# Mechanisms of Enteroendocrine Cell Adaptation to High Fat Diet in Zebrafish

> **NIH NIH F30** · DUKE UNIVERSITY · 2024 · $41,774

## Abstract

ABSTRACT
Enteroendocrine cells (EECs) are key sensory cells in the intestinal epithelium that secrete diverse hormones
important in many processes dysregulated in metabolic disease in humans, such as satiety signaling and glucose
homeostasis. EECs are divided into subtypes based on their predominant hormone. As enteroendocrine
hormones have different and sometimes antagonistic metabolic effects, this subdivision enables finely-tuned
control of metabolism in response to a variety of dietary stimuli. Many reports have shown that this careful
balance is disturbed in humans and mice with obesity and metabolic disease, including changes in the number
of EECs, EEC subtype distribution, and circulating EEC hormone levels. Despite these advances, we still do not
understand the processes that regulate EEC adaptation to diet and how these processes may differ across EEC
subtypes. To address these gaps in knowledge, my mentors’ labs recently established zebrafish as a model
system for studying EEC physiology. The optical transparency of larval zebrafish enables live imaging to observe
EEC adaptations in vivo and in real time, a level of resolution not available in live mammals. Using the zebrafish,
we discovered a novel phenomenon of acute change in EEC morphology and reduction in EEC nutrient
sensitivity after high fat feeding we named “EEC silencing.” The objective of this proposal is to understand the
molecular and cellular mechanisms underlying this high fat feeding-induced EEC adaptation. Specifically, I will
test the contributions of lipid signaling from enterocytes and hormone signaling from an inhibitory EEC subtype
in mediating high fat feeding-induced EEC silencing. This work is expected to significantly advance our
understanding of the fundamental physiology of intestinal adaptation to diet with important implications for human
metabolic disease.

## Key facts

- **NIH application ID:** 10757326
- **Project number:** 5F30DK135357-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Margaret Morash
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $41,774
- **Award type:** 5
- **Project period:** 2023-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757326

## Citation

> US National Institutes of Health, RePORTER application 10757326, Mechanisms of Enteroendocrine Cell Adaptation to High Fat Diet in Zebrafish (5F30DK135357-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10757326. Licensed CC0.

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