Objective: Obesity-related glomerulopathy (ORG) is an important complication of obesity. The pathophysiological mechanism of glomerular injury in ORG is incompletely understood. Gene expression profiles in the glomeruli obtained from renal biopsy samples of patients with ORG were investigated, using microdissection technique combined with Affymetrix microarray analysis.

Methods: Six patients presented with obesity, proteinuria and biopsy-proven ORG were enrolled. Two sex- and age- matched donor kidneys were applied as the controls. Glomeruli were dissected out from renal biopsy samples under microscope, and total RNA was extracted using Rneasy Micro kit. After two rounds of T7 promoter-based RNA amplification, gene expression profiles of the glomeruli samples were detected using Affymetrix U133A genechips. Bioinformatic tools were applied to analyze the microarray data. Results of candidate ORG-related genes were further confirmed by real-time quantitative PCR and immunohistochemistry staining using renal biopsy samples of a larger pool of 15 ORG patients.

Results: Genes related to lipid metabolism, inflammatory cytokines and insulin resistance were the most highlighted subgroups that significantly changed in the glomerular gene expression profiles of the ORG patients, compared with the controls. The expression levels of several key genes in lipid metabolism were increased over two folds, including LDL receptor, fatty acid binding protein 3 and sterol regulatory element binding protein-1. Moreover, some inflammatory cytokines and their down-stream molecules were increased as well, including tumor necrosis factor and its receptors, interleukin 6 signal transducer and interferon . As the indicators of insulin resistance in the local glomerular cells, levels of glucose-transporter 1, leptin receptor, peroxisome proliferator-activated receptor and vascular endothelial growth factor increased too.

Conclusion: In addition to lipid dysmetabolism and insulin resistance, the activation of inflammatory process in the glomeruli might play a unique role in the development of obesity-related glomerulopathy. Our results expand the understanding of obesity-induced glomerular injuries and shed light on new approaches in the treatment of this disease.