The role of FGF21 and its analogs on liver associated diseases

Kimia Falamarzi; Mahdi Malekpour; Mobin Fallah Tafti; Negar Azarpira; Mehrdad Behboodi; Mohammad Zarei

doi:10.3389/fmed.2022.967375

The role of FGF21 and its analogs on liver associated diseases

Front Med (Lausanne). 2022 Nov 15:9:967375. doi: 10.3389/fmed.2022.967375. eCollection 2022.

Authors

Kimia Falamarzi^{1

2}, Mahdi Malekpour^{1

2}, Mobin Fallah Tafti^{1

2}, Negar Azarpira², Mehrdad Behboodi^{1

2}, Mohammad Zarei^{3

4}

Affiliations

¹ Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.
² Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
³ Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
⁴ John B. Little Center for Radiation Sciences, Harvard T. H. Chan School of Public Health, Boston, MA, United States.

Abstract

Fibroblast growth factor 21 (FGF21), a member of fibroblast growth factor family, is a hormone-like growth factor that is synthesized mainly in the liver and adipose tissue. FGF21 regulates lipid and glucose metabolism and has substantial roles in decreasing lipogenesis and increasing hepatic insulin sensitivity which causing lipid profile improvement. FGF21 genetic variations also affect nutritional and addictive behaviors such as smoking and alcohol consumption and eating sweets. The role of FGF21 in metabolic associated diseases like diabetes mellitus had been confirmed previously. Recently, several studies have demonstrated a correlation between FGF21 and liver diseases. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease worldwide. NAFLD has a wide range from simple steatosis to steatohepatitis with or without fibrosis and cirrhosis. Elevated serum levels of FGF21 associated with NAFLD and its pathogenesis. Alcoholic fatty liver disease (AFLD), another condition that cause liver injury, significantly increased FGF21 levels as a protective factor; FGF21 can reverse the progression of AFLD and can be a potential therapeutic agent for it. Also, NAFLD and AFLD are the most important risk factors for hepatocellular carcinoma (HCC) which is the fourth deadliest cancer in the world. Several studies showed that lack of FGF21 induced oncogenic condition and worsened HCC. In this review article, we intend to discuss different aspects of FGF21 in NAFLD, AFLD and HCC; including the role of FGF21 in pathophysiology of these conditions, the effects of FGF21 mutations, the possible use of the FGF21 as a biomarker in different stages of these diseases, as well as the usage of FGF21 and its analog molecules in the treatment of these diseases.

Keywords: FGF21 analogs; FGF21 polymorphism; HCC; MAFLDs; NAFLD; NASH; fibroblast growth factor 21 (FGF21).

Publication types

Review