MiR-19b Is Regulated By Glucocorticoid And Controls The Browning Effects Of Adipose Tissue

Objective. Whereas physiological levels of glucocorticoids are required for proper metabolic control, aberrant glucocorticoid action has been linked to a variety of pandemic metabolic diseases, such as type II diabetes and obesity. Based on its importance for human health, studies of the molecular mechanisms of within the glucocorticoid signaling axis have become a major focus in biomedical research. In particular, the understanding of tissue-specific functions of the glucocorticoid receptor pathway has been proven to be of substantial value for the development of novel therapies in the treatment of chronic metabolic disorders. Therefore, we focus on the consequences of experimental modulation of glucocorticoid receptor expression for metabolic homeostasis and dysregulation, particularly emphasizing tissue-specific contributions of the glucocorticoid pathway to the control of energy metabolism. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. The origin of newly formed brown adipocytes in the adipose organ of cold-exposed animals – a phenomenon referred to as ‘browning’. The regulatory role of some mi RNAs varies in different species or different cells microRNAs appear to play important roles in adipocyte differentiation, lipid metabolism.Methods. we used mi RNA microarray analysis of human white adipocytes treated with dexamethasone for 24 hours to identify miRNAs which were regulated by dexamethasone,. We further examined the expression of miR-19 b by real-time PCR to verificate the miRNA microarray. To further investigate the function of miR-19 b in the browning of white fat, mimic-miR19 b or anti-miR-19 b was transfected into primary cells of SAT and VAT. To identify potential mi R-19 b target genes, the miRNA target prediction web site TargetScan was employed. A putative miR-19 b target site was identified at a highly evolutionarily conserved octamer seed motif within the 3’UTR of ADRB1. To determine whether miR-19 b could directly target ADRB1 mRNA, we cloned the 3’ UTR segment of Prdm16 containing the putative miR-19 b target site into a pMiRGLO luciferase reporter construct. To verify these findings at the protein level, miR-19 b expression was modulated in SAT or VAT by transfecting anti-miR-19 b.Results. miR-19 b was one of the most upregulated microRNAs after treated by dexamethasone. Glucocoticoid regulated the transcription of the miR-19 b gene via the binding of GR to the promoter region of mi R-19 b. miR-19 b served as a potent negative regulator of the browning effects on white adipocyte. A putative miR-19 b target site was identified at a highly evolutionarily conserved octamer seed motif within the 3’UTR of ADRB1, a factor that regulate both the brown fat functions and the browning of white fat.Conclusions. In brief, according to our data,miR-19 b was upregulated by glucocorticoid and pointed to a critical role for miR-19 b in the control of the browning effect on WAT and the functions of BAT via ADRB1. It was suggested that miR-19 b might represent a promising therapeutic target for the treatment of obesity and metabolic disorders.