ArticleCell metabolism2025
Portal vein-enriched metabolites as intermediate regulators of the gut microbiome in insulin resistance.
Article in Cell metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Transcriptomic timeseries links hepatic gene expression to an early and self-limited systemic response to enteric infection.PLoS pathogens · 2026Article
- Gut microbiota in health and disease.Molecular biomedicine · 2026Review
- The bacteroidal metabolite O-LysoPE facilitates hepatocyte-mediated immunosuppression in autoimmune hepatitis.Nature communications · 2026Article
- A retrospective cohort study identifies differential diabetes progression among Han, Dai, and Yi groups in Yunnan.iScience · 2026Article
- Proteomic and Lipidomic Atlas of Gut-Associated Lymph and Venous Depots in Female Piglets.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- The Gut-Liver Axis in MASLD: From Host-Microbiome Crosstalk to Precision Therapeutics.Microorganisms · 2026Review
- Itaconate-based nanoparticles induce immunometabolic reprogramming in macrophages and alleviate diet-induced obesity.Research square · 2026Article
- The effects of starter feed on intestinal fungi and non-targeted metabolomics of blood in calf yaks.BMC microbiology · 2026Article
- Gut microbiota-derived metabolites in immunomodulation and gastrointestinal cancer immunotherapy.Frontiers in immunology · 2025Review
- Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis.Nature microbiology · 2024Article
- Essential oil supplementation improves insulin sensitivity and modulates the plasma metabolome of hyperinsulinemic horses.Frontiers in veterinary science · 2024Article
- Systemic multiomics evaluation of the therapeutic effect ofMicrobiology spectrum · 2023Article
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Authors and funding
18 authors.
Funding
Abstract
Diet and obesity contribute to insulin resistance and type 2 diabetes, in part via the gut microbiome. To explore the role of gut-derived metabolites in this process, we assessed portal/peripheral blood metabolites in mice with different risks of obesity/diabetes, challenged with a high-fat diet (HFD) + antibiotics. In diabetes/obesity-prone C57BL/6J mice, 111 metabolites were portally enriched and 74 were peripherally enriched, many of which differed in metabolic-syndrome-resistant 129S1/129S6 mice. Vancomycin treatment of HFD-fed C57BL/6J mice modified the microbiome and the portal/peripheral ratio of many metabolites, including upregulating tricarboxylic acid (TCA) cycle-related metabolites, like mesaconate, in portal blood. Treatment of isolated hepatocytes with mesaconate, itaconate, or citraconate improved insulin signaling and transcriptionally regulated genes involved in gluconeogenesis, fatty acid oxidation, and lipogenesis in vitro and in vivo. In humans, citraconate levels are inversely correlated with plasma glucose. Thus, portal versus peripheral metabolites play important roles in mediating effects of the microbiome on hepatic metabolism and the pathogenesis of HFD-related insulin resistance.
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