and metabolomics profiles in Sprague–Dawley rats with steatosis induced by a high-fat diet. Two concentrations of spinach powder (2.5 and 5%) were used in two types of diet: high-fat (H) and standard (N). Although rats fed diet H showed an accumulation of fat in hepatocytes, they did not show differences in the values of adiponectin, tumor necrosis factor alpha (TNF-α), and oxygen radical absorption (ORAC) in plasma or of isoprostanes in urine compared with animals fed diet N. The consumption of spinach and the accumulation of α and β carotenes and lutein in the liver was inversely correlated with serum total cholesterol and glucose and the content of hepatic cholesterol, increasing monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA) and reducing cholesterol in the livers of rats fed diet H and spinach. In addition, changes in the expression of genes related to the fatty liver condition occurred, and the expression of genes involved in the metabolism of fatty acids and cholesterol increased, mainly through the overexpression of peroxisome proliferator activated receptors (PPARs). Related to liver metabolites, animals fed with diet H showed hypoaminoacidemia, mainly for the glucogenic aminoacids. Although no changes were observed in inflammation and oxidative stress biomarkers, the consumption of spinach modulated the lipid metabolism in liver, which must be taken into consideration during the dietary treatment of steatosis.

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Serum and hepatic sphingolipids relate to insulin resistance, hepatic mitochondrial capacity and oxidative stress in non-alcoholic fatty liver disease

Diabetologie und Stoffwechsel ◽

10.1055/s-0037-1601637 ◽

2017 ◽

Vol 12 (S 01) ◽

pp. S1-S84

Author(s):

M Apostolopoulou ◽

R Gordillo ◽

C Koliaki ◽

S Gancheva ◽

T Jelenik ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

And Oxidative Stress ◽

Alcoholic Fatty Liver Disease ◽

Mitochondrial Capacity

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Addressing the liver progenitor cell response and hepatic oxidative stress in experimental non-alcoholic fatty liver disease/non-alcoholic steatohepatitis using amniotic epithelial cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02476-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mihiri Goonetilleke ◽

Nathan Kuk ◽

Jeanne Correia ◽

Alex Hodge ◽

Gregory Moore ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Epithelial Cells ◽

Fatty Liver ◽

Progenitor Cells ◽

Fatty Liver Disease ◽

Hepatic Inflammation ◽

Alcoholic Fatty Liver ◽

And Oxidative Stress ◽

Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease is the most common liver disease globally and in its inflammatory form, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). Currently, patient education and lifestyle changes are the major tools to prevent the continued progression of NASH. Emerging therapies in NASH target known pathological processes involved in the progression of the disease including inflammation, fibrosis, oxidative stress and hepatocyte apoptosis. Human amniotic epithelial cells (hAECs) were previously shown to be beneficial in experimental models of chronic liver injury, reducing hepatic inflammation and fibrosis. Previous studies have shown that liver progenitor cells (LPCs) response plays a significant role in the development of fibrosis and HCC in mouse models of fatty liver disease. In this study, we examined the effect hAECs have on the LPC response and hepatic oxidative stress in an experimental model of NASH. Methods Experimental NASH was induced in C57BL/6 J male mice using a high-fat, high fructose diet for 42 weeks. Mice received either a single intraperitoneal injection of 2 × 106 hAECs at week 34 or an additional hAEC dose at week 38. Changes to the LPC response and oxidative stress regulators were measured. Results hAEC administration significantly reduced the expansion of LPCs and their mitogens, IL-6, IFNγ and TWEAK. hAEC administration also reduced neutrophil infiltration and myeloperoxidase production with a concurrent increase in heme oxygenase-1 production. These observations were accompanied by a significant increase in total levels of anti-fibrotic IFNβ in mice treated with a single dose of hAECs, which appeared to be independent of c-GAS-STING activation. Conclusions Expansion of liver progenitor cells, hepatic inflammation and oxidative stress associated with experimental NASH were attenuated by hAEC administration. Given that repeated doses did not significantly increase efficacy, future studies assessing the impact of dose escalation and/or timing of dose may provide insights into clinical translation.

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Fructose, Omega 3 Fatty Acids, and Vitamin E: Involvement in Pediatric Non-Alcoholic Fatty Liver Disease

Nutrients ◽

10.3390/nu12113531 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3531

Author(s):

Gigliola Alberti ◽

Juan Cristóbal Gana ◽

José L. Santos

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Liver Disease ◽

Vitamin E ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is currently the most common form of liver disease in both adults and children, becoming the leading cause for liver transplant in many countries. Its prevalence has increased considerably in recent years, mainly due to the explosive increase in pediatric obesity rates. NAFLD is strongly associated with central obesity, diabetes, dyslipidemia and insulin resistance, and it has been considered as the hepatic manifestation of the metabolic syndrome. Its complex pathophysiology involves a series of metabolic, inflammatory and oxidative stress processes, among others. Given the sharp increase in the prevalence of NAFLD and the lack of an appropriate pharmacological approach, it is crucial to consider the prevention/management of the disease based on lifestyle modifications such as the adoption of a healthy nutrition pattern. Herein, we review the literature and discuss the role of three key nutrients involved in pediatric NAFLD: fructose and its participation in metabolism, Omega-3 fatty acids and its anti-inflammatory effects and vitamin E and its action on oxidative stress.

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The Bisphenol A Induced Oxidative Stress in Non-Alcoholic Fatty Liver Disease Male Patients: A Clinical Strategy to Antagonize the Progression of the Disease

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17103369 ◽

2020 ◽

Vol 17 (10) ◽

pp. 3369 ◽

Cited By ~ 1

Author(s):

Alessandro Federico ◽

Marcello Dallio ◽

Antonietta Gerarda Gravina ◽

Nadia Diano ◽

Sonia Errico ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Bisphenol A ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Free Form ◽

Alcoholic Fatty Liver ◽

Male Patients ◽

And Oxidative Stress ◽

Alcoholic Fatty Liver Disease

Introduction: Bisphenol A (BPA) exposure has been correlated to non-alcoholic fatty liver disease (NAFLD) development and progression. We investigated, in a clinical model, the effects of the administration of 303 mg of silybin phospholipids complex, 10 μg of vitamin D, and 15 mg of vitamin E (RealSIL, 100D, IBI-Lorenzini, Aprilia, Italy) in male NAFLD patients exposed to BPA on metabolic, hormonal, and oxidative stress-related parameters. Methods: We enrolled 32 male patients with histologic diagnosis of NAFLD and treated them with Realsil 100D twice a day for six months. We performed at baseline clinical, biochemical, and food consumption assessments as well as the evaluation of physical exercise, thiobarbituric acid reactive substances (TBARS), plasmatic and urinary BPA and estrogen levels. The results obtained were compared with those of healthy control subjects and, in the NAFLD group, between baseline and the end of treatment. Results: A direct proportionality between TBARS levels and BPA exposure was shown (p < 0.0001). The therapy determined a reduction of TBARS levels (p = 0.011), an improvement of alanine aminotransferase, aspartate aminotransferase, insulinemia, homeostatic model assessment insulin resistance, C reactive protein, tumor necrosis factor alpha (p < 0.05), an increase of conjugated BPA urine amount, and a reduction of its free form (p < 0.0001; p = 0.0002). Moreover, the therapy caused an increase of plasmatic levels of the native form of estrogens (p = 0.03). Conclusions: We highlighted the potential role of BPA in estrogen oxidation and oxidative stress in NAFLD patients. The use of Realsil 100D could contribute to fast BPA detoxification and to improve cellular antioxidant power, defending the integrity of biological estrogen-dependent pathways.

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