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A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
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Acta Diabetologica

10-04-2024 | Obesity | Original Article

Anti-adipogenesis effect of indole-3-acrylic acid on human preadipocytes and HFD-induced zebrafish

Authors: Ling Zhang, Jing Zhao, Zhou Peng, Zhongxiao Zhang, Shan Huang, Xiaohua Dong, Jianfang Gao, Xirong Guo

Published in: Acta Diabetologica

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Abstract

Background

Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people’s quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity.

Aims

However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear.

Methods

We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography–mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA.

Results

We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1.

Conclusions

Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.

Graphic Abstract

Appendix
Available only for authorised users
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Metadata
Title
Anti-adipogenesis effect of indole-3-acrylic acid on human preadipocytes and HFD-induced zebrafish
Authors
Ling Zhang
Jing Zhao
Zhou Peng
Zhongxiao Zhang
Shan Huang
Xiaohua Dong
Jianfang Gao
Xirong Guo
Publication date
10-04-2024
Publisher
Springer Milan
Keywords
Obesity
Obesity
Published in
Acta Diabetologica
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-024-02256-7
Obesity Clinical Trial Summary

At a glance: The STEP trials

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A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

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