Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery

International Journal of Obesity : Journal of the International Association for the Study of Obesity
Q WuNigel J Gooderham

Abstract

Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent wi...Continue Reading

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Citations

Jan 1, 2015·Nature Reviews. Disease Primers·Elizabeth M BruntMary E Rinella
Oct 21, 2016·Obesity Surgery·Caroline M J TheunissenBarbara S Langenhoff
Jun 2, 2016·Cardiovascular Diabetology·Concepción PeiróCarlos F Sánchez-Ferrer
Mar 28, 2017·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Y O Nunez LopezA A Seyhan
Sep 9, 2018·Glia·Marta FumagalliClaudia Verderio
Jul 14, 2018·Diabetes/metabolism Research and Reviews·Nadeeja N WijayatungaNaima Moustaid-Moussa
Jul 14, 2017·Proceedings. Biological Sciences·David R SamsonCharles L Nunn
Aug 25, 2019·Journal of Clinical Medicine·Gladys LangiAdam Kretowski
Nov 5, 2020·International Journal of Molecular Sciences·Lucia La Sala, Antonio E Pontiroli
Aug 16, 2021·The Journal of Physiology·Bruna Brasil BrandaoC Ronald Kahn

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Methods Mentioned

BETA
gastric bypass
NMR
nuclear magnetic resonance
PCR

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