MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling

Yoon Keun Cho, Yeonho Son, Sang Nam Kim, Hyun Doo Song, Minsu Kim, Ji Hyun Park, Young Suk Jung, Sang Yeop Ahn, Abhirup Saha, James G. Granneman, Yun Hee Lee

Research output: Contribution to journalArticle

Abstract

Objective: This study investigated the role of microRNAs generated from adipose tissue macrophages (ATMs) during adipose tissue remodeling induced by pharmacological and nutritional stimuli. Methods: Macrophage-specific Dicer knockout (KO) mice were used to determine the roles of microRNA generated in macrophages in adipose tissue remodeling induced by the β3-adrenergic receptor agonist CL316,243 (CL). RNA-seq was performed to characterize microRNA and mRNA expression profiles in isolated macrophages and PDGFRα+ adipocyte stem cells (ASCs). The role of miR-10a-5p was further investigated in cell culture, and in adipose tissue remodeling induced by CL treatment and high fat feeding. Results: Macrophage-specific deletion of Dicer elevated pro-inflammatory gene expression and prevented CL-induced de novo beige adipogenesis in gonadal white adipose tissue (gWAT). Co-culture of ASCs with ATMs of wild type mice promoted brown adipocyte gene expression upon differentiation, but co-culture with ATMs of Dicer KO mice did not. Bioinformatic analysis of RNA expression profiles identified miR-10a-5p as a potential regulator of inflammation and differentiation in ATMs and ASCs, respectively. CL treatment increased levels of miR-10a-5p in ATMs and ASCs in gWAT. Interestingly, CL treatment elevated levels of pre-mir-10a in ATMs but not in ASCs, suggesting possible transfer from ATMs to ASCs. Elevating miR-10a-5p levels inhibited proinflammatory gene expression in cultured RAW 264.7 macrophages and promoted the differentiation of C3H10T1/2 cells into brown adipocytes. Furthermore, treatment with a miR-10a-5p mimic in vivo rescued CL-induced beige adipogenesis in Dicer KO mice. High fat feeding reduced miR-10a-5p levels in ATMs of gWAT, and treatment of mice with a miR-10a-5p mimic suppressed pro-inflammatory responses, promoted the appearance of new white adipocytes in gWAT, and improved systemic glucose tolerance. Conclusions: These results demonstrate an important role of macrophage-generated microRNAs in adipogenic niches and identify miR-10a-5p as a key regulator that reduces adipose tissue inflammation and promotes therapeutic adipogenesis.

Original languageEnglish
Pages (from-to)86-98
Number of pages13
JournalMolecular Metabolism
Volume29
DOIs
Publication statusPublished - 2019 Nov

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MicroRNAs
Adipose Tissue
Macrophages
Adipocytes
White Adipose Tissue
Stem Cells
Adipogenesis
Therapeutics
Knockout Mice
Brown Adipocytes
Coculture Techniques
Gene Expression
White Adipocytes
Fats
RNA
Inflammation
Adrenergic Agonists
Computational Biology
disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
Cell Culture Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Cho, Yoon Keun ; Son, Yeonho ; Kim, Sang Nam ; Song, Hyun Doo ; Kim, Minsu ; Park, Ji Hyun ; Jung, Young Suk ; Ahn, Sang Yeop ; Saha, Abhirup ; Granneman, James G. ; Lee, Yun Hee. / MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling. In: Molecular Metabolism. 2019 ; Vol. 29. pp. 86-98.
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title = "MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling",
abstract = "Objective: This study investigated the role of microRNAs generated from adipose tissue macrophages (ATMs) during adipose tissue remodeling induced by pharmacological and nutritional stimuli. Methods: Macrophage-specific Dicer knockout (KO) mice were used to determine the roles of microRNA generated in macrophages in adipose tissue remodeling induced by the β3-adrenergic receptor agonist CL316,243 (CL). RNA-seq was performed to characterize microRNA and mRNA expression profiles in isolated macrophages and PDGFRα+ adipocyte stem cells (ASCs). The role of miR-10a-5p was further investigated in cell culture, and in adipose tissue remodeling induced by CL treatment and high fat feeding. Results: Macrophage-specific deletion of Dicer elevated pro-inflammatory gene expression and prevented CL-induced de novo beige adipogenesis in gonadal white adipose tissue (gWAT). Co-culture of ASCs with ATMs of wild type mice promoted brown adipocyte gene expression upon differentiation, but co-culture with ATMs of Dicer KO mice did not. Bioinformatic analysis of RNA expression profiles identified miR-10a-5p as a potential regulator of inflammation and differentiation in ATMs and ASCs, respectively. CL treatment increased levels of miR-10a-5p in ATMs and ASCs in gWAT. Interestingly, CL treatment elevated levels of pre-mir-10a in ATMs but not in ASCs, suggesting possible transfer from ATMs to ASCs. Elevating miR-10a-5p levels inhibited proinflammatory gene expression in cultured RAW 264.7 macrophages and promoted the differentiation of C3H10T1/2 cells into brown adipocytes. Furthermore, treatment with a miR-10a-5p mimic in vivo rescued CL-induced beige adipogenesis in Dicer KO mice. High fat feeding reduced miR-10a-5p levels in ATMs of gWAT, and treatment of mice with a miR-10a-5p mimic suppressed pro-inflammatory responses, promoted the appearance of new white adipocytes in gWAT, and improved systemic glucose tolerance. Conclusions: These results demonstrate an important role of macrophage-generated microRNAs in adipogenic niches and identify miR-10a-5p as a key regulator that reduces adipose tissue inflammation and promotes therapeutic adipogenesis.",
author = "Cho, {Yoon Keun} and Yeonho Son and Kim, {Sang Nam} and Song, {Hyun Doo} and Minsu Kim and Park, {Ji Hyun} and Jung, {Young Suk} and Ahn, {Sang Yeop} and Abhirup Saha and Granneman, {James G.} and Lee, {Yun Hee}",
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Cho, YK, Son, Y, Kim, SN, Song, HD, Kim, M, Park, JH, Jung, YS, Ahn, SY, Saha, A, Granneman, JG & Lee, YH 2019, 'MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling', Molecular Metabolism, vol. 29, pp. 86-98. https://doi.org/10.1016/j.molmet.2019.08.015

MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling. / Cho, Yoon Keun; Son, Yeonho; Kim, Sang Nam; Song, Hyun Doo; Kim, Minsu; Park, Ji Hyun; Jung, Young Suk; Ahn, Sang Yeop; Saha, Abhirup; Granneman, James G.; Lee, Yun Hee.

In: Molecular Metabolism, Vol. 29, 11.2019, p. 86-98.

Research output: Contribution to journalArticle

TY - JOUR

T1 - MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling

AU - Cho, Yoon Keun

AU - Son, Yeonho

AU - Kim, Sang Nam

AU - Song, Hyun Doo

AU - Kim, Minsu

AU - Park, Ji Hyun

AU - Jung, Young Suk

AU - Ahn, Sang Yeop

AU - Saha, Abhirup

AU - Granneman, James G.

AU - Lee, Yun Hee

PY - 2019/11

Y1 - 2019/11

N2 - Objective: This study investigated the role of microRNAs generated from adipose tissue macrophages (ATMs) during adipose tissue remodeling induced by pharmacological and nutritional stimuli. Methods: Macrophage-specific Dicer knockout (KO) mice were used to determine the roles of microRNA generated in macrophages in adipose tissue remodeling induced by the β3-adrenergic receptor agonist CL316,243 (CL). RNA-seq was performed to characterize microRNA and mRNA expression profiles in isolated macrophages and PDGFRα+ adipocyte stem cells (ASCs). The role of miR-10a-5p was further investigated in cell culture, and in adipose tissue remodeling induced by CL treatment and high fat feeding. Results: Macrophage-specific deletion of Dicer elevated pro-inflammatory gene expression and prevented CL-induced de novo beige adipogenesis in gonadal white adipose tissue (gWAT). Co-culture of ASCs with ATMs of wild type mice promoted brown adipocyte gene expression upon differentiation, but co-culture with ATMs of Dicer KO mice did not. Bioinformatic analysis of RNA expression profiles identified miR-10a-5p as a potential regulator of inflammation and differentiation in ATMs and ASCs, respectively. CL treatment increased levels of miR-10a-5p in ATMs and ASCs in gWAT. Interestingly, CL treatment elevated levels of pre-mir-10a in ATMs but not in ASCs, suggesting possible transfer from ATMs to ASCs. Elevating miR-10a-5p levels inhibited proinflammatory gene expression in cultured RAW 264.7 macrophages and promoted the differentiation of C3H10T1/2 cells into brown adipocytes. Furthermore, treatment with a miR-10a-5p mimic in vivo rescued CL-induced beige adipogenesis in Dicer KO mice. High fat feeding reduced miR-10a-5p levels in ATMs of gWAT, and treatment of mice with a miR-10a-5p mimic suppressed pro-inflammatory responses, promoted the appearance of new white adipocytes in gWAT, and improved systemic glucose tolerance. Conclusions: These results demonstrate an important role of macrophage-generated microRNAs in adipogenic niches and identify miR-10a-5p as a key regulator that reduces adipose tissue inflammation and promotes therapeutic adipogenesis.

AB - Objective: This study investigated the role of microRNAs generated from adipose tissue macrophages (ATMs) during adipose tissue remodeling induced by pharmacological and nutritional stimuli. Methods: Macrophage-specific Dicer knockout (KO) mice were used to determine the roles of microRNA generated in macrophages in adipose tissue remodeling induced by the β3-adrenergic receptor agonist CL316,243 (CL). RNA-seq was performed to characterize microRNA and mRNA expression profiles in isolated macrophages and PDGFRα+ adipocyte stem cells (ASCs). The role of miR-10a-5p was further investigated in cell culture, and in adipose tissue remodeling induced by CL treatment and high fat feeding. Results: Macrophage-specific deletion of Dicer elevated pro-inflammatory gene expression and prevented CL-induced de novo beige adipogenesis in gonadal white adipose tissue (gWAT). Co-culture of ASCs with ATMs of wild type mice promoted brown adipocyte gene expression upon differentiation, but co-culture with ATMs of Dicer KO mice did not. Bioinformatic analysis of RNA expression profiles identified miR-10a-5p as a potential regulator of inflammation and differentiation in ATMs and ASCs, respectively. CL treatment increased levels of miR-10a-5p in ATMs and ASCs in gWAT. Interestingly, CL treatment elevated levels of pre-mir-10a in ATMs but not in ASCs, suggesting possible transfer from ATMs to ASCs. Elevating miR-10a-5p levels inhibited proinflammatory gene expression in cultured RAW 264.7 macrophages and promoted the differentiation of C3H10T1/2 cells into brown adipocytes. Furthermore, treatment with a miR-10a-5p mimic in vivo rescued CL-induced beige adipogenesis in Dicer KO mice. High fat feeding reduced miR-10a-5p levels in ATMs of gWAT, and treatment of mice with a miR-10a-5p mimic suppressed pro-inflammatory responses, promoted the appearance of new white adipocytes in gWAT, and improved systemic glucose tolerance. Conclusions: These results demonstrate an important role of macrophage-generated microRNAs in adipogenic niches and identify miR-10a-5p as a key regulator that reduces adipose tissue inflammation and promotes therapeutic adipogenesis.

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