TGR5 Signaling Mitigates Parenteral Nutrition Associated Liver Disease.

TGR5 Signaling Mitigates Parenteral Nutrition Associated Liver Disease. Am J Physiol Gastrointest Liver Physiol. 2020 Jan 06;: Authors: Willis KA, Gomes CK, Rao PK, Micic D, Moran ER, Stephenson EJ, Puchowicz MA, Al Abdallah Q, Mims TS, Gosain A, Yin D, Talati AJ, Chang EB, Han JC, Pierre JF Abstract Bile acid receptors regulate the metabolic and immune functions of circulating enterohepatic bile acids. This process is disrupted by administration of parenteral nutrition (PN), which may induce progressive hepatic injury for unclear reasons, especially in the newborn, leading to PN-associated liver disease. To explore the role of bile acid signaling on neonatal hepatic function, we initially observed that TGR5-specific bile acids were negatively correlated with worsening clinical disease markers in the plasma of human newborns with prolonged PN exposure. To test our resulting hypothesis that TGR5 regulates critical liver functions to PN exposure, we used TGR5 receptor deficient mice (TGR5-/-). We observed PN significantly increased liver weight, cholestasis, and serum hepatic stress enzymes in TGR5-/- mice compared with controls. Mechanistically, PN reduced bile acid synthesis genes in TGR5-/-. Serum bile acid composition revealed that PN increased unconjugated primary bile acids and secondary bile acids in TGR5-/- mice, while increasing conjugated primary bile acid levels in TGR5-competent mice. Simultaneously, PN elevated hepatic IL-...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research