The SS^LepR mutant rat represents a novel model to study obesity-induced renal injury before puberty

Prepubertal obesity (PPO) has emerged as a major health problem over the past few decades and is a risk factor for the development of proteinuria. The current study investigated whether the development of renal injury in the obese SS^LepR mutant strain occurs before puberty. When determining the temporal changes in serum sex hormones in female and male SS and SS^LepR mutant rats between 4 and 10 wk of age, we only observed significant increases in estradiol and testosterone levels in female and male SS rats at 10 wk of age than at 4 wk of age. The results suggest that studying both strains between 4 and 8 wk of age is appropriate to study the effects of PPO on renal injury in this model. Proteinuria was significantly higher in SS^LepR mutant rats as opposed to the values observed in SS rats at 8 wk of age, and we did not observe any sex differences in proteinuria in either strain. The kidneys from the SS^LepR mutant rats displayed significant glomerular and tubular injury and renal fibrosis versus the values measured in SS rats without any sex differences. Overall, we observed increased immune cell infiltration in the kidneys from SS^LepR mutant rats compared with SS rats. Interestingly, female SS^LepR mutant rats displayed significant increases in not only M1 macrophages (proinflammatory) but also M2 macrophages (anti-inflammatory) versus male SS^LepR mutant rats. These results suggest the SS^LepR mutant rat may be a useful model to study early progression of obesity-related renal injury before the onset of puberty.