ArticleCardiovascular research2022
Pharmacological treatment with FGF21 strongly improves plasma cholesterol metabolism to reduce atherosclerosis.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 72 citations in OpenAlex.
- The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial.Nature medicine · 2023Trial
- A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders.Science advances · 2026Article
- Novel Endocrine Signaling Axis in Cardiovascular-Kidney-Metabolic Syndrome: Interactions and Therapeutic Potential of FGF21 and GDF15.Journal of cellular biochemistry · 2026Review
- Assessment of triglyceride-glucose composite indices associated mortality risk in diabetes-related heart failure.Journal of diabetes investigation · 2026Article
- Distinct From the Adult Paradigm: Re-Evaluate the Pathophysiological and Therapeutic Framework in Children and Adolescent Hyperlipidaemia.Current obesity reports · 2026Review
- Perivascular adipokine signaling in abdominal aortic aneurysm: cardiometabolic drivers of vascular remodeling and translational opportunities.Cardiovascular diabetology · 2026Review
- Article
- Current Drug Development Pipeline for MASLD and MASH: Focusing on Cardiovascular Comorbidities.Biomedicines · 2026Review
- 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
- From endocrine to immune: therapeutic potential of brown adipose tissue in remodelling the cardiovascular immune microenvironment.Frontiers in immunology · 2026Review
- Establishing an atherosclerosis diagnostic model based on WGCNA and machine learning algorithms with key genes in cholesterol metabolism and ferroptosis, and revealing the regulatory role of HMOX1 in cellular ferroptosis.Frontiers in cardiovascular medicine · 2026Article
- Article
- Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity.PeerJ · 2026Review
- Triglyceride-lowering therapies for hepatic steatosis: mechanisms, efficacy, and clinical perspectives.Frontiers in pharmacology · 2026Review
- Beyond conventional therapies: Gut microbiota modulation and macromolecular drugs in the battle against cardiometabolic diseases.Journal of pharmaceutical analysis · 2026Review
- The designer cytokine IC7Fc attenuates atherosclerosis development by targeting hyperlipidemia in mice.Science advances · 2025Article
- Engineering chimeric PCSK9 for a vaccine against atherosclerosis.Molecular therapy. Methods & clinical development · 2025Article
- Elevation of p53 sensitizes obese kidney to adriamycin-induced aberrant lipid homeostasis via repressing HNF4α-mediated FGF21 sensitivity.Journal of advanced research · 2025Article
- Association between FIB-4 index and lower extremity arterial disease in MASLD patients: a cross-sectional study.Lipids in health and disease · 2025Article
- Enhanced FGF21 Delivery via Neutrophil-Membrane-Coated Nanoparticles Improves Therapeutic Efficacy for Myocardial Ischemia-Reperfusion Injury.Nanomaterials (Basel, Switzerland) · 2025Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsFibroblast growth factor (FGF) 21, a key regulator of energy metabolism, is currently evaluated in humans for treatment of type 2 diabetes and non-alcoholic steatohepatitis. However, the effects of FGF21 on cardiovascular benefit, particularly on lipoprotein metabolism in relation to atherogenesis, remain elusive. METHODS AND
resultsHere, the role of FGF21 in lipoprotein metabolism in relation to atherosclerosis development was investigated by pharmacological administration of a half-life extended recombinant FGF21 protein to hypercholesterolaemic APOE*3-Leiden.CETP mice, a well-established model mimicking atherosclerosis initiation and development in humans. FGF21 reduced plasma total cholesterol, explained by a reduction in non-HDL-cholesterol. Mechanistically, FGF21 promoted brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning, thereby enhancing the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT and into browned WAT, consequently accelerating the clearance of the cholesterol-enriched remnants by the liver. In addition, FGF21 reduced body fat, ameliorated glucose tolerance and markedly reduced hepatic steatosis, related to up-regulated hepatic expression of genes involved in fatty acid oxidation and increased hepatic VLDL-triglyceride secretion. Ultimately, FGF21 largely decreased atherosclerotic lesion area, which was mainly explained by the reduction in non-HDL-cholesterol as shown by linear regression analysis, decreased lesion severity, and increased atherosclerotic plaque stability index.
conclusionFGF21 improves hypercholesterolaemia by accelerating triglyceride-rich lipoprotein turnover as a result of activating BAT and browning of WAT, thereby reducing atherosclerotic lesion severity and increasing atherosclerotic lesion stability index. We have thus provided additional support for the clinical use of FGF21 in the treatment of atherosclerotic cardiovascular disease.
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