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

Ling Zhang; Jing Zhao; Zhou Peng; Zhongxiao Zhang; Shan Huang; Xiaohua Dong; Jianfang Gao; Xirong Guo

doi:10.1007/s00592-024-02256-7

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

Acta Diabetol. 2024 Apr 10. doi: 10.1007/s00592-024-02256-7. Online ahead of print.

Authors

Ling Zhang¹, Jing Zhao¹, Zhou Peng¹, Zhongxiao Zhang¹, Shan Huang², Xiaohua Dong¹, Jianfang Gao³, Xirong Guo⁴

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.
² Endocrinology Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
³ Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, 200336, People's Republic of China. jfgao@shsmu.edu.cn.
⁴ Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, 200336, People's Republic of China. xrguo@shsmu.edu.cn.

PMID: 38598139
DOI: 10.1007/s00592-024-02256-7

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.

Keywords: 3-Indole acrylic acid; Adipogenesis; Obesity; STAT1; Zebrafish.

Abstract

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