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

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.