# Mechanisms involved in the early development of renal disease associated with prepubertal obesity

> **NIH NIH R01** · UNIVERSITY OF MISSISSIPPI MED CTR · 2021 · $348,750

## Abstract

Project Abstract
Prepubertal childhood obesity has emerged as an epidemic and major health problem in the United States.
Recent studies suggest that that childhood obesity is associated with increased risk of renal injury in children.
Although the link between obesity and the development of type II diabetic nephropathy is well-documented, the
consequences of childhood obesity as an independent risk factor in the absence of diabetes in the development
of renal disease has received less attention. Currently, there are several obese animal models that develop
renal disease, but these models have limited use in the investigation of the early mechanisms responsible for
the development of renal injury prior to hypertension, diabetes, and/or puberty. As most of these obese models
do not develop progressive proteinuria and chronic kidney disease (CKD). Recently, we observed our obese rat
model (prepubertal obese - PPO) develops podocyte injury and 3-fold increase in proteinuria prior to the
development of hypertension and diabetes at 6 weeks of age (childhood), which progresses to severe
hypertension, CKD by 18 weeks of age (adulthood). In the current proposal, we will use our model of prepubertal
obesity to explore several mechanisms that may contribute to the development of renal disease. The proposed
studies will test whether glomerular hyperfiltration and lipid accumulation stimulate podocyte injury and
macrophage inflitration leading to proteinuria and renal injury during prepubertal obesity. We will compare early
changes in glomerular capillary pressure (Pgc) between the PPO model and their control-lean counterparts and
determine whether there is a direct effect of mechanical strain/cyclic stretch on lipid accumulation in podocytes
isolated from both strains. We also will evaluate the role of macrophages on the early development of proteinuria
in the PPO model. These results should provide the scientific community with an obese animal model system
that develops proteinuria, prior to puberty, to study mechanisms involved in renal injury and provide information
critical to develop new treatments for the prevention of renal disease associated with prepubertal childhood
obesity.

## Key facts

- **NIH application ID:** 10151455
- **Project number:** 5R01DK109133-05
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Jan Michael Williams
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $348,750
- **Award type:** 5
- **Project period:** 2017-06-13 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151455

## Citation

> US National Institutes of Health, RePORTER application 10151455, Mechanisms involved in the early development of renal disease associated with prepubertal obesity (5R01DK109133-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10151455. Licensed CC0.

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