Roux-en-Y gastric bypass stimulates hypothalamic miR-122 and inhibits cardiac and hepatic miR-122 expressions

Abstract

Background: MicroRNAs (miRNAs) are endogenous noncoding small ribonucleic acids that have emerged as one of the central players of gene expression regulation. This study was designed to determine and identify miRNAs that are associated with Roux-en-Y gastric bypass (RYGB). Methods: Male SpragueeDawley rats were divided into two groups: sham and RYGB. Changes in food intake and body weight were measured. miRNA microarray analyses on the brain hypothalamus and heart were performed. The expressions of miR-122 were analyzed, and the activities of adenosine monophosphateeactivated protein kinase (AMPK) were determined in the hypothalamus, heart, and liver. Antisense oligonucleotide miR-122 was transfected into hepatocellular carcinoma cells to validate in vivo results. Results: Body weights decreased in the RYGB group compared with those in sham group. Food intake was different between sham and RYGB groups. Of 350 miRNAs that were investigated, we observed that miR-122, being predominantly found in the liver, markedly increased (>35-fold) in the hypothalamus and decreased (>4-fold) in the heart. Quantitative polymerase chain reaction analysis revealed that expression of miR-122 was induced in hypothalamus but attenuated in the heart and liver of the RYGB group. Activities of AMPK were decreased in the hypothalamus but increased in the heart and liver. Knockdown of miR-122 in hepatocellular carcinoma cells stimulated phosphorylation levels AMPK. Conclusions: The results in this study suggest that RYGB regulates the expressions of miR- 122 in the hypothalamus, heart, and liver, which in turn may modulate the activities of AMPK, the master regulator of metabolism.