Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non‐alcoholic fatty liver disease by up‐regulating the FGF21/PGC‐1α pathway

Wu, Liwei; Mo, Wenhui; Jiao, Feng; Li, Jingjing; Yu, Qiang; Li, Sainan; Jie, Zhang; Chen, Kan; Ji, Jie; Dai, Weiqi; Wu, Jianye; Xu, Xuanfu; Mao, Yuqing; Guo, Chuanyong

doi:10.1111/bph.15099

Cited by 95 publications

(57 citation statements)

References 64 publications

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“…Astaxanthin, a marine carotenoid well-known for its potent antioxidant capacity, effectively prevented hepatic lipid accumulation by down-regulating lipogenic genes and improved mitochondrial oxidative metabolism by protecting mitochondrial redox homeostasis and functional integrity against oxidative stress [6]. Nitzschia laevis extract (NLE) was found in our previous study to reduce lipid content of C57BL/6J mice [7].…”

Section: Introductionmentioning

confidence: 96%

Lipid-Lowering Bioactivity of Microalga Nitzschia laevis Extract Containing Fucoxanthin in Murine Model and Carcinomic Hepatocytes

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis, is one of the most common liver diseases worldwide. So far, no definitive medical treatment has been established to treat NAFLD except for lifestyle medication. Nitzschia laevis extract (NLE), a microalgal extract rich in fucoxanthin, has been previously demonstrated to reduce bodyweight in high-fat-diet (HFD) C57BL/6J mice, indicating potential for prevention of NAFLD. In the present study, we investigated the lipid-lowering effects of NLE in HFD-induced steatosis murine model and palmitate-treated HepG2 cells. The results showed that NLE significantly lowered inguinal fat and attenuated hepatic steatosis in C57BL/6J mice. Especially, NLE significantly prevented lipid accumulation in HepG2 cells. This was probably due to its capability to enhance hepatic mitochondrial function as evidenced by the increased oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), and repress fatty acid synthesis through phosphorylation of acetyl-CoA carboxylase (ACC). Moreover, fucoxanthin was identified to be responsible for the lipid-lowering effect of NLE. Taken together, NLE or other microalgal fucoxanthin-rich products are promising natural products that may help prevent against NAFLD.

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Section: Introductionmentioning

confidence: 96%

Lipid-Lowering Bioactivity of Microalga Nitzschia laevis Extract Containing Fucoxanthin in Murine Model and Carcinomic Hepatocytes

et al. 2021

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“…Astaxanthin, a xanthophyll carotenoid extracted from seafood, possesses various biological functions including anti‐oxidative and neuroprotective effects (Wu et al, 2015; Wu et al, 2020; Zhang, Wang, et al, 2017). Unlike other carotenoids, astaxanthin contains two additional oxygenated groups on each ring structure with more powerful anti‐oxidant property (Zhang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice

Zhang

et al. 2021

British J Pharmacology

112

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Background and Purpose Oxidative stress and neuronal apoptosis play key roles in traumatic brain injury. We investigated the protective effects of astaxanthin against traumatic brain injury and its underlying mechanisms of action. Experimental Approach A weight‐drop model of traumatic brain injury in vivo and hydrogen peroxide exposure in vitro model were established. Brain oedema, behaviour tests, western blot, biochemical analysis, lesion volume, histopathological study and cell viability were performed. Key Results Astaxanthin significantly reduced oxidative insults on Days 1, 3 and 7 after traumatic brain injury. Neuronal apoptosis was also ameliorated on Day 3. Additionally, astaxanthin improved neurological functions up to 3 weeks after traumatic brain injury. Astaxanthin treatment dramatically enhanced the expression of peroxiredoxin 2 (Prx2), nuclear factor‐erythroid 2‐related factor 2 (NRF2/Nrf2) and sirtuin 1 (SIRT1), while it down‐regulated the phosphorylation of apoptosis signal‐regulating kinase 1 (ASK1) and p38. Inhibition of Prx2 by siRNA injection reversed the beneficial effects of astaxanthin against traumatic brain injury. Additionally, Nrf2 knockout prevented the neuroprotective effects of astaxanthin in traumatic brain injury. In contrast, overexpression of Prx2 in Nrf2 knockout mice attenuated the secondary brain injury after traumatic brain injury. Moreover, inhibiting SIRT1 by EX527 dramatically inhibited the neuroprotective effects of astaxanthin and suppressed SIRT1/Nrf2/Prx2/ASK1/p38 pathway both in vivo and in vitro. Conclusion and Implications Astaxanthin improved the neurological functions and protected the brain from injury after traumatic brain injury, primarily by reducing oxidative stress and neuronal death via SIRT1/Nrf2/Prx2/ASK1/p38 signalling pathway and might be a new candidate to ameliorate traumatic brain injury.

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“…Adenosine A2a receptor activation, which is expected to reduce lipotoxicity [387] and suppress inflammatory activation of macrophages [388] , regulated CD4 + T-cells response (proliferation of Th1 and Th17 in liver tissue). It was confirmed that the pathological condition of NASH in C57BL/6 mice that were fed an MCD was improved by suppressing the deterioration of IL-17-induced JNK-dependent lipotoxicity [389] . Astaxanthin is expected to suppress mitochondrial dysfunction in NAFLD [390] and protect against ischemia-reperfusion injury in fatty liver [391] .…”

Section: Changes In Immune Dynamics Owing To Therapeutic Intervention In Nafld Modelmentioning

confidence: 77%

Role of CD4+ T-cells in the pathology of non-alcoholic fatty liver disease and related diseases

Seike¹,

Mizukoshi²,

Kaneko³

2021

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Non-alcoholic fatty liver disease (NAFLD), which is considered a liver phenotype of metabolic diseases, is becoming a major cause of chronic liver disease. Multiple factors influence and interact with each other in a complex manner to form this pathological condition. As evidenced by low-grade chronic inflammation in obesity, which is a basic pathological feature of NAFLD, immune cell infiltration can occur in various organs, and immune cell infiltration into the liver plays an important role in the development of steatohepatitis. In recent years, an increasing number of reports indicate the involvement of innate immunity and adaptive immunity in the pathogenesis of NAFLD. CD4 + T-cells, which serve as an essential and complex element of the immune system and major regulators of host health and disease, are differentiated into functional T helper 1 (Th1), Th2, Th9, Th17, Th22, T follicular helper, and regulatory T-cells upon antigen stimulation in a special cytokine environment. In NAFLD patients, various pathological conditions such as obesity, diabetes, dyslipidemia, and adipose tissue inflammation coexist. Hence, T-cells can be affected by each of these pathological conditions. This review covers and discusses the reports on NAFLD and its associated pathologies as well as their effects on CD4 + T-cells.

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Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non‐alcoholic fatty liver disease by up‐regulating the FGF21/PGC‐1α pathway

Cited by 95 publications

References 64 publications

Lipid-Lowering Bioactivity of Microalga Nitzschia laevis Extract Containing Fucoxanthin in Murine Model and Carcinomic Hepatocytes

Lipid-Lowering Bioactivity of Microalga Nitzschia laevis Extract Containing Fucoxanthin in Murine Model and Carcinomic Hepatocytes

Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice

Role of CD4+ T-cells in the pathology of non-alcoholic fatty liver disease and related diseases

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