MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling
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...
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Format: | Article |
Language: | English |
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Elsevier
2019-11-01
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Series: | Molecular Metabolism |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877819307367 |
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doaj-9ca3c8ec8d104219b3a36053a453e9d7 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling Molecular Metabolism |
author_facet |
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 |
author_sort |
Yoon Keun Cho |
title |
MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling |
title_short |
MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling |
title_full |
MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling |
title_fullStr |
MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling |
title_full_unstemmed |
MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling |
title_sort |
microrna-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling |
publisher |
Elsevier |
series |
Molecular Metabolism |
issn |
2212-8778 |
publishDate |
2019-11-01 |
description |
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. Keywords: Dicer, microRNA, Adipose tissue macrophages, Adipocyte stem cells, Adipogenic niches |
url |
http://www.sciencedirect.com/science/article/pii/S2212877819307367 |
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doaj-9ca3c8ec8d104219b3a36053a453e9d72020-11-25T01:37:19ZengElsevierMolecular Metabolism2212-87782019-11-01298698MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodelingYoon Keun Cho0Yeonho Son1Sang-Nam Kim2Hyun-Doo Song3Minsu Kim4Ji-Hyun Park5Young-Suk Jung6Sang-Yeop Ahn7Abhirup Saha8James G. Granneman9Yun-Hee Lee10College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of KoreaCollege of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, 21983, Republic of KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of KoreaCollege of Pharmacy, Pusan National University, Republic of KoreaCollege of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, 21983, Republic of KoreaCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of KoreaCenter for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA; Center for Integrative Metabolic and Endocrine Research, Wayne State University, Detroit, MI, USA; Corresponding author. Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea; Corresponding author. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 29-Room # 311,1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea. Fax: +82 2 872 1795.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. Keywords: Dicer, microRNA, Adipose tissue macrophages, Adipocyte stem cells, Adipogenic nicheshttp://www.sciencedirect.com/science/article/pii/S2212877819307367 |