Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice
Abstract Background Adipose tissue plays a pivotal role in systemic metabolism and maintaining bodily homeostasis. Exosomes from adipose tissues, known as AT-Exos, are recognized as important messengers in the communication between adipose tissue and other organs. Despite this, the alterations in ex...
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2025-02-01
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| Online Access: | https://doi.org/10.1186/s12929-025-01124-y |
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| author | Yun-kai Lin Yu-fei Pan Tian-yi Jiang Yi-bin Chen Tai-yu Shang Meng-you Xu Hui-bo Feng Yun-han Ma Ye-xiong Tan Hong-yang Wang Li-wei Dong |
| author_facet | Yun-kai Lin Yu-fei Pan Tian-yi Jiang Yi-bin Chen Tai-yu Shang Meng-you Xu Hui-bo Feng Yun-han Ma Ye-xiong Tan Hong-yang Wang Li-wei Dong |
| author_sort | Yun-kai Lin |
| collection | DOAJ |
| description | Abstract Background Adipose tissue plays a pivotal role in systemic metabolism and maintaining bodily homeostasis. Exosomes from adipose tissues, known as AT-Exos, are recognized as important messengers in the communication between adipose tissue and other organs. Despite this, the alterations in exosome composition and the functional disparities among depot-specific AT-Exos in obesity remain elusive. Methods In this work, we utilized lipidomics and microRNA (miRNA) sequencing to elucidate the lipid and miRNA profiles of AT-Exos in a diet-induced obesity model. We identified obesity-related miRNAs in AT-Exos and further explored their mechanisms using gain- and loss-of-function experiments. To evaluate the metabolic effects of AT-Exos on adipocytes, we conducted RNA-sequencing (RNA-seq) and confirmed our findings through Quantitative Real-time PCR (qPCR) and Western bolt analyses. Meanwhile, a mouse model with intraperitoneal injections was utilized to validate the role of exosomes derived from visceral white adipose tissue (vWAT-Exos) in obesity progression in vivo. Finally, we explored potential therapeutic intervention strategies targeting AT-Exos, particularly focusing on modulating the SIRPα-CD47 axis to enhance macrophage phagocytosis using Leptin-deficient (ob/ob) mice and SIRPα knock-out mice. Results Our study revealed that obesity-related metabolism affects the biological processes of AT-Exos, with depot-specific secretion patterns. In obesity, the lipidome profile of AT-Exos was significantly altered, and diet can modify the miRNA content and function within these exosomes, influencing lipid metabolism and inflammatory pathways that contribute to metabolic dysregulation. Specifically, we identified that miR-200a-3p and miR-200b-3p promoted lipid accumulation in 3T3L1 cells partly through the PI3K/AKT/mTOR pathway. RNA-Seq analysis revealed that AT-Exos from different fat depots exerted distinct effects on adipocyte metabolism, with obese vWAT-Exos being notably potent in triggering inflammation and lipid accumulation in diet-induced obesity. Additionally, we found that inhibiting the SIRPα-CD47 axis can mitigate metabolic disorders induced by obese vWAT-Exos or ob/ob mice, partly due to the enhanced clearance of vWAT-Exos. Consistent with this, SIRPα-deficient mice exhibited a reduction in vWAT-Exos and displayed greater resistance to obesity. Conclusions This study elucidates that diet-induced obesity altered the lipid and miRNA profiles of AT-Exos, which involved in modulating adipocyte inflammation and metabolic balance. The SIRPα-CD47 axis emerges as a potential therapeutic target for obesity and its associated complications. |
| format | Article |
| id | doaj-art-3cec9303dcfa4e00adb32489d926a688 |
| institution | DOAJ |
| issn | 1423-0127 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Journal of Biomedical Science |
| spelling | doaj-art-3cec9303dcfa4e00adb32489d926a6882025-08-20T02:54:36ZengBMCJournal of Biomedical Science1423-01272025-02-0132112510.1186/s12929-025-01124-yBlocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in miceYun-kai Lin0Yu-fei Pan1Tian-yi Jiang2Yi-bin Chen3Tai-yu Shang4Meng-you Xu5Hui-bo Feng6Yun-han Ma7Ye-xiong Tan8Hong-yang Wang9Li-wei Dong10International Cooperation Laboratory On Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical UniversityOncology Pharmacy Laboratory, National Center for Liver CancerOncology Pharmacy Laboratory, National Center for Liver CancerOncology Pharmacy Laboratory, National Center for Liver CancerOncology Pharmacy Laboratory, National Center for Liver CancerOncology Pharmacy Laboratory, National Center for Liver CancerOncology Pharmacy Laboratory, National Center for Liver CancerInternational Cooperation Laboratory On Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical UniversityInternational Cooperation Laboratory On Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical UniversityInternational Cooperation Laboratory On Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical UniversityInternational Cooperation Laboratory On Signal Transduction, Eastern Hepatobiliary Surgery Hospital, Naval Medical UniversityAbstract Background Adipose tissue plays a pivotal role in systemic metabolism and maintaining bodily homeostasis. Exosomes from adipose tissues, known as AT-Exos, are recognized as important messengers in the communication between adipose tissue and other organs. Despite this, the alterations in exosome composition and the functional disparities among depot-specific AT-Exos in obesity remain elusive. Methods In this work, we utilized lipidomics and microRNA (miRNA) sequencing to elucidate the lipid and miRNA profiles of AT-Exos in a diet-induced obesity model. We identified obesity-related miRNAs in AT-Exos and further explored their mechanisms using gain- and loss-of-function experiments. To evaluate the metabolic effects of AT-Exos on adipocytes, we conducted RNA-sequencing (RNA-seq) and confirmed our findings through Quantitative Real-time PCR (qPCR) and Western bolt analyses. Meanwhile, a mouse model with intraperitoneal injections was utilized to validate the role of exosomes derived from visceral white adipose tissue (vWAT-Exos) in obesity progression in vivo. Finally, we explored potential therapeutic intervention strategies targeting AT-Exos, particularly focusing on modulating the SIRPα-CD47 axis to enhance macrophage phagocytosis using Leptin-deficient (ob/ob) mice and SIRPα knock-out mice. Results Our study revealed that obesity-related metabolism affects the biological processes of AT-Exos, with depot-specific secretion patterns. In obesity, the lipidome profile of AT-Exos was significantly altered, and diet can modify the miRNA content and function within these exosomes, influencing lipid metabolism and inflammatory pathways that contribute to metabolic dysregulation. Specifically, we identified that miR-200a-3p and miR-200b-3p promoted lipid accumulation in 3T3L1 cells partly through the PI3K/AKT/mTOR pathway. RNA-Seq analysis revealed that AT-Exos from different fat depots exerted distinct effects on adipocyte metabolism, with obese vWAT-Exos being notably potent in triggering inflammation and lipid accumulation in diet-induced obesity. Additionally, we found that inhibiting the SIRPα-CD47 axis can mitigate metabolic disorders induced by obese vWAT-Exos or ob/ob mice, partly due to the enhanced clearance of vWAT-Exos. Consistent with this, SIRPα-deficient mice exhibited a reduction in vWAT-Exos and displayed greater resistance to obesity. Conclusions This study elucidates that diet-induced obesity altered the lipid and miRNA profiles of AT-Exos, which involved in modulating adipocyte inflammation and metabolic balance. The SIRPα-CD47 axis emerges as a potential therapeutic target for obesity and its associated complications.https://doi.org/10.1186/s12929-025-01124-yAdipose tissueExosomesmiRNAsObesityMacrophagesSIRPα-CD47 |
| spellingShingle | Yun-kai Lin Yu-fei Pan Tian-yi Jiang Yi-bin Chen Tai-yu Shang Meng-you Xu Hui-bo Feng Yun-han Ma Ye-xiong Tan Hong-yang Wang Li-wei Dong Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice Journal of Biomedical Science Adipose tissue Exosomes miRNAs Obesity Macrophages SIRPα-CD47 |
| title | Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice |
| title_full | Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice |
| title_fullStr | Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice |
| title_full_unstemmed | Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice |
| title_short | Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice |
| title_sort | blocking the sirpα cd47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice |
| topic | Adipose tissue Exosomes miRNAs Obesity Macrophages SIRPα-CD47 |
| url | https://doi.org/10.1186/s12929-025-01124-y |
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