MH-76, a Novel Non-Quinazoline α1-Adrenoceptor Antagonist, but Not Prazosin Reduces Inflammation and Improves Insulin Signaling in Adipose Tissue of Fructose-Fed Rats

MH-76 是一种新型非喹唑啉 α1-肾上腺素能受体拮抗剂,而非哌唑嗪,可减轻果糖喂养大鼠脂肪组织中的炎症并改善胰岛素信号传导

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作者:Monika Kubacka, Szczepan Mogilski, Monika Zadrożna, Barbara Nowak, Małgorzata Szafarz, Bartosz Pomierny, Henryk Marona, Anna Waszkielewicz, Wojciech Jawień, Jacek Sapa, Marek Bednarski, Joanna Knutelska, Magdalena Kotańska

Background

Quinazoline α1-adrenoceptors antagonists have been shown to exert moderately favorable effects on the metabolic profile in hypertensive patients. However, based on AntiHypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Conclusion

MH-76 may improve insulin signaling in adipose tissue by reducing the pro-inflammatory cytokine production and inhibiting the inflammatory cells recruitment. In contrast, in adipose tissue from animals treated with prazosin, the inflammatory effect was clearly enhanced.

Methods

Abdominal adipose tissue was collected from four groups of fructose-fed rats (Control, Fructose, Fructose + MH-76 and Fructose + Prazosin) and subjected to biochemical, histopathological and immunohistochemical studies. Moreover, selected tissue distribution studies were performed.

Results

Treatment with MH-76 but not with prazosin improved endothelial integrity, reduced adipose tissue inflammation and infiltration by immune cells, resulting in lowering leptin, MCP-1, IL-6, TNF-α and PAI-1 levels. In adipose tissue from Fructose + MH-76 animals, a higher amount of eosinophils accompanied with higher IL-4 concentration was observed. Treatment with MH-76 but not with prazosin markedly reduced phosphorylation of IRS-1 at Ser307.

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