MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism.
OBJECTIVE
Mechanisms 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.


RESULTS
First, 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).


CONCLUSIONS
We 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.
Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan; Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Masayoshi
M
Ishida
Department of Cardio-Diabetes Medicine, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.
Michio
M
Shimabukuro
Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.
Shusuke
S
Yagi
Department of Nutrition and Metabolism, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.
Sachiko
S
Nishimoto
Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Chisayo
C
Kozuka
Department of Cardio-Diabetes Medicine, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.
Daiju
D
Fukuda
Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.
Takeshi
T
Soeki
Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Hiroaki
H
Masuzaki
Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Masato
M
Tsutsui
Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences, Tokushima, Japan.
Masataka
M
Sata
D020413:3' Untranslated Regions / Q000235:genetics; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D016297:Mutagenesis, Site-Directed; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020413:3' Untranslated Regions; D052242:Adiponectin; C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha