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Biochimica et biophysica acta. Molecular cell research. 2025 Apr 5:119952. doi: 10.1016/j.bbamcr.2025.119952 Q23.72025

Browning of inguinal white adipose tissue by the novel lignan (-)-secoisolariciresinol 4-O-methyl ether attenuates diet-induced obesity through mitochondrial and Peroxisomal activation

新型木脂素(-)-松脂素-4-O-甲基醚棕色化腹股沟白色脂肪组织并通过线粒体和过氧化物酶体激活来缓解饮食诱导的肥胖症 翻译改进

Wenjun Jiao  1, Woo Yong Park  2, Yong-Il Kim  3, Jin-Hyung Kim  4, Beomsu Kim  1, Gahee Song  2, Ja Yeon Park  1, Se Jin Jung  1, Hyun Jeong Kwak  5, Seong-Kyu Choe  3, Jong-Hyun Lee  6, Jae-Young Um  7

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作者单位

  • 1 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Kyung Hee Institute of Convergence Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
  • 2 Kyung Hee Institute of Convergence Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
  • 3 Department of Microbiology, Wonkwang University School of Medicine, Iksan 54538, Republic of Korea.
  • 4 Department of Biomedical and Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
  • 5 Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
  • 6 College of Pharmacy, Dongduk Women's University, 60 Hwarang-ro 13-gil, Seongbuk-gu, Seoul, 02748, Republic of Korea.
  • 7 Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Kyung Hee Institute of Convergence Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: jyum@khu.ac.kr.

    • DOI: 10.1016/j.bbamcr.2025.119952 PMID: 40194601

    摘要 中英对照阅读

    Studies indicate that the induction and activation of brown and beige adipocytes, which can enhance energy expenditure, may be beneficial for managing obesity and its associated diseases. This study investigated whether a novel lignan (-)-secoisolariciresinol 4-O-methyl ether (S4M) obtained from arctigenin inhibited diet-induced obesity by the browning of white adipose tissue (WAT). S4M treatment inhibited adipogenesis and lipid accumulation in white-induced 3 T3-L1 adipocytes and in zebrafish embryonic development. Moreover, S4M treatment promoted browning in white adipocytes by increasing TOM20, UCP1, and PGC1α protein levels and consequently upregulating the mitochondrial content. S4M treatment significantly promoted mitochondrial fission by increasing the expression of DRP1. Furthermore, it enhanced peroxisome biogenesis and function by inducing PEX13, ACOX1, and catalase. Mdivi-1, a mitochondrial dynamics inhibitor, diminished the browning effect of white adipocytes by the S4M treatment. This study found that S4M treatment inhibited weight gain in high-fat diet-induced obese mice, decreased the weight of WAT, and increased the abundance and function of mitochondria and peroxisomes in inguinal WAT, suggesting that S4M treatment could increase energy expenditure. The results suggest that S4M has potential as a therapeutic agent for combating obesity and its associated metabolic disorders.

    Keywords: (−)-secoisolariciresinol 4-O-methyl ether; Browning; Mitochondria; Obesity; Peroxisome.

    Keywords：diet-induced obesity; peroxisomal activation; mitochondrial activation; secoisolariciresinol

    研究表明，诱导和激活棕色和米色脂肪细胞（这些细胞可以增加能量消耗）可能对管理和治疗肥胖及其相关疾病有益。本研究调查了一种新型木脂素(-)-secoisolariciresinol 4-O-甲基醚(S4M)能否通过使白色脂肪组织(WAT)褐变来抑制由饮食引起的肥胖。S4M处理可抑制白化诱导的3T3-L1脂肪细胞中的脂肪生成和脂质积累，并在斑马鱼胚胎发育中显示出类似效果。此外，S4M处理促进了白色脂肪细胞的褐变过程，通过增加TOM20、UCP1和PGC1α蛋白水平来提高线粒体含量。S4M处理还显著促进线粒体分裂，通过上调DRP1的表达实现这一目标。同时，它增强了过氧化物体生物发生和功能，诱导了PEX13、ACOX1和CAT（过氧化氢酶）的生成。Mdivi-1是一种线粒体动力学抑制剂，可以削弱S4M处理对白色脂肪细胞褐变效果的影响。本研究发现，在高脂饮食引起的肥胖小鼠中，S4M处理可抑制体重增加、减少WAT重量，并在腹股沟WAT中提高线粒体和过氧化物体的数量及功能，表明S4M处理可能有助于增加能量消耗。研究表明，S4M作为一种治疗剂对抗肥胖及其相关代谢紊乱具有潜在的疗效。

    关键词：(-)-secoisolariciresinol 4-O-甲基醚；褐变；线粒体；肥胖；过氧化物体。

    关键词：饮食诱导的肥胖; 过氧化物酶体激活; 线粒体激活; secoisolariciresinol

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    期刊名：Biochimica et biophysica acta-molecular cell research

    缩写：BBA-MOL CELL RES

    ISSN：0167-4889

    e-ISSN：1879-2596

    IF/分区：3.7/Q2

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    Browning of inguinal white adipose tissue by the novel lignan (-)-secoisolariciresinol 4-O-methyl ether attenuates diet-induced obesity through mitochondrial and Peroxisomal activation