Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai, 200336, People's Republic of China.
Endocrinology Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Acta Diabetol. 2024 Aug;61(8):975-985. doi: 10.1007/s00592-024-02256-7. Epub 2024 Apr 10.
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.
However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear.
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.
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.
Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.
肥胖定义为体内脂肪过度或异常积累，这会显著增加心血管疾病、2 型糖尿病（T2DM）等疾病的风险，并严重影响人们的生活质量。目前全球有超过 20 亿人超重，肥胖的发病率正在迅速上升，已成为全球广泛关注的公共卫生问题。大量证据表明，活性代谢物参与肥胖的病理生理过程。
然而，色氨酸的下游代谢产物 3-吲哚丙烯酸（IA）是否参与肥胖的发生尚不清楚。
我们收集了肥胖症和健康对照组外周血血清样本，通过液相色谱-质谱（LC-MS）鉴定 IA 在血浆中的水平。此外，通过细胞活力测定、流式细胞术分析、油红 O 染色、总胆固醇（T-CHO）、甘油三酯（TG）和非酯化游离脂肪酸（NEFA）测定和尼罗红染色，验证了 IA 对人前体脂肪细胞和高脂肪饮食（HFD）诱导的斑马鱼的潜在益处。RNA-Seq、功能分析和 Western blot 揭示了 IA 功能的作用机制。
我们发现超重人群外周血血清中 IA 的含量明显低于正常人。此外，在高脂肪饮食（HFD）诱导的斑马鱼幼虫中补充 IA 可显著减少 HFD 诱导的脂质积累。IA 对前体脂肪细胞的增殖和凋亡没有影响，但通过下调 CEBPα 和 PPARγ 显著抑制前体脂肪细胞的脂肪生成。RNA-Seq 和功能分析表明，IA 通过刺激 STAT1 磷酸化来调节前体脂肪细胞的脂肪生成。
综上所述，IA 已被确定为预防或治疗肥胖的有效代谢物。
