NS1 Reduces Phosphoenolpyruvate Carboxylase Expression by Regulating HNF4α Transcriptional Activity.

Probiotics have been known to reduce high-fat diet (HFD)-induced metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. We recently observed that NS1 (LNS1), distinctly suppresses increase of blood glucose levels and insulin resistance in HFD-fed mice. In the present study, we demonstrated that oral administration of LNS1 with HFD feeding to mice significantly reduces hepatic expression of phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme in gluconeogenesis which is highly increased by HFD feeding. This suppressive effect of LNS1 on hepatic expression of PEPCK was further confirmed in HepG2 cells by treatment of LNS1 conditioned media (LNS1-CM). LNS1-CM strongly and specifically inhibited HNF4α-induced PEPCK promoter activity in HepG2 cells without change of HNF4α mRNA levels. Together, these data demonstrate that LNS1 suppresses PEPCK expression in the liver by regulating HNF4α transcriptional activity, implicating its role as a preventive or therapeutic approach for metabolic diseases.