# TULP3 Regulates Proliferation and Differentiation of 3T3-L1 Preadipocytes Through the Hedgehog Signaling Pathway

**Authors:** Xinlin Jin, Yu Zhang, Yunzhou Wang, Hongzhen Cao, Qi Song, Jingsen Huang, Wei Chen, Hui Tang, Yongqing Zeng

PMC · DOI: 10.3390/biology14040369 · Biology · 2025-04-03

## TL;DR

This study shows that TULP3 promotes the growth and development of fat cells by inhibiting the Hedgehog signaling pathway, offering new insights into obesity and metabolic disorders.

## Contribution

The study reveals TULP3 as a negative regulator of the Hedgehog pathway in adipocyte differentiation, a previously unknown role.

## Key findings

- TULP3 expression increases during 3T3-L1 preadipocyte differentiation.
- TULP3 promotes proliferation and differentiation of preadipocytes.
- TULP3 inhibits the Hedgehog signaling pathway to support adipogenesis.

## Abstract

Adipose tissue is a metabolically active organ that plays a crucial role in maintaining overall health and in the pathogenesis of various diseases. TULP3 is prominently expressed in adipocytes, yet its specific function within adipose tissue remains unclear. In this study, we observed that TULP3 expression increased during the differentiation of 3T3-L1 preadipocytes and found that it promoted both the proliferation and differentiation of these cells. Moreover, TULP3 acts as a negative regulator of the Hedgehog signaling pathway, inhibiting its activity to further support the differentiation of precursor adipocytes. These findings uncover the role of TULP3 in adipocyte differentiation and suggest that targeting TULP3 may offer a promising strategy for treating obesity and related metabolic disorders.

The TULP family was first identified in progressively obese mice, and TULP3, as a member of its family, has been much studied in tumor cells, but studies on its role in adipocytes have not yet been reported. This study found that the expression of TULP3 showed an increasing trend in the differentiation of 3T3-L1 cells, and overexpression of TULP3 enhanced the proliferation and differentiation capacity of the cells, while inhibition caused the opposite result. TULP3 is a negative regulator of the Hedgehog signaling pathway, which can control lipid metabolism in adipose tissues, but whether TULP3 can play a role in adipose tissues through the Hedgehog signaling pathway is not yet known. It was experimentally found that TULP3 could promote adipogenic differentiation of precursor adipocytes by inhibiting the activity of the Hedgehog signaling pathway. Our results elucidate the role of TULP3 in the generation of precursor adipocytes and provide useful information for a deeper understanding of the molecular mechanisms of adipocytogenesis, which will contribute to the improvement of the treatment of adipose tissue dysfunction or uncontrolled adipogenesis-related diseases.

## Linked entities

- **Genes:** TULP3 (TUB like protein 3) [NCBI Gene 7289]
- **Diseases:** obesity (MONDO:0011122)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Tulp3 (TUB like protein 3) [NCBI Gene 22158] {aka 2310022L06Rik}
- **Diseases:** tumor (MESH:D009369), adipose tissue dysfunction (MESH:D018205), obese (MESH:D009765)
- **Chemicals:** lipid (MESH:D008055)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** 3T3-L1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0123)

## Full text

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## Figures

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## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12024758/full.md

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Source: https://tomesphere.com/paper/PMC12024758