{"doi":"10.1016/j.cbd.2025.101429","title":"Effects of fasting and inflammatory challenges on the swine hepatic metabolome","abstract":"The liver is simultaneously impacted by environmental challenges and modulates the response to these insults. Efforts to understand the effects of stressors on the activity of the liver typically consider one type of challenge (e.g., nutrition, toxin, disease), profile targeted molecules, or study the hepatic disruptions in one sex. The present study characterized hepatic changes in the metabolome of females and males exposed to the nutritional challenge of fasting and inflammatory signals elicited by the viral mimetic Poly(I:C). The hepatic metabolome of pigs was profiled using untargeted liquid chromatography-mass spectrometry analysis enabling the quantification of metabolites. The analysis of pathways enriched among metabolites showing sex-by-distress interactions revealed molecular processes affected by fasting and immune stresses in a sex-specific manner, including SLC-mediated transmembrane transport, the urea cycle, and G-protein coupled receptor signaling. Metabolites differentially abundant across sex-distress groups in the previous pathways included creatine, taurine, and glycine derivatives. Pathways over-represented among metabolites significantly affected by distress included glucose homeostasis, the Krebs cycle, and the metabolism of water-soluble vitamins, with key metabolites including S-adenosylmethionine, histidine, glycerophosphocholine, and lactic acid. These results indicate that 24-h fasting, and low-grade systemic inflammation modulate the liver metabolism. The detection of metabolic disruption that varies with sex enforces the need to develop therapies that can restore hepatic homeostasis in females and males. • The liver is a metabolic hub vital for nutrient management and immune response, impacted by stressors in both sexes. • Fasting and low-grade inflammation alter glucose homeostasis, Krebs cycle, and vitamin metabolism in the liver.Liver metabolite responses, including SLC transport and GPCR signaling, vary between males and females under stress. • The pattern of metabolites like creatine, taurine, and S-adenosylmethionine suggest potential biomarkers for liver health assessment. • Fasting and immune stress affect male and female liver metabolism differently, emphasizing the need for sex-specific interventions.","journal":"Comparative Biochemistry and Physiology Part D Genomics and Proteomics","year":2025,"id":560830,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":707267,"name":"Bruce R. Southey","orcid":"0000-0002-8959-7709","position":1,"is_corresponding":false},{"id":707266,"name":"María B. Villamil","orcid":"0000-0003-3559-8981","position":2,"is_corresponding":false},{"id":707268,"name":"Sandra L. Rodriguez‐Zas","orcid":"0000-0003-1122-4758","position":3,"is_corresponding":false},{"id":1462100,"name":"Andrea N Gomez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T02:55:46.921885Z","pmid":"39889585","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}