ArticleScience (New York, N.Y.)2022
An evolutionary trade-off between host immunity and metabolism drives fatty liver in male mice.
Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 88 citations in OpenAlex.
- Sex Differences in Hepatic VLDLR Response to Protein Restriction and Its Relationship with Hepatic Lipid Accumulation.Nutrients · 2026Article
- Intestinal cGAS-STING-IFN signalling promotes obesity by downregulating microbiota-derived IAA in male mice.Nature metabolism · 2026Article
- Liver sinusoidal endothelial TGF-β signaling accelerates partial endothelial-mesenchymal transition and MASH through Notch.JHEP reports : innovation in hepatology · 2026Article
- Gene Expansion and Regulatory Rewiring Shape Sex-Biased Evolution of the Mouse Submandibular Gland Secretome.bioRxiv : the preprint server for biology · 2026Article
- HDI-STARR-seq Identifies Functional GH-regulated Sex-Biased Hepatocyte Enhancers Linked to Liver Metabolism and Disease.bioRxiv : the preprint server for biology · 2026Article
- The transcription factor HHEX maintains glucocorticoid levels and protects adrenals from androgen-induced lipid depletion.Nature communications · 2026Article
- Evolutionary Balancing of Genetic Consequence and Innovation in Mammals Through Variable Number Tandem Repeats.Genome biology and evolution · 2026Review
- The importance of sex dimorphism in liver metabolism and progressive liver diseases.Biology of sex differences · 2025Review
- Single Nucleus MultiOmics Links Novel Transcription Factor Motifs to Murine Hepatic Sex Differences in Chromatin Accessibility and Metabolic Dysfunction-Associated Steatotic Liver Disease.bioRxiv : the preprint server for biology · 2025Article
- Tabula Sapiens reveals transcription factor expression, senescence effects, and sex-specific features in cell types from 28 human organs and tissues.bioRxiv : the preprint server for biology · 2025Article
- Curcumin ameliorates hepatic steatosis and insulin resistance through the JNK2/FOXO1/Bcl6 axis and regulate the intestinal flora structure.Journal of physiology and biochemistry · 2025Article
- Comprehensive Transcriptomic and Epigenomic Insights into Environmental Toxicant Exposures: The TaRGET II Resource.bioRxiv : the preprint server for biology · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- Steatosis and Interferon Associated with HBsAg Immune Control in Chronic Hepatitis B: A Real-World Propensity Score-Matched Study.Biomedicines · 2025Article
- Gut Microbiota Colonization in Early Life Influences Susceptibility to Adulthood Hepatic Lipid Accumulation in High-Fat-Diet-Fed Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transcriptomic and lipidomic analysis of aging-associated inflammatory signature in mouse liver.Inflammation and regeneration · 2025Article
- Chr23-miR-200s and Dmrt1 Control Sexually Dimorphic Trade-Off Between Reproduction and Growth in Zebrafish.International journal of molecular sciences · 2025Article
- Liver-specific actions of GH and IGF1 that protect against MASLD.Nature reviews. Endocrinology · 2025 · on this mapReview
- BCL6 Inhibitors Exhibit Therapeutic Effects on Breast Cancer Cells through the BCL6-STAT4 Pathway.Anti-cancer agents in medicinal chemistry · 2025Article
- Evolutionary View of Liver Pathology.Evolutionary applications · 2024Review
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11 authors at 4 institutions in 3 countries.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.