Hyperphagia as a mediator of renal disease initiation in obese Zucker rats

Frazier T. Stevenson, Carrie M. Wheeldon, Matthew D. Gades, Harry Van Goor, Judith S. Stern

Research output: Contribution to journalArticle

19 Scopus citations

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 end-organ effects of obesity.

Original languageEnglish (US)
Pages (from-to)492-499
Number of pages8
JournalObesity Research
Volume9
Issue number8
StatePublished - Aug 2001

Keywords

  • Glomerular disease
  • Hyperlipidemia
  • Hyperphagia
  • Zucker rats

ASJC Scopus subject areas

  • Food Science
  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Public Health, Environmental and Occupational Health

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    Stevenson, F. T., Wheeldon, C. M., Gades, M. D., Van Goor, H., & Stern, J. S. (2001). Hyperphagia as a mediator of renal disease initiation in obese Zucker rats. Obesity Research, 9(8), 492-499.