Dataset Information

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

ABSTRACT: Proinflammatory processes in adipose tissue contribute to development of breast cancer and insulin resistance. Crown-like structures (CLS) are histologic hallmarks of the proinflammatory process in adipose tissue. CLS are microscopic foci of dying adipocytes surrounded by macrophages mostly derived from monocytes in blood. Estrogen receptor ? (ER?) is expressed in microglia, macrophages within the central nervous system (CNS), where it evokes an anti-inflammatory response. The present study investigates the function of ER? in macrophages within CLS. We report that even though monocytes in the blood have no detectable levels of ER?, macrophages in CLS do express ER?. In ER?-/- mice, there was a significant increase in the number of CLS in both subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). CLS in these mice were dominated by pro-inflammatory macrophages (M1 macrophages) with higher expression of osteopontin (OPN) and an increase in number of proliferating macrophages. In mice made obese by Western diet, treatment with an ER? selective agonist (LY3201) reduced the number of CLS in both SAT and VAT with downregulation of OPN, activated hypoxia-inducible factor-1? (HIF-1?), proliferation and upregulation prolyl hydroxylase 2 (PHD2), the enzyme which prevents activation of HIF1?, in macrophages. We conclude that ER? expression is induced in macrophages in CLS within adipose tissue where it plays a pivotal role in suppression of CLS. Thus ER? agonists may be used to alleviate CLS-related breast cancer and insulin resistance in adipose tissue.

SUBMITTER: Wang L

PROVIDER: S-EPMC6823357 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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

Wang Li L Zhao Rui-Peng RP Song Xiao-Yu XY Wu Wan-Fu WF

Scientific reports 20191031 1

Proinflammatory processes in adipose tissue contribute to development of breast cancer and insulin resistance. Crown-like structures (CLS) are histologic hallmarks of the proinflammatory process in adipose tissue. CLS are microscopic foci of dying adipocytes surrounded by macrophages mostly derived from monocytes in blood. Estrogen receptor β (ERβ) is expressed in microglia, macrophages within the central nervous system (CNS), where it evokes an anti-inflammatory response. The present study inve ...[more]

PMID: 31673032

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Project description:Insulin has anti-inflammatory effects in short-term experiments. However, the effects of chronic insulin administration on inflammation are unknown. We hypothesised that chronic insulin administration would beneficially alter adipose tissue inflammation and several circulating inflammatory markers.We administered two forms of long-acting insulin, insulin glargine (A21Gly,B31Arg,B32Arg human insulin) and insulin detemir (B29Lys[?-tetradecanoyl],desB30 human insulin), to LDL-receptor-deficient mice. After 8 weeks on a diet that causes obesity, hyperglycaemia, adipose tissue macrophage accumulation and atherosclerosis, the mice received subcutaneous glargine, detemir or NaCl (control) for 12 weeks. Serum amyloid A (SAA) and serum amyloid P (SAP), metabolic variables, adipose tissue macrophages and aortic atherosclerosis were evaluated.Weight gain was equivalent in all groups. The glycated haemoglobin level fell equivalently in both insulin-treated groups. Plasma cholesterol and triacylglycerol levels, and hepatic triacylglycerol level significantly improved in the glargine compared with the detemir or control groups. Levels of mRNA expression for monocyte chemotactic protein-1 and F4/80, a macrophage marker, in adipose tissue were decreased only in the glargine group (p?<?0.05). Visceral adipose tissue macrophage content decreased in both insulin groups (p?<?0.05), whereas atherosclerosis decreased only in the glargine group. Circulating SAA and SAP did not decrease in either insulin-treated group, but IL-6 levels fell in the glargine-treated mice.While chronic insulin administration did not decrease SAA and SAP, administration of glargine but not detemir insulin improved dyslipidaemia, IL-6 levels and atherosclerosis, and both insulins reduced macrophage accumulation in visceral adipose tissue. Thus, chronic insulin therapy has beneficial tissue effects independent of circulating inflammatory markers in this murine model of diet-induced obesity and diabetes.

Dataset Information

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

Publications

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

Similar Datasets

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