miR-669a-5p promotes adipogenic differentiation and induces browning in preadipocytes

Xiaoqiong Tan; Tingting Zhu; Linqiang Zhang; Lin Fu; Ying Hu; Huiqin Li; Chengbin Li; Jingjing Zhang; Bin Liang; Jing Liu

doi:10.1080/21623945.2022.2030570

miR-669a-5p promotes adipogenic differentiation and induces browning in preadipocytes

Adipocyte. 2022 Dec;11(1):120-132. doi: 10.1080/21623945.2022.2030570.

Authors

Xiaoqiong Tan^{1

2

3

4}, Tingting Zhu^{1

2}, Linqiang Zhang^{1

2}, Lin Fu⁵, Ying Hu⁶, Huiqin Li^{1

2}, Chengbin Li⁵, Jingjing Zhang⁵, Bin Liang⁵, Jing Liu⁵

Affiliations

¹ Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
² Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China.
³ Department of Respiratory and Critical Care Medicine, The First People's Hospital of Yunnan Province, Kunming, China.
⁴ Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
⁵ Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China.
⁶ School of Traditional Chinese Medicine, Yunnan University of Chinese Medicine, Kunming, China.

Abstract

Obesity is a major global health issue that contributes to the occurrence of metabolic disorders. Based on this fact, understanding the underlying mechanisms and to uncover promising therapeutic approaches for obesity have attracted intense investigation. Brown adipose tissue (BAT) can help burns excess calories. Therefore, promoting White adipose tissue (WAT) browning and BAT activation is an attractive strategy for obesity treatment. MicroRNAs (miRNAs) are small, non-coding RNAs, which are involved in regulation of adipogenic processes and metabolic functions. Evidence is accumulating that miRNAs are important regulators for both brown adipocyte differentiation and white adipocyte browning. Here we report that the expression of miR-669a-5p increases during the adipogenic differentiation of 3T3-L1 and C3H10T1/2 adipocytes. miR-669a-5p supplementation promotes adipogenic differentiation and causes browning of 3T3-L1 and C3H10T1/2 cells. Moreover, the expression of miR-669a-5p is upregulated in iWAT of mice exposed to cold. These data demonstrate that miR-669a-5p plays a role in regulating adipocyte differentiation and fat browning.Abbreviations: Acadl: long-chain acyl-Coenzyme A dehydrogenase; Acadm: medium-chain acyl-Coenzyme A dehydrogenase; Acadvl: very long-chain acyl-Coenzyme A dehydrogenase, very long chain; Aco2: mitochondrial aconitase 2; BAT: brown adipose tissue; Bmper: BMP-binding endothelial regulator; Cpt1-b:carnitine palmitoyltransferase 1b; Cpt2: carnitine palmitoyltransferase 2; Crat: carnitine acetyltransferase; Cs: citrate synthase; C2MC: Chromosome 2 miRNA cluster; DMEM: Dulbecco's modified Eagle medium; eWAT: epididymal white adipose tissue; ETC: electron transport chain; FAO: fatty acid oxidation; Fabp4:fatty acid binding protein 4; FBS: fetal bovine serum; Hadha: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; Hadhb: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta; HFD: high fat diet; Idh3a: isocitrate dehydrogenase 3 alpha; iWAT: inguinal subcutaneous white adipose tissue; Lpl: lipoprotein lipase; Mdh2: malate dehydrogenase 2; NBCS: NewBorn Calf Serum; mt-Nd1: mitochondrial NADH dehydrogenase 1; Ndufb8:ubiquinone oxidoreductase subunit B8; Nrf1: nuclear respiratory factor 1; Pgc1α: peroxisome proliferative activated receptor gamma coactivator 1 alpha; Pgc1b: peroxisome proliferative activated receptor, gamma, coactivator 1 beta; Pparγ: peroxisome proliferator activated receptor gamma; Prdm16: PR domain containing 16; Rgs4: regulator of G-protein signaling 4; Sdhb: succinate dehydrogenase complex, subunit B; Sdhc: succinate dehydrogenase complex, subunit C; Sdhd: succinate dehydrogenase complex, subunit D; Sh3d21: SH3 domain containing 21; Sfmbt2: Scm-like with four mbt domains 2; TG: triglyceride; TCA: tricarboxylic acid cycle; Tfam: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine, methyl ester; Ucp1: uncoupling protein 1; Uqcrc2: ubiquinol cytochrome c reductase core protein 2; WAT: White adipose tissue.

Keywords: 3T3-L1; C3H10T1/2; adipocyte browning; adipocyte differentiation; miR-669a-5p; microRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3-L1 Cells
Acyl-CoA Dehydrogenase / metabolism
Adipocytes, White / metabolism
Adipose Tissue, Brown / metabolism
Adipose Tissue, White / metabolism
Animals
Carnitine O-Palmitoyltransferase / metabolism
Coenzyme A / metabolism
Mice
MicroRNAs* / genetics
MicroRNAs* / metabolism
Nuclear Proteins / metabolism
Obesity / metabolism
Repressor Proteins / metabolism
Succinate Dehydrogenase* / metabolism
Transcription Factors / genetics

Substances

MicroRNAs
Nuclear Proteins
Ppargc1b protein, mouse
Repressor Proteins
Sfmbt2 protein, mouse
Transcription Factors
Acyl-CoA Dehydrogenase
Succinate Dehydrogenase
Carnitine O-Palmitoyltransferase
Coenzyme A

Grants and funding

This work was supported by the Ministry of Science and Technology of the People’s Republic of China (2018YFA0800700), the National Natural Science Foundation of China (U1702288, 81700520, U1702287), the Yunnan Applied Basic Research Projects (2019FY003021, 2017FA007).