Expression Profiling of PPARγ-Regulated MicroRNAs in Human Subcutaneous and Visceral Adipogenesis in both Genders

Abstract

Clinical evidence shows that visceral fat accumulation decreases whereas sc fat increases in patients treated with thiazolidinediones (TZDs), a type of peroxisome proliferator-activated receptor (PPAR)γ agonist. To clarify the molecular mechanism of the differential effects of PPARγ agonists on sc and visceral adipose, we investigated expression profiling of PPARγ-regulated micro-RNAs (miRNAs) using miRNA microarray. The level of 182 miRNAs changed in human sc adipose treated with pioglitazone, whereas only 46 miRNAs changed in visceral adipose. Among these miRNAs, 27 miRNAs changed in both human sc and visceral adipocytes. Specifically, 7 miRNAs changed at the same direction in sc and visceral adipocytes, whereas 20 miRNAs changed at opposite directions in these two fat depots. Bioinformatics analysis showed that these miRNAs and the predicted target genes were involved in TGF-β-, Wnt/β-catenin-, and insulin-signaling pathways and related to metabolic regulation or cell cycle. Among the miRNAs changed at the same direction in sc and visceral adipocytes, miR-378, located in the first intron of PPARγ coactivator 1β (PGC1β), was coordinately expressed with PGC1β during adipogenesis. Moreover, miR-378 and PGC1β were both up-regulated by PPARγ agonist. We also provided evidence that miR-378 promoted adipogenesis in sc fat, but not in visceral fat. These results display miRNAs expression profiling altered in sc and visceral adipogenesis regulated by PPARγ and suggest a potential mechanism underlying the differential effects of TZDs on the 2 fat depot accumulations.

Lauric acid can improve the sensitization of Cetuximab in KRAS/BRAF mutated colorectal cancer cells by retrievable microRNA-378 expression

“…Apparently, stable high expression level of miR-378 is required for CRC cells response to Cetuximab, irrespective of their BRAF or KRAS status (Fig. 4a, Table I) (24). We noted a contradictory effect on the cell survival between BRAF and KRAS mutated CRC cells after performing miR-378 transfection in vitro.…”

Transcriptional and Epigenomic Regulation of Adipogenesis

“…Studies have suggested that several miRNAs play a role in adipose tissue development and associated metabolism (155). A study used miRNA microarray analysis to profile PPAR␥-regulated miRNAs in human adipocytes (156). Among 27 miRNAs whose expression was altered by treatment of pioglitazone, a synthetic PPAR␥ ligand, miR-378, has been shown to promote adipogenesis of subcutaneous adipocytes but not of visceral adipocytes.…”

Potential role of microRNAs in the regulation of adipocytes liposecretion and adipose tissue physiology

“…Accordingly, the exposure of adipocytes to thiazolidinediones, a fat-cell differentiation driver, resulted in the over-expression of around 200 miRNAs in subcutaneous adipocytes, whereas only a small number of these miRNAs were found to be expressed in visceral-derived adipocytes (Yu et al, 2014). Furthermore, regional differences in levels of miRNA expression within subcutaneous white adipose tissue have also been described (Rantalainen et al, 2011).…”