The role of FGF21 and its analogs on liver associated diseases

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.

Advancements in metabolic‐associated steatotic liver disease research: Diagnostics, small molecule developments, and future directions

“…It is an Fc‐FGF21 fusion protein with a 3–3.5‐day half‐life, which is substantially longer than that of other FGF21 analogs described above. For a complete analysis of FGF21 and its analogs, readers can access two excellent recent reviews 68,69 …”

“…It is an Fc-FGF21 fusion protein with a 3-3.5-day half-life, which is substantially longer than that of other FGF21 analogs described above. For a complete analysis of FGF21 and its analogs, readers can access two excellent recent reviews 68,69. Glucagon-like peptide-1 receptor agonistsGlucagon-like peptide-1 receptor agonists are a class of medications used to treat type 2 diabetes.…”

GDF11: An emerging therapeutic target for liver diseases and fibrosis

“…It is subject to various chronic diseases caused by metabolic syndromes, obesity, excessive alcohol consumption, viral hepatitis and other chronic conditions. These diseases can lead to liver fibrosis, steatohepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) 2,3 . Globally, liver diseases cause two million deaths each year and can result in severe disabilities 4 .…”

“…Although studies have discovered new therapeutic targets for curing CLDs, enough proper therapeutics have not yet been discovered. Growth differentiation factor 11 (GDF11) protein is one of the emerging targets with beneficial effects on reducing liver fibrosis and cirrhosis 3,6,7 …”

Serum Fibroblast Growth Factor 21 Is Markedly Decreased following Exercise Training in Patients with Biopsy-Proven Nonalcoholic Steatohepatitis

“…Fibroblast growth factor (FGF) 21 is a hepatokine that regulates carbohydrate, lipid, and energy metabolism [ 13 ]. FGF21 is implicated in NAFLD development and disease progression to NASH; in fact, NAFLD and NASH are felt to be FGF21-resistant states, where an elevated serum FGF21 is observed as a compensatory response [ 14 , 15 ]. FGF21 has been identified as a therapeutic target, and early-phase trials in patients with NASH are underway or have been completed [ 16 , 17 , 18 ].…”