UC Merced

High fat diet (HFD) accelerates diabetic nephropathy while renin angiotensin aldosterone system blockade improves the proteinuria and antinatriuresis associated with diabetic nephropathy. Whether angiotensin receptor blockade (ARB) can improve sodium handling defects associated with HFD during insulin resistance remains unknown. The epithelial sodium channel (ENaC) is the rate-limiting step to renal sodium handling and is sensitive to aldosterone. The present study shows that HFD exacerbates oxidative damage and podocyte injury while ARB eliminates these increases. The data demonstrate that insulin resistance and HFD increase urine aldosterone excretion (UaldoV), and ARB reduces this increase. The changes in ENaC protein expression correlates with the changes in UaldoV and negatively correlates with UNaV suggesting that the changes in urinary aldosterone provide a robust indication of the observed changes in ENaC over time. Collectively, these data suggest that both insulin resistance and dietary fat affect renal Na+ transport via aldosterone-induced changes in ENaC.