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Publication
Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does
not regulate glucose homeostasis.
Authors Watanabe M, Singhal G, Fisher FM, Beck TC, Morgan DA, Socciarelli F, Mather ML,
Risi R, Bourke J, Rahmouni K, McGuinness OP, Flier JS, Maratos-Flier E
Submitted By Submitted Externally on 5/28/2020
Status Published
Journal Endocrine
Year 2020
Date Published 1/1/2020
Volume : Pages 67 : 95 - 108
PubMed Reference 31728756
Abstract Fibroblast growth factor 21 (FGF21) is expressed in several metabolically active
tissues, including liver, fat, and acinar pancreas, and has pleiotropic effects
on metabolic homeostasis. The dominant source of FGF21 in the circulation is the
liver., To analyze the physiological functions of hepatic FGF21, we generated a
hepatocyte-specific knockout model (LKO) by mating albumin-Cre mice with FGF21
flox/flox (fl/fl) mice and challenged it with different nutritional models.,
Mice fed a ketogenic diet typically show increased energy expenditure; this
effect was attenuated in LKO mice. LKO on KD also developed hepatic pathology
and altered hepatic lipid homeostasis. When evaluated using
hyperinsulinemic-euglycemic clamps, glucose infusion rates, hepatic glucose
production, and glucose uptake were similar between fl/fl and LKO DIO mice., We
conclude that liver-derived FGF21 is important for complete adaptation to
ketosis but has a more limited role in the regulation of glycemic homeostasis.




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