Premium
Sex Differences in the Development of Renal Injury in Obese Dahl Salt‐Sensitive Leptin Receptor Mutant Rats During Prepubertal Obesity
Author(s) -
Poudel Bibek,
Shields Corbin Anthony,
Cornelius Denise C.,
Williams Jan M.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.906.5
Subject(s) - microalbuminuria , medicine , endocrinology , proteinuria , cd36 , leptin , obesity , renal injury , glomerulosclerosis , kidney , receptor , blood pressure
Recent studies show that prepubertal obesity (PPO) is associated with increased risk of renal injury in children. Furthermore, nearly 40% of obese children develop microalbuminuria. Additionally, studies examining the impact of sex on the development of renal injury associated with PPO have been limited. Recently, we reported that, prior to puberty, male Dahl salt‐sensitive leptin receptor mutant (SS LepR mutant ‐ PPO model) rats display proteinuria and podocyte injury by 6 weeks of age independent of hyperglycemia and elevations in arterial pressure. However, female PPO rats were not examined during the same time period. Therefore, in the current study, we investigated whether there were sex differences during the development of renal injury associated with prepubertal obesity. Proteinuria was significantly higher in female and male PPO rats as opposed to the values observed in Control rats at 4 weeks of age (65±12 and 64.7±13 vs 2±1 and 2±0.3 mg/day, respectively, n=4). While we observed minimal increases in proteinuria in Control rats at 8 weeks of age, proteinuria increased to 266.6±65 and 376±56 mg/day in female and male PPO rats, respectively. The kidneys from the PPO rats displayed significant glomerular injury and marked renal fibrosis when compared to the values measured in Control rats. Interestingly, the development of proteinuria and glomerular injury in the PPO model was associated with increased infiltration of CD68 + macrophages expressing Lamp2 and CD36, markers for lysosomes and fatty acid translocase, respectively. Additionally, we assessed renal inflammation via the Bio‐Plex Pro Rat Cytokine 23‐Plex Immunoassay and observed that macrophage inflammatory protein‐3a (MIP‐3a) levels were significantly elevated in both female and male PPO rats (3059±364 and 2545±333 ng/mg of protein, respectively) compared to the values measured in Control rats (1579±291 and 1138±95 ng/mg of protein, respectively). Overall these data indicate that the early development of renal injury in the PPO model might be due to macrophage infiltration stimulating progressive proteinuria independent of hypertension and diabetes. Support or Funding Information This study was supported by P20GM104357 and R01 DK109133‐01. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .