MicroRNA-378 Regulates Adiponectin Expression in Adipose Tissue: A New Plausible Mechanism

Abstract

AimsMechanisms regulating adiponectin expression have not been fully clarified. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are involved in biological processes, including obesity and insulin resistance. We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression.Methods and ResultsFirst, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3′-UTR binding site. Addition of tumor necrosis factor-α (TNFα) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r = −0.624, p = 0.004).ConclusionsWe found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence-binding site. Our findings warrant further investigations into the role of miRNAs in regulating the adiponectin expression.

Mapping Research in the Obesity, Adipose Tissue, and MicroRNA Field: A Bibliometric Analysis

“…Huang et al demonstrated that inhibition of MAPK1 by overexpressing mir-378a-5p in 3T3-L cells promotes adipogenesis and lipid accumulation [98]. Similar to this study, Ishida et al showed that the expression of miR-378a-5p is inversely correlated with the expression of adiponectin in obese rats, otherwise it positively correlates with the increase of TNF-α [104].…”

MicroRNA-193b Controls Adiponectin Production in Human White Adipose Tissue

“…Research in the field describes the regulation of miRNAs by adiponectin (11) or the regulation of adiponectin receptor expression by miRNAs (12,13). In murine cells, miR-21 and miR-378 have been reported to regulate adiponectin expression (14,15). Our results thus add an additional regulatory layer, namely the regulation of adiponectin itself by miRNA in human adipocytes.…”

miR-876-3p regulates glucose homeostasis and insulin sensitivity by targeting adiponectin

“…miR-378 has been shown to regulate adiponectin level by binding to the 3′UTR of the adiponectin. Further, overexpression of miR-378 in 3T3L1 cells decreased mRNA and protein levels of adiponectin (Ishida et al 2014). A similar study in humans have shown significant association of serum adiponectin level with increased expression of miR-193b in white adipose tissue (Belarbi et al 2015).…”