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 journalArticlepeer-review

36 Citations (Scopus)


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
Publication statusPublished - 2019 Nov

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) ( 2014R1A6A3A04056472 (Y.H.L.), 2019R1C1C1002014 (Y.H.L), 2018R1A5A2024425 ), the Bio & Medical Technology Development Program of the NRF ( 2016M3A9D5A01953818 (Y.H.L.), 2013M3A9D5072550 ), and the United States Public Health Service ( NIH R01 DK-062292 to J.G.G.).

Publisher Copyright:
© 2019 The Authors

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'MicroRNA-10a-5p regulates macrophage polarization and promotes therapeutic adipose tissue remodeling'. Together they form a unique fingerprint.

Cite this