Cytokine gene expression profiles in kidney medulla and cortex of obese hypertensive dogs

Background. The molecular mechanisms linking abnormal kidney function and obesity hypertension are poorly understood. This study compared gene expression profiles in the kidney medulla and cortex of obese and lean dogs. Methods. Lean dogs (N = 4) were fed a standard kennel ration and obese dogs (N = 4) were fed the standard diet plus 0.5 to 0.9 kg of cooked beef fat per day for 10 weeks. The dogs were instrumented for continuous monitoring of mean arterial pressure (MAP), heart rate, glomerular filtration rate (GFR), and effective renal plasma flow (RPF). The relative mRNA levels of 375 genes in renal cortex and medulla were determined simultaneously using cDNA membrane arrays (R&D Systems). Results. The high fat diet increased body weight by 57% and MAP increased by 24 mm Hg (112 ± 1 mm Hg vs. 88 ± 3 mm Hg) in obese compared to lean dogs. In obese dogs, expression of 11 and 13 genes changed significantly (N = 4; P < 0.05) in the renal medulla and the cortex, respectively, relative to the lean dogs. Differences in renal gene expression profiles between lean and obese dogs were closely related to functional pathways, including those associated with sympathetic activation, inflammatory response, matrix formation, angiogenesis, endothelial dysfunction, attenuated actions of leptin, and attenuated cell survival. Conclusion. A high fat diet in dogs is associated with marked changes in renal gene expression profiles that provide potential molecular links to pathways associated with altered renal function and structure in obesity hypertension.