ArticleArchives of toxicology2021
Sex-dependent dynamics of metabolism in primary mouse hepatocytes.
Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Re: ASGR1 Deficiency Promotes Liver Fibrosis by Enhancing Pro-Inflammatory Arachidonic Acid Metabolism and ALP Secretion.Immunity, inflammation and disease · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- Transcriptomic Profiling Reveals Inflammatory, Fibrotic, and Apoptotic Signatures in a Methionine-Choline-Deficient Diet-Induced Murine Model of Metabolism-Dysfunction-Associated Steatohepatitis.International journal of molecular sciences · 2026Article
- Circadian dysregulation as a factor in impaired hepatic protein-synthetic function under chronic photoperiod disruption: the role of sex and chronobiotic correction.Biology of sex differences · 2026Article
- From prioritization to implementation: updating the PARC WP5 project portfolio through the second prioritization round.Frontiers in toxicology · 2026Review
- Liver androgen receptor knockout attenuates high-fructose diet-induced glucose dysregulation in female mice.American journal of physiology. Endocrinology and metabolism · 2025Article
- Sex Hormones and Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2025Review
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.bioRxiv : the preprint server for biology · 2025Article
- Advanced N-glycoproteomics and proteomics approach revealed sexually dimorphic molecular signatures in primary mouse hepatocyte.Analytical and bioanalytical chemistry · 2025Article
- Hallmarks of Cancer Cachexia: Sexual Dimorphism in Related Pathways.International journal of molecular sciences · 2025Review
- Phospholipid isotope tracing suggests β-catenin-driven suppression of phosphatidylcholine metabolism in hepatocellular carcinoma.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Article
- Combined transcriptomics and proteomics unveil the impact of vitamin C in modulating specific protein abundance in the mouse liver.Biological research · 2024Article
- A Panoramic View of Cell Population Dynamics in Mammalian Aging.bioRxiv : the preprint server for biology · 2024Article
- Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice.Cell metabolism · 2023Article
- Phospholipid isotope tracing reveals β-catenin-driven suppression of phosphatidylcholine metabolism in hepatocellular carcinoma.bioRxiv : the preprint server for biology · 2023Article
- Metabolic modeling of sex-specific liver tissue suggests mechanism of differences in toxicological responses.PLoS computational biology · 2023Article
- Gender Dimorphism in Hepatic Carcinogenesis-Related Gene Expression Associated with Obesity as a Low-Grade Chronic Inflammatory Disease.International journal of molecular sciences · 2022Article
- Interplay Between GH-regulated, Sex-biased Liver Transcriptome and Hepatic Zonation Revealed by Single-Nucleus RNA Sequencing.Endocrinology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The liver is one of the most sexually dimorphic organs. The hepatic metabolic pathways that are subject to sexual dimorphism include xenobiotic, amino acid and lipid metabolism. Non-alcoholic fatty liver disease and hepatocellular carcinoma are among diseases with sex-dependent prevalence, progression and outcome. Although male and female livers differ in their abilities to metabolize foreign compounds, including drugs, sex-dependent treatment and pharmacological dynamics are rarely applied in all relevant cases. Therefore, it is important to consider hepatic sexual dimorphism when developing new treatment strategies and to understand the underlying mechanisms in model systems. We isolated primary hepatocytes from male and female C57BL6/N mice and examined the sex-dependent transcriptome, proteome and extracellular metabolome parameters in the course of culturing them for 96 h. The sex-specific gene expression of the general xenobiotic pathway altered and the female-specific expression of Cyp2b13 and Cyp2b9 was significantly reduced during culture. Sex-dependent differences of several signaling pathways increased, including genes related to serotonin and melatonin degradation. Furthermore, the ratios of male and female gene expression were inversed for other pathways, such as amino acid degradation, beta-oxidation, androgen signaling and hepatic steatosis. Because the primary hepatocytes were cultivated without the influence of known regulators of sexual dimorphism, these results suggest currently unknown modulatory mechanisms of sexual dimorphism in vitro. The large sex-dependent differences in the regulation and dynamics of drug metabolism observed during cultivation can have an immense influence on the evaluation of pharmacodynamic processes when conducting initial preclinical trials to investigate potential new drugs.
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Registered trials
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 Socratic graph.