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miR-30a targets gene networks that promote browning of human and mouse adipocytes.


ABSTRACT: 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-γ (PPARγ) 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 PPARγ target genes ADIPOQ and FABP4 relative to lean counterparts. In human adipocytes, miR-30a required PPARγ for maximal expression, and the PPARγ 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 PPARγ activity and advancing metabolic programs of white to beige fat conversion.

SUBMITTER: Saha PK 

PROVIDER: S-EPMC7864240 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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<i>miR-30a</i> targets gene networks that promote browning of human and mouse adipocytes.

Saha Pradip K PK   Hamilton Mark P MP   Rajapakshe Kimal K   Putluri Vasanta V   Felix Jessica B JB   Masschelin Peter P   Cox Aaron R AR   Bajaj Mandeep M   Putluri Nagireddy N   Coarfa Cristian C   Hartig Sean M SM  

American journal of physiology. Endocrinology and metabolism 20200817 4


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 <i>miR-30a</i> expression contributes to 2% of all miRNA expression in human tissues. However, molecular mechanisms of <i>miR-30a</i> function in fat cells remain unclear. Here, we expanded our understanding of how <i>miR-30a</i> expression contributes to antidiabetic peroxisome proliferator-activated receptor  ...[more]

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