Discipline: Biological Sciences
Subcategory: Physiology and Health
Joan Ndungu - Kennesaw State University
Co-Author(s): Sarmistha Mukherjee, Karthikeyani Chellapa, and Joseph A. Baur, University of Pennsylvania, Philadelphia, PA
The liver is a vital organ with the remarkable ability to regenerate in response to surgical resection or chemical injury. The hepatocytes extensively proliferate to repair or replace the lost/injured cells. However, the mechanisms underlying this highly regulated process are not well understood. During liver regeneration, the concentration of nicotinamide adenine nucleotide (NAD) has been shown to be lower than normal (1). It was proposed that metabolic competition existed between NAD synthesis and nucleic acid synthesis for the availability of common precursors, such as phosphoribosyl pyrophosphate (PRPP). To investigate whether NAD availability is limiting in regeneration we administered nicotinamide riboside (NR). NR is a biosynthetic precursor that does not require PRPP to generate NAD. NR was added to the drinking water of C57BL6/J mice and then subjected to two thirds partial hepatectomy, a well-established model for liver injury. Animals were sacrificed at 24h, 48h and 192h after hepatectomy. The liver to body weight ratio and DNA synthesis in NR treated mice were significantly increased than the controls. In both pre and post hepatectomy, NR treatment showed significantly higher liver NAD and ATP content compared to controls. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. The results demonstrate that NAD supplementation promotes liver regeneration and NR may be therapeutic in settings of acute liver injury.
References: Ferris, G. M., & Clark, J. B. (1971). Nicotinamide nucleotide synthesis in regenerating rat liver. Biochemical Journal, 121(4), 655-662.
Funder Acknowledgement(s): I thank Dr. Arnaldo Diaz program director of SUIP. Funding was provided by grants from the NHLBI (National Heart Lung Blood Institute), Office of Research Training Programs, and Biomedical Graduate Studies University of Pennsylvania.
Faculty Advisor: Joseph Baur, email@example.com
Role: I was responsible of running the NAD and ATP assays and preparing the NR (nicotinamide riboside) treated water in addition to prepping the tissue samples which meant dividing the samples in order to the respective studies.