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Endocrine Abstracts (2024) 99 EP58 | DOI: 10.1530/endoabs.99.EP58

1Endocrinology Metabolism Consulting, LLC, Hassan Heshmati and Valerie Shaw Endocrine Research, Anthem, AZ, United States; 2Mayo Clinic, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Rochester, MN, United States


Introduction: Fibroblast growth factor 21 (FGF21), a 181 amino acid peptide hormone predominantly produced by the liver, is a member of the endocrine FGF subfamily. It is involved in multiple physiological regulations and plays an important role in several pathological conditions. This literature analysis provides an update on the relevance of FGF21 in health and diseases.

Methods: A systematic search of literature was conducted using the search terms fibroblast growth factor 21, health, diseases, role, and analog.

Results: FGF21 is a stress hormone with various functions. It is involved in the regulation of energy expenditure and metabolism of lipids and glucose by acting on the adipose tissue and central nervous system. In normal subjects, serum FGF21 levels increase gradually with aging. There is an increase in FGF21 secretion under stressful conditions (e.g., fasting status, protein restriction, exercise, several metabolic disorders, kidney diseases, cardiovascular diseases, and sepsis). The increased serum FGF21 levels observed in metabolic disorders (e.g., obesity, nonalcoholic fatty liver disease ‘NAFLD’, and type 2 diabetes) and other conditions (e.g., kidney failure, heart failure, and sepsis) can be associated with a state of FGF21 resistance that is related in part to the presence of high circulating levels of fibroblast activation protein, a protease that inactivates FGF21. In contrast, low serum FGF21 levels have been reported in anorexia nervosa. Serum FGF21 level has the potential to be used as a biomarker in several metabolic disorders (e.g., NAFLD and type 2 diabetes) and other conditions (e.g., heart failure). In view of the multiple FGF21 functions related to energy expenditure and metabolism of lipids and glucose, long-acting FGF21 analogs (e.g., LY2405319, PF-05231023, pegozafermin, AKR-001, and LLF580) have been used in clinical trials for the treatment of various conditions such as obesity, NAFLD, dyslipidemia, and type 2 diabetes. The results of these trials show that FGF21 analogs can reduce body weight, liver fat, circulating lipids, and fasting insulin/insulin resistance. Thus far, these analogs are considered safe and well tolerated.

Conclusions: FGF21 is a peptide hormone synthesized predominantly by the liver and involved in the maintenance of metabolic homeostasis. FGF21 plays an important role in multiple pathological conditions. Serum FGF21 levels are increased in several diseases in a setting of FGF21 resistance. Although FGF21-based therapy appears to be an attractive approach to treat metabolic disorders, additional clinical studies are necessary before practical recommendations can be made for the use of FGF21 analogs.

Volume 99

26th European Congress of Endocrinology

Stockholm, Sweden
11 May 2024 - 14 May 2024

European Society of Endocrinology 

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