Li Xuan, Yu Huihui, Tian Ruixian, Wang Xingxing, Xing Ting, Xu Chenyi, Li Tengteng, Du Xue, Cui Qianqian, Yu Biao, Cao Yunxia, Yin Zongzhi
Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Rd, Hefei, Anhui Province, 230022, China.
NHC Key Laboratory of the Study of Abnormal Gametes and the Reproductive Tract, Anhui Medical University, Hefei, Anhui Province, 230022, China.
Adv Sci (Weinh). 2025 Jul;12(25):e2501077. doi: 10.1002/advs.202501077. Epub 2025 Apr 7.
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.
晚期妊娠的肥胖孕妇更容易出现子宫平滑肌功能障碍，但其潜在机制仍不清楚。在此，研究表明足月肥胖孕妇的子宫肌层、高脂饮食（HFD）诱导的肥胖小鼠以及棕榈酸处理的子宫平滑肌细胞（USMCs）中脂肪酸结合蛋白4（FABP4）水平升高。FABP4在将脂肪酸从细胞外转运到细胞内区室中起关键作用。从机制上讲，肥胖会促进脂肪酸过度摄取，导致USMCs中脂质异常积累和ATP生成减少。这些异常源于线粒体相关膜的耦联减弱，而线粒体相关膜对于钙、脂质和代谢物交换至关重要。此外，向正常饮食小鼠注射腺病毒以提高FABP4水平可模拟在HFD小鼠中观察到的效应。总的来说，这些发现突出了FABP4作为肥胖中子宫肌层功能障碍的关键驱动因素以及改善肥胖妊娠分娩结局的潜在治疗靶点。
