Rebalancing of mitochondrial homeostasis through an NAD⁺-SIRT1 pathway preserves intestinal barrier function in severe malnutrition.

ABSTRACT:

Background

The intestine of children with severe malnutrition (SM) shows structural and functional changes that are linked to increased infection and mortality. SM dysregulates the tryptophan-kynurenine pathway, which may impact processes such as SIRT1- and mTORC1-mediated autophagy and mitochondrial homeostasis. Using a mouse and organoid model of SM, we studied the repercussions of these dysregulations on malnutrition enteropathy and the protective capacity of maintaining autophagy activity and mitochondrial health.

Methods

SM was induced through feeding male weanling C57BL/6 mice a low protein diet (LPD) for 14-days. Mice were either treated with the NAD⁺-precursor, nicotinamide; an mTORC1-inhibitor, rapamycin; a SIRT1-activator, resveratrol; or SIRT1-inhibitor

SUBMITTER: Ling C 

PROVIDER: S-EPMC10520344 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature