TY - JOUR
T1 - The role of the tryptophan-NAD + pathway in a mouse model of severe malnutrition induced liver dysfunction
AU - Hu, Guanlan
AU - Ling, Catriona
AU - Chi, Lijun
AU - Thind, Mehakpreet K.
AU - Furse, Samuel
AU - Koulman, Albert
AU - Swann, Jonathan R.
AU - Lee, Dorothy
AU - Calon, Marjolein M.
AU - Bourdon, Celine
AU - Versloot, Christian J.
AU - Bakker, Barbara M.
AU - Gonzales, Gerard Bryan
AU - Kim, Peter K.
AU - Bandsma, Robert H.J.
PY - 2022/12/8
Y1 - 2022/12/8
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-35317-y
DO - 10.1038/s41467-022-35317-y
M3 - Article
C2 - 36481684
AN - SCOPUS:85143566913
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
M1 - 7576
ER -
