Blocking the SIRPα-CD47 axis promotes macrophage phagocytosis of exosomes derived from visceral adipose tissue and improves inflammation and metabolism in mice

作者：Yun‐Kai Lin, Yufei Pan, Tianyi Jiang, Yibin Chen, Taiyu Shang, Min Xu, Hui-bo Feng, Yunhan Ma, Yexiong Tan, Hongyang Wang, Liwei Dong · 发表于：Journal of Biomedical Science · 年份：2025 · DOI：10.1186/s12929-025-01124-y · 被引用次数：17 · 研究领域：Extracellular vesicles in disease、Adipokines, Inflammation, and Metabolic Diseases、Phagocytosis and Immune Regulation

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-...