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Updated: May 7, 2026
Isolation of Adipose Tissue Immune Cells
Published on: May 22, 2013
Relaxin-3 attenuates lipid-induced macrophage immunometabolic changes in diabetic adipose tissue associated with
Jingzhi Wang1, Xinfang Liang1, Jiaxin Xue1
1The Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Aims:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
