Back

Deletion of Nudt19 Increases Albuminuria in Mice Fed a High Fat Diet

Saporito, D. C.; King, R. D.; Vickers, S. D.; Wyda, E. A.; Balaji, S.; King, J. A.; Leonardi, R.

2025-03-25 physiology
10.1101/2025.03.22.644727 bioRxiv
Show abstract

Nudix hydrolase 19 (NUDT19) is a peroxisomal enzyme that hydrolyzes CoA species at the phosphodiester bond and has been linked to peroxisomal dysfunction in the context of diabetic kidney disease. Despite its predominant expression in mouse kidneys, the physiological role of NUDT19 remains poorly understood. To investigate its function under metabolic stress, we fed Nudt19-/- mice a high fat diet (HFD) for 15 weeks. Nudt19 deletion exacerbated HFD-induced albuminuria, suggesting a previously unrecognized role in kidney function. This phenotype was associated with altered lipid metabolism in the kidneys, including reduced levels of non-esterified fatty acids and specific mono-acyl lipids, as well as differential expression of proteins involved in lipid metabolism. These included ECH1, THIKB, and ECHD2, enzymes involved in peroxisomal and mitochondrial {beta}-oxidation; C19orf12, a lipid droplet-associated protein; and the lipolysis-stimulated lipoprotein receptor (LSR). These findings highlight NUDT19 as a key regulator of renal lipid homeostasis and suggest that its loss contributes to kidney dysfunction under conditions of dietary lipid overload.

Matching journals

The top 8 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.