Loss of renal tubular PGC-1 exacerbates diet-induced renal steatosis and age-related urinary sodium excretion in mice

The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor coactivator 1 (PGC-1) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1 is a central transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1 in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1 seems largely dispensable for basal renal physiology. However, the central role of PGC-1 in renal mitochondrial biogenesis indicates that activation of PGC-1 in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction.

16