FGF21 activates AMPK signaling: impact on metabolic regulation and the aging process.
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.
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland. antero.salminen@uef.fi.
Antero
A
Salminen
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.
Anu
A
Kauppinen
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, FI-70211, Kuopio, Finland.|Department of Ophthalmology, Kuopio University Hospital, P.O. Box 100, FI-70029 KYS, Kuopio, Finland.
Kai
K
Kaarniranta
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000502:physiology; D008136:Longevity / Q000502:physiology*; D051379:Mice
D052242:Adiponectin; D000305:Adrenal Cortex Hormones; D008055:Lipids; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D055372:AMP-Activated Protein Kinases; D005947:Glucose
AMPK; Adiponectin; Ageing; FGF21; Klotho; Metabolic disorders
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