FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1

Fibroblast growth factor 21 (FGF21)-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1) levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at redu...

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Main Authors: Michelle M. Kwon, Shannon M. O’Dwyer, Robert K. Baker, Scott D. Covey, Timothy J. Kieffer
Format: Article
Language:English
Published: Elsevier 2015-11-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124715011754
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author Michelle M. Kwon
Shannon M. O’Dwyer
Robert K. Baker
Scott D. Covey
Timothy J. Kieffer
author_facet Michelle M. Kwon
Shannon M. O’Dwyer
Robert K. Baker
Scott D. Covey
Timothy J. Kieffer
author_sort Michelle M. Kwon
collection DOAJ
description Fibroblast growth factor 21 (FGF21)-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1) levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT) temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.
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spelling doaj.art-1106a4fc32fc4b6688f80a62613bc5f82022-12-21T18:39:36ZengElsevierCell Reports2211-12472015-11-011381521152710.1016/j.celrep.2015.10.021FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1Michelle M. Kwon0Shannon M. O’Dwyer1Robert K. Baker2Scott D. Covey3Timothy J. Kieffer4Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T 1Z3, CanadaFibroblast growth factor 21 (FGF21)-mediated weight loss and improvements in glucose metabolism correlate with increased uncoupling protein 1 (Ucp1) levels in adipose tissues, suggesting that UCP1-dependent thermogenesis may drive FGF21 action. It was reported that FGF21 is equally effective at reducing body weight and improving glucose homeostasis without UCP1. We find while FGF21 can lower body weight in both wild-type and Ucp1 knockout mice, rapid clearance of glucose by FGF21 is defective in the absence of UCP1. Furthermore, in obese wild-type mice there is a fall in brown adipose tissue (BAT) temperature during glucose excursion, and FGF21 improves glucose clearance while preventing the fall in BAT temperature. In Ucp1 knockout mice, the fall in BAT temperature during glucose excursion and FGF21-mediated changes in BAT temperature are lost. We conclude FGF21-mediated improvements in clearance of a glucose challenge require UCP1 and evoke UCP1-dependent thermogenesis as a method to increase glucose disposal.http://www.sciencedirect.com/science/article/pii/S2211124715011754
spellingShingle Michelle M. Kwon
Shannon M. O’Dwyer
Robert K. Baker
Scott D. Covey
Timothy J. Kieffer
FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
Cell Reports
title FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
title_full FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
title_fullStr FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
title_full_unstemmed FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
title_short FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1
title_sort fgf21 mediated improvements in glucose clearance require uncoupling protein 1
url http://www.sciencedirect.com/science/article/pii/S2211124715011754
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AT robertkbaker fgf21mediatedimprovementsinglucoseclearancerequireuncouplingprotein1
AT scottdcovey fgf21mediatedimprovementsinglucoseclearancerequireuncouplingprotein1
AT timothyjkieffer fgf21mediatedimprovementsinglucoseclearancerequireuncouplingprotein1