Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury
Joint Authors
Kumar Jain, Ajay
Teckman, Jeffrey H.
Source
International Journal of Inorganic Chemistry
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-06-25
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
Total parenteral nutrition (TPN), a lifesaving therapy, involves providing nutrition by bypassing the gut.
Unfortunately it is associated with significant complications including gut atrophy and parenteral nutrition associated liver disease (PNALD).
PNALD includes steatosis, cholestasis, disrupted glucose metabolism, disrupted lipid metabolism, cirrhosis, and liver failure.
The etiopathogenesis remains poorly defined; however, an altered enterohepatic circulation, disrupting nuclear receptor signaling, is emerging as a promising mechanism.
Rodent models and our piglet TPN model have shown that, during regular feeding, bile acids activate farnesoid X receptor (FXR) in the gut and enhance fibroblast growth factor 19 (FGF19) level.
FGF19 regulates bile acid, lipid, and glucose metabolism.
We noted reduced FGF19 with TPN use and substantial improvement in FGF19, bilirubin, and metabolic profiles with the FXR agonist chenodeoxycholic acid (CDCA).
Additionally, CDCA caused gut growth and enhanced expression of glucagon like peptides (GLPs).
GLPs regulate gut trophic effects, insulin, glucose homeostasis, and hepatic steatosis.
GLP secretion is regulated by the CDCA activated receptor TGR5.
This leads to an important conclusion that, in addition to a disrupted FXR-FGF19 axis, a disrupted TGR5-GLP axis may contribute to TPN related pathologies.
Thus modulators of FXR-FGF19 and the TGR5-GLP axis could help bring forward novel treatment strategies.
American Psychological Association (APA)
Kumar Jain, Ajay& Teckman, Jeffrey H.. 2014. Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury. International Journal of Inorganic Chemistry،Vol. 2014, no. 2014, pp.1-7.
https://search.emarefa.net/detail/BIM-485847
Modern Language Association (MLA)
Kumar Jain, Ajay& Teckman, Jeffrey H.. Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury. International Journal of Inorganic Chemistry No. 2014 (2014), pp.1-7.
https://search.emarefa.net/detail/BIM-485847
American Medical Association (AMA)
Kumar Jain, Ajay& Teckman, Jeffrey H.. Newly Identified Mechanisms of Total Parenteral Nutrition Related Liver Injury. International Journal of Inorganic Chemistry. 2014. Vol. 2014, no. 2014, pp.1-7.
https://search.emarefa.net/detail/BIM-485847
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-485847