Journal article
Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis
Endocrine, Vol.67(1), pp.95-108
01/2020
DOI: 10.1007/s12020-019-02124-3
PMCID: PMC7948212
PMID: 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.
Details
- Title: Subtitle
- Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis
- Creators
- Mikiko Watanabe - Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161, Rome, ItalyGarima Singhal - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USAFfolliott M Fisher - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USAThomas C Beck - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USADonald A Morgan - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAFabio Socciarelli - Department of Oncology-Pathology, Karolinska Institutet, 171 76, Stockholm, SwedenMarie L Mather - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USARenata Risi - Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161, Rome, ItalyJared Bourke - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USAKamal Rahmouni - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USAOwen P McGuinness - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USAJeffrey S Flier - Department of Neurobiology, Harvard Medical School, Boston, MA, 02215, USAEleftheria Maratos-Flier - Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. emaratos@bidmc.harvard.edu
- Resource Type
- Journal article
- Publication Details
- Endocrine, Vol.67(1), pp.95-108
- DOI
- 10.1007/s12020-019-02124-3
- PMID
- 31728756
- PMCID
- PMC7948212
- NLM abbreviation
- Endocrine
- ISSN
- 1355-008X
- eISSN
- 1559-0100
- Publisher
- United States
- Grant note
- R01 DK078188 / NIDDK NIH HHS P30 DK034854 / NIDDK NIH HHS P30 DK020593 / NIDDK NIH HHS P60 DK020593 / NIDDK NIH HHS R01 DK043748 / NIDDK NIH HHS 14EIA18860041 / American Heart Association R01 DK028082 / NIDDK NIH HHS P30 DK057521 / NIDDK NIH HHS U24 DK059637 / NIDDK NIH HHS P30 DK046200 / NIDDK NIH HHS P01 HL084207 / NHLBI NIH HHS R37 DK028082 / NIDDK NIH HHS P30 DK054759 / NIDDK NIH HHS DK028082 / NIH HHS
- Language
- English
- Date published
- 01/2020
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984070683702771
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