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

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 su

SUBMITTER: Hu G 

PROVIDER: S-EPMC9732354 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature