scholarly journals Targeting Autophagy to Counteract Obesity-Associated Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 102
Author(s):  
Federico Pietrocola ◽  
José Manuel Bravo-San Pedro

Reactive oxygen species (ROS) operate as key regulators of cellular homeostasis within a physiological range of concentrations, yet they turn into cytotoxic entities when their levels exceed a threshold limit. Accordingly, ROS are an important etiological cue for obesity, which in turn represents a major risk factor for multiple diseases, including diabetes, cardiovascular disorders, non-alcoholic fatty liver disease, and cancer. Therefore, the implementation of novel therapeutic strategies to improve the obese phenotype by targeting oxidative stress is of great interest for the scientific community. To this end, it is of high importance to shed light on the mechanisms through which cells curtail ROS production or limit their toxic effects, in order to harness them in anti-obesity therapy. In this review, we specifically discuss the role of autophagy in redox biology, focusing on its implication in the pathogenesis of obesity. Because autophagy is specifically triggered in response to redox imbalance as a quintessential cytoprotective mechanism, maneuvers based on the activation of autophagy hold promises of efficacy for the prevention and treatment of obesity and obesity-related morbidities.

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 687
Author(s):  
Daniela Gabbia ◽  
Luana Cannella ◽  
Sara De De Martin

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.


2013 ◽  
Vol 144 (5) ◽  
pp. S-1013
Author(s):  
Billur Canbakan ◽  
Hakan Senturk ◽  
Murat Tuncer ◽  
Ibrahim Hatemi ◽  
Emine Koroglu ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1732
Author(s):  
Francesco Baratta ◽  
Daniele Pastori ◽  
Simona Bartimoccia ◽  
Vittoria Cammisotto ◽  
Nicholas Cocomello ◽  
...  

Oxidative stress plays a pivotal role in non-alcoholic fatty liver disease (NAFLD). Factors inducing oxidative stress in NAFLD may be several; however, a relationship with the adherence to Mediterranean Diet (Med-diet) and with serum lipopolysaccharide (LPS) has been poorly investigated in this setting. The aim was to investigate factors associated with impaired oxidative stress in NAFLD, focusing on the potential role of LPS and Med-diet. We enrolled 238 consecutive outpatients from the PLINIO study, in whom we measured the soluble Nox2-derived peptide (sNox2-dp), a marker of systemic oxidative stress, and serum LPS. Adherence to Med-diet was investigated by a nine-item validated dietary questionnaire. Serum sNox2-dp and LPS were higher in patients with NAFLD compared to those without (25.0 vs. 9.0 pg/mL, p < 0.001 and 62.0 vs. 44.9 pg/mL, p < 0.001, respectively). In patients with NAFLD, the highest sNox2-dp tertile was associated with the top serum LPS tertile (Odds Ratio (OR): 4.71; p < 0.001), APRI > 0.7 (OR: 6.96; p = 0.005) and Med-diet-score > 6 (OR: 0.14; p = 0.026). Analyzing individual foods, the daily consumption of wine (OR: 0.29, p = 0.046) and the adequate weekly consumption of fish (OR: 0.32, p = 0.030) inversely correlated with the top sNox2-dp tertile. In conclusion, patients with NAFLD showed impaired oxidative stress. Levels of sNox2 correlated with serum LPS and with low adherence to Med-Diet.


Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 229 ◽  
Author(s):  
Laura Inés Elvira-Torales ◽  
Javier García-Alonso ◽  
María Jesús Periago-Castón

The consumption of carotenoids has beneficial effects on health, reducing the risk of certain forms of cancer, cardiovascular diseases, and macular degeneration, among others. The mechanism of action of carotenoids has not been clearly identified; however, it has been associated with the antioxidant capacity of carotenoids, which acts against reactive oxygen species and inactivating free radicals, although it has also been shown that carotenoids modulate gene expression. Dietary carotenoids are absorbed and accumulated in the liver and other organs, where they exert their beneficial effects. In recent years, it has been described that the intake of carotenoids can significantly reduce the risk of suffering from liver diseases, such as non-alcoholic fatty liver disease (NAFLD). This disease is characterized by an imbalance in lipid metabolism producing the accumulation of fat in the hepatocyte, leading to lipoperoxidation, followed by oxidative stress and inflammation. In the first phases, the main treatment of NAFLD is to change the lifestyle, including dietary habits. In this sense, carotenoids have been shown to have a hepatoprotective effect due to their ability to reduce oxidative stress and regulate the lipid metabolism of hepatocytes by modulating certain genes. The objective of this review was to provide a description of the effects of dietary carotenoids from fruits and vegetables on liver health.


2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Mohammad T. Elnakish ◽  
Amany A. E. Ahmed ◽  
Peter J. Mohler ◽  
Paul M. L. Janssen

Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 174
Author(s):  
Johanna C. Arroyave-Ospina ◽  
Zongmei Wu ◽  
Yana Geng ◽  
Han Moshage

Oxidative stress (OxS) is considered a major factor in the pathophysiology of inflammatory chronic liver diseases, including non-alcoholic liver disease (NAFLD). Chronic impairment of lipid metabolism is closely related to alterations of the oxidant/antioxidant balance, which affect metabolism-related organelles, leading to cellular lipotoxicity, lipid peroxidation, chronic endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Increased OxS also triggers hepatocytes stress pathways, leading to inflammation and fibrogenesis, contributing to the progression of non-alcoholic steatohepatitis (NASH). The antioxidant response, regulated by the Nrf2/ARE pathway, is a key component in this process and counteracts oxidative stress-induced damage, contributing to the restoration of normal lipid metabolism. Therefore, modulation of the antioxidant response emerges as an interesting target to prevent NAFLD development and progression. This review highlights the link between disturbed lipid metabolism and oxidative stress in the context of NAFLD. In addition, emerging potential therapies based on antioxidant effects and their likely molecular targets are discussed.


Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1041 ◽  
Author(s):  
Hung-Yu Lin ◽  
Ya-Ling Yang ◽  
Pei-Wen Wang ◽  
Feng-Sheng Wang ◽  
Ying-Hsien Huang

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and ranges from steatosis to steatohepatitis and to liver fibrosis. Lipotoxicity in hepatocytes, elevated oxidative stress and the activation of proinflammatory mediators of Kupffer cells, and fibrogenic pathways of activated hepatic stellate cells can contribute to the development of NAFLD. MicroRNAs (miRs) play a crucial role in the dysregulated metabolism and inflammatory signaling connected with NAFLD and its progression towards more severe stages. Of note, the protective effect of non-coding miR-29a on liver damage and its versatile action on epigenetic activity, mitochondrial homeostasis and immunomodulation may improve our perception of the pathogenesis of NAFLD. Herein, we review the biological functions of critical miRs in NAFLD, as well as highlight the emerging role of miR-29a in therapeutic application and the recent advances in molecular mechanisms underlying its liver protective effect.


Author(s):  
Pallavi M. ◽  
Suchitra M. M. ◽  
Alok Sachan ◽  
Lakshmi A. Y. ◽  
Srinivasa Rao P. V. L. N.

Background: Type 2 diabetes mellitus (T2DM) is associated with chronic inflammation and oxidative stress, implicated in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Present study aimed to assess the role of adipokines, oxidative stress, and endotoxins in the pathogenesis of NAFLD in T2DM.Methods: Present cross-sectional observational study included healthy controls (n=50; group 1); T2DM patients without NAFLD (n=50; group 2), T2DM patients with NAFLD (n=50; group 3). Study subjects were age and gender matched.Results: Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high sensitive C-reactive protein (hs-CRP), endotoxin, malondialdehyde (MDA) were significantly elevated and adiponectin, ferric reducing ability of plasma (FRAP), and glutathione (GSH) were significantly lower (p<0.001) in T2DM patients with NAFLD when compared to T2DM patients without NAFLD and controls. Endotoxin showed significant positive correlation with TNF-α (r=0.304; p<0.001), hs-CRP (r=0.193; p=0.018), and MDA (r=0.420; p<0.001), and significant negative correlation with adiponectin (r=-0.406; p<0.001). TNF-α and IL-6 showed significant positive correlation with MDA (r=0.526; p<0.001, r=0.229; p=0.005) and significant negative correlation with adiponectin (r=-0.396; p<0.001, r=-0.318; p<0.001), FRAP (r=-0.418; p<00.001, r=-0.170; p=0.038), and GSH (r=-0.353; p<0.001, r=-0.301; p<0.001).Conclusions: Authors observed elevated endotoxin, oxidative stress, inflammation and lower adiponectin levels in T2DM subjects compared to controls. These changes were more pronounced in T2DM with NAFLD when compared to T2DM without NAFLD.  Lower adiponectin levels were found to be a better predictor of NALFD in T2DM and is associated with oxidative stress and systemic inflammation.


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