# Bacterial Regulation of Intestinal Lipid Metabolism

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $33,898

## Abstract

Project Summary
The worldwide obesity epidemic presents a significant public health crisis that is progressively worsening. This
has led to intensive efforts to identify the host and environmental factors that regulate human metabolism and
energy homeostasis. The gut microbiota has been identified as an environmental factor that regulates lipid
metabolism and absorption in the intestine, and thus promotes high fat diet-induced obesity. However, a major
knowledge gap remains about the specific bacterial and host factors that regulate intestinal lipid absorption and
metabolism. The overall goal of this proposal is therefore to identify the intestinal bacteria and host immune
recognition pathways that regulate intestinal lipid metabolism. Prior work by our group identified the circadian
transcription factor NFIL3 as essential for the gut microbiota’s role in driving obesity in mice fed a high-fat, high
sugar Western-style diet. NFIL3 expression is regulated by the microbiota, and promotes the transcription of
intestinal epithelial genes that regulate lipid absorption and metabolism. Preliminary studies of monocolonized
mice revealed that flagellated Gram-negative bacteria induced NFIL3 expression. Therefore, my central
hypothesis is that Gram-negative flagellated bacterial species, such as Escherichia coli, selectively promote lipid
absorption in intestinal epithelium. I will test this hypothesis by using gnotobiotic mice and genetic manipulation
of both mice and bacteria. My first aim is to identify intestinal bacteria that regulate intestinal lipid uptake and
metabolism through NFIL3. Monocolonized mice will be fed a Western style diet and analyzed for lipid content,
gene expression changes in the small intestine, and metabolic syndrome. I will then use genetically-altered
bacteria to identify specific bacterial factors that are required to promote intestinal lipid absorption. My second
aim is to identify the host immune pathways that are required for bacterial activation of NFIL3-regulated metabolic
pathways. Genetically altered mice with deletions of specific pattern recognition receptors will be used to identify
host factors required for lipid uptake and metabolism. These studies will provide new insight into how the
microbiota regulates lipid metabolism of the host and should identify new avenues for therapeutic interventions
into obesity.

## Key facts

- **NIH application ID:** 10233732
- **Project number:** 1F31DK126391-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Eugene Koo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,898
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233732

## Citation

> US National Institutes of Health, RePORTER application 10233732, Bacterial Regulation of Intestinal Lipid Metabolism (1F31DK126391-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10233732. Licensed CC0.

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