Endocrinol Metab.  2014 Jun;29(2):105-111. 10.3803/EnM.2014.29.2.105.

Transcriptional Regulation of Fibroblast Growth Factor 21 Expression

• Bae KH
• Kim JG
• Park KG

• KMID: 2169412
• DOI: http://doi.org/10.3803/EnM.2014.29.2.105

Abstract

Fibroblast growth factor 21 (FGF21) is an attractive target for treating metabolic disease due to its wide-ranging beneficial effects on glucose and lipid metabolism. Circulating FGF21 levels are increased in insulin-resistant states; however, endogenous FGF21 fails to improve glucose and lipid metabolism in obesity, suggesting that metabolic syndrome is an FGF21-resistant state. Therefore, transcription factors for FGF21 are potential drug targets that could increase FGF21 expression in obesity and reduce FGF21 resistance. Despite many studies on the metabolic effects of FGF21, the transcriptional regulation of FGF21 gene expression remains controversial and is not fully understood. As the FGF21 transcription factor pathway is one of the most promising targets for the treatment of metabolic syndrome, further investigation of FGF21 transcriptional regulation is required.

Keyword

Fibroblast growth factor 21; Transcription factors; Diabetes mellitus; Insulin resistance

MeSH Terms

Diabetes Mellitus
Fibroblast Growth Factors*
Gene Expression
Glucose
Insulin Resistance
Lipid Metabolism
Metabolic Diseases
Obesity
Transcription Factors
Fibroblast Growth Factors
Glucose
Transcription Factors

Figure

• 

  Fig. 1 Endocrine, autocrine, and pharmacological actions of fibroblast growth factor 21 (FGF21) and its transcription factors. Fasting induces FGF21 expression in the liver through several transcription factors, and FGF21 acts as an endocrine hormone to induce ketogenesis, gluconeogenesis, fatty acid oxidation, and torpor and to inhibit somatic growth. In the fed state, FGF21 expression in white adipose tissue is induced by peroxisome proliferator-activated receptor gamma (PPARγ), and FGF21 acts through an autocrine or paracrine mechanism to increase PPARγ activity. Pharmacological administration of recombinant FGF21 (rFGF21) affects multiple tissues and has beneficial effects on lipid and glucose metabolism in metabolic disease, including obesity and diabetes mellitus. Recent studies have demonstrated that several metabolically-active drugs produce hepatic FGF21, suggesting a relationship between their actions in glucose and lipid metabolism with the up-regulation of FGF21 production. CREBH, cyclic adenosine monophosphate (AMP) response element-binding protein H; RARβ, retinoic acid (RA) receptor β; RORα, RA receptor-related orphan receptor α; Nur77, nerve growth factor IB; TRβ, thyroid hormone receptor β; T2DM, type 2 diabetes mellitus.

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