ArticleLaboratory investigation; a journal of technical methods and pathology2022
Hepatocyte-specific fibroblast growth factor 21 overexpression ameliorates high-fat diet-induced obesity and liver steatosis in mice.
Article in Laboratory investigation; a journal of technical methods and pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 50 citations in OpenAlex.
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- Early Hepatic Transcriptomic Responses to High-Fat Diet in Apolipoprotein A-IV Knockout Mice.Metabolites · 2026Article
- Article
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- FGF21 and SHBG as Putative Hepatic Axes in Maternal Metabolic Adaptation: A Hypothetical Framework for Postpartum Insulin Sensitivity Restoration.Biomolecules · 2026Review
- Targeting lipophagy in atherosclerosis: Molecular mechanisms, pathogenesis and therapeutic interventions (Review).Molecular medicine reports · 2026Review
- PLGA nanoparticles encapsulating fibroblast growth factor 21 alleviate acetaminophen-induced acute liver injury.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A Combination of Plant-Derived Extracts Modulates Nutrient-Responsive Metabolic Signalling in an In Vitro Gut-Liver-Adipose Model.Nutrients · 2026Article
- Acceleration of Lactate Uptake and Utilization Contributes to Neuroprotective Action of FGF21 Involved in Naturally Aging Mice.Aging cell · 2026Article
- Plasma FGF21 is associated with intracranial atherosclerotic stenosis in patients with type 2 diabetes mellitus.Frontiers in neurology · 2026Article
- Fibroblast Growth Factor 21: Mechanisms, Therapeutic Potential, and Clinical Translation in Metabolic Dysfunction.Drug design, development and therapy · 2026Review
- Exercise and cold exposure as dual physiological stressors in MASLD: AMPK-mediated metabolic adaptation and interorgan crosstalk.Frontiers in physiology · 2026Review
- Gut microbiota regulates hepatic ketogenesis and lipid accumulation in ketogenic diet-induced hyperketonemia by disrupting bile acid metabolism.Gut microbes · 2025Article
- Gene therapy strategies for aging intervention.Cell insight · 2025Review
- Metabolic dysfunction-associated steatotic liver disease: A story of muscle and mass.World journal of gastroenterology · 2025Article
- MOB1 deletion in murine mature adipocytes ameliorates obesity and diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Influence of Physical Exercise, Ketogenic Diet, and Time-Restricted Eating on De Novo Lipogenesis: A Narrative Review.Nutrients · 2025Review
- Advances in Oral Biomacromolecule Therapies for Metabolic Diseases.Pharmaceutics · 2025Review
- Nuclear Receptor-Targeted Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of drug discovery and pharmacology · 2025Article
- The Predictive Role of FGF21 in Acute Liver Injury Caused by Bacterial Infectious Diseases in Critical Care: A Retrospective Cohort Study.Journal of inflammation research · 2025Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor (FGF) 21 is an endocrine growth factor mainly secreted by the liver in response to a ketogenic diet and alcohol consumption. FGF21 signaling requires co-receptor β-klotho (KLB) co-acting with FGF receptors, which has pleiotropic metabolic effects, including induced hepatic fatty acid oxidation and ketogenesis, in human and animal models of obesity. We examined the hepatocyte-specific enhancer/promoter of FGF21 expression plasmids in high-fat diet-fed mice for 12 weeks. Hydrodynamic injection for FGF21 delivery every 6 weeks sustained high circulating levels of FGF21, resulting in marked reductions in body weight, epididymal fat mass, insulin resistance, and liver steatosis. FGF21-induced lipolysis in the adipose tissue enabled the liver to be flooded with fat-derived FFAs. The hepatic expression of Glut2 and Bdh1 was upregulated, whereas that of gluconeogenesis-related genes, G6p and Pepck, and lipogenesis-related genes, Srebp-1 and Srebp-2, was significantly suppressed. FGF21 induced the phosphorylation of AMPK at Thr172 and Raptor at ser792 and suppressed that of mTOR at ser2448, which downregulated mTORC1 signaling and reduced IRS-1 phosphorylation at ser1101. Finally, in the skeletal muscle, FGF21 increased Glut4 and Mct2, a membrane protein that acts as a carrier for ketone bodies. Enzymes for ketone body catabolism (Scot) and citrate cycle (Cs, Idh3a), and a marker of regenerating muscle (myogenin) were also upregulated via increased KLB expression. Thus, FGF21-induced lipolysis was continuously induced by a high-fat diet and fat-derived FFAs might cause liver damage. Hepatic fatty acid oxidation and ketone body synthesis may act as hepatic FFAs' disposal mechanisms and contribute to improved liver steatosis. Liver-derived ketone bodies might be used for energy in the skeletal muscle. The potential FGF21-related crosstalk between the liver and extraliver organs is a promising strategy to prevent and treat metabolic syndrome-related nonalcoholic steatohepatitis.
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