The role of FGF19 in metabolic regulation: insights from preclinical models to clinical trials

Am J Physiol Endocrinol Metab. 2024 Sep 1;327(3):E279-E289. doi: 10.1152/ajpendo.00156.2024. Epub 2024 Jul 17.

Abstract

Fibroblast growth factor 19 (FGF19) is a hormone synthesized in enterocytes in response to bile acids. This review explores the pivotal role of FGF19 in metabolism, addressing the urgent global health concern of obesity and its associated pathologies, notably type 2 diabetes. The intriguing inverse correlation between FGF19 and body mass or visceral adiposity, as well as its rapid increase following bariatric surgery, emphasizes its potential as a therapeutic target. This article meticulously examines the impact of FGF19 on metabolism by gathering evidence primarily derived from studies conducted in animal models or cell lines, using both FGF19 treatment and genetic modifications. Overall, these studies demonstrate that FGF19 has antidiabetic and antiobesogenic effects. A thorough examination across metabolic tissues, including the liver, adipose tissue, skeletal muscle, and the central nervous system, is conducted, unraveling the intricate interplay of FGF19 across diverse organs. Moreover, we provide a comprehensive overview of clinical trials involving an FGF19 analog called aldafermin, emphasizing promising results in diseases such as nonalcoholic steatohepatitis and diabetes. Therefore, we aim to foster a deeper understanding of FGF19 role and encourage further exploration of its clinical applications, thereby advancing the field and offering innovative approaches to address the escalating global health challenge of obesity and related metabolic conditions.

Keywords: FGF19; diabetes; metabolic syndrome; metabolism; obesity.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Fibroblast Growth Factors* / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Obesity* / metabolism

Substances

  • Fibroblast Growth Factors
  • FGF19 protein, human
  • Hypoglycemic Agents