| First Author | Saha PK | Year | 2020 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 319 |
| Issue | 4 | Pages | E667-E677 |
| PubMed ID | 32799658 | Mgi Jnum | J:296862 |
| Mgi Id | MGI:6469160 | Doi | 10.1152/ajpendo.00045.2020 |
| Citation | Saha PK, et al. (2020) miR-30a targets gene networks that promote browning of human and mouse adipocytes. Am J Physiol Endocrinol Metab 319(4):E667-E677 |
| abstractText | MicroRNA-30a (miR-30a) impacts adipocyte function, and its expression in white adipose tissue (WAT) correlates with insulin sensitivity in obesity. Bioinformatic analysis demonstrates that miR-30a expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of miR-30a function in fat cells remain unclear. Here, we expanded our understanding of how miR-30a expression contributes to antidiabetic peroxisome proliferator-activated receptor-gamma (PPARgamma) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced miR-30a levels and diminished expression of the canonical PPARgamma target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, miR-30a required PPARgamma for maximal expression, and the PPARgamma agonist rosiglitazone robustly induced miR-30a but not other miR-30 family members. Transcriptional activity studies in human adipocytes also revealed that ectopic expression of miR-30a enhanced the activity of rosiglitazone coupled with higher expression of fatty acid and glucose metabolism markers. Diabetic mice that overexpress ectopic miR-30a in subcutaneous WAT display durable reductions in serum glucose and insulin levels for more than 30 days. In agreement with our in vitro findings, RNA-seq coupled with Gene Set Enrichment Analysis (GSEA) suggested that miR-30a enabled activation of the beige fat program in vivo, as evidenced by enhanced mitochondrial biogenesis and induction of UCP1 expression. Metabolomic and gene expression profiling established that the long-term effects of ectopic miR-30a expression enable accelerated glucose metabolism coupled with subcutaneous WAT hyperplasia. Together, we establish a putative role of miR-30a in mediating PPARgamma activity and advancing metabolic programs of white to beige fat conversion. |
