FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance

FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance

FGF21 is a key metabolic regulator modulating physiological processes and its pharmacological administration improves metabolic profile in preclinical species and humans. We used native-FGF21 and a long-acting FGF21 (PF-05231023), to determine the contribution of liver and brown adipose tissue (BAT)...

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Main Authors: Bernardo, Barbara, Lu, Min, Bandyopadhyay, Gautam, Li, Pingping, Zhou, Yingjiang, Huang, Jie, Levin, Nancy, Tomas, Eva M., Calle, Roberto A., Erion, Derek M., Rolph, Timothy P., Brenner, Martin, Talukdar, Saswata
Format: Online
Language:English
Published: Nature Publishing Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495598/
id pubmed-4495598
recordtype oai_dc
spelling pubmed-44955982015-07-13 FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance Bernardo, Barbara Lu, Min Bandyopadhyay, Gautam Li, Pingping Zhou, Yingjiang Huang, Jie Levin, Nancy Tomas, Eva M. Calle, Roberto A. Erion, Derek M. Rolph, Timothy P. Brenner, Martin Talukdar, Saswata Article FGF21 is a key metabolic regulator modulating physiological processes and its pharmacological administration improves metabolic profile in preclinical species and humans. We used native-FGF21 and a long-acting FGF21 (PF-05231023), to determine the contribution of liver and brown adipose tissue (BAT) towards metabolic improvements in Zucker rats and DIO mice (DIOs). FGF21 improved glucose tolerance and liver insulin sensitivity in Zuckers without affecting BW and improved liver function by decreased lipogenesis, increased fatty acid oxidation and improved insulin signaling. Through detailed lipidomic analyses of liver metabolites in DIOs, we demonstrate that FGF21 favorably alters liver metabolism. We observed a dose-dependent increase of [18F]-FDG-glucose uptake in interscapular BAT (iBAT) of DIOs upon FGF21 administration. Upon excision of iBAT (X-BAT) and administration of FGF21 to mice housed at 80 °F or 72 °F, the favorable effects of FGF21 on BW and glucose excursion were fully retained in both sham and X-BAT animals. Taken together, we demonstrate the liver as an organ that integrates the actions of FGF21 and provide metabolic benefits of FGF21 in Zucker rats and DIOs. Finally, our data demonstrates iBAT does not play a role in mediating favorable metabolic effects of FGF21 administration in DIOs housed at 80 °F or 72 °F. Nature Publishing Group 2015-07-08 /pmc/articles/PMC4495598/ /pubmed/26153793 http://dx.doi.org/10.1038/srep11382 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Bernardo, Barbara
Lu, Min
Bandyopadhyay, Gautam
Li, Pingping
Zhou, Yingjiang
Huang, Jie
Levin, Nancy
Tomas, Eva M.
Calle, Roberto A.
Erion, Derek M.
Rolph, Timothy P.
Brenner, Martin
Talukdar, Saswata
spellingShingle Bernardo, Barbara
Lu, Min
Bandyopadhyay, Gautam
Li, Pingping
Zhou, Yingjiang
Huang, Jie
Levin, Nancy
Tomas, Eva M.
Calle, Roberto A.
Erion, Derek M.
Rolph, Timothy P.
Brenner, Martin
Talukdar, Saswata
FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance
author_facet Bernardo, Barbara
Lu, Min
Bandyopadhyay, Gautam
Li, Pingping
Zhou, Yingjiang
Huang, Jie
Levin, Nancy
Tomas, Eva M.
Calle, Roberto A.
Erion, Derek M.
Rolph, Timothy P.
Brenner, Martin
Talukdar, Saswata
author_sort Bernardo, Barbara
title FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance
title_short FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance
title_full FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance
title_fullStr FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance
title_full_unstemmed FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance
title_sort fgf21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance
description FGF21 is a key metabolic regulator modulating physiological processes and its pharmacological administration improves metabolic profile in preclinical species and humans. We used native-FGF21 and a long-acting FGF21 (PF-05231023), to determine the contribution of liver and brown adipose tissue (BAT) towards metabolic improvements in Zucker rats and DIO mice (DIOs). FGF21 improved glucose tolerance and liver insulin sensitivity in Zuckers without affecting BW and improved liver function by decreased lipogenesis, increased fatty acid oxidation and improved insulin signaling. Through detailed lipidomic analyses of liver metabolites in DIOs, we demonstrate that FGF21 favorably alters liver metabolism. We observed a dose-dependent increase of [18F]-FDG-glucose uptake in interscapular BAT (iBAT) of DIOs upon FGF21 administration. Upon excision of iBAT (X-BAT) and administration of FGF21 to mice housed at 80 °F or 72 °F, the favorable effects of FGF21 on BW and glucose excursion were fully retained in both sham and X-BAT animals. Taken together, we demonstrate the liver as an organ that integrates the actions of FGF21 and provide metabolic benefits of FGF21 in Zucker rats and DIOs. Finally, our data demonstrates iBAT does not play a role in mediating favorable metabolic effects of FGF21 administration in DIOs housed at 80 °F or 72 °F.
publisher Nature Publishing Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4495598/
_version_ 1613245566281580544

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