Fibroblast Growth Factor-Based Pharmacotherapies for the Treatment of Obesity-Related Metabolic Complications.
Annu Rev Pharmacol Toxicol
; 63: 359-382, 2023 Jan 20.
Article
em En
| MEDLINE
| ID: mdl-36100222
ABSTRACT
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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Hepatopatia Gordurosa não Alcoólica
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article