Serpina3c serves as a potential therapeutic target for preventing susceptibility to fetal-origin MASLD induced by prenatal prednisone exposure (PPE) in offspring.

A study by Professor Wang Hui's team at Wuhan University's Taikang Medical School has been published in the medical journal Signal Transduction and Targeted Therapy.

The study, Serpina3c protects against metabolic dysfunction-associated steatotic liver disease in offspring induced by prenatal prednisone exposure, presents findings on a new target for preventing metabolic dysfunction-associated steatotic liver disease (MASLD) originating from prenatal factors.

The research confirms that prenatal prednisone exposure (PPE) can lead to glucose and lipid metabolism disorders in the liver of offspring, increasing their susceptibility to MASLD.

The study conducted full-term simulations in pregnant rodents (rats and mice) and found that PPE leads to glucose and lipid metabolic disorders in the livers of offspring, making them susceptible to adult MASLD.

The underlying mechanism involves active prednisone metabolite activation of the liver GR-HDAC3 signaling pathway, reducing H3K27ac levels/expression in the Serpina3c promoter region, which persists post-birth.

This activates the chymase-Ang II-AT1R pathway, reducing fatty acid oxidation and glucose uptake, leading to metabolic dysfunction and increased MASLD susceptibility in adulthood.

The study also shows that early postnatal overexpression of Serpina3c in the liver can mitigate adult MASLD susceptibility in PPE offspring.