High‐Fat Diet Exacerbates Diabetic Kidney Injury in Mice Lacking eNOS

Abstract

Diabetic nephropathy is the leading cause of chronic kidney disease and end stage renal disease. It has been shown that deficiency in endothelial nitric oxide synthase (eNOS), and/or reduced eNOS activity is associated with diabetic nephropathy progression in humans. This study was designed to examine whether high fat diet (HFD) would enhance diabetic kidney injury in eNOS deficient mice. To induce diabetes, six‐week old eNOS deficient mice were placed on normal diet (ND) or HFD (42% from fat). Two weeks later, half of them were rendered diabetic with alloxan. Proteinuria/albuminuria and urinary levels of kidney injury markers were measured in control and diabetic animals 4 months post alloxan injection. There is no difference in urinary total protein among four groups. HFD treatment increased urinary albumin as well as proinflammatory cytokine osteopontin, whereas urinary parameters remained normal in alloxan‐induced diabetic mice fed with normal diet. A combination of HFD and alloxan treatment resulted in a more pronounced albuminuria as well as increased glomerular and tubular damage as evidenced by an elevation of urinary synaptopodin, matrix metalloproteinase‐9 and kidney injury molecule‐1. These results demonstrate that HFD accelerates diabetic kidney injury in eNOS deficient mice. Thus eNOS deficient mice may be suitable for studying the roles of albuminuria and renal lipotoxicity in development and progression of diabetic nephropathy.Support or Funding InformationNIH (SC1DK112151), NIH/NCRR/RCMI (8G12MD007602) and (8U54MD007588)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.