# A cardiac Wingless-Snail-Tep2 axis directs normal lipid homeostasis and protects against diet-induced obesity

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $140,450

## Abstract

Abstract
 The heart is now recognized as an important organ in the regulation of systemic lipid homeostasis;
however, our understanding of the molecular basis remains limited. It was recently shown that Wingless (Wg)
signaling in the heart controls systemic lipid homeostasis. However, how cardiac Wg signaling controls this
process is unknown. In a genetic screen in Drosophila, we discovered that the Snail family of transcription
factors (Sna TFs) act in the heart to regulate systemic lipid metabolism. Our preliminary results also showed
that Wg signaling in the heart activates the cardiac expression of Sna TFs. These findings led us to
hypothesize that a Wg-Sna TF axis in the heart regulates lipid homeostasis in a systemic manner. This
hypothesis will be tested in Aim 1. Building on our previous proteomic analysis of fly hemolymph (blood), we
further discovered that a soluble protein thioester-containing protein 2 (Tep2), a secreted protein previously
unknown to be involved in lipid metabolism, is up-regulated in the heart by Sna signaling and secreted to the
circulation. Our further preliminary data showed that Tep2 mutation alters systemic lipid levels and that both
Sna TF and Tep2 control TGF signaling in the fat body, in which TGF is known to be implicated in lipid
metabolism. We therefore hypothesize that Tep2 secreted from heart to circulation serves as a functional
effector of Wg-Sna axis in regulating systemic lipid homeostasis by modulating TGF pathway in fat body. This
hypothesis will be tested in Aim 2. Furthermore, we found that high fat diet (HFD) induces the cardiac
expression of Wg and Sna TFs. Based on our preliminary observation that activation of Sna TFs decreases
systemic lipid levels, we hypothesize that a cardiac WgSna TF–Tep2 axis protects against HFD-induced
obesity. This hypothesis will be tested in Aim 3. Together, this proposal will reveal novel insights into the heart
control of normal systemic lipid homeostasis and provide knowledge that may help guide future therapeutics
for human obesity and its comorbidities.

## Key facts

- **NIH application ID:** 10808120
- **Project number:** 5R01HL152205-05
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Hui-Ying Lim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $140,450
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-07-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808120

## Citation

> US National Institutes of Health, RePORTER application 10808120, A cardiac Wingless-Snail-Tep2 axis directs normal lipid homeostasis and protects against diet-induced obesity (5R01HL152205-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10808120. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*