BioAcyl Corp
BioAcyl Corp |
|
 |
 |
 |
|
Nikkanen, J., Leong, Y. A., & Krause, W. C. (2022). An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice. Science, 378(6617), 290–295. Added by: Dr. Enrique Feoli (03/08/2025, 23:27) Last edited by: Dr. Enrique Feoli (03/08/2025, 23:30) |
 |
| Resource type: Journal Article DOI: 10.1126/science.abn9886 BibTeX citation key: Nikkanen2022 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Peer review Creators: Krause, Leong, Nikkanen Collection: Science |
Views: 3/17
|
| 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. It is well known that there are sex-specific differences in the incidence of various diseases. It is likewise understood that some genes associated with metabolic disease and other medical conditions were likely selected during evolution because they were adaptive under other circumstances. In an example that ties together both of these concepts, Nikkanen et al. used mice to show that the hepatic transcription factor BCL6 plays a key role in determining the genetic program active in male versus female mice and hence their survival in different conditions (see the Perspective by Waxman and Kineman). Male mice had a high expression of BCL6, resulting in protection from infection but vulnerability to metabolic disease, and the opposite was observed in the female mice. —YN Sex-dependent programs in the liver establish a trade-off between infectious and dietary pressures in mice.
|