摘要： 细胞核激素受体调节多种代谢途径，如LRH-1（也称为NR5A2）调节胆汁酸生物合成 。 DLPC是LRH-1体外配体 。 DLPC治疗容易诱导小鼠胆汁酸酶的活性增加，以及降低肝脏甘油三酯和血糖的浓度。 结果表明的LRH-1的信号转导通路调节胆汁酸代谢和维持血糖稳态。
磷脂合成通路
Nuclear hormone receptors regulate diverse metabolic pathways and the orphan nuclear receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis 1 , 2 . Structural studies have identified phospholipids as potential LRH-1 ligands 3 , 4 , 5 , but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro . DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.
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