The role of fibroblast growth factor 19 in the pathogenesis of nonalcoholic fatty liver disease

ABSTRACT

Introduction

Nonalcoholic fatty liver disease (NAFLD) has emerged as the predominant cause of chronic liver injury worldwide. Bile acids and their receptors are profoundly implicated in the pathogenesis of NAFLD and its progression to nonalcoholic steatohepatitis and cirrhosis.

Areas covered

We conducted extensive literature search using PubMed database, and we summarized the relevant literature. We provided an overview of the fibroblast growth factor 19 (FGF-19)–farnesoid X receptor (FXR) axis and summarized the latest findings derived from animal and human studies concerning the impact of FGF-19 on NAFLD.

Expert opinion

FGF-19, a nutritionally regulated endocrine post-prandial hormone, governs bile acid metabolism, lipid oxidation, lipogenesis, and energy homeostasis. As no approved medication for NAFLD exists, FGF-19 seems to be a propitious therapeutic opportunity for NAFLD, since its administration was associated with ameliorated results in hepatic steatosis, liver inflammation and fibrosis. Furthermore, promising results have been derived from clinical trials concerning the beneficial efficacy of FGF-19 on histological findings and laboratory parameters of NAFLD. However, we should bear in mind the pleiotropic effects of FGF-19 on various metabolically active tissues along with its potential tumorigenic reservoir. Further clinical research is required to determine the clinical application of FGF-19-based therapies on NAFLD.

KEYWORDS:

• Nonalcoholic fatty liver disease
• bile acids
• fibroblast growth factor-19
• fatty acid oxidation
• lipid metabolism
• clinical limitations

Article highlights

• Non-alcoholic fatty liver disease (NAFLD) is already the predominant cause of chronic liver injury worldwide and is projected to emerge as the leading cause for liver transplantation in the near future.

• Fibroblast growth factor 19 (FGF-19) is a post-prandial endocrine hormone and chief regulator of bile acid homeostasis and metabolism, key mechanisms of NAFLD pathogenesis and progression.

• Animal studies have highlighted the effects of FGF-19 administration against liver fat accumulation, inflammation, and liver fibrosis, while current human clinical trials evaluated the potential clinical applicability of FGF-19 with promising results.

• FGF-19 stimulates fatty acid oxidation while inhibiting insulin-mediated lipogenesis. Also, it stimulates glycogen and protein synthesis and inhibits gluconeogenesis in an insulin-independent manner and without activating lipogenesis, which may have important clinical implications for patients with advanced type 2 diabetes, who are on insulin therapy, in the context of NAFLD.

• The definition of the lipid-associated effects of FGF-19 administration due to the pleiotropic signaling along with its potential tumorigenic reservoir are considered as limitations for the FGF-19 targeted therapies for NAFLD.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.