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Fibroblast growth factor-based pharmacotherapies for the treatment of obesity-related metabolic complications
Open accessAbstract
The fibroblast growth factor (FGF) family, which comprises 22 structurally related proteins, plays diverse roles in cell proliferation, differentiation, development, and metabolism. Among them, two classical members (FGF1 and FGF4) and two endocrine members (FGF19 and FGF21) are important regulators of whole-body energy homeostasis, glucose/lipid metabolism, and insulin sensitivity. Preclinical studies have consistently demonstrated the therapeutic benefits of these FGFs for the treatment of obesity, diabetes, dyslipidemia, and nonalcoholic steatohepatitis (NASH). Several genetically engineered FGF19 and FGF21 analogs with improved pharmacodynamic and pharmacokinetic properties have been developed and progressed into various stages of clinical trials. These FGF analogs are effective in alleviating hepatic steatosis, steatohepatitis, and liver fibrosis in biopsy-confirmed NASH patients, whereas their antidiabetic and antiobesity effects are mildand vary greatly in different clinical trials. This review summarizes recent advances in biopharmaceutical development of FGF-based therapies against obesity-related metabolic complications, highlights major challenges in clinical implementation, and discusses possible strategies to overcome these hurdles.
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Metadata
- Authors
- Jin, L., Yang, R., Geng, L., & Xu, A.
- Affiliations
- University of Hong Kong (HK)
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2023-01-20
- Volume
- 63
- Issue
- 1
- Pages
- 359-382
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- OpenAlex
- W4295758313
- Cited by
- 71
- References
- 40
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 27 · 2023: 10
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion, cc-by-nc-nd)
- Funders
- National Natural Science Foundation of China (82161138026, (82070860, 32000816)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Peptidase Inhibition and Analysis
- Keywords
- fibroblast growth factor, FGF1, FGF4, FGF19, FGF21, obesity, nonalcoholic steatohepatitis, hepatic steatosis, liver fibrosis, diabetes mellitus, dyslipidemia, energy homeostasis, insulin sensitivity, glycolipid metabolism, biopharmaceutical development, clinical trials
- MeSH terms
- Fibroblast Growth Factors, Humans, Hypoglycemic Agents, Insulin Resistance, Obesity, Non-alcoholic Fatty Liver Disease
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