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FGF21 activates AMPK signaling: impact on metabolic regulation and the aging process

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Abstract

Fibroblast growth factor 21 (FGF21) has a significant role in the regulation of energy metabolism, e.g., in the control of systemic glucose and lipid metabolism. For instance, FGF21 enhances insulin sensitivity, increases glucose uptake, and thus can decrease serum hyperglycemia, while it also increases lipid oxidation and inhibits lipogenesis. AMP-activated protein kinase (AMPK) is a tissue energy sensor involved in maintaining the energy balance and tissue integrity. It is known that AMPK signaling generates an energy metabolic profile which displays a remarkable overlap with that of FGF21. There is convincing evidence that endocrine FGF21 signaling activates the AMPK pathway, either directly through FGFR1/β-klotho signaling or indirectly by stimulating the secretion of adiponectin and corticosteroids, which consequently can activate AMPK signaling in their target tissues. By activating AMPK, FGF21 can promote a healthy aging process and thus extend mammalian lifespan. We will examine the signaling mechanisms through which FGF21 can activate the AMPK pathway and then discuss the significance of the close connection between FGF21 and AMPK signaling in the control of metabolic disorders and the aging process.

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Acknowledgments

This study was financially supported by the grants from the Academy of Finland, the University of Eastern Finland, VTR funding from Kuopio University Hospital, the Finnish Cultural Foundation, the Finnish Eye Foundation, and the Alfred Kordelin Foundation. The authors thank Dr. Ewen MacDonald for checking the language of the manuscript.

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Authors and Affiliations

  1. Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland

    Antero Salminen

  2. School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland

    Anu Kauppinen

  3. Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland

    Kai Kaarniranta

  4. Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, FI-70029 KYS, Kuopio, Finland

    Kai Kaarniranta

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  1. Antero Salminen
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  2. Anu Kauppinen
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  3. Kai Kaarniranta
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Correspondence to Antero Salminen.

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Salminen, A., Kauppinen, A. & Kaarniranta, K. FGF21 activates AMPK signaling: impact on metabolic regulation and the aging process. J Mol Med 95, 123–131 (2017). https://doi.org/10.1007/s00109-016-1477-1

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  • DOI: https://doi.org/10.1007/s00109-016-1477-1

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