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Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis

Reduced mitochondrial electron transport chain activity promotes longevity and improves energy homeostasis via cell-autonomous and –non-autonomous factors in multiple model systems. This mitohormetic effect is thought to involve the mitochondrial unfolded protein response (UPR(mt)), an adaptive stre...

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Autores principales: Chung, Hyo Kyun, Ryu, Dongryeol, Kim, Koon Soon, Chang, Joon Young, Kim, Yong Kyung, Yi, Hyon-Seung, Kang, Seul Gi, Choi, Min Jeong, Lee, Seong Eun, Jung, Saet-Byel, Ryu, Min Jeong, Kim, Soung Jung, Kweon, Gi Ryang, Kim, Hail, Hwang, Jung Hwan, Lee, Chul-Ho, Lee, Se-Jin, Wall, Christopher E., Downes, Michael, Evans, Ronald M., Auwerx, Johan, Shong, Minho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223607/
https://www.ncbi.nlm.nih.gov/pubmed/27986797
http://dx.doi.org/10.1083/jcb.201607110
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author Chung, Hyo Kyun
Ryu, Dongryeol
Kim, Koon Soon
Chang, Joon Young
Kim, Yong Kyung
Yi, Hyon-Seung
Kang, Seul Gi
Choi, Min Jeong
Lee, Seong Eun
Jung, Saet-Byel
Ryu, Min Jeong
Kim, Soung Jung
Kweon, Gi Ryang
Kim, Hail
Hwang, Jung Hwan
Lee, Chul-Ho
Lee, Se-Jin
Wall, Christopher E.
Downes, Michael
Evans, Ronald M.
Auwerx, Johan
Shong, Minho
author_facet Chung, Hyo Kyun
Ryu, Dongryeol
Kim, Koon Soon
Chang, Joon Young
Kim, Yong Kyung
Yi, Hyon-Seung
Kang, Seul Gi
Choi, Min Jeong
Lee, Seong Eun
Jung, Saet-Byel
Ryu, Min Jeong
Kim, Soung Jung
Kweon, Gi Ryang
Kim, Hail
Hwang, Jung Hwan
Lee, Chul-Ho
Lee, Se-Jin
Wall, Christopher E.
Downes, Michael
Evans, Ronald M.
Auwerx, Johan
Shong, Minho
author_sort Chung, Hyo Kyun
collection PubMed
description Reduced mitochondrial electron transport chain activity promotes longevity and improves energy homeostasis via cell-autonomous and –non-autonomous factors in multiple model systems. This mitohormetic effect is thought to involve the mitochondrial unfolded protein response (UPR(mt)), an adaptive stress-response pathway activated by mitochondrial proteotoxic stress. Using mice with skeletal muscle–specific deficiency of Crif1 (muscle-specific knockout [MKO]), an integral protein of the large mitoribosomal subunit (39S), we identified growth differentiation factor 15 (GDF15) as a UPR(mt)-associated cell–non-autonomous myomitokine that regulates systemic energy homeostasis. MKO mice were protected against obesity and sensitized to insulin, an effect associated with elevated GDF15 secretion after UPR(mt) activation. In ob/ob mice, administration of recombinant GDF15 decreased body weight and improved insulin sensitivity, which was attributed to elevated oxidative metabolism and lipid mobilization in the liver, muscle, and adipose tissue. Thus, GDF15 is a potent mitohormetic signal that safeguards against the onset of obesity and insulin resistance.
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spelling pubmed-52236072017-07-02 Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis Chung, Hyo Kyun Ryu, Dongryeol Kim, Koon Soon Chang, Joon Young Kim, Yong Kyung Yi, Hyon-Seung Kang, Seul Gi Choi, Min Jeong Lee, Seong Eun Jung, Saet-Byel Ryu, Min Jeong Kim, Soung Jung Kweon, Gi Ryang Kim, Hail Hwang, Jung Hwan Lee, Chul-Ho Lee, Se-Jin Wall, Christopher E. Downes, Michael Evans, Ronald M. Auwerx, Johan Shong, Minho J Cell Biol Research Articles Reduced mitochondrial electron transport chain activity promotes longevity and improves energy homeostasis via cell-autonomous and –non-autonomous factors in multiple model systems. This mitohormetic effect is thought to involve the mitochondrial unfolded protein response (UPR(mt)), an adaptive stress-response pathway activated by mitochondrial proteotoxic stress. Using mice with skeletal muscle–specific deficiency of Crif1 (muscle-specific knockout [MKO]), an integral protein of the large mitoribosomal subunit (39S), we identified growth differentiation factor 15 (GDF15) as a UPR(mt)-associated cell–non-autonomous myomitokine that regulates systemic energy homeostasis. MKO mice were protected against obesity and sensitized to insulin, an effect associated with elevated GDF15 secretion after UPR(mt) activation. In ob/ob mice, administration of recombinant GDF15 decreased body weight and improved insulin sensitivity, which was attributed to elevated oxidative metabolism and lipid mobilization in the liver, muscle, and adipose tissue. Thus, GDF15 is a potent mitohormetic signal that safeguards against the onset of obesity and insulin resistance. The Rockefeller University Press 2017-01-02 /pmc/articles/PMC5223607/ /pubmed/27986797 http://dx.doi.org/10.1083/jcb.201607110 Text en © 2017 Chung et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Chung, Hyo Kyun
Ryu, Dongryeol
Kim, Koon Soon
Chang, Joon Young
Kim, Yong Kyung
Yi, Hyon-Seung
Kang, Seul Gi
Choi, Min Jeong
Lee, Seong Eun
Jung, Saet-Byel
Ryu, Min Jeong
Kim, Soung Jung
Kweon, Gi Ryang
Kim, Hail
Hwang, Jung Hwan
Lee, Chul-Ho
Lee, Se-Jin
Wall, Christopher E.
Downes, Michael
Evans, Ronald M.
Auwerx, Johan
Shong, Minho
Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
title Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
title_full Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
title_fullStr Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
title_full_unstemmed Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
title_short Growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
title_sort growth differentiation factor 15 is a myomitokine governing systemic energy homeostasis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5223607/
https://www.ncbi.nlm.nih.gov/pubmed/27986797
http://dx.doi.org/10.1083/jcb.201607110
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