, Volume 49, Issue 11, pp 1081–1089 | Cite as

Fibroblast Growth Factor-21 and the Beneficial Effects of Long-Chain n-3 Polyunsaturated Fatty Acids

  • Joan Villarroya
  • Pavel Flachs
  • Ibon Redondo-Angulo
  • Marta Giralt
  • Dasa Medrikova
  • Francesc Villarroya
  • Jan Kopecky
  • Anna PlanavilaEmail author
Original Article


Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) in the diet protect against insulin resistance and obesity. Fibroblast growth factor-21 (Fgf21) is a hormonal factor released mainly by the liver that has powerful anti-diabetic effects. Here, we tested whether the beneficial metabolic effects of LC n-3 PUFA involve the induction of Fgf21. C57BL/6 J mice were exposed to an obesogenic, corn-oil-based, high-fat diet (cHF), or a diet in which corn oil was replaced with a fish-derived LC n-3 PUFA concentrate (cHF + F) using two experimental settings: short-term (3 weeks) and long-term treatment (8 weeks). CHF + F reduced body weight gain, insulinemia, and triglyceridemia compared to cHF. cHF increased plasma Fgf21 levels and hepatic Fgf21 gene expression compared with controls, but these effects were less pronounced or absent in cHF + F-fed mice. In contrast, hepatic expression of peroxisome proliferator-activated receptor (PPAR)-α target genes were more strongly induced by cHF + F than cHF, especially in the short-term treatment setting. The expression of genes encoding Fgf21, its receptors, and Fgf21 targets was unaltered by short-term LC n-3 PUFA treatment, with the exception of Ucp1 (uncoupling protein 1) and adiponectin genes, which were specifically up-regulated in white fat. In the long-term treatment setting, the expression of Fgf21 target genes and receptors was not differentially affected by LC n-3 PUFA. Collectively, our findings indicate that increased Fgf21 levels do not appear to be a major mechanism through which LC n-3 PUFA ameliorates high-fat-diet-associated metabolic disorders.


Fibroblast growth factor-21 Long-chain n-3 polyunsaturated fatty acids 



Acyl-coenzyme A oxidase


Brown adipose tissue


Carnitine palmitoyltransferase-2


Docosahexaenoic acid


Bifunctional enzyme or enoyl-coenzyme A, hydratase/3-hydroxyacyl coenzyme A dehydrogenase


Eicosapentaenoic acid


Fibroblast growth factor-21


Fibroblast growth factor receptor


Glucose transporter-1


Medium chain acyl-CoA dehydrogenase




Peroxisome proliferator-activated receptor


Polyunsaturated fatty acids


Uncoupling protein-1


White adipose tissue



Supported by Ministerio de Ciencia e Innovación (SAF2011-23636) and Instituto de Salud Carlos III (PI11/00376) Spain; and the Czech Science Foundation (13-00871S), Czech Republic. IR-A was supported by a pre-doctoral fellowship from Gobierno Vasco (Programa de Formación de Investigadores del DEUI).

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

11745_2014_3948_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)


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Copyright information

© AOCS 2014

Authors and Affiliations

  • Joan Villarroya
    • 1
    • 2
  • Pavel Flachs
    • 3
  • Ibon Redondo-Angulo
    • 1
    • 4
  • Marta Giralt
    • 1
    • 4
  • Dasa Medrikova
    • 3
  • Francesc Villarroya
    • 1
    • 4
  • Jan Kopecky
    • 3
  • Anna Planavila
    • 1
    • 4
    Email author
  1. 1.Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB)University of BarcelonaBarcelonaSpain
  2. 2.Hospital de la Santa Creu i Sant PauBarcelonaSpain
  3. 3.Department of Adipose Tissue BiologyInstitute of Physiology of Academy of Sciences of the Czech RepublicPragueCzech Republic
  4. 4.CIBER Fisiopatologia de la Obesidad y NutriciónBarcelonaSpain

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