Influence of Obesity in the Development of Chronic Kidney Disease: Contribution of Leptin and Angiotensin II in Inflammatory Processes
Authors: Cardoso Vanessa Gerolde , de Ponte Mariana Charleaux , de Souza Maria Oliveira 
Published: June 2021

Introduction

Obesity is associated with leptin resistance, as well as hyperactivity of the renin‐angiotensin system (RAS). Angiotensin II (Ang II) is an important pro‐inflammatory and pro‐fibrotic agent and is associated with the progression of chronic kidney disease (CKD). Therefore, the aim of this study is to investigate the contribution of Ang II and leptin in the development of CKD associated with obesity.

Methods

The protocols are in agreement with CEUA (nº 13/2017). Twenty‐four mice aged 18 weeks were used: Six C57BL / 6J were assigned to the lean control group (CTL) and 18 ob/ob were randomly assigned to obese control group (ob ob) and obese treated with leptin group (ob ob ‐ lep). Treatment with leptin was done by osmotic mini‐pump insertion. Mini‐pumps were filled with a solution containing leptin at a dose of 3.5 μg/day for 42 days. During treatment period animals were kept in individual cages and food intake was monitored daily. Weight gain and blood glucose were monitored weekly. At the end of the treatment period, animals were kept in metabolic cages for 24 hours to evaluate water intake and urine collection. Ultimately, animals were submitted to euthanasia. Renal function was assessed by plasma creatinine and urea concentration. Renal tissue was used for evaluation of gene expression by qPCR. Statistical analysis was performed by one‐way ANOVA, followed by Bonferroni post‐test. Values of p <0.05 were considered statistically significant.

Results

Ob ob ‐lep animals had a reduction in food intake when compared to the ob ob group. Food intake in ob ob – lep was similar to CTL group. In ob ob ‐ lep animals there was also a reduction in body weight compared to ob ob. There were no changes in water intake, urine flow and blood glucose among groups. There were also no changes in plasma creatinine values among groups, however, in the ob ob group there was an increase in serum urea and the leptin treatment partially reversed this parameter to values closer to CTL group. Regarding gene expression of RAS components, ob ob animals showed an increase in mRNA expression for angiotensinogen compared to CTL group and leptin treatment did not reverse this parameter. The expression of mRNA for renin is also increased in the ob ob group, however, leptin treatment reversed this increase to values similar to control. Inflammation in obese animals was confirmed by increased IL6 mRNA expression and leptin did not reverse this parameter. There was no significant difference in mRNA expression for MCP1 among groups, however, there was a tendency to an increase in the expression of this gene in obese animals and decrease in leptin treatment. Obesity increased nephrine and αSMA mRNA expression compared to CTL, and leptin reversed this increase. Obesity increased the mRNA expression for collagen I and leptin did not reverse this parameter.

Conclusion

Leptin treatment was efficient because it decreased food intake and weight gain in obese animals. Obesity impairs renal function, increases the activation of intra‐renal RAS, inflammation and fibrosis, and leptin therapy partially reverses these parameters, taking renoprotective role.

Support or Funding Information

CNPq, CAPES and FAPESP.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.