Renal injury in obese and diabetic mice involves upregulation of inflammatory chemokines and cytokines.

Mice deficient in the leptin receptor develop obesity, insulin-resistance, and progress to nephropathy similar to that seen in human diabetes type II with interstitial macrophage infiltration and glomerulosclerosis. Adipocyte secreted cytokines are thought to mediate this progression by altering insulin sensitivity. We hypothesized that increased renal cytokines and inflammatory mediators contribute to renal complications in obesity and diabetes. Thus we profiled renal cortical gene expression with pathway targeted real-time RT-PCR arrays in male 22-week-old obese and lean mice (n=6 each) with body weights of 54.6±0.6 g and 30.9±0.7 g, respectively. Obese mice exhibited albuminuria of 204±57 µg/day vs. 51±9 µg/day in lean and had increased plasma monocyte chemotactic protein-1 (MCP-1) of 89.0±30.7 pg/ml vs. 35.0±7.5 pg/ml in lean. Cytokines that increase insulin resistance were upregulated: interleukin-6 (43-fold), resistin (17-fold), and tumor necrosis factor-a (3.7-fold). Obese mice also had upregulated message for macrophage chemotactic and adhesion molecules such as MCP-1 (3-fold), E-selectin (17-fold), P-selectin (9-fold), vascular cell adhesion molecule-1 (2.5-fold), and intercellular adhesion molecule-1 (2.3-fold). These data suggest that upregulated renal cytokines, chemokines, and adhesion molecules contribute to obesity induced insulin-resistance and renal injury. [ABSTRACT FROM AUTHOR]