Cell Biology – Immunology – Pathology
Kidney International (1999) 56, 1779–1787; doi:10.1046/j.1523-1755.1999.00731.x
Brief periods of hyperphagia cause renal injury in the obese Zucker rat
Matthew D Gades, Harry van Goor, George A Kaysen, Patricia R Johnson, Barbara A Horwitz and Judith S Stern
Department of Nutrition and Department of Neurobiology, Physiology, and Behavior, Division of Clinical Nutrition and Metabolism and Division of Nephrology, Department of Internal Medicine, University of California Davis School of Medicine, Davis, California, USA; Department of Pathology, University of Groningen, Groningen, The Netherlands; and Department of Veterans Affairs Northern California Health Care System, Mather, California, USA
Correspondence: Dr George A. Kaysen, Division of Nephrology, Department of Internal Medicine, TB 136, University of California, Davis, California 95616, USA. E-mail: gakaysen@ucdavis.edu
Received 4 November 1998; Revised 7 June 1999; Accepted 8 June 1999.
Abstract
Brief periods of hyperphagia cause renal injury in the obese Zucker rat.
Background
Female obese (fa/fa) Zucker rats are maximally hyperphagic from the beginning of access to solid food until 20 weeks of age and die primarily from renal failure. We documented that urinary albumin excretion (UAE) rises early in obese rats during this time of greatest hyperphagia. This study was conducted to examine if this early surge of hyperphagia is critical to the initiation of glomerular damage.
Methods
Three groups of six-week-old rats were used: (a) obese females fed ad libitum (AL-obese), (b) obese females pair fed to lean controls until 21 weeks and then allowed to eat ad libitum until 57 weeks (PF.AL-obese), (c) lean (Fa/Fa) Zucker rats fed ad libitum (AL-lean). Cohorts of AL-obese and PF.AL-obese rats were allowed to continue to death or 57 weeks of age, and the rest were terminated at 21 weeks for renal histology.
Results
At 21 weeks, neither PF.AL-obese nor AL-lean rats had elevated UAE or glomerular histopathology. In contrast, glomerular injury was severe in AL-obese rats. UAE increased by 10 and 29 weeks in AL- and PF.AL-obese rats, respectively. Plasma triglycerides increased prior to UAE in both PF.AL- and AL-obese rats.
Conclusions
In obese rats fed ad libitum, hyperphagia is followed within a few weeks by hypertriglyceridemia and then by glomerular injury regardless of when ad libitum feeding is initiated. These events do not occur in lean rats or in obese rats pair fed to lean rats. Protective effects of pair feeding did not extend into the period of ad libitum feeding for PF.AL-obese rats. Hyperphagia quickly initiates glomerular injury in obese female Zucker rats.
Keywords:
albuminuria, nutrition, nephrotic syndrome, glomerulosclerosis, lipids, obesity, mesangial expansion
