MicroRNA-130b attenuates dexamethasone-induced increase of lipid accumulation in porcine preadipocytes by suppressing PPAR-γ expression

Abstract

In this study, two experiments were conducted to determine the role of miR-130b in dexamethasone (DEX)-induced lipid accumulation. Porcine preadipocytes were treated with 10−6 M DEX for 48 h to investigate effects of DEX in lipid accumulation. Next, in order to illustrate the regulatory role of miR-130b on lipid accumulation induced by DEX, miRNA scrambled control (miR-SC), miR-130b overexpression plasmid and miR-130b inhibitor were respectively transfected into porcine preadipocytes at 24 h before DEX treatment for 48 h (miR-SC-DEX, miR-130b-DEX and miR-130b-inhibitor-DEX). Results showed that 10−6 M DEX significantly increased TG concentration and expression of miR-130b as well as its target gene peroxisome proliferator-activated receptor-γ (PPAR-γ). Dual-luciferase reporter assays indicated that PPAR-γ expression was negatively regulated by miR-130b, while this effect was abolished with cotransfection of miR-130b and miR-130b inhibitor. In addition, miR-130b-DEX did not change cell proliferation but significantly decreased TG concentration and PPAR-γ expression compared to miR-SC-DEX cells, while miR-130b-inhibitor-DEX cells presented opposite results. Furthermore, miR-130b-DEX significantly reduced expression of PPAR-γ downstream factor perilipin 1 as well as adipogenesis genes fatty acid synthase, acetyl coenzyme A carboxylase, 11β hydroxysteroid dehydrogenase type 1 and fat mass and obesity-associated gene, whereas expression as well as enzyme activity of adipose triglyceride lipase and hormone-sensitive lipase were greatly increased. Overall, these results clarified the role of miR-130b in DEX-induced increase of lipid accumulation in porcine preadipocytes, suggesting that miR-130b might be deemed as a novel potential therapeutic target for DEX-induced increase of lipid accumulation, and consequently provide new insights in obesity control.

miR-130b is a potent stimulator of hepatic very-low-density lipoprotein assembly and secretion via marked induction of microsomal triglyceride transfer protein

“…S6A). These results are in alignment with the previous reports that showed miR-130b-3p could directly target PPAR-␥ (19,(25)(26)(27)(28)48), TNF␣ (51), and STAT3 (50) and decrease the expression of SIK1 mRNA (42).…”

CRISPR/Cas9-Mediated Knockout of miR-130b Affects Mono- and Polyunsaturated Fatty Acid Content via PPARG-PGC1α Axis in Goat Mammary Epithelial Cells

“…The concentration of intracellular TAG, which is made up of fatty acids and glycerol, was increased after knocking out miR-130b in our research, which agrees with previous studies in porcine and mice [ 45 , 46 ]. In agreement with the function of GPAM, AGPAT6, and DGAT1 enzymes in TAG synthesis [ 47 ], the mRNA expression of these three genes was upregulated in miR-130b knockout cells.…”

Dexamethasone Suppresses Palatal Cell Proliferation through miR-130a-3p

“…Excessive atRA, DEX, and phenytoin induce CP in mice [24,39,40]. Excessive atRA induces CP through upregulated miR-124-3p expression [11], and DEX induces miR-130b and miR-155 in porcine pre-adipocytes and differentiating 3T3-L1 pre-adipocytes, respectively [41,42]. DEX also inhibits miR-132 expression through TGF-β signaling in pancreatic cancer [43].…”