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

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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

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Data availability

The authors declare that all data supporting the findings of this study are available from the corresponding author upon reasonable request.

The datasets generated and analysed during the current study are available in NCBI’s Gene Expression Omnibus and are accessible through GEO Series accession number GSE246843 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE246843).

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Acknowledgements

We thank Bullet Edits Limited for the linguistic editing and proofreading of the manuscript.

Funding

This project was supported by the National Key Research and Development Program of China (2021YFC2701900, 2021YFC2701903), National Natural Science Foundation of China (No. 82170869, No. 82100915), Natural Science Foundation Project of Shanghai Scientific and technological innovation plan (No.22ZR1457000) and the Master and Doctor innovation talent base for endocrine and metabolic diseases (RCJD2021S03).

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Authors and Affiliations

  1. Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, 200336, People’s Republic of China

    Ling Zhang, Jing Zhao, Zhou Peng, Zhongxiao Zhang, Xiaohua Dong, Jianfang Gao & Xirong Guo

  2. Endocrinology Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

    Shan Huang

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  1. Ling Zhang
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Contributions

XG, XD, SH, and JG designed the project and edited the manuscript. LZ, JZ, and JG performed the experiment and manuscript preparation. ZP, ZZ, and LZ performed the data analyses and statistics analysis.

Corresponding authors

Correspondence to Jianfang Gao or Xirong Guo.

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Conflict of interest

The authors report no conflict of interest.

Ethical approval

The study involving human participants was approved by the Medical Ethics Committee of Shanghai Tongren Hospital of China (approval No. 2021-059-01). The patients/participants provided their written informed consent to participate in this study. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).

The experimental procedures of animal were approved by the Medical Ethics Committee of Shanghai Tongren Hospital of China (approval No. A2022-017-01). All experiments were performed in accordance with ARRIVE guidelines and regulations.

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All persons gave their informed consent prior to their inclusion in the study.

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Supplementary Information

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592_2024_2256_MOESM1_ESM.jpg

Figure S1. The effect of IA on the early development and survival rate of zebrafish embryos. (A) Mortality rate at 72hpf. (B) Morphology changes at 72hpf. Data were obtained from three experiments (n > 30), and the graph shows the mean ± SD. hpf, hours post fertilization. (JPG 81 KB)

Supplementary file2 (XLSX 14 KB)

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Zhang, L., Zhao, J., Peng, Z. et al. Anti-adipogenesis effect of indole-3-acrylic acid on human preadipocytes and HFD-induced zebrafish. Acta Diabetol (2024). https://doi.org/10.1007/s00592-024-02256-7

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