The impaired redox balance in peroxisomes of catalase knockout mice accelerates nonalcoholic fatty liver disease through endoplasmic reticulum stress

Hwang, Inah; Uddin, Jamal; Pak, Eun Seon; Kang, Hunseung; Jin, Eun Hyo; Jo, Su-In; Kang, Dongmin; Lee, Hyukjin; Ha, Hunjoo

doi:10.1016/j.freeradbiomed.2019.12.025

Cited by 38 publications

(31 citation statements)

References 47 publications

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“…The excessive hepatic fat accumulation in the absence of any clear reason like alcohol consumption is unique to NAFLD, making this condition one of the leading causes of death worldwide [7,8]. Many studies have linked enhanced markers of oxidative stress with the pathogenesis of NAFLD [4,[9][10][11]. However, beyond oxidative stress, inflammation has been another crucial component that influences liver function in NAFLD.…”

Section: Methods For Study Inclusionmentioning

confidence: 99%

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

et al. 2020

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Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.

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Section: Methods For Study Inclusionmentioning

confidence: 99%

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

et al. 2020

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“…Oxidative stress is a key factor of the "second hit" theory during NAFLD [24]. Accumulation of lipid in hepatocytes leads to acceleration of mitochondrial β oxidation capacity to compensate, which in turn enhances production of ROS that often exceeds the antioxidant capacity of liver and causes oxidative stress [25]. Studies found that the serum SOD and GSH decreased while MDA increased significantly in NAFLD [26].…”

Section: Discussionmentioning

confidence: 99%

“…ER is the major organelle for properly folding and post-translational modifications of proteins and acts as a major intracellular calcium reservoir in the cell. High-fat diets activate ER stress in liver [25]…”

Section: Discussionmentioning

confidence: 99%

Agastache rugosa alleviates the multi-hit effect on hepatic lipid metabolism, inflammation and oxidative stress during nonalcoholic fatty liver disease

Cui¹,

Chang²,

Wang³

et al. 2020

Preprint

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Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and has high rates of morbidity and mortality worldwide. Agastache rugosa (AR) possesses unique anti-oxidant, anti‑inflammatory and anti-atherosclerosis characteristics. Methods To investigate the effects and the underlying mechanism of AR on NAFLD, we fed mice a high-fat diet (HFD) to establish NAFLD model of mice in vivo experiment and induced lipidosis in AML12 hepatocytes through a challenge with free fatty acids (FFA) in vitro. The contents of total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver homogenates were measured. Pathological changes in liver tissue were evaluated by HE staining. Oil red O staining was used to determine degree of lipid accumulation in liver tissue, and Western blot was used to detect abundance of inflammation-, lipid metabolism- and endoplasmic reticulum stress-related proteins. Results Supply of AR alleviated accumulation of lipid in hepatocytes induced by HFD in vivo and challenged with free fatty acids (FFA) in vitro. Compared with the HFD group, supplementing AR decreased p-NF-κB/NF-κB and p-IκB/IκB protein and inhibited abundance of PERK, IRE1 and ATF6 (P < 0.05). Furthermore, AR reduced lipid accumulation within hepatocytes by downregulating abundance of SREBP, ACC1 and FAS (P < 0.05). Supply of AR significantly attenuated ROS accumulation and MDA production by improving antioxidant enzymatic activity including SOD and GSH (P < 0.01). Conclusion Supply of AR attenuates disordered lipid metabolism and enhances the antioxidative defense associated with NAFLD induced by HFD in mice. Results underscore the potential of plants used in traditional Chinese medicine to achieve pharmacological benefits through a multi-tier cellular response.

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“…The capacity of CAT to reduce lipolysis was demonstrated in CAT KO mice (CKO). These animals have heightened plasma TAG, Free FA, and insulin when fed a high-fat diet (HFD) [79]. Although not demonstrated in AT, HSL activity in the liver was enhanced while ATGL expression decreased [80].…”

Section: Catalasementioning

confidence: 99%

Redox Regulation of Lipid Mobilization in Adipose Tissues

Abou-Rjeileh

Contreras

2021

Antioxidants

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Lipid mobilization in adipose tissues, which includes lipogenesis and lipolysis, is a paramount process in regulating systemic energy metabolism. Reactive oxygen and nitrogen species (ROS and RNS) are byproducts of cellular metabolism that exert signaling functions in several cellular processes, including lipolysis and lipogenesis. During lipolysis, the adipose tissue generates ROS and RNS and thus requires a robust antioxidant response to maintain tight regulation of redox signaling. This review will discuss the production of ROS and RNS within the adipose tissue, their role in regulating lipolysis and lipogenesis, and the implications of antioxidants on lipid mobilization.

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The impaired redox balance in peroxisomes of catalase knockout mice accelerates nonalcoholic fatty liver disease through endoplasmic reticulum stress

Cited by 38 publications

References 47 publications

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

Agastache rugosa alleviates the multi-hit effect on hepatic lipid metabolism, inflammation and oxidative stress during nonalcoholic fatty liver disease

Redox Regulation of Lipid Mobilization in Adipose Tissues

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