The regulation of FGF21 gene expression by metabolic factors and nutrients

Anjeza Erickson, Régis Moreau

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Fibroblast growth factor 21 (FGF21) gene expression is altered by a wide array of physiological, metabolic, and environmental factors. Among dietary factors, high dextrose, low protein, methionine restriction, short-chain fatty acids (butyric acid and lipoic acid), and all-trans-retinoic acid were repeatedly shown to induce FGF21 expression and circulating levels. These effects are usually more pronounced in liver or isolated hepatocytes than in adipose tissue or isolated fat cells. Although peroxisome proliferator-activated receptor α (PPARα) is a key mediator of hepatic FGF21 expression and function, including the regulation of gluconeogenesis, ketogenesis, torpor, and growth inhibition, there is increasing evidence of PPARα-independent transactivation of the FGF21 gene by dietary molecules. FGF21 expression is believed to follow the circadian rhythm and be placed under the control of first order clock-controlled transcription factors, retinoic acid receptor-related orphan receptors (RORs) and nuclear receptors subfamily 1 group D (REV-ERBs), with FGF21 rhythm being anti-phase to REV-ERBs. Key metabolic hormones such as glucagon, insulin, and thyroid hormone have presumed or clearly demonstrated roles in regulating FGF21 transcription and secretion. The control of the FGF21 gene by glucagon and insulin appears more complex than first anticipated. Some discrepancies are noted and will need continued studies. The complexity in assessing the significance of FGF21 gene expression resides in the difficulty to ascertain (i) when transcription results in local or systemic increase of FGF21 protein; (ii) if FGF21 is among the first or second order genes upregulated by physiological, metabolic, and environmental stimuli, or merely an epiphenomenon; and (iii) whether FGF21 may have some adverse effects alongside beneficial outcomes.

Original languageEnglish (US)
Article number20160016
JournalHormone Molecular Biology and Clinical Investigation
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Gene Expression
Food
Peroxisome Proliferator-Activated Receptors
Glucagon
fibroblast growth factor 21
Torpor
Insulin
Thioctic Acid
Retinoic Acid Receptors
Gene Order
Butyric Acid
Gluconeogenesis
Volatile Fatty Acids
Liver
Cytoplasmic and Nuclear Receptors
Circadian Rhythm
Tretinoin
Thyroid Hormones
Adipocytes
Methionine

Keywords

  • butyric acid
  • curcumin
  • lipoic acid
  • methionine
  • retinoic acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Endocrinology

Cite this

The regulation of FGF21 gene expression by metabolic factors and nutrients. / Erickson, Anjeza; Moreau, Régis.

In: Hormone Molecular Biology and Clinical Investigation, Vol. 30, No. 1, 20160016, 01.01.2017.

Research output: Contribution to journalReview article

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