Cargando…

Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro

Free fatty acids (FFA), hyperglycemia, and inflammatory cytokines are major mediators of β-cell toxicity in type 2 diabetes mellitus, impairing mitochondrial metabolism. Glutaredoxin 5 (Glrx5) is a mitochondrial protein involved in the assembly of iron–sulfur clusters required for complexes of the r...

Descripción completa

Detalles Bibliográficos
Autores principales: Petry, Sebastian Friedrich, Römer, Axel, Rawat, Divya, Brunner, Lara, Lerch, Nina, Zhou, Mengmeng, Grewal, Rekha, Sharifpanah, Fatemeh, Sauer, Heinrich, Eckert, Gunter Peter, Linn, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025089/
https://www.ncbi.nlm.nih.gov/pubmed/35453472
http://dx.doi.org/10.3390/antiox11040788
_version_ 1784690781284466688
author Petry, Sebastian Friedrich
Römer, Axel
Rawat, Divya
Brunner, Lara
Lerch, Nina
Zhou, Mengmeng
Grewal, Rekha
Sharifpanah, Fatemeh
Sauer, Heinrich
Eckert, Gunter Peter
Linn, Thomas
author_facet Petry, Sebastian Friedrich
Römer, Axel
Rawat, Divya
Brunner, Lara
Lerch, Nina
Zhou, Mengmeng
Grewal, Rekha
Sharifpanah, Fatemeh
Sauer, Heinrich
Eckert, Gunter Peter
Linn, Thomas
author_sort Petry, Sebastian Friedrich
collection PubMed
description Free fatty acids (FFA), hyperglycemia, and inflammatory cytokines are major mediators of β-cell toxicity in type 2 diabetes mellitus, impairing mitochondrial metabolism. Glutaredoxin 5 (Glrx5) is a mitochondrial protein involved in the assembly of iron–sulfur clusters required for complexes of the respiratory chain. We have provided evidence that islet cells are deprived of Glrx5, correlating with impaired insulin secretion during diabetes in genetically obese mice. In this study, we induced diabesity in C57BL/6J mice in vivo by feeding the mice a high-fat diet (HFD) and modelled the diabetic metabolism in MIN6 cells through exposure to FFA, glucose, or inflammatory cytokines in vitro. qRT-PCR, ELISA, immunohisto-/cytochemistry, bioluminescence, and respirometry were employed to study Glrx5, insulin secretion, and mitochondrial biomarkers. The HFD induced a depletion of islet Glrx5 concomitant with an obese phenotype, elevated FFA in serum and reactive oxygen species in islets, and impaired glucose tolerance. Exposure of MIN6 cells to FFA led to a loss of Glrx5 in vitro. The FFA-induced depletion of Glrx5 coincided with significantly altered mitochondrial biomarkers. In summary, we provide evidence that Glrx5 is regulated by FFA in type 2 diabetes mellitus and is linked to mitochondrial dysfunction and blunted insulin secretion.
format Online
Article
Text
id pubmed-9025089
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90250892022-04-23 Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro Petry, Sebastian Friedrich Römer, Axel Rawat, Divya Brunner, Lara Lerch, Nina Zhou, Mengmeng Grewal, Rekha Sharifpanah, Fatemeh Sauer, Heinrich Eckert, Gunter Peter Linn, Thomas Antioxidants (Basel) Article Free fatty acids (FFA), hyperglycemia, and inflammatory cytokines are major mediators of β-cell toxicity in type 2 diabetes mellitus, impairing mitochondrial metabolism. Glutaredoxin 5 (Glrx5) is a mitochondrial protein involved in the assembly of iron–sulfur clusters required for complexes of the respiratory chain. We have provided evidence that islet cells are deprived of Glrx5, correlating with impaired insulin secretion during diabetes in genetically obese mice. In this study, we induced diabesity in C57BL/6J mice in vivo by feeding the mice a high-fat diet (HFD) and modelled the diabetic metabolism in MIN6 cells through exposure to FFA, glucose, or inflammatory cytokines in vitro. qRT-PCR, ELISA, immunohisto-/cytochemistry, bioluminescence, and respirometry were employed to study Glrx5, insulin secretion, and mitochondrial biomarkers. The HFD induced a depletion of islet Glrx5 concomitant with an obese phenotype, elevated FFA in serum and reactive oxygen species in islets, and impaired glucose tolerance. Exposure of MIN6 cells to FFA led to a loss of Glrx5 in vitro. The FFA-induced depletion of Glrx5 coincided with significantly altered mitochondrial biomarkers. In summary, we provide evidence that Glrx5 is regulated by FFA in type 2 diabetes mellitus and is linked to mitochondrial dysfunction and blunted insulin secretion. MDPI 2022-04-15 /pmc/articles/PMC9025089/ /pubmed/35453472 http://dx.doi.org/10.3390/antiox11040788 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Petry, Sebastian Friedrich
Römer, Axel
Rawat, Divya
Brunner, Lara
Lerch, Nina
Zhou, Mengmeng
Grewal, Rekha
Sharifpanah, Fatemeh
Sauer, Heinrich
Eckert, Gunter Peter
Linn, Thomas
Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro
title Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro
title_full Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro
title_fullStr Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro
title_full_unstemmed Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro
title_short Loss and Recovery of Glutaredoxin 5 Is Inducible by Diet in a Murine Model of Diabesity and Mediated by Free Fatty Acids In Vitro
title_sort loss and recovery of glutaredoxin 5 is inducible by diet in a murine model of diabesity and mediated by free fatty acids in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025089/
https://www.ncbi.nlm.nih.gov/pubmed/35453472
http://dx.doi.org/10.3390/antiox11040788
work_keys_str_mv AT petrysebastianfriedrich lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT romeraxel lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT rawatdivya lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT brunnerlara lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT lerchnina lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT zhoumengmeng lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT grewalrekha lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT sharifpanahfatemeh lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT sauerheinrich lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT eckertgunterpeter lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro
AT linnthomas lossandrecoveryofglutaredoxin5isinduciblebydietinamurinemodelofdiabesityandmediatedbyfreefattyacidsinvitro