作者
Catriona Ling, Christian J Versloot, Matilda E Arvidsson Kvissberg, Guanlan Hu, Nathan Swain, José M Horcas-Nieto, Emily Miraglia, Mehakpreet K Thind, Amber Farooqui, Albert Gerding, Karen van Eunen, Mirjam H Koster, Niels J Kloosterhuis, Lijun Chi, YueYing ChenMi, Miriam Langelaar-Makkinje, Celine Bourdon, Jonathan Swann, Marieke Smit, Alain de Bruin, Sameh A Youssef, Marjon Feenstra, Theo H van Dijk, Kathrin Thedieck, Johan W Jonker, Peter K Kim, Barbara M Bakker, Robert HJ Bandsma
发表日期
2023/10/1
期刊
EBioMedicine
卷号
96
出版商
Elsevier
简介
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, EX-527. Malnutrition enteropathy was induced in enteric organoids through amino-acid deprivation. Features of and pathways …
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