ArticleDiabetes2023
IL-6 Trans-Signaling Is Increased in Diabetes, Impacted by Glucolipotoxicity, and Associated With Liver Stiffness and Fibrosis in Fatty Liver Disease.
Article in Diabetes, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Exerkines in precision management of metabolic diseases.Chinese medical journal · 2026Review
- Epigenetic regulation in a high-sugar environment (Review).International journal of molecular medicine · 2026Review
- Targeting DNA fragment extrusion: a new therapeutic avenue for CClMolecular biology reports · 2026Article
- Enhancing future liver remnant hypertrophy: innovative preoperative strategies and emerging technologies.Translational gastroenterology and hepatology · 2026Review
- Blockade of Interleukin-6 Trans-signaling in the Presence of Certain Gut Microbiota Induces Mature-onset Obesity in Mice.Gastro hep advances · 2026Article
- Paeoniflorin Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by SYK/SH3BP2 Signaling Pathway.Research (Washington, D.C.) · 2026Article
- Jiangtang Decoction for Type 2 Diabetes and NAFLD: Integrative AnalysisEndocrine, metabolic & immune disorders drug targets · 2026Article
- Causal pathways of plasma metabolites: unveiling metabolic associations in liver diseases.Nutrition & metabolism · 2025Article
- Methotrexate and biological therapy are not associated with fatty liver in rheumatoid arthritis-a cross-sectional study.Rheumatology international · 2025Article
- Mediating role of Interleukin-6 in the predictive association of diabetes with Hippocampus atrophy, Amyloid, Tau, and Neurofilament pathology at pre-clinical stages of diabetes-related cognitive impairment.Brain, behavior, & immunity - health · 2025Article
- Chronic hepatitis B with type 2 diabetes mellitus: Association between glycemic control and liver fibrosis.World journal of diabetes · 2025Article
- Sex differences in the mediating role of brain-derived neurotrophic factor between inflammation and memory in cirrhotic patients with minimal hepatic encephalopathy.Brain, behavior, & immunity - health · 2025Article
- Saturated phosphatidic acids induce mTORC1-driven integrated stress response contributing to glucolipotoxicity in hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Type 2 Diabetes Mellitus: A Metabolic Model of Accelerated Aging - Multi-Organ Mechanisms and Intervention Approaches.Aging and disease · 2025Review
- Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease: A cross-sectional study.World journal of gastroenterology · 2025Article
- The role of macrophages in hypertrophic scarring: molecular to therapeutic insights.Frontiers in immunology · 2025Review
- Antagonizing IL-6 receptor restores pancreatic tissue resident NK cells activation and ameliorates pancreatic injury in the mouse model of MASH.Frontiers in pharmacology · 2025Article
- Inflammation: a key mechanism connecting metabolic-associated steatotic liver disease and systemic arterial hypertension.Frontiers in immunology · 2025Review
- Regulation of the immune microenvironment by SUMO in diabetes mellitus.Frontiers in immunology · 2025Review
- Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Many people living with diabetes also have nonalcoholic fatty liver disease (NAFLD). Interleukin-6 (IL-6) is involved in both diseases, interacting with both membrane-bound (classical) and circulating (trans-signaling) soluble receptors. We investigated whether secretion of IL-6 trans-signaling coreceptors are altered in NAFLD by diabetes and whether this might associate with the severity of fatty liver disease. Secretion patterns were investigated with use of human hepatocyte, stellate, and monocyte cell lines. Associations with liver pathology were investigated in two patient cohorts: 1) biopsy-confirmed steatohepatitis and 2) class 3 obesity. We found that exposure of stellate cells to high glucose and palmitate increased IL-6 and soluble gp130 (sgp130) secretion. In line with this, plasma sgp130 in both patient cohorts positively correlated with HbA1c, and subjects with diabetes had higher circulating levels of IL-6 and trans-signaling coreceptors. Plasma sgp130 strongly correlated with liver stiffness and was significantly increased in subjects with F4 fibrosis stage. Monocyte activation was associated with reduced sIL-6R secretion. These data suggest that hyperglycemia and hyperlipidemia can directly impact IL-6 trans-signaling and that this may be linked to enhanced severity of NAFLD in patients with concomitant diabetes. ARTICLE HIGHLIGHTS: IL-6 and its circulating coreceptor sgp130 are increased in people with fatty liver disease and steatohepatitis. High glucose and lipids stimulated IL-6 and sgp130 secretion from hepatic stellate cells. sgp130 levels correlated with HbA1c, and diabetes concurrent with steatohepatitis further increased circulating levels of all IL-6 trans-signaling mediators. Circulating sgp130 positively correlated with liver stiffness and hepatic fibrosis. Metabolic stress to liver associated with fatty liver disease might shift the balance of IL-6 classical versus trans-signaling, promoting liver fibrosis that is accelerated by diabetes.
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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 OpenQuestion graph.