研究人员表明，在致命的细菌感染期间，性别依赖的肝脏基因程序赋予雄性小鼠强大的（约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雄性化，对这一优势至关重要。然而，在饮食过量的情况下，BCL6蛋白的保护是有代价的，这导致了雄性的明显脂肪肝和葡萄糖不耐受。删除肝脏BCL6可逆转这些表型，但在感染期间明显降低了雄性的存活率，从而在宿主防御和新陈代谢系统之间建立了一种性别依赖性的折衷。
这项发现提供了强有力的证据，表明目前一些有性别偏好的疾病植根于免疫和代谢之间的古老演化权衡。
据悉，对传染病和饮食压力的适应塑造了哺乳动物的生理学和疾病风险。这种适应性如何影响基于性别的疾病仍然没有得到充分的研究。
附：英文原文
Title: An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice
Author: Joni Nikkanen, Yew Ann Leong, William C. Krause, Denis Dermadi, J. Alan Maschek, Tyler Van Ry, James E. Cox, Ethan J. Weiss, Omer Gokcumen, Ajay Chawla, Holly A. Ingraham
Issue&Volume: 2022-10-21
Abstract: 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.
DOI: abn9886
Source: https://www.science.org/doi/10.1126/science.abn9886