The Role of the Tryptophan-NAD + pathway in a Mouse Model of Severe Malnutrition Induced Liver Dysfunction

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Dec 8

PMID 36481684

Authors

Guanlan Hu

Catriona Ling

Lijun Chi

Mehakpreet K Thind

Samuel Furse

Albert Koulman

Jonathan R Swann

Dorothy Lee

Marjolein M Calon

Celine Bourdon

Christian J Versloot

Barbara M Bakker

Gerard Bryan Gonzales

Peter K Kim

Robert H J Bandsma

Affiliations

Soon will be listed here.

Abstract

Mortality in children with severe malnutrition is strongly related to signs of metabolic dysfunction, such as hypoglycemia. Lower circulating tryptophan levels in children with severe malnutrition suggest a possible disturbance in the tryptophan-nicotinamide adenine dinucleotide (TRP-NAD+) pathway and subsequently in NAD+ dependent metabolism regulator sirtuin1 (SIRT1). Here we show that severe malnutrition in weanling mice, induced by 2-weeks of low protein diet feeding from weaning, leads to an impaired TRP-NAD+ pathway with decreased NAD+ levels and affects hepatic mitochondrial turnover and function. We demonstrate that stimulating the TRP-NAD+ pathway with NAD+ precursors improves hepatic mitochondrial and overall metabolic function through SIRT1 modulation. Activating SIRT1 is sufficient to induce improvement in metabolic functions. Our findings indicate that modulating the TRP-NAD+ pathway can improve liver metabolic function in a mouse model of severe malnutrition. These results could lead to the development of new interventions for children with severe malnutrition.

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