Exercise-induced renal tubular Cdo1 protects against diabetic nephropathy

Here, we identify cysteine dioxygenase type 1 (Cdo1) as a mediator of exercise-induced renal protection. Exercise upregulates renal tubular Cdo1 expression via the α-ketoglutarate-TET-DNA demethylation pathway.

Tubular epithelial cell-specific deletion of Cdo1 exacerbates DN and attenuates exercise-mediated alleviation of DN, whereas Cdo1 overexpression improves renal function and synergizes with exercise in ameliorating DN. Mechanistically, tubular Cdo1 promotes taurine production, which suppresses macrophage glycolysis and inflammatory activation by disrupting PKM2-HIF-1α interaction. Taurine supplementation rescues kidney injury in Cdo1-deficient mice, and alleviates DN in synergy with exercise.