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METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice

Physical activity has many beneficial effects on metabolic disorders, such as obesity, insulin resistance, and diabetes. Meteorin-like protein (METRNL), a novel secreted protein homologous to the neurotrophin Metrn, is induced after exercise in the skeletal muscle. Herein, we investigated the effect...

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Autores principales: Jung, Tae Woo, Lee, Sung Hoon, Kim, Hyoung-Chun, Bang, Joon Seok, Abd El-Aty, A. M., Hacımüftüoğlu, Ahmet, Shin, Yong Kyoo, Jeong, Ji Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137187/
https://www.ncbi.nlm.nih.gov/pubmed/30213948
http://dx.doi.org/10.1038/s12276-018-0147-5
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author Jung, Tae Woo
Lee, Sung Hoon
Kim, Hyoung-Chun
Bang, Joon Seok
Abd El-Aty, A. M.
Hacımüftüoğlu, Ahmet
Shin, Yong Kyoo
Jeong, Ji Hoon
author_facet Jung, Tae Woo
Lee, Sung Hoon
Kim, Hyoung-Chun
Bang, Joon Seok
Abd El-Aty, A. M.
Hacımüftüoğlu, Ahmet
Shin, Yong Kyoo
Jeong, Ji Hoon
author_sort Jung, Tae Woo
collection PubMed
description Physical activity has many beneficial effects on metabolic disorders, such as obesity, insulin resistance, and diabetes. Meteorin-like protein (METRNL), a novel secreted protein homologous to the neurotrophin Metrn, is induced after exercise in the skeletal muscle. Herein, we investigated the effects of METRNL on lipid-mediated inflammation and insulin resistance in skeletal muscle via AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPARδ). Treatment with METRNL suppressed inflammatory markers, such as nuclear factor κB (NFκB) nuclear translocation, inhibitory κBα (IκBα) phosphorylation, interleukin-6 (IL-6) expression, and pro-inflammatory cytokines (such as TNFα and MCP-1). METRNL treatment also attenuated the impaired insulin response both in palmitate-treated differentiated C2C12 cells and the skeletal muscle of high-fat diet (HFD)-fed mice. Furthermore, METRNL administration rescued glucose intolerance and reduced HFD-induced body weight gain in mice; however, METRNL did not affect calorie intake. METRNL treatment increased AMPK phosphorylation and PPARδ expression both in differentiated C2C12 cells and mouse skeletal muscle. siRNA-mediated suppression of AMPK and PPARδ abrogated the suppressive effects of METRNL on palmitate-induced inflammation and insulin resistance. Moreover, METRNL augmented the mRNA expression of fatty acid oxidation-associated genes, such as carnitine palmitoyltransferase 1 (CPT1), acyl-CoA oxidase (ACO), and fatty acid binding protein 3 (FABP3). siRNAs for AMPK and PPARδ reversed these changes. In the current study, we report for the first time that METRNL alleviates inflammation and insulin resistance and induces fatty acid oxidation through AMPK or PPARδ-dependent signaling in skeletal muscle.
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spelling pubmed-61371872018-09-18 METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice Jung, Tae Woo Lee, Sung Hoon Kim, Hyoung-Chun Bang, Joon Seok Abd El-Aty, A. M. Hacımüftüoğlu, Ahmet Shin, Yong Kyoo Jeong, Ji Hoon Exp Mol Med Article Physical activity has many beneficial effects on metabolic disorders, such as obesity, insulin resistance, and diabetes. Meteorin-like protein (METRNL), a novel secreted protein homologous to the neurotrophin Metrn, is induced after exercise in the skeletal muscle. Herein, we investigated the effects of METRNL on lipid-mediated inflammation and insulin resistance in skeletal muscle via AMP-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor δ (PPARδ). Treatment with METRNL suppressed inflammatory markers, such as nuclear factor κB (NFκB) nuclear translocation, inhibitory κBα (IκBα) phosphorylation, interleukin-6 (IL-6) expression, and pro-inflammatory cytokines (such as TNFα and MCP-1). METRNL treatment also attenuated the impaired insulin response both in palmitate-treated differentiated C2C12 cells and the skeletal muscle of high-fat diet (HFD)-fed mice. Furthermore, METRNL administration rescued glucose intolerance and reduced HFD-induced body weight gain in mice; however, METRNL did not affect calorie intake. METRNL treatment increased AMPK phosphorylation and PPARδ expression both in differentiated C2C12 cells and mouse skeletal muscle. siRNA-mediated suppression of AMPK and PPARδ abrogated the suppressive effects of METRNL on palmitate-induced inflammation and insulin resistance. Moreover, METRNL augmented the mRNA expression of fatty acid oxidation-associated genes, such as carnitine palmitoyltransferase 1 (CPT1), acyl-CoA oxidase (ACO), and fatty acid binding protein 3 (FABP3). siRNAs for AMPK and PPARδ reversed these changes. In the current study, we report for the first time that METRNL alleviates inflammation and insulin resistance and induces fatty acid oxidation through AMPK or PPARδ-dependent signaling in skeletal muscle. Nature Publishing Group UK 2018-09-13 /pmc/articles/PMC6137187/ /pubmed/30213948 http://dx.doi.org/10.1038/s12276-018-0147-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Jung, Tae Woo
Lee, Sung Hoon
Kim, Hyoung-Chun
Bang, Joon Seok
Abd El-Aty, A. M.
Hacımüftüoğlu, Ahmet
Shin, Yong Kyoo
Jeong, Ji Hoon
METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice
title METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice
title_full METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice
title_fullStr METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice
title_full_unstemmed METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice
title_short METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or PPARδ-dependent pathways in skeletal muscle of mice
title_sort metrnl attenuates lipid-induced inflammation and insulin resistance via ampk or pparδ-dependent pathways in skeletal muscle of mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137187/
https://www.ncbi.nlm.nih.gov/pubmed/30213948
http://dx.doi.org/10.1038/s12276-018-0147-5
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