Yuanfeng Gu, Wenjun He, Wenxuan Li, Jingshu Cai, Zhuyun Wang, Kemeng Li, Guangcheng Qin, Xiaojie Gu, Xiaojing Lin, Li Ma, Xiaoqiu Xiao, Yi Hou, Ting Luo
{"title":"牛蒡子素是一种木脂素化合物，通过激活腺苷A2A受体来促进脂肪组织褐化和能量消耗。","authors":"Yuanfeng Gu, Wenjun He, Wenxuan Li, Jingshu Cai, Zhuyun Wang, Kemeng Li, Guangcheng Qin, Xiaojie Gu, Xiaojing Lin, Li Ma, Xiaoqiu Xiao, Yi Hou, Ting Luo","doi":"10.1186/s10020-025-01249-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The activation of brown adipose tissue (BAT) or the browning of white adipose tissue (WAT) represents a promising therapeutic strategy for obesity. Arctiin (ARC), a lignan compound known for its anti-inflammatory, anti-tumor, and hypoglycemic properties, has not been fully elucidated regarding its effects and mechanisms on obesity.</p><p><strong>Methods: </strong>In the present study, we established both high-fat diet-induced obese mouse models and mature adipocyte cultures to comprehensively investigate the therapeutic effects of ARC on obesity. Systemic energy metabolism and thermogenic capacity were assessed through metabolic cage monitoring and cold stimulation tests. Histopathological alterations in adipose tissues were examined using hematoxylin and eosin (H&E) staining, while key gene expression in adipocytes was determined by Western blotting (WB), immunohistochemistry, and immunofluorescence staining. To further elucidate the molecular mechanisms underlying ARC's anti-obesity effects, we employed an integrated approach combining network pharmacology analysis, molecular docking simulations, cellular thermal shift assay (CETSA), and WB to identify potential molecular targets and delineate the associated signaling pathways modulated by ARC treatment.</p><p><strong>Results: </strong>In diet-induced obese mice, ARC administration at doses of 20 and 60 mg/kg/day ameliorated metabolic dysfunction through enhanced WAT browning and increased energy expenditure. In C3H10T1/2-induced adipocytes, ARC upregulated the protein expression of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and other brown-specific marker genes, promoting mitochondrial function and browning of adipocytes. Mechanistically, our findings suggest that ARC may promote adipocyte browning via the A<sub>2A</sub>R-cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway.</p><p><strong>Conclusion: </strong>In summary, ARC exerts protective effects against obesity by promoting the browning of white adipocytes and holds promise as a potentially beneficial therapeutic agent for the treatment of obesity.</p>","PeriodicalId":18813,"journal":{"name":"Molecular Medicine","volume":"31 1","pages":"188"},"PeriodicalIF":6.0000,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079995/pdf/","citationCount":"0","resultStr":"{\"title\":\"Arctiin, a lignan compound, enhances adipose tissue browning and energy expenditure by activating the adenosine A<sub>2A</sub> receptor.\",\"authors\":\"Yuanfeng Gu, Wenjun He, Wenxuan Li, Jingshu Cai, Zhuyun Wang, Kemeng Li, Guangcheng Qin, Xiaojie Gu, Xiaojing Lin, Li Ma, Xiaoqiu Xiao, Yi Hou, Ting Luo\",\"doi\":\"10.1186/s10020-025-01249-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The activation of brown adipose tissue (BAT) or the browning of white adipose tissue (WAT) represents a promising therapeutic strategy for obesity. Arctiin (ARC), a lignan compound known for its anti-inflammatory, anti-tumor, and hypoglycemic properties, has not been fully elucidated regarding its effects and mechanisms on obesity.</p><p><strong>Methods: </strong>In the present study, we established both high-fat diet-induced obese mouse models and mature adipocyte cultures to comprehensively investigate the therapeutic effects of ARC on obesity. Systemic energy metabolism and thermogenic capacity were assessed through metabolic cage monitoring and cold stimulation tests. Histopathological alterations in adipose tissues were examined using hematoxylin and eosin (H&E) staining, while key gene expression in adipocytes was determined by Western blotting (WB), immunohistochemistry, and immunofluorescence staining. To further elucidate the molecular mechanisms underlying ARC's anti-obesity effects, we employed an integrated approach combining network pharmacology analysis, molecular docking simulations, cellular thermal shift assay (CETSA), and WB to identify potential molecular targets and delineate the associated signaling pathways modulated by ARC treatment.</p><p><strong>Results: </strong>In diet-induced obese mice, ARC administration at doses of 20 and 60 mg/kg/day ameliorated metabolic dysfunction through enhanced WAT browning and increased energy expenditure. In C3H10T1/2-induced adipocytes, ARC upregulated the protein expression of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and other brown-specific marker genes, promoting mitochondrial function and browning of adipocytes. Mechanistically, our findings suggest that ARC may promote adipocyte browning via the A<sub>2A</sub>R-cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway.</p><p><strong>Conclusion: </strong>In summary, ARC exerts protective effects against obesity by promoting the browning of white adipocytes and holds promise as a potentially beneficial therapeutic agent for the treatment of obesity.</p>\",\"PeriodicalId\":18813,\"journal\":{\"name\":\"Molecular Medicine\",\"volume\":\"31 1\",\"pages\":\"188\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-05-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079995/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s10020-025-01249-8\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10020-025-01249-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Arctiin, a lignan compound, enhances adipose tissue browning and energy expenditure by activating the adenosine A2A receptor.
Background: The activation of brown adipose tissue (BAT) or the browning of white adipose tissue (WAT) represents a promising therapeutic strategy for obesity. Arctiin (ARC), a lignan compound known for its anti-inflammatory, anti-tumor, and hypoglycemic properties, has not been fully elucidated regarding its effects and mechanisms on obesity.
Methods: In the present study, we established both high-fat diet-induced obese mouse models and mature adipocyte cultures to comprehensively investigate the therapeutic effects of ARC on obesity. Systemic energy metabolism and thermogenic capacity were assessed through metabolic cage monitoring and cold stimulation tests. Histopathological alterations in adipose tissues were examined using hematoxylin and eosin (H&E) staining, while key gene expression in adipocytes was determined by Western blotting (WB), immunohistochemistry, and immunofluorescence staining. To further elucidate the molecular mechanisms underlying ARC's anti-obesity effects, we employed an integrated approach combining network pharmacology analysis, molecular docking simulations, cellular thermal shift assay (CETSA), and WB to identify potential molecular targets and delineate the associated signaling pathways modulated by ARC treatment.
Results: In diet-induced obese mice, ARC administration at doses of 20 and 60 mg/kg/day ameliorated metabolic dysfunction through enhanced WAT browning and increased energy expenditure. In C3H10T1/2-induced adipocytes, ARC upregulated the protein expression of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and other brown-specific marker genes, promoting mitochondrial function and browning of adipocytes. Mechanistically, our findings suggest that ARC may promote adipocyte browning via the A2AR-cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway.
Conclusion: In summary, ARC exerts protective effects against obesity by promoting the browning of white adipocytes and holds promise as a potentially beneficial therapeutic agent for the treatment of obesity.
期刊介绍：
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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