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Gut microbiota metabolite tyramine ameliorates high-fat diet-induced insulin resistance via increased Ca2+ signaling.
The EMBO Journal ( IF 9.4 ) Pub Date : 2024-07-04 , DOI: 10.1038/s44318-024-00162-w
Peng Ma 1 , Yao Zhang 1 , Youjie Yin 1 , Saifei Wang 1 , Shuxin Chen 1 , Xueping Liang 1 , Zhifang Li 1 , Hansong Deng 1
The EMBO Journal ( IF 9.4 ) Pub Date : 2024-07-04 , DOI: 10.1038/s44318-024-00162-w
Peng Ma 1 , Yao Zhang 1 , Youjie Yin 1 , Saifei Wang 1 , Shuxin Chen 1 , Xueping Liang 1 , Zhifang Li 1 , Hansong Deng 1
Affiliation
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.
中文翻译:
肠道微生物代谢产物酪胺通过增加 Ca2+ 信号传导改善高脂饮食诱导的胰岛素抵抗。
肠道微生物群及其代谢物与肥胖相关疾病(例如 2 型糖尿病)密切相关,但它们的因果关系和潜在机制在很大程度上仍然难以捉摸。在这里,我们发现,果蝇和小鼠中,生态失调诱导的酪胺(TA)抑制高脂饮食(HFD)介导的胰岛素抵抗。在果蝇中,HFD 会增加肠上皮细胞中的胞质 Ca2+ 信号传导,从而抑制肠道脂质水平。 16 S rRNA 测序和代谢组学显示,HFD 会导致表达酪氨酸脱羧酶 (Tdc) 的细菌数量增加,并导致酪胺产生。酪胺作用于酪胺受体 TyrR1,促进胞质 Ca2+ 信号传导和 CRTC-CREB 复合物的激活,从而转录抑制肠细胞中的膳食脂质消化和脂肪生成,同时促进线粒体生物发生。此外,酪胺诱导的胞质 Ca2+ 信号传导足以抑制果蝇中 HFD 诱导的肥胖和胰岛素抵抗。在小鼠中,摄入酪胺还可以改善高脂饮食下的葡萄糖耐量和胰岛素敏感性。这些结果表明,生态失调诱导的酪胺可抑制高脂饮食下的果蝇和小鼠的胰岛素抵抗,这表明了糖尿病等相关代谢性疾病的潜在治疗策略。
更新日期:2024-07-04
中文翻译:
肠道微生物代谢产物酪胺通过增加 Ca2+ 信号传导改善高脂饮食诱导的胰岛素抵抗。
肠道微生物群及其代谢物与肥胖相关疾病(例如 2 型糖尿病)密切相关,但它们的因果关系和潜在机制在很大程度上仍然难以捉摸。在这里,我们发现,果蝇和小鼠中,生态失调诱导的酪胺(TA)抑制高脂饮食(HFD)介导的胰岛素抵抗。在果蝇中,HFD 会增加肠上皮细胞中的胞质 Ca2+ 信号传导,从而抑制肠道脂质水平。 16 S rRNA 测序和代谢组学显示,HFD 会导致表达酪氨酸脱羧酶 (Tdc) 的细菌数量增加,并导致酪胺产生。酪胺作用于酪胺受体 TyrR1,促进胞质 Ca2+ 信号传导和 CRTC-CREB 复合物的激活,从而转录抑制肠细胞中的膳食脂质消化和脂肪生成,同时促进线粒体生物发生。此外,酪胺诱导的胞质 Ca2+ 信号传导足以抑制果蝇中 HFD 诱导的肥胖和胰岛素抵抗。在小鼠中,摄入酪胺还可以改善高脂饮食下的葡萄糖耐量和胰岛素敏感性。这些结果表明,生态失调诱导的酪胺可抑制高脂饮食下的果蝇和小鼠的胰岛素抵抗,这表明了糖尿病等相关代谢性疾病的潜在治疗策略。