Funded Research

Role of Enterocyte Glut9 in Intestinal Urate Handling and Energy Homeostasis
Principal Investigator(s):
  • Brian DeBosch, M.D., Ph.D. Pediatrics
Status:
Completed
Center(s):
  • Center for Metabolism and Immunity
Award Mechanism:
Faculty Recruitment/Scholar Award
Project Period:
7/1/2014 - 6/30/2019
Total Amount:
$300,000

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, afflicting over a billion children and adults worldwide. The goal of this project was to identify and develop NAFLD therapies for children. Obese children have an approximately 90% probability of developing NAFLD. NAFLD not only is a leading cause of liver scarring, liver cancer and liver failure, having NAFLD independently predicts development of metabolic syndrome and type 2 diabetes mellitus and cardiovascular disease mortality. Therefore, this major source of morbidity and lost potential for the pediatric population. This project utilized two novel experimental models of altered hepatic glucose transporter (GLUT) family member expression to uncover the molecular pathways that cause NAFLD. In defining these pathways, we identified treatment targets to block or reverse NAFLD in children.

Specific Aims:

  • We identified the facilitative hepatic glucose transporter, GLUT8, as the hepatic transporters that modulate development of hepatic fat accumulation.
  • We identified upstream and downstream GLUT effectors that mitigate hepatic fat accumulation. This includes hepatocyte Arginase 2 and ALOXE3.

Potential impact: GLUT family members represent an underappreciated target pathway underlying NAFLD - a major source of morbidity in children. This project uncovered and has begun to translate these target pathways and modifiers to treat or prevent NAFLD in children.  

This research could lead to novel therapeutic measures or lifestyle interventions to treat or prevent Type 2 diabetes and pre-diabetes in children.