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.
Highlights
Adipose tissue secretes adipocytokine/adipokine, which play critical roles in energy and vascular homeostasis [1,2]
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 = 20.624, p = 0.004)
We found that levels of miRNA-378 could modulate adiponectin expression via the 3 prime untranslated region (3’UTR) sequence-binding site
Summary
Adipose tissue secretes adipocytokine/adipokine, which play critical roles in energy and vascular homeostasis [1,2]. Regulation of these adipocytokine/adipokine triggers the development of a pro-inflammatory state, which is considered to form the ‘‘common soil’’ for the pathogenesis of obesity-linked disorders [1,2]. It is known that adiponectin gene expression in adipose tissues is down-regulated in subjects with obesity and insulin resistance [3,4]; the mechanisms of the down-regulation are largely unknown. Since hypoadiponectinemia has links to metabolic and cardiovascular abnormalities associated with obesity and insulin resistance [7,8], exploring the mechanisms regulating adiponectin expression and posttranslational modification is crucial for understanding obesitylinked disorders
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