ArticleeLife2023
FGF21 protects against hepatic lipotoxicity and macrophage activation to attenuate fibrogenesis in nonalcoholic steatohepatitis.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Key Hepatokines Linking MASLD and Type 2 Diabetes: From Pathophysiological Mechanisms to Therapeutic Modulation.International journal of molecular sciences · 2026Review
- Beneficial Hepatokines in MASLD/MASH: Therapeutic Potentials and Drug Delivery Challenges.International journal of molecular sciences · 2026Review
- Reprogramming macrophages to treat liver diseases.Hepatology (Baltimore, Md.) · 2026Review
- The clinical significance of serum complement fibroblast growth factor 21 in patients with rheumatoid arthritis.BMC immunology · 2026Article
- A unimolecular GLP-1 and FGF21 dual agonist for treatment of metabolic dysfunction-associated steatohepatitis.Communications medicine · 2026Article
- Pre-vaccination biomarkers of enteric dysfunction, inflammation and nutritional status associate with seroconversion to oral cholera vaccine and are perturbed during natural infection.Frontiers in immunology · 2026Article
- Heart-liver co-management: epidemiology, mechanisms, and novel therapeutic approaches for metabolic dysfunction-associated steatotic liver disease and coronary artery disease.Frontiers in cardiovascular medicine · 2026Review
- Predictive lipidaemic and clinical factors for PVR formation after RRD surgery in nondiabetic patients.International journal of ophthalmology · 2026Article
- Hepatic FGF21 Deletion Improves Glucose Metabolism, Alters Lipogenic andInternational journal of molecular sciences · 2025Article
- Inflammation-Insulin Resistance Crosstalk and the Central Role of Myokines.International journal of molecular sciences · 2025Review
- Role of ChREBP-PPARα-FGF21 Axis in Metabolic Dysfunction of MASLD.International journal of molecular sciences · 2025Article
- Melinjo-derived Gnetin C restores metabolic balance via dual adipose and hepatic effects in high-fat diet mice.Scientific reports · 2025Article
- TSG attenuated NAFLD and facilitated weight loss in HFD-fed mice via activating the RUNX1/FGF21 signaling axis.Acta pharmacologica Sinica · 2025Article
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- High-Fat Diet Differentially Regulates Fibroblast Growth Factor Expression in Metabolic Tissues of Young and Aged Male Mice.Journal of the Endocrine Society · 2025Article
- Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications.MedComm · 2025Review
- FGF21 promotes longevity in diet-induced obesity through metabolic benefits independent of growth suppression.Cell metabolism · 2025Article
- Skeletal muscle and MASLD: Mechanistic and clinical insights.Hepatology communications · 2025Review
- Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets.Signal transduction and targeted therapy · 2025Review
- The Impact of Human Liver Transplantation on the Concentration of Fibroblast Growth Factors: FGF19 and FGF21.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Analogues of the hepatokine fibroblast growth factor 21 (FGF21) are in clinical development for type 2 diabetes and nonalcoholic steatohepatitis (NASH) treatment. Although their glucose-lowering and insulin-sensitizing effects have been largely unraveled, the mechanisms by which they alleviate liver injury have only been scarcely addressed. Here, we aimed to unveil the mechanisms underlying the protective effects of FGF21 on NASH using APOE*3-Leiden.CETP mice, a well-established model for human-like metabolic diseases. Liver-specific FGF21 overexpression was achieved in mice, followed by administration of a high-fat high-cholesterol diet for 23 weeks. FGF21 prevented hepatic lipotoxicity, accompanied by activation of thermogenic tissues and attenuation of adipose tissue inflammation, improvement of hyperglycemia and hypertriglyceridemia, and upregulation of hepatic programs involved in fatty acid oxidation and cholesterol removal. Furthermore, FGF21 inhibited hepatic inflammation, as evidenced by reduced Kupffer cell (KC) activation, diminished monocyte infiltration, and lowered accumulation of monocyte-derived macrophages. Moreover, FGF21 decreased lipid- and scar-associated macrophages, which correlated with less hepatic fibrosis as demonstrated by reduced collagen accumulation. Collectively, hepatic FGF21 overexpression limits hepatic lipotoxicity, inflammation, and fibrogenesis. Mechanistically, FGF21 blocks hepatic lipid influx and accumulation through combined endocrine and autocrine signaling, respectively, which prevents KC activation and lowers the presence of lipid- and scar-associated macrophages to inhibit fibrogenesis.
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