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Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21

Objective: Ileal transposition (IT) surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21) is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with t...

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Autores principales: Yan, Kemin, Chen, Weijie, Zhu, Huijuan, Lin, Guole, Pan, Hui, Li, Naishi, Wang, Linjie, Yang, Hongbo, Liu, Meijuan, Gong, Fengying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854974/
https://www.ncbi.nlm.nih.gov/pubmed/29593555
http://dx.doi.org/10.3389/fphys.2018.00191
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author Yan, Kemin
Chen, Weijie
Zhu, Huijuan
Lin, Guole
Pan, Hui
Li, Naishi
Wang, Linjie
Yang, Hongbo
Liu, Meijuan
Gong, Fengying
author_facet Yan, Kemin
Chen, Weijie
Zhu, Huijuan
Lin, Guole
Pan, Hui
Li, Naishi
Wang, Linjie
Yang, Hongbo
Liu, Meijuan
Gong, Fengying
author_sort Yan, Kemin
collection PubMed
description Objective: Ileal transposition (IT) surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21) is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK) rats. Methods: Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group) or sham surgery without the ileum transposition (Sham-IT group). Rats in the no surgery group did not receive any surgical intervention. Six weeks later, body weight, fat mass, fasting blood glucose (FBG), and serum levels of FGF21 and leptin were measured. The expression of the FGF21 signaling pathway and white adipose tissue (WAT) browning-related genes in the WAT and liver were evaluated by real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blot. Results: IT surgery significantly decreased the body weights and FBG levels and increased the insulin sensitivity of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats decreased by 26.3 and 61.7%, respectively (all P < 0.05). The mRNA levels of fibroblast growth factor receptor 1 (FGFR1) and its co-receptor β klotho (KLB) in the perirenal WAT (pWAT) of the IT rats were 1.4- and 2.4-fold that of the Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the Sham-IT rats (all P < 0.05). In accordance with the pWAT, the protein levels of FGFR1 and KLB in the epididymal WAT (eWAT) of the IT rats notably increased to 3.0- and 3.9-fold of the Sham-IT rats (P < 0.05). Furthermore, uncoupling protein 1 (UCP1) protein levels in the eWAT and pWAT of the IT rats also increased to 2.2- and 2.3-fold of the Sham-IT rats (P < 0.05). However, the protein levels of FGFR1 and KLB in the subcutaneous WAT (sWAT) of the IT rats decreased by 34.4 and 72.1%, respectively, compared with the Sham-IT rats (P < 0.05). In addition, the protein levels of FGF21 and KLB in the livers of IT rats were 3.9- and 2.3-fold of the Sham-IT rats (all P < 0.05). Conclusions: IT surgery significantly decreased fat mass and improved glucose metabolism in diabetic GK rats. These beneficial roles of IT surgery were probably associated with its stimulatory action on the expression of FGFR1 and KLB in both the eWAT and the pWAT, thereby promoting UCP1 expression in these tissues.
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spelling pubmed-58549742018-03-28 Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21 Yan, Kemin Chen, Weijie Zhu, Huijuan Lin, Guole Pan, Hui Li, Naishi Wang, Linjie Yang, Hongbo Liu, Meijuan Gong, Fengying Front Physiol Physiology Objective: Ileal transposition (IT) surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21) is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK) rats. Methods: Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group) or sham surgery without the ileum transposition (Sham-IT group). Rats in the no surgery group did not receive any surgical intervention. Six weeks later, body weight, fat mass, fasting blood glucose (FBG), and serum levels of FGF21 and leptin were measured. The expression of the FGF21 signaling pathway and white adipose tissue (WAT) browning-related genes in the WAT and liver were evaluated by real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blot. Results: IT surgery significantly decreased the body weights and FBG levels and increased the insulin sensitivity of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats decreased by 26.3 and 61.7%, respectively (all P < 0.05). The mRNA levels of fibroblast growth factor receptor 1 (FGFR1) and its co-receptor β klotho (KLB) in the perirenal WAT (pWAT) of the IT rats were 1.4- and 2.4-fold that of the Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the Sham-IT rats (all P < 0.05). In accordance with the pWAT, the protein levels of FGFR1 and KLB in the epididymal WAT (eWAT) of the IT rats notably increased to 3.0- and 3.9-fold of the Sham-IT rats (P < 0.05). Furthermore, uncoupling protein 1 (UCP1) protein levels in the eWAT and pWAT of the IT rats also increased to 2.2- and 2.3-fold of the Sham-IT rats (P < 0.05). However, the protein levels of FGFR1 and KLB in the subcutaneous WAT (sWAT) of the IT rats decreased by 34.4 and 72.1%, respectively, compared with the Sham-IT rats (P < 0.05). In addition, the protein levels of FGF21 and KLB in the livers of IT rats were 3.9- and 2.3-fold of the Sham-IT rats (all P < 0.05). Conclusions: IT surgery significantly decreased fat mass and improved glucose metabolism in diabetic GK rats. These beneficial roles of IT surgery were probably associated with its stimulatory action on the expression of FGFR1 and KLB in both the eWAT and the pWAT, thereby promoting UCP1 expression in these tissues. Frontiers Media S.A. 2018-03-09 /pmc/articles/PMC5854974/ /pubmed/29593555 http://dx.doi.org/10.3389/fphys.2018.00191 Text en Copyright © 2018 Yan, Chen, Zhu, Lin, Pan, Li, Wang, Yang, Liu and Gong. http://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 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 Physiology
Yan, Kemin
Chen, Weijie
Zhu, Huijuan
Lin, Guole
Pan, Hui
Li, Naishi
Wang, Linjie
Yang, Hongbo
Liu, Meijuan
Gong, Fengying
Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21
title Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21
title_full Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21
title_fullStr Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21
title_full_unstemmed Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21
title_short Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21
title_sort ileal transposition surgery decreases fat mass and improves glucose metabolism in diabetic gk rats: possible involvement of fgf21
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854974/
https://www.ncbi.nlm.nih.gov/pubmed/29593555
http://dx.doi.org/10.3389/fphys.2018.00191
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