The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction.

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Hu, Guanlan 
Ling, Catriona 
Chi, Lijun 
Thind, Mehakpreet K 

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.

Article, /631/80/642/333/1465, /692/699/1702/295, /692/4020/4021/1607, /82/80, /64, /64/60, /59, /14/34, /96, /96/1, article
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Nat Commun
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Springer Science and Business Media LLC
Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) (OPP1185057)
Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) (156307)