| Summary: | Bariatric surgery offers sustained dramatic weight loss and remission of diabetes, yet the mechanisms of these health benefits are not clear. In the present study, I profiled circulating and colorectal miRNAome in response to bariatric surgery (Roux-en-Y gastric bypass). Indeed, the response of circulating and colorectal miRNA profiles to RYGB were striking and selective. Fourteen circulating microRNA and thirteen colorectal microRNA exhibited significantly alteration post RYGB. Interestingly, circulating miR-122 decreased dramatically (56 fold) post RYGB surgery. The expression of hepatic miR-122 and its metabolic targets were examined both in in vivo RYGB surgical model and in an in vitro mechanistic model. Manipulation of miRNA-122 cold induce changes of key enzymes involved in energy metabolism, glucose transport, glycolysis, TCA cycle, pentose phosphate shunt, fatty acid oxidation and gluconeogenesis, suggesting an overall increased energy expenditure status after RYGB. Furthermore, potential mechanisms involved in the control of hepatic miR-122 were investigated, with focus on metabolites (glucose, and fatty acids), hormones (glucocorticoid) and transcription factors (PPARs). Finally, by correlating the circulating miRNAome and metabolome data, we were able to generate a comprehensive landscape of the crosstalk between miRNAs and metabolic pathways. Follow-up studies will allow a detailed understanding of miRNAs responsible for regulating specific metabolic pathways, and conversely identifying metabolites capable of regulating the expression and activity of specific miRNAs.
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