FABP4 是肥胖症患者脂质代谢和妊娠子宫功能障碍的介质

FABP4 as a Mediator of Lipid Metabolism and Pregnant Uterine Dysfunction in Obesity

FABP4 是肥胖症患者脂质代谢和妊娠子宫功能障碍的介质

Authors: Xuan Li, Huihui Yu, Ruixian Tian, Xingxing Wang, Ting Xing, Chenyi Xu, Tengteng Li, Xue Du, Qianqian Cui, Biao Yu, Yunxia Cao, Zongzhi Yin

Source: Advanced Science

PMID: 40192565

DOI: 10.1002/advs.202501077 

Abstract

Obese pregnant women in late pregnancy are more susceptible to uterine smooth muscle dysfunction, but the underlying mechanisms remain elusive. Here, elevated levels of fatty acid binding protein 4 (FABP4) in the myometrium of obese pregnant women at term, high-fat diet (HFD)-induced obese mice, and palmitic acid-treated uterine smooth muscle cells (USMCs), are demonstrated. FABP4 plays a critical role in transporting fatty acids from the extracellular to the intracellular compartment. Mechanistically, obesity promotes excessive fatty acid uptake, leading to aberrant lipid accumulation and reduced ATP production in USMCs. These abnormalities stem from weakened coupling of mitochondria-associated membranes, which are essential for calcium, lipids, and metabolites exchange. Furthermore, adenoviral injection to elevate FABP4 levels in normal-diet mice mimicks the effects observed in HFD mice. Collectively, these findings highlight FABP4 as a key driver of myometrial dysfunction in obesity and a potential therapeutic target for improving labor outcomes in obese pregnancies.

Keywords: fatty acid binding protein 4; high‐fat diet; obesity; pregnancy; uterine contraction.

摘要

妊娠晚期的肥胖孕妇更容易出现子宫平滑肌功能障碍，但其潜在机制仍难以捉摸。本文研究表明，临产肥胖孕妇的子宫肌层、高脂饮食（HFD）诱导的肥胖小鼠和棕榈酸处理的子宫平滑肌细胞（USMCs）中脂肪酸结合蛋白 4（FABP4）的水平升高。FABP4 在将脂肪酸从细胞外运输到细胞内的过程中发挥着关键作用。从机理上讲，肥胖会促进脂肪酸的过度吸收，从而导致 USMCs 的异常脂质积累和 ATP 生成减少。这些异常源于线粒体相关膜耦合的减弱，而线粒体相关膜对于钙、脂质和代谢物的交换至关重要。此外，通过注射腺病毒来提高正常饮食小鼠的 FABP4 水平，可以模拟在高纤维脂肪饮食小鼠中观察到的效果。总之，这些发现强调了FABP4是肥胖症子宫肌功能障碍的关键驱动因素，也是改善肥胖妊娠分娩结局的潜在治疗靶点。

关键词：脂肪酸结合蛋白4；高脂饮食；肥胖；妊娠；子宫收缩