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

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• 作者：Antero Salminen ; Anu Kauppinen ; Kai Kaarniranta
• 关键词：Adiponectin ; Ageing ; AMPK ; FGF21 ; Klotho ; Metabolic disorders
• 刊名：Journal of Molecular Medicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：95
• 期：2
• 页码：123-131
• 全文大小：
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Molecular Medicine; Human Genetics; Internal Medicine;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-1440
• 卷排序：95

文摘

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.