Aurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue
Abstract Background Obesity is frequently linked to chronic systamic inflammation and presents significant challenges to public health. Aurantio-obtusin (AO) boosted the brown adipose tissue (BAT) thermogenesis in diet-induced obesity. However, the specific mechanisms by which injured mitochondria-r...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-03-01
|
| Series: | Chinese Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13020-025-01097-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849392450616950784 |
|---|---|
| author | Ruiyu Wu Runping Liu Ranyun Chen Yijie Li Xiaoyong Xue Yinhao Zhang Fanghong Li Jiaorong Qu Lingling Qin Chen Wang Xiaojiaoyang Li |
| author_facet | Ruiyu Wu Runping Liu Ranyun Chen Yijie Li Xiaoyong Xue Yinhao Zhang Fanghong Li Jiaorong Qu Lingling Qin Chen Wang Xiaojiaoyang Li |
| author_sort | Ruiyu Wu |
| collection | DOAJ |
| description | Abstract Background Obesity is frequently linked to chronic systamic inflammation and presents significant challenges to public health. Aurantio-obtusin (AO) boosted the brown adipose tissue (BAT) thermogenesis in diet-induced obesity. However, the specific mechanisms by which injured mitochondria-related damage signals derived from overwhelmed BAT can transmit to liver and exacerbate metabolic disorders and whether AO can reverse this process remain unknown. Materials and methods After applying high-fat diet and glucose-fructose water (HFHS)-induced obesity mice, different BAT transplant procedures and primary BAT adipocytes, we investigated the anti-obesity effects and mechanism of AO through RNA sequencing and biology techniques. Results AO improved whole-body lipid accumulation, mitochondrial metabolism in BAT and hepatic inflammation in HFHS-induced obesity mice. Interscapular transplant of BAT-derived from obese donor mice triggered hepatic inflammation of chow diet-fed recipient mice, which was protected by AO. Furthermore, the transplantation of BAT-derived from AO-treated mice protected hepatic inflammation in obese mice. In vivo and in lipid-challenged primary BAT adipocytes, AO decreased kexin type 9 (PCSK9), prevented mPTP opening and mitochondrial DNA (mtDNA) release in extracellular vesicles (EVs) manner by inhibiting the acetylation of cyclophilin D associated with adenine nucleotide translocase, suppressing oligomerization of voltage-dependent anion channel 1 and activating mitophagy. Ultimately, AO inhibited mtDNA-containing EVs-induced cyclic GMP-AMP synthase/stimulator of interferon genes (STING) activation and hepatic inflammation, which was confirmed by Sting−/− mice. Conclusion AO not only improves thermogenesis and mitochondrial function of BAT but also prevents liver inflammation by repairing mitochondrial function and blocking the transfer of mtDNA from BAT to the liver. Graphic abstract |
| format | Article |
| id | doaj-art-3b51d5e17aaa44e2af8f0b3c3e491bbc |
| institution | Kabale University |
| issn | 1749-8546 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj-art-3b51d5e17aaa44e2af8f0b3c3e491bbc2025-08-20T03:40:45ZengBMCChinese Medicine1749-85462025-03-0120112110.1186/s13020-025-01097-yAurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissueRuiyu Wu0Runping Liu1Ranyun Chen2Yijie Li3Xiaoyong Xue4Yinhao Zhang5Fanghong Li6Jiaorong Qu7Lingling Qin8Chen Wang9Xiaojiaoyang Li10School of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Life Sciences, Beijing University of Chinese MedicineSchool of Life Sciences, Beijing University of Chinese MedicineSchool of Life Sciences, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Life Sciences, Beijing University of Chinese MedicineDepartment of Science and Technology, Beijing University of Chinese MedicineSchool of Chinese Materia Medica, Beijing University of Chinese MedicineSchool of Life Sciences, Beijing University of Chinese MedicineAbstract Background Obesity is frequently linked to chronic systamic inflammation and presents significant challenges to public health. Aurantio-obtusin (AO) boosted the brown adipose tissue (BAT) thermogenesis in diet-induced obesity. However, the specific mechanisms by which injured mitochondria-related damage signals derived from overwhelmed BAT can transmit to liver and exacerbate metabolic disorders and whether AO can reverse this process remain unknown. Materials and methods After applying high-fat diet and glucose-fructose water (HFHS)-induced obesity mice, different BAT transplant procedures and primary BAT adipocytes, we investigated the anti-obesity effects and mechanism of AO through RNA sequencing and biology techniques. Results AO improved whole-body lipid accumulation, mitochondrial metabolism in BAT and hepatic inflammation in HFHS-induced obesity mice. Interscapular transplant of BAT-derived from obese donor mice triggered hepatic inflammation of chow diet-fed recipient mice, which was protected by AO. Furthermore, the transplantation of BAT-derived from AO-treated mice protected hepatic inflammation in obese mice. In vivo and in lipid-challenged primary BAT adipocytes, AO decreased kexin type 9 (PCSK9), prevented mPTP opening and mitochondrial DNA (mtDNA) release in extracellular vesicles (EVs) manner by inhibiting the acetylation of cyclophilin D associated with adenine nucleotide translocase, suppressing oligomerization of voltage-dependent anion channel 1 and activating mitophagy. Ultimately, AO inhibited mtDNA-containing EVs-induced cyclic GMP-AMP synthase/stimulator of interferon genes (STING) activation and hepatic inflammation, which was confirmed by Sting−/− mice. Conclusion AO not only improves thermogenesis and mitochondrial function of BAT but also prevents liver inflammation by repairing mitochondrial function and blocking the transfer of mtDNA from BAT to the liver. Graphic abstracthttps://doi.org/10.1186/s13020-025-01097-yObesityAurantio-obtusinBrown adipose tissueMitochondrial DNAInflammation |
| spellingShingle | Ruiyu Wu Runping Liu Ranyun Chen Yijie Li Xiaoyong Xue Yinhao Zhang Fanghong Li Jiaorong Qu Lingling Qin Chen Wang Xiaojiaoyang Li Aurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue Chinese Medicine Obesity Aurantio-obtusin Brown adipose tissue Mitochondrial DNA Inflammation |
| title | Aurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue |
| title_full | Aurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue |
| title_fullStr | Aurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue |
| title_full_unstemmed | Aurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue |
| title_short | Aurantio-obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue |
| title_sort | aurantio obtusin improves obesity and protects hepatic inflammation by rescuing mitochondrial damage in overwhelmed brown adipose tissue |
| topic | Obesity Aurantio-obtusin Brown adipose tissue Mitochondrial DNA Inflammation |
| url | https://doi.org/10.1186/s13020-025-01097-y |
| work_keys_str_mv | AT ruiyuwu aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT runpingliu aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT ranyunchen aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT yijieli aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT xiaoyongxue aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT yinhaozhang aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT fanghongli aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT jiaorongqu aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT linglingqin aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT chenwang aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue AT xiaojiaoyangli aurantioobtusinimprovesobesityandprotectshepaticinflammationbyrescuingmitochondrialdamageinoverwhelmedbrownadiposetissue |