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The role of microRNA-23b-5p in regulating brown adipogenesis and thermogenic program.

ABSTRACT: Enhanced brown adipose tissue (BAT) mass and activity have been demonstrated to promote the expenditure of excess stored energy and reduce prevalence of obesity. Cold is known as a potent stimulator of BAT and activates BAT primarily through the ?3-adrenergic-cAMP signaling. Here, we performed RNA-sequencing to identify differential miRNAs in mouse BAT upon cold exposure and a total of 20 miRNAs were validated. With the treatment of CL-316,243 (CL) and forskolin (Fsk) in mouse and human differentiated brown adipocyte cells in vitro, miR-23b-5p, miR-133a-3p, miR-135-5p, miR-491-5p, and miR-150-3p expression decreased and miR-455-5p expression increased. Among these deferentially expressed miRNAs, miR-23b-5p expression was differentially regulated in activated and aging mouse BAT and negatively correlated with Ucp1 expression. Overexpression of miR-23b-5p in the precursor cells from BAT revealed no significant effects on lipid accumulation, but diminished mitochondrial function and decreased expression of BAT specific markers. Though luciferase reporter assays did not confirm the positive association of miR-23b-5p with the 3'UTRs of the predicted target Ern1, miR-23b-5p overexpression may affect brown adipocyte thermogenic capacity mainly through regulating genes expression involving in lipolysis and fatty acid ?-oxidation pathways. Our results suggest that miRNAs are involved in cold-mediated BAT thermogenic activation and further acknowledged miR-23b-5p as a negative regulator in controlling thermogenic programs, further providing potential molecular therapeutic targets to increase surplus energy and treat obesity.

SUBMITTER: You L

PROVIDER: S-EPMC7274556 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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The role of microRNA-23b-5p in regulating brown adipogenesis and thermogenic program.

You Lianghui L Wang Yan Y Gao Yao Y Wang Xingyun X Cui Xianwei X Zhang Yanyan Y Pang Lingxia L Ji Chenbo C Guo Xirong X Chi Xia X

Endocrine connections 20200501 5

Enhanced brown adipose tissue (BAT) mass and activity have been demonstrated to promote the expenditure of excess stored energy and reduce prevalence of obesity. Cold is known as a potent stimulator of BAT and activates BAT primarily through the β3-adrenergic-cAMP signaling. Here, we performed RNA-sequencing to identify differential miRNAs in mouse BAT upon cold exposure and a total of 20 miRNAs were validated. With the treatment of CL-316,243 (CL) and forskolin (Fsk) in mouse and human differen ...[more]

PMID: 32348962

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Project description:MicroRNAs (miRNAs), a class of small, non-coding RNA molecules, play an important role in the posttranscriptional regulation of gene expression, thereby influencing important cellular functions. In adipocytes, miRNAs show import regulatory features and are described to influence differentiation as well as metabolic, endocrine, and inflammatory functions. We previously identified miR-27a being upregulated under inflammatory conditions in human adipocytes and aimed to elucidate its function in adipocyte biology. Both strands of miR-27a, miR-27a-3p and -5p, were downregulated during the adipogenic differentiation of Simpson-Golabi-Behmel syndrome (SGBS) cells, human multipotent adipose-derived stem cells (hMADS), and human primary adipose-derived stromal cells (hASCs). Using miRNA-mimic transfection, we observed that miR-27a-3p is a crucial regulator of adipogenesis, while miR-27a-5p did not alter the differentiation capacity in SGBS cells. In silico screening predicted lipoprotein lipase (LPL) and peroxisome proliferator activated receptor γ (PPARγ) as potential targets of miR-27a-3p. The downregulation of both genes was verified in vitro, and the interaction of miR-27-3p with target sites in the 3' UTRs of both genes was confirmed via a miRNA-reporter-gene assay. Here, the knockdown of LPL did not interfere with adipogenic differentiation, while PPARγ knockdown decreased adipogenesis significantly, suggesting that miR-27-3p exerts its inhibitory effect on adipogenesis by repressing PPARγ. Taken together, we identified and validated a crucial role for miR-27a-3p in human adipogenesis played by targeting the essential adipogenic transcription factor PPARγ. Though we confirmed LPL as an additional target of miR-27a-3p, it does not appear to be involved in regulating human adipogenesis. Thereby, our findings call the conclusions drawn from previous studies, which identified LPL as a crucial regulator for murine and human adipogenesis, into question.

Dataset Information

The role of microRNA-23b-5p in regulating brown adipogenesis and thermogenic program.

Publications

The role of microRNA-23b-5p in regulating brown adipogenesis and thermogenic program.

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