Targeting ERβ in Macrophage Reduces Crown-like Structures in Adipose Tissue by Inhibiting Osteopontin and HIF-1α.

摘要: Proinflammatory processes in adipose tissue contribute to development of breast cancer and insulin resistance. Crown-like structures (CLS) are histologic hallmarks the proinflammatory process tissue. CLS microscopic foci dying adipocytes surrounded by macrophages mostly derived from monocytes blood. Estrogen receptor β (ERβ) is expressed microglia, within central nervous system (CNS), where it evokes an anti-inflammatory response. The present study investigates function ERβ CLS. We report that even though blood have no detectable levels ERβ, do express ERβ. In ERβ-/- mice, there was a significant increase number both subcutaneous (SAT) visceral (VAT). these mice were dominated pro-inflammatory (M1 macrophages) with higher expression osteopontin (OPN) proliferating macrophages. made obese Western diet, treatment selective agonist (LY3201) reduced SAT VAT downregulation OPN, activated hypoxia-inducible factor-1α (HIF-1α), proliferation upregulation prolyl hydroxylase 2 (PHD2), enzyme which prevents activation HIF1α, conclude induced plays pivotal role suppression Thus agonists may be used alleviate CLS-related resistance