Language
English
Publication Date
10-1-2020
Journal
American Journal of Physiology-Endocrinology and Metabolism
DOI
10.1152/ajpendo.00045.2020
PMID
32799658
PMCID
PMC7864240
PubMedCentral® Posted Date
8-17-2020
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Adipocytes, Brown, Adipocytes, White, Animals, Blood Glucose, Cells, Cultured, Fatty Acid-Binding Proteins, Gene Regulatory Networks, Humans, Hypoglycemic Agents, Insulin Resistance, Metabolomics, Mice, MicroRNAs, Oligopeptides, Organelle Biogenesis, PPAR gamma, Rosiglitazone, etabolism, microRNA, mitochondria, PPARγ, subcutaneous adipocytes
Published Open-Access
yes
Recommended Citation
Saha, Pradip K; Hamilton, Mark P; Rajapakshe, Kimal; et al., "miR-30a Targets Gene Networks That Promote Browning of Human and Mouse Adipocytes" (2020). Faculty, Staff and Students Publications. 763.
https://digitalcommons.library.tmc.edu/baylor_docs/763