Abstract：
The pituitary is the central endocrine gland with effects on metabolic dysfunction-associated steatotic liver disease (MASLD). However, it is not clear whether the pituitary responds to free fatty acid (FFA) toxicity, thus dysregulating hepatic lipid metabolism. Here, we demonstrate that decreased prolactin (PRL) levels are involved in the association between FFA and MASLD based on a liver biospecimen-based cohort. Moreover, overloaded FFAs decrease serum PRL levels, thus promoting liver steatosis in mice with both dynamic diet intervention and stereotactic pituitary FFA injection. Mechanistic studies show that excessive FFA sensing in pituitary lactotrophs inhibits the synthesis and secretion of PRL in a cell-autonomous manner. Notably, inhibiting excessive lipid uptake using pituitary stereotaxic virus injection or a specific drug delivery system effectively ameliorates hepatic lipid accumulation by improving PRL levels. Targeted inhibition of pituitary FFA sensing may be a potential therapeutic target for liver steatosis.
摘要：
垂体是中央内分泌腺，对代谢功能障碍相关的脂肪变性肝病（MASLD）有影响。然而,目前尚不清楚垂体是否对游离脂肪酸（FFA）毒性有反应，从而使肝脏脂质代谢失调。这里,我们证明,基于肝脏生物样本的队列,降低的催乳素(PRL)水平与FFA和MASLD之间的关联有关.此外，过载的FFA降低血清PRL水平，因此，通过动态饮食干预和立体定向垂体FFA注射促进小鼠肝脏脂肪变性。机制研究表明，垂体催乳菌中过度的FFA感应以细胞自主的方式抑制PRL的合成和分泌。值得注意的是,使用垂体立体定向病毒注射或特定的药物递送系统抑制过度脂质摄取，通过改善PRL水平有效改善肝脏脂质积累。靶向抑制垂体FFA感知可能是肝脏脂肪变性的潜在治疗靶点。
