松弛素-3减弱糖尿病脂肪组织中与LDHA相关的组蛋白乳酸化相关的脂质诱导的巨噬细胞免疫代谢变化
Relaxin-3 attenuates lipid-induced macrophage immunometabolic changes in diabetic adipose tissue associated with LDHA-related histone lactylation.
摘要(中文译文)
糖尿病脂肪组织中脂质代谢失调和慢性炎症共同导致代谢功能障碍。本研究探讨了Relaxin-3是否调节脂质过载诱导的巨噬细胞免疫代谢改变和炎症反应，重点关注LDHA相关的组蛋白乳酸化。将RAW264.7巨噬细胞暴露于高糖和棕榈酸酯（HG + PA）以模拟脂质过载相关的代谢应激。使用LDHA敲低巨噬细胞评估LDHA在乳酸相关信号传导和巨噬细胞极化相关变化中的参与。在体内，对链脲佐菌素联合高脂饮食诱导的糖尿病大鼠给予Relaxin-3治疗，以评估其对脂肪组织炎症和糖尿病相关代谢变化的影响。评估了糖酵解相关酶、乳酸生成、H3K18la、巨噬细胞极化相关标志物、炎症介质以及选定的代谢指标。HG + PA诱导了糖酵解相关酶的变化，增加了细胞内和细胞外乳酸积累，升高了H3K18la，并改变了巨噬细胞极化相关标志物。Relaxin-3治疗与M1相关标志物减少、选定的M2相关标志物增加以及乳酸积累、H3K18la和LDHA相关信号的进一步变化相关。这些效应在LDHA敲低后被减弱。在糖尿病大鼠中，Relaxin-3减轻了脂肪组织炎症，并与选定的代谢变化的改善相关。Relaxin-3减轻糖尿病中的脂肪组织炎症，并与巨噬细胞极化、乳酸代谢和H3K18la相关信号的变化相关。现有数据支持LDHA参与这一过程。这些发现为进一步研究糖尿病脂肪组织中乳酸化相关的免疫代谢调控提供了基础。
Abstract
Dysregulated lipid metabolism and chronic inflammation in diabetic adipose tissue jointly contribute to metabolic dysfunction. This study investigated whether Relaxin-3 modulates lipid overload-induced macrophage immunometabolic changes and inflammatory responses, with a focus on LDHA-related histone lactylation. RAW264.7 macrophages were exposed to high glucose and palmitate (HG + PA) to model lipid overload-associated metabolic stress. LDHA-knockdown macrophages were used to assess the involvement of LDHA in lactate-associated signaling and macrophage polarization-related changes. In vivo, diabetic rats induced by streptozotocin combined with a high-fat diet were treated with Relaxin-3 to evaluate its effects on adipose tissue inflammation and diabetes-related metabolic changes. Glycolysis-related enzymes, lactate production, H3K18la, macrophage polarization-related markers, inflammatory mediators, and selected metabolic indices were assessed. HG + PA induced changes in glycolysis-related enzymes, increased intracellular and extracellular lactate accumulation, elevated H3K18la, and altered macrophage polarization-related markers. Relaxin-3 treatment was associated with reduced M1-related markers, increased selected M2-related markers, and further changes in lactate accumulation, H3K18la, and LDHA-related signaling. These effects were attenuated after LDHA knockdown. In diabetic rats, Relaxin-3 reduced adipose tissue inflammation and was associated with improvement in selected metabolic changes. Relaxin-3 alleviates adipose tissue inflammation in diabetes and is associated with changes in macrophage polarization, lactate metabolism, and H3K18la-related signaling. The available data support the involvement of LDHA in this process. These findings provide a basis for further investigation of lactylation-associated immunometabolic regulation in diabetic adipose tissue.
如何引用
AMA
Jingzhi Wang, Xinfang Liang, Jiaxin Xue, Yuxin Yang, Xiaoqi Liu, Siting Hong, et al. Relaxin-3 attenuates lipid-induced macrophage immunometabolic changes in diabetic adipose tissue associated with LDHA-related histone lactylation.. International immunopharmacology. 2026; doi:10.1016/j.intimp.2026.116768.
APA
Jingzhi Wang, Xinfang Liang, Jiaxin Xue, Yuxin Yang, Xiaoqi Liu, Siting Hong, et al (2026). Relaxin-3 attenuates lipid-induced macrophage immunometabolic changes in diabetic adipose tissue associated with LDHA-related histone lactylation.. International immunopharmacology. https://doi.org/10.1016/j.intimp.2026.116768
GB/T 7714
Jingzhi Wang, Xinfang Liang, Jiaxin Xue, Yuxin Yang, Xiaoqi Liu, Siting Hong, et al. Relaxin-3 attenuates lipid-induced macrophage immunometabolic changes in diabetic adipose tissue associated with LDHA-related histone lactylation.[J]. International immunopharmacology, 2026 doi:10.1016/j.intimp.2026.116768.
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