Renoprotective effect of a novel selective PPARα modulator K-877 in db/db mice: A role of diacylglycerol-protein kinase C-NAD(P)H oxidase pathway

K-877 administration ameliorates diabetic nephropathy, at least in part, via inhibition of renal lipid content and oxidative stress. The underlying mechanism may be mediated by modulating the renal AMPK-ACC pathway, subsequent acceleration of fatty acid β-oxidation and inhibition of fatty acid synthesis, and thus inhibition of the DAG-PKC-NAD(P)H oxidase pathway, in addition to its systemic effect including improvement of the plasma lipid profile and glycemic control.