targets gene networks that promote browning of human and mouse adipocytes.

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 expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of function in fat cells remain unclear. Here, we expanded our understanding of how expression contributes to antidiabetic peroxisome proliferator-activated receptor-γ (PPARγ) agonist activity and metabolic functions in adipocytes. We found that WAT isolated from diabetic patients shows reduced levels and diminished expression of the canonical PPARγ target genes and relative to lean counterparts. In human adipocytes, required PPARγ for maximal expression, and the PPARγ agonist rosiglitazone robustly induced but not other miR-30 family members. Transcriptional activity studies in human adipocytes also revealed that ectopic expression of enhanced the activity of rosiglitazone coupled with higher expression of fatty acid and glucose metabolism markers. Diabetic mice that overexpress ectopic 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 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 expression enable accelerated glucose metabolism coupled with subcutaneous WAT hyperplasia. Together, we establish a putative role of in mediating PPARγ activity and advancing metabolic programs of white to beige fat conversion.