Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome.
Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome.
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葡萄糖代谢中的性别二态性是由雄激素驱动的肠道微生物组决定的
DOI：
10.1038/s41467-021-27187-7
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发表时间：
2021-12-06
影响因子：
16.6
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Gao A;Su J;Liu R;Zhao S;Li W;Xu X;Li D;Shi J;Gu B;Zhang J;Li Q;Wang X;Zhang Y;Xu Y;Lu J;Ning G;Hong J;Bi Y;Gu W;Wang J;Wang W
男性通常比女性更容易患葡萄糖代谢受损和2型糖尿病（T2 D）。然而，其根本机制仍有待确定。在这里，我们揭示了肠道微生物组耗竭消除了葡萄糖代谢中的性别二型性。将雄性供体微生物群转移到接受抗肿瘤药物治疗的雌性小鼠中，导致受体更具胰岛素抵抗性。通过阉割消耗雄激素改变了雄性小鼠的肠道微生物组，使其与雌性小鼠的肠道微生物组更相似，并改善了葡萄糖代谢，而重新引入双氢睾酮（DHT）则逆转了这些改变。更重要的是，当肠道微生物组耗尽时，雄激素对葡萄糖代谢的影响在很大程度上被消除。接下来，我们证明了雄激素调节循环谷氨酰胺和谷氨酰胺/谷氨酸（Gln/Glu）比值部分取决于肠道微生物组，谷氨酰胺补充剂在体外增加胰岛素敏感性。我们的研究通过调节肠道微生物组和循环谷氨酰胺和Gln/Glu比值，确定了雄激素在葡萄糖稳态恶化中的作用，从而导致两性之间葡萄糖代谢的差异。男性是糖代谢受损和2型糖尿病的危险因素。在这里，作者确定雄激素调节肠道微生物组，这驱动了胰岛素抵抗，并导致小鼠葡萄糖代谢的性别二型性。
Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes. Male sex is a risk factor for impaired glucose metabolism and type 2 diabetes. Here the authors identify that androgen modulates the gut microbiome, which drives insulin resistance and contributes to sexual dimorphism in glucose metabolism in mice.
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影响因子：
20.3
作者：
Kautzky-Willer A;Harreiter J;Pacini G
通讯作者：
Pacini G
影响因子：
3.7
作者：
Dominianni C;Sinha R;Goedert JJ;Pei Z;Yang L;Hayes RB;Ahn J
通讯作者：
Ahn J
影响因子：
37.8
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Cheng S;Rhee EP;Larson MG;Lewis GD;McCabe EL;Shen D;Palma MJ;Roberts LD;Dejam A;Souza AL;Deik AA;Magnusson M;Fox CS;O'Donnell CJ;Vasan RS;Melander O;Clish CB;Gerszten RE;Wang TJ
通讯作者：
Wang TJ
影响因子：
7.7
作者：
Nishizawa, H;Shimomura, H;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
5.9
作者：
Abboud, Kahlile Youssef;Reis, Sabrina Karen;Prada, Patricia Oliveira
通讯作者：
Prada, Patricia Oliveira