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 primar ily from renal failure. We documented that urinary albumin excretion (UAE) rises early in obese rats during this time of greatest hyperphagia. This st udy 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 2 1 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 an d PF.AL-obese rats were allowed to continue to death or 57 weeks of age, an d 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 rat s, 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 fe eding did not extend into the period of ad libitum feeding for PF.AL-obese rats. Hyperphagia quickly initiates glomerular injury in obese female Zucke r rats.