Gut microbiota metabolite tyramine ameliorates high-fat diet-induced insulin resistance via increased Ca2+ signaling

被引:3
作者
Ma, Peng [1 ]
Zhang, Yao [1 ]
Yin, Youjie [1 ]
Wang, Saifei [1 ]
Chen, Shuxin [1 ]
Liang, Xueping [1 ]
Li, Zhifang [1 ]
Deng, Hansong [1 ]
机构
[1] Tongji Univ, Yangzhi Rehabil Hosp, Sunshine Rehabil Ctr, Frontier Sci Ctr Stem Cell Res,Sch Life Sci & Tech, Shanghai 20092, Peoples R China
基金
中国国家自然科学基金;
关键词
Diet-induced Obesity; Microbiota; Insulin Resistance; Ca2+ Signaling; TYROSINE DECARBOXYLASE; BIOGENIC-AMINES; OBESITY; HOMEOSTASIS; CREB; DYSFUNCTION; METAGENOME; INHIBITORS; EXPRESSION; PATHWAY;
D O I
10.1038/s44318-024-00162-w
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The gut microbiota and their metabolites are closely linked to obesity-related diseases, such as type 2 diabetes, but their causal relationship and underlying mechanisms remain largely elusive. Here, we found that dysbiosis-induced tyramine (TA) suppresses high-fat diet (HFD)-mediated insulin resistance in both Drosophila and mice. In Drosophila, HFD increases cytosolic Ca2+ signaling in enterocytes, which, in turn, suppresses intestinal lipid levels. 16 S rRNA sequencing and metabolomics revealed that HFD leads to increased prevalence of tyrosine decarboxylase (Tdc)-expressing bacteria and resulting tyramine production. Tyramine acts on the tyramine receptor, TyrR1, to promote cytosolic Ca2+ signaling and activation of the CRTC-CREB complex to transcriptionally suppress dietary lipid digestion and lipogenesis in enterocytes, while promoting mitochondrial biogenesis. Furthermore, the tyramine-induced cytosolic Ca2+ signaling is sufficient to suppress HFD-induced obesity and insulin resistance in Drosophila. In mice, tyramine intake also improves glucose tolerance and insulin sensitivity under HFD. These results indicate that dysbiosis-induced tyramine suppresses insulin resistance in both flies and mice under HFD, suggesting a potential therapeutic strategy for related metabolic disorders, such as diabetes.
引用
收藏
页码:3466 / 3493
页数:28
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