Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats

Abstract

Objective: We sought to determine whether prevention of overeating would block the very earliest manifestations of renal injury in young obese Zucker rats (OZRs). Research Methods and Procedures: Three groups of rats were studied, obese (fa/fa) Zucker rats and lean (Fa/Fa). Zucker controls were allowed to feed ad libitum, whereas a group of obese (fa/fa) Zucker rats was pair-fed to the lean group. Urine albumin and serum lipids were studied weekly from 6 to 10 weeks of age. Renal pathology and renal glomerular gene expression were examined when the rats were killed at 10 weeks of age. Results: Obese rats fed ad libitum developed significant albuminuria by 6 weeks of age, increasing at each subsequent time-point. This increase was completely blocked by pair-feeding. Serum triglycerides were significantly increased in obese rats fed ad libitum vs. the other groups. Urine albumin correlated significantly with both body weight and serum triglyceride level. Renal histopathology was normal in all groups. Analysis of gene expression of glomerular proteins by reverse transcriptase-polymerase chain reaction revealed that pair-feeding attenuated the increased expression of glomerular desmin, fibronectin, and the 92-kDa collagenase that was seen in obese animals fed ad libitum. Discussion: Prevention of overeating in young OZR normalizes albuminuria and attenuates the pathogenic alterations in glomerular gene expression seen at the initiation of renal disease in obese animals allowed to feed ad libitum. This model may be relevant for studying the early endorgan effects of obesity.

Rofecoxib decreases renal injury in obese Zucker rats

“…These rats have impaired glucose tolerance and increased blood glucose levels, endothelial dysfunction, and die of renal failure [5][6][7][8][9]. The mechanisms responsible for renal injury in syndrome X patients and the obese Zucker rats are not well understood.…”

“…life [5][6][7][8][9]. These rats have impaired glucose tolerance and increased blood glucose levels, endothelial dysfunction, and die of renal failure [5][6][7][8][9].…”

Brown Norway Chromosome 1 Congenic Reduces Symptoms of Renal Disease in Fatty Zucker Rats

“…ZUC either homozygous or heterozygous for the wildtype allele ( Lepr + or Lepr faSte/+ ) are lean and are designated lean ZUC in this paper. Previous studies of ZUC rats also reported that hyperphagia and hypertriglyceridemia accelerate renal disease [4], [5]. However, studies comparing lean and obese ZUC rats cannot distinguish between effects caused by obesity due to the chromosome 4 Lepr mutation from those caused by an interaction of Lepr with specific alleles from other chromosomes such as obesity-dependent renal and type 2 diabetes alleles.…”

Leptin receptor interacts with rat chromosome 1 to regulate renal disease traits

“…ZUC rats exhibit many other traits including renal disease and Type 2 diabetes (7,10,13). Renal disease in Zucker rats is accelerated by hyperphagia and is correlated with hypertriglyceridemia (7,21).…”