# Role of gut bacteria and renal lipids in obesity-related kidney disease

> **NIH NIH R01** · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · 2020 · $344,250

## Abstract

PROJECT SUMMARY / ABSTRACT
Obesity affects 1 in 3 adults in the United States. Among the health problems associated with obesity is a
higher risk for the development of chronic kidney disease (CKD) and for CKD progression. The association
between obesity and CKD persists even after statistical adjustment for diabetes and hypertension, which are
known CKD risk factors that are often present in people with obesity. This suggests that obesity itself,
independent of other comorbid conditions, contributes to CKD. The pathogenic mechanisms linking obesity to
CKD are incompletely understood. This project tests a highly innovative model integrating existing knowledge
with new findings in multiple areas of human pathophysiology and microbial biology. This model is divided into
three hypotheses that are conceptually interrelated but independently testable: 1. Obesity-associated
alterations in the microbes that normally reside in the intestine lead to excess acid production by microbial
metabolism. This excess acid is absorbed by the intestine and then excreted by the kidney, as the kidney is
tasked with preventing excess acid from accumulating in the body. 2. Excess acid excretion by the kidney
mandates increased glutamine metabolism to generate ammonium (important for acid excretion), but since the
resulting glutamine metabolites are used in the cell to generate energy, this reduces the utilization of other
energy substrates such as fatty acids by substrate competition. In turn, this makes more fatty acids available
for entry into alternative metabolic pathways, resulting in renal lipid accumulation (steatosis) and toxic effects
(lipotoxicity). 3. Finally, excess acid excretion contributes to CKD progression via decreased fatty acid
utilization, steatosis and lipotoxicity, and this effect is made worse by the fact that kidney lipid metabolism is
already disturbed in obesity. These hypotheses will be tested using a combination of in vitro, animal and
human studies employing some of the latest technologies in magnetic resonance imaging, nuclear magnetic
resonance spectroscopy, germ-free mouse research and targeted mouse genetics, combined with classical
physiology and biochemistry. In summary, this project aims to advance the field by testing previously
unexplored, but clear and plausible hypotheses linking obesity, intestinal microbes, increased acid excretion by
the kidney, kidney lipid abnormalities, and CKD progression. This project will generate new knowledge that will
form the basis for new logical interventions to prevent CKD progression. This is in keeping with the overarching
mission of the NIH of improving human health through science.

## Key facts

- **NIH application ID:** 9957051
- **Project number:** 5R01DK113377-04
- **Recipient organization:** TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
- **Principal Investigator:** Ion Alexandru Bobulescu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,250
- **Award type:** 5
- **Project period:** 2017-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9957051

## Citation

> US National Institutes of Health, RePORTER application 9957051, Role of gut bacteria and renal lipids in obesity-related kidney disease (5R01DK113377-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9957051. Licensed CC0.

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