Ontology highlight
ABSTRACT: Background
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.Objective and methods
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.Results
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.Conclusions
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.
SUBMITTER: Watanabe M
PROVIDER: S-EPMC7948212 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Watanabe Mikiko M Singhal Garima G Fisher Ffolliott M FM Beck Thomas C TC Morgan Donald A DA Socciarelli Fabio F Mather Marie L ML Risi Renata R Bourke Jared J Rahmouni Kamal K McGuinness Owen P OP Flier Jeffrey S JS Maratos-Flier Eleftheria E
Endocrine 20191114 1
<h4>Background</h4>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.<h4>Objective and methods</h4>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 differ ...[more]