Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice

Spinal cord injury (SCI) results in dysregulation of carbohydrate and lipid metabolism; the underlying cellular and physiological mechanisms remain unclear. Fibroblast growth factor 21 (FGF21) is a circulating protein primarily secreted by the liver that lowers blood glucose levels, corrects abnorma...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Xin-Hua, Graham, Zachary A., Harlow, Lauren, Pan, Jiangping, Azulai, Daniella, Bauman, William A., Yarrow, Joshua, Cardozo, Christopher P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147560/
https://www.ncbi.nlm.nih.gov/pubmed/34046014
http://dx.doi.org/10.3389/fendo.2021.668984
_version_ 1783697655020388352
author Liu, Xin-Hua
Graham, Zachary A.
Harlow, Lauren
Pan, Jiangping
Azulai, Daniella
Bauman, William A.
Yarrow, Joshua
Cardozo, Christopher P.
author_facet Liu, Xin-Hua
Graham, Zachary A.
Harlow, Lauren
Pan, Jiangping
Azulai, Daniella
Bauman, William A.
Yarrow, Joshua
Cardozo, Christopher P.
author_sort Liu, Xin-Hua
collection PubMed
description Spinal cord injury (SCI) results in dysregulation of carbohydrate and lipid metabolism; the underlying cellular and physiological mechanisms remain unclear. Fibroblast growth factor 21 (FGF21) is a circulating protein primarily secreted by the liver that lowers blood glucose levels, corrects abnormal lipid profiles, and mitigates non-alcoholic fatty liver disease. FGF21 acts via activating FGF receptor 1 and ß-klotho in adipose tissue and stimulating release of adiponectin from adipose tissue which in turn signals in the liver and skeletal muscle. We examined FGF21/adiponectin signaling after spinal cord transection in mice fed a high fat diet (HFD) or a standard mouse chow. Tissues were collected at 84 days after spinal cord transection or a sham SCI surgery. SCI reduced serum FGF21 levels and hepatic FGF21 expression, as well as β-klotho and FGF receptor-1 (FGFR1) mRNA expression in adipose tissue. SCI also reduced serum levels and adipose tissue mRNA expression of adiponectin and leptin, two major adipokines. In addition, SCI suppressed hepatic type 2 adiponectin receptor (AdipoR2) mRNA expression and PPARα activation in the liver. Post-SCI mice fed a HFD had further suppression of serum FGF21 levels and hepatic FGF21 expression. Elevated serum free fatty acid (FFA) levels after HFD feeding were observed in post-SCI mice but not in sham-mice, suggesting defective FFA uptake after SCI. Moreover, after SCI several genes that are implicated in insulin’s action had reduced expression in tissues of interest. These findings suggest that downregulated FGF21/adiponectin signaling and impaired responsiveness of adipose tissues to FGF21 may, at least in part, contribute to the overall picture of metabolic dysfunction after SCI.
format Online
Article
Text
id pubmed-8147560
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-81475602021-05-26 Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice Liu, Xin-Hua Graham, Zachary A. Harlow, Lauren Pan, Jiangping Azulai, Daniella Bauman, William A. Yarrow, Joshua Cardozo, Christopher P. Front Endocrinol (Lausanne) Endocrinology Spinal cord injury (SCI) results in dysregulation of carbohydrate and lipid metabolism; the underlying cellular and physiological mechanisms remain unclear. Fibroblast growth factor 21 (FGF21) is a circulating protein primarily secreted by the liver that lowers blood glucose levels, corrects abnormal lipid profiles, and mitigates non-alcoholic fatty liver disease. FGF21 acts via activating FGF receptor 1 and ß-klotho in adipose tissue and stimulating release of adiponectin from adipose tissue which in turn signals in the liver and skeletal muscle. We examined FGF21/adiponectin signaling after spinal cord transection in mice fed a high fat diet (HFD) or a standard mouse chow. Tissues were collected at 84 days after spinal cord transection or a sham SCI surgery. SCI reduced serum FGF21 levels and hepatic FGF21 expression, as well as β-klotho and FGF receptor-1 (FGFR1) mRNA expression in adipose tissue. SCI also reduced serum levels and adipose tissue mRNA expression of adiponectin and leptin, two major adipokines. In addition, SCI suppressed hepatic type 2 adiponectin receptor (AdipoR2) mRNA expression and PPARα activation in the liver. Post-SCI mice fed a HFD had further suppression of serum FGF21 levels and hepatic FGF21 expression. Elevated serum free fatty acid (FFA) levels after HFD feeding were observed in post-SCI mice but not in sham-mice, suggesting defective FFA uptake after SCI. Moreover, after SCI several genes that are implicated in insulin’s action had reduced expression in tissues of interest. These findings suggest that downregulated FGF21/adiponectin signaling and impaired responsiveness of adipose tissues to FGF21 may, at least in part, contribute to the overall picture of metabolic dysfunction after SCI. Frontiers Media S.A. 2021-05-11 /pmc/articles/PMC8147560/ /pubmed/34046014 http://dx.doi.org/10.3389/fendo.2021.668984 Text en Copyright © 2021 Liu, Graham, Harlow, Pan, Azulai, Bauman, Yarrow and Cardozo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Liu, Xin-Hua
Graham, Zachary A.
Harlow, Lauren
Pan, Jiangping
Azulai, Daniella
Bauman, William A.
Yarrow, Joshua
Cardozo, Christopher P.
Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice
title Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice
title_full Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice
title_fullStr Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice
title_full_unstemmed Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice
title_short Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice
title_sort spinal cord injury reduces serum levels of fibroblast growth factor-21 and impairs its signaling pathways in liver and adipose tissue in mice
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147560/
https://www.ncbi.nlm.nih.gov/pubmed/34046014
http://dx.doi.org/10.3389/fendo.2021.668984
work_keys_str_mv AT liuxinhua spinalcordinjuryreducesserumlevelsoffibroblastgrowthfactor21andimpairsitssignalingpathwaysinliverandadiposetissueinmice
AT grahamzacharya spinalcordinjuryreducesserumlevelsoffibroblastgrowthfactor21andimpairsitssignalingpathwaysinliverandadiposetissueinmice
AT harlowlauren spinalcordinjuryreducesserumlevelsoffibroblastgrowthfactor21andimpairsitssignalingpathwaysinliverandadiposetissueinmice
AT panjiangping spinalcordinjuryreducesserumlevelsoffibroblastgrowthfactor21andimpairsitssignalingpathwaysinliverandadiposetissueinmice
AT azulaidaniella spinalcordinjuryreducesserumlevelsoffibroblastgrowthfactor21andimpairsitssignalingpathwaysinliverandadiposetissueinmice
AT baumanwilliama spinalcordinjuryreducesserumlevelsoffibroblastgrowthfactor21andimpairsitssignalingpathwaysinliverandadiposetissueinmice
AT yarrowjoshua spinalcordinjuryreducesserumlevelsoffibroblastgrowthfactor21andimpairsitssignalingpathwaysinliverandadiposetissueinmice
AT cardozochristopherp spinalcordinjuryreducesserumlevelsoffibroblastgrowthfactor21andimpairsitssignalingpathwaysinliverandadiposetissueinmice