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

• Main Authors: Lianghui You, Yan Wang, Yao Gao, Xingyun Wang, Xianwei Cui, Yanyan Zhang, Lingxia Pang, Chenbo Ji, Xirong Guo, Xia Chi
• Format: Article
• Language: English
• Published: Bioscientifica 2020-06-01
• Series: Endocrine Connections
• Subjects: brown adipose; cold stimulation; mir-23b-5p; lipolysis; β-oxidation
• Online Access: https://ec.bioscientifica.com/view/journals/ec/9/5/EC-20-0124.xml

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 a nd 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 re vealed no significant effects on lipid accumulation, but diminished mitochondrial func tion and decreased expression of BAT specific markers. Though luciferase reporter a ssays 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 β-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.