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Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling

Skeletal muscle-fat interaction is essential for maintaining organismal energy homeostasis and managing obesity by secreting cytokines and exosomes, but the role of the latter as a new mediator in inter-tissue communication remains unclear. Recently, we discovered that miR-146a-5p was mainly enriche...

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Autores principales: Qin, Mengran, Xing, Lipeng, Wu, Jiahan, Wen, Shulei, Luo, Junyi, Chen, Ting, Fan, Yaotian, Zhu, Jiahao, Yang, Lekai, Liu, Jie, Xiong, Jiali, Chen, Xingping, Zhu, Canjun, Wang, Songbo, Wang, Lina, Shu, Gang, Jiang, Qingyan, Zhang, Yongliang, Sun, Jiajie, Xi, Qianyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003660/
https://www.ncbi.nlm.nih.gov/pubmed/36901991
http://dx.doi.org/10.3390/ijms24054561
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author Qin, Mengran
Xing, Lipeng
Wu, Jiahan
Wen, Shulei
Luo, Junyi
Chen, Ting
Fan, Yaotian
Zhu, Jiahao
Yang, Lekai
Liu, Jie
Xiong, Jiali
Chen, Xingping
Zhu, Canjun
Wang, Songbo
Wang, Lina
Shu, Gang
Jiang, Qingyan
Zhang, Yongliang
Sun, Jiajie
Xi, Qianyun
author_facet Qin, Mengran
Xing, Lipeng
Wu, Jiahan
Wen, Shulei
Luo, Junyi
Chen, Ting
Fan, Yaotian
Zhu, Jiahao
Yang, Lekai
Liu, Jie
Xiong, Jiali
Chen, Xingping
Zhu, Canjun
Wang, Songbo
Wang, Lina
Shu, Gang
Jiang, Qingyan
Zhang, Yongliang
Sun, Jiajie
Xi, Qianyun
author_sort Qin, Mengran
collection PubMed
description Skeletal muscle-fat interaction is essential for maintaining organismal energy homeostasis and managing obesity by secreting cytokines and exosomes, but the role of the latter as a new mediator in inter-tissue communication remains unclear. Recently, we discovered that miR-146a-5p was mainly enriched in skeletal muscle-derived exosomes (SKM-Exos), 50-fold higher than in fat exosomes. Here, we investigated the role of skeletal muscle-derived exosomes regulating lipid metabolism in adipose tissue by delivering miR-146a-5p. The results showed that skeletal muscle cell-derived exosomes significantly inhibited the differentiation of preadipocytes and their adipogenesis. When the skeletal muscle-derived exosomes co-treated adipocytes with miR-146a-5p inhibitor, this inhibition was reversed. Additionally, skeletal muscle-specific knockout miR-146a-5p (mKO) mice significantly increased body weight gain and decreased oxidative metabolism. On the other hand, the internalization of this miRNA into the mKO mice by injecting skeletal muscle-derived exosomes from the Flox mice (Flox-Exos) resulted in significant phenotypic reversion, including down-regulation of genes and proteins involved in adipogenesis. Mechanistically, miR-146a-5p has also been demonstrated to function as a negative regulator of peroxisome proliferator-activated receptor γ (PPARγ) signaling by directly targeting growth and differentiation factor 5 (GDF5) gene to mediate adipogenesis and fatty acid absorption. Taken together, these data provide new insights into the role of miR-146a-5p as a novel myokine involved in the regulation of adipogenesis and obesity via mediating the skeletal muscle-fat signaling axis, which may serve as a target for the development of therapies against metabolic diseases, such as obesity.
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spelling pubmed-100036602023-03-11 Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling Qin, Mengran Xing, Lipeng Wu, Jiahan Wen, Shulei Luo, Junyi Chen, Ting Fan, Yaotian Zhu, Jiahao Yang, Lekai Liu, Jie Xiong, Jiali Chen, Xingping Zhu, Canjun Wang, Songbo Wang, Lina Shu, Gang Jiang, Qingyan Zhang, Yongliang Sun, Jiajie Xi, Qianyun Int J Mol Sci Article Skeletal muscle-fat interaction is essential for maintaining organismal energy homeostasis and managing obesity by secreting cytokines and exosomes, but the role of the latter as a new mediator in inter-tissue communication remains unclear. Recently, we discovered that miR-146a-5p was mainly enriched in skeletal muscle-derived exosomes (SKM-Exos), 50-fold higher than in fat exosomes. Here, we investigated the role of skeletal muscle-derived exosomes regulating lipid metabolism in adipose tissue by delivering miR-146a-5p. The results showed that skeletal muscle cell-derived exosomes significantly inhibited the differentiation of preadipocytes and their adipogenesis. When the skeletal muscle-derived exosomes co-treated adipocytes with miR-146a-5p inhibitor, this inhibition was reversed. Additionally, skeletal muscle-specific knockout miR-146a-5p (mKO) mice significantly increased body weight gain and decreased oxidative metabolism. On the other hand, the internalization of this miRNA into the mKO mice by injecting skeletal muscle-derived exosomes from the Flox mice (Flox-Exos) resulted in significant phenotypic reversion, including down-regulation of genes and proteins involved in adipogenesis. Mechanistically, miR-146a-5p has also been demonstrated to function as a negative regulator of peroxisome proliferator-activated receptor γ (PPARγ) signaling by directly targeting growth and differentiation factor 5 (GDF5) gene to mediate adipogenesis and fatty acid absorption. Taken together, these data provide new insights into the role of miR-146a-5p as a novel myokine involved in the regulation of adipogenesis and obesity via mediating the skeletal muscle-fat signaling axis, which may serve as a target for the development of therapies against metabolic diseases, such as obesity. MDPI 2023-02-25 /pmc/articles/PMC10003660/ /pubmed/36901991 http://dx.doi.org/10.3390/ijms24054561 Text en © 2023 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
Qin, Mengran
Xing, Lipeng
Wu, Jiahan
Wen, Shulei
Luo, Junyi
Chen, Ting
Fan, Yaotian
Zhu, Jiahao
Yang, Lekai
Liu, Jie
Xiong, Jiali
Chen, Xingping
Zhu, Canjun
Wang, Songbo
Wang, Lina
Shu, Gang
Jiang, Qingyan
Zhang, Yongliang
Sun, Jiajie
Xi, Qianyun
Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling
title Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling
title_full Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling
title_fullStr Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling
title_full_unstemmed Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling
title_short Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling
title_sort skeletal muscle-derived exosomal mir-146a-5p inhibits adipogenesis by mediating muscle-fat axis and targeting gdf5-pparγ signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003660/
https://www.ncbi.nlm.nih.gov/pubmed/36901991
http://dx.doi.org/10.3390/ijms24054561
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