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

Mengran Qin; Lipeng Xing; Jiahan Wu; Shulei Wen; Junyi Luo; Ting Chen; Yaotian Fan; Jiahao Zhu; Lekai Yang; Jie Liu; Jiali Xiong; Xingping Chen; Canjun Zhu; Songbo Wang; Lina Wang; Gang Shu; Qingyan Jiang; Yongliang Zhang; Jiajie Sun; Qianyun Xi

doi:10.3390/ijms24054561

International Journal of Molecular Sciences (Feb 2023)

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

Mengran Qin,
Lipeng Xing,
Jiahan Wu,
Shulei Wen,
Junyi Luo,
Ting Chen,
Yaotian Fan,
Jiahao Zhu,
Lekai Yang,
Jie Liu,
Jiali Xiong,
Xingping Chen,
Canjun Zhu,
Songbo Wang,
Lina Wang,
Gang Shu,
Qingyan Jiang,
Yongliang Zhang,
Jiajie Sun,
Qianyun Xi

Affiliations

Mengran Qin: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Lipeng Xing: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Jiahan Wu: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Shulei Wen: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Junyi Luo: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Ting Chen: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Yaotian Fan: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Jiahao Zhu: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Lekai Yang: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Jie Liu: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Jiali Xiong: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Xingping Chen: Jiangxi Province Key Laboratory of Animal Nutrition, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, China
Canjun Zhu: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Songbo Wang: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Lina Wang: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Gang Shu: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Qingyan Jiang: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Yongliang Zhang: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Jiajie Sun: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China
Qianyun Xi: Guangdong Provincial Key Laboratory of Animal Nutrition Control, State Key Laboratory of Livestock and Poultry Breeding, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, No. 483 Wushan Road, Guangzhou 510642, China

DOI: https://doi.org/10.3390/ijms24054561
Journal volume & issue: Vol. 24, no. 5
p. 4561

Abstract

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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.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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