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鱼腥草素钠通过AMPK-NRF2-HO1途径抑制铁死亡促进白色脂肪组织褐变。

Sodium Houttuybonate Promotes the Browning of White Adipose Tissue by Inhibiting Ferroptosis via the AMPK-NRF2-HO1 Pathway.

作者信息

Liu Wenhui, Zou Huren, You Danming, Zhang Huijie, Xu Lingling

机构信息

Department of Endocrinology, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, China.

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China.

出版信息

Antioxidants (Basel). 2024 Aug 30;13(9):1057. doi: 10.3390/antiox13091057.

DOI:10.3390/antiox13091057
PMID:39334717
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11428211/
Abstract

The rising prevalence of obesity has resulted in an increased demand for innovative and effective treatment strategies. Thunb. has demonstrated promising potential in preventing obesity. However, the mechanism underlying the anti-obesity effects of and its bioactive component, sodium houttuybonate (SH), remains unclear. Our study reveals that SH treatment promotes the browning of inguinal white adipose tissue (iWAT) and prevents the obesity induced by a high-fat diet. SH significantly mitigates ferroptosis by upregulating glutathione peroxidase 4 () and decreasing malondialdehyde (MDA) levels, while also enhancing superoxide dismutase (SOD) levels. Furthermore, SH promotes the phosphorylation of AMP-activated protein kinase (AMPK), which subsequently increases the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the iWAT. However, the effects of SH were attenuated by ML385, an Nrf2 inhibitor. Collectively, our findings suggest that SH induces iWAT browning and prevents diet-induced obesity primarily through the AMPK/NRF2/HO-1 pathway by inhibiting ferroptosis.

摘要

肥胖患病率的不断上升导致对创新且有效的治疗策略的需求增加。土荆芥已在预防肥胖方面展现出了有前景的潜力。然而,土荆芥及其生物活性成分鱼腥草素钠(SH)的抗肥胖作用机制仍不清楚。我们的研究表明,SH处理可促进腹股沟白色脂肪组织(iWAT)的褐变,并预防高脂饮食诱导的肥胖。SH通过上调谷胱甘肽过氧化物酶4()和降低丙二醛(MDA)水平,同时还提高超氧化物歧化酶(SOD)水平,显著减轻铁死亡。此外,SH促进AMP活化蛋白激酶(AMPK)的磷酸化,随后增加iWAT中核因子红细胞2相关因子2(NRF2)和血红素加氧酶-1(HO-1)的表达。然而,SH的作用被Nrf2抑制剂ML385减弱。总体而言,我们的研究结果表明,SH主要通过抑制铁死亡,经由AMPK/NRF2/HO-1途径诱导iWAT褐变并预防饮食诱导的肥胖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/b9ffec387916/antioxidants-13-01057-g007a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/c95a808b8939/antioxidants-13-01057-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/7edb59f05723/antioxidants-13-01057-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/1974c80e02ea/antioxidants-13-01057-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/5e2e8fa11ba1/antioxidants-13-01057-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/9a0f6d2b6a66/antioxidants-13-01057-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/f5b6964e46d3/antioxidants-13-01057-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/b9ffec387916/antioxidants-13-01057-g007a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/c95a808b8939/antioxidants-13-01057-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/7edb59f05723/antioxidants-13-01057-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/1974c80e02ea/antioxidants-13-01057-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/5e2e8fa11ba1/antioxidants-13-01057-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/9a0f6d2b6a66/antioxidants-13-01057-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/f5b6964e46d3/antioxidants-13-01057-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9cda/11428211/b9ffec387916/antioxidants-13-01057-g007a.jpg

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本文引用的文献

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Perivascular Adipose Tissue Oxidative Stress in Obesity.肥胖症中的血管周围脂肪组织氧化应激
Antioxidants (Basel). 2023 Aug 10;12(8):1595. doi: 10.3390/antiox12081595.
2
Pharmacological Effects of Thunb (): A Comprehensive Review.茵陈的药理作用:综述
Pharmaceuticals (Basel). 2022 Aug 29;15(9):1079. doi: 10.3390/ph15091079.
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AMPK and NRF2: Interactive players in the same team for cellular homeostasis?AMPK 和 NRF2:细胞内稳态的同一团队中的互动玩家?
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Nrf2 attenuates ferroptosis-mediated IIR-ALI by modulating TERT and SLC7A11.Nrf2 通过调节 TERT 和 SLC7A11 来减轻铁死亡介导的 II 型呼吸窘迫综合征相关性急性肺损伤。
Cell Death Dis. 2021 Oct 29;12(11):1027. doi: 10.1038/s41419-021-04307-1.
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Effects of Fermented Thunb. on Diabetic Rats Induced by a High-Fat Diet with Streptozotocin and on Insulin Resistance in 3T3-L1 Adipocytes.发酵的[植物名称(原文未完整给出,推测是某种植物)]对高脂饮食联合链脲佐菌素诱导的糖尿病大鼠及3T3-L1脂肪细胞胰岛素抵抗的影响
J Nutr Metab. 2021 Aug 6;2021:6936025. doi: 10.1155/2021/6936025. eCollection 2021.
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Identification of phytocompounds from Houttuynia cordata Thunb. as potential inhibitors for SARS-CoV-2 replication proteins through GC-MS/LC-MS characterization, molecular docking and molecular dynamics simulation.通过 GC-MS/LC-MS 表征、分子对接和分子动力学模拟鉴定鱼腥草中的植物化合物作为 SARS-CoV-2 复制蛋白的潜在抑制剂。
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Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association.肥胖与心血管疾病:美国心脏协会科学声明
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J Exp Clin Cancer Res. 2019 Jun 7;38(1):242. doi: 10.1186/s13046-019-1255-3.