An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice.
An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice.
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DOI：
10.1126/science.abn9886
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发表时间：
2022-10-21
期刊：
影响因子：
56.9
通讯作者：
Ingraham, Holly A.
中科院分区：
文献类型：
--
作者：
Nikkanen, Joni;Leong, Yew Ann;Krause, William C.;Dermadi, Denis;Maschek, J. Alan;Van Ry, Tyler;Cox, James E.;Weiss, Ethan J.;Gokcumen, Omer;Chawla, Ajay;Ingraham, Holly A.
对传染病和饮食压力的适应决定了哺乳动物的生理和疾病风险。这种适应如何影响性别偏见疾病仍未得到充分研究。在这项研究中，我们发现性别依赖的肝脏基因程序赋予雄性小鼠在致命细菌感染期间强大的（~300%）生存优势。转录因子B细胞淋巴瘤6 （BCL6）在青春期使肝脏基因表达男性化，对这种优势至关重要。然而，在饮食过量的情况下，BCL6蛋白的保护是有代价的，这会导致男性明显的脂肪肝和葡萄糖耐受不良。删除肝脏BCL6逆转了这些表型，但显著降低了感染期间男性的存活率，从而在宿主防御和代谢系统之间建立了性别依赖的权衡。我们的发现提供了强有力的证据，表明目前一些性别偏见的疾病根植于古老的免疫和新陈代谢之间的进化权衡。
Adaptations to infectious and dietary pressures shape mammalian physiology and disease risk. How such adaptations affect sex-biased diseases remains insufficiently studied. In this study, we show that sex-dependent hepatic gene programs confer a robust (~300%) survival advantage for male mice during lethal bacterial infection. The transcription factor B cell lymphoma 6 (BCL6), which masculinizes hepatic gene expression at puberty, is essential for this advantage. However, protection by BCL6 protein comes at a cost during conditions of dietary excess, which result in overt fatty liver and glucose intolerance in males. Deleting hepatic BCL6 reverses these phenotypes but markedly lowers male survival during infection, thus establishing a sex-dependent trade-off between host defense and metabolic systems. Our findings offer strong evidence that some current sex-biased diseases are rooted in ancient evolutionary trade-offs between immunity and metabolism.
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影响因子：
20.8
作者：
Salisbury DA;Casero D;Zhang Z;Wang D;Kim J;Wu X;Vergnes L;Mirza AH;Leon-Mimila P;Williams KJ;Huertas-Vazquez A;Jaffrey SR;Reue K;Chen J;Sallam T
通讯作者：
Sallam T
影响因子：
158.5
作者：
GALLIN, JI;KAYE, D;OLEARY, WM
通讯作者：
OLEARY, WM
影响因子：
1.4
作者：
Strawbridge, R. J.;Karvestedt, L.;Brismar, K.
通讯作者：
Brismar, K.
DOI：
10.1073/pnas.1701535115
发表时间：
2018-01-23
影响因子：
11.1
作者：
Zarulli V;Barthold Jones JA;Oksuzyan A;Lindahl-Jacobsen R;Christensen K;Vaupel JW
通讯作者：
Vaupel JW
影响因子：
5.3
作者：
Lau-Corona D;Suvorov A;Waxman DJ
通讯作者：
Waxman DJ