杂合花生酸代谢异常与多种病理生理条件相关，并且下游前列腺素水平与肥胖症中脂肪细胞功能障碍相关。然而，TXA2在肥胖症中的作用仍不清楚。我们观察到，TXA2通过其受体TP，在肥胖和代谢性疾病中是一种候选介质。与采用阿司匹林治疗相比，具有上调TXA2生物合成（TBXAS1）和TXA2受体（TP）表达的肥胖小鼠造成胰岛素抵抗和白色脂肪组织中巨噬细胞M1极化，该病症可被预防。在机制上，TXA2-TP信号轴的激活导致蛋白激酶Cɛ（PKCɛ）的积累，从而增强游离脂肪酸（FFA）诱导Toll样受体4（TLR4）促炎性巨噬细胞的激活和肿瘤坏死因子-a（TNF-a）在脂肪组织中的产生。重要的是，TP基因敲除小鼠减少了WAT中促炎性巨噬细胞和脂肪细胞肥大的积累。在这项工作中，我们确立了TXA2-TP轴在WAT中之前不知道的作用。这些发现可能为胰岛素抵抗的分子发病机制提供新的见解，并表明在未来有理地针对TXA2通路以改善肥胖及其相关代谢性疾病。版权所有©2023 Elsevier Inc.

Aberrant arachidonic acid metabolism has been implicated in multiple pathophysiological conditions, and the downstream prostanoids levels are associated with adipocyte dysfunction in obesity. However, the role of thromboxane A2 (TXA2) in obesity remains unclear. We observed that TXA2, through its receptor TP, is a candidate mediator in obesity and metabolic disorders. Obese mice with upregulated TXA2 biosynthesis (TBXAS1) and TXA2 receptor (TP) expression in caused insulin resistance and macrophage M1 polarization in white adipose tissue (WAT), which can be prevented by treatment with aspirin. Mechanistically, the activation of TXA2-TP signaling axis leads to accumulation of protein kinase Cɛ (PKCɛ), thereby enhancing free fat acid (FFA) induced Toll-like receptor4 (TLR4) proinflammatory macrophage activation and the tumor necrosis factor-a (TNF-a) production in adipose tissues. Importantly, TP knockout mice reduced the accumulation of proinflammatory macrophages and adipocyte hypertrophy in WAT. In this work, we establish previously unknown role of TXA2-TP axis in WAT. These findings might provide new insight into the molecular pathogenesis of insulin resistance, and indicate rational targeting TXA2 pathway to improve obesity and its associated metabolic disorders in future.Copyright © 2023. Published by Elsevier Inc.