FGF19 as a Postprandial, Insulin-Independent Activator of Hepatic Protein and Glycogen Synthesis

By Serkan Kir, S. Beddow, V. Samuel, P. Miller, S. Previs, K. Suino-Powell, H. Xu, Gerald I. Shulman, S. Kliewer, D. Mangelsdorf. Science, 2011

608 citations recorded by the source corpus.

Fibroblast growth factor 19 regulates liver metabolism through a mechanism distinct from that of insulin. Fibroblast growth factor (FGF) 19 is an enterokine synthesized and released when bile acids are taken up into the ileum. We show that FGF19 stimulates hepatic protein and glycogen synthesis but does not induce lipogenesis. The effects of FGF19 are independent of the activity of either insulin or the protein kinase Akt and, instead, are mediated through a mitogen-activated protein kinase signaling pathway that activates components of the protein translation machinery and stimulates glycogen synthase activity. Mice lacking FGF15 (the mouse FGF19 ortholog) fail to properly maintain blood concentrations of glucose and normal postprandial amounts of liver glycogen. FGF19 treatment restored the loss of glycogen in diabetic animals lacking insulin. Thus, FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/441f52655781cab65e179120cd0256ca9b17b5eb

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Citations in the corpus

• Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease. (2013, background): “Treatment with FGF19 also restores glycogen loss in insulin-deficient diabetic animals, activating an insulin-independent endocrine pathway.(25) Obeticholic acid (OCA; INT-747), a 6a-ethyl derivative of chenodeoxycholic acid, is a first-in-class selective FXR agonist with anticholestatic and hepatop”
• Pleiotropic Roles of Bile Acids in Metabolism (2013, background): “More recent studies indicate that FGF15, secreted from the ileum following activation of FXR, has insulin-like actions including inhibition of hepatic gluconeogenesis (Kir et al., 2011; Potthoff et al., 2011; Potthoff et al., 2012; Schaap, 2012).”
• Lipotoxicity and the gut-liver axis in NASH pathogenesis. (2018, background): “been demonstrated to reduce liver steatosis, insulin resistance and ameliorate the metabolic profile [144-147].”
• Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR (2012, background): “Furthermore, FGF19 mediates insulin-independent effects on hepatic glycogen synthesis in the absence of effects on lipogenesi”
• FGF/FGFR signaling in health and disease (2020, background): “accumulation and protein synthesis in the liver of fasted mice, which is independent of insulin action.(541) FGF15/19 also suppresses hepatic metabolic, such as the tricarboxylic acid cycle flux and gluconeogenesis, through inhibiting CREB-PGC-1α (cyclic AMP response element binding protein-peroxiso”