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

Lipids volume 49, pages 1081–1089 (2014)Cite this article

Abstract

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.

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Abbreviations

Acox1:

Acyl-coenzyme A oxidase

BAT:

Brown adipose tissue

CPT2:

Carnitine palmitoyltransferase-2

DHA:

Docosahexaenoic acid

Ehhadh:

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

EPA:

Eicosapentaenoic acid

FGF21:

Fibroblast growth factor-21

FGFR:

Fibroblast growth factor receptor

Slc2a1:

Glucose transporter-1

Acadm:

Medium chain acyl-CoA dehydrogenase

Ppargc1a:

PPARgamma-coactivator-1α

PPAR:

Peroxisome proliferator-activated receptor

PUFA:

Polyunsaturated fatty acids

UCP1:

Uncoupling protein-1

WAT:

White adipose tissue

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Acknowledgments

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.

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Authors and Affiliations

  1. Departament de Bioquimica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB), University of Barcelona, Barcelona, Spain

    Joan Villarroya, Ibon Redondo-Angulo, Marta Giralt, Francesc Villarroya & Anna Planavila

  2. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Joan Villarroya

  3. Department of Adipose Tissue Biology, Institute of Physiology of Academy of Sciences of the Czech Republic, v.v.i, Prague, Czech Republic

    Pavel Flachs, Dasa Medrikova & Jan Kopecky

  4. CIBER Fisiopatologia de la Obesidad y Nutrición, Barcelona, Spain

    Ibon Redondo-Angulo, Marta Giralt, Francesc Villarroya & Anna Planavila

Authors
  1. Joan Villarroya
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  2. Pavel Flachs
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  3. Ibon Redondo-Angulo
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  4. Marta Giralt
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  6. Francesc Villarroya
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  7. Jan Kopecky
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  8. Anna Planavila
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Correspondence to Anna Planavila.

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Villarroya, J., Flachs, P., Redondo-Angulo, I. et al. Fibroblast Growth Factor-21 and the Beneficial Effects of Long-Chain n-3 Polyunsaturated Fatty Acids. Lipids 49, 1081–1089 (2014). https://doi.org/10.1007/s11745-014-3948-x

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Keywords

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