Y O Nunez Lopez1, P M Coen1,2, B H Goodpaster1,2, A A Seyhan1,2,3. 1. Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL, USA. 2. Sanford Burnham Prebys Medical Discovery Institute, Lake Nona, FL, USA. 3. Massachusetts Institute of Technology, Chemical Engineering Department Cambridge, MA, USA.
Abstract
BACKGROUND/ OBJECTIVES:Roux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (SI) and β-cell function in obese non-diabetic subjects. Exercise also improves SI and may be an effective adjunct therapy to RYGB surgery. However, the mechanisms by which exercise or weight loss improve peripheral SI after RYGB surgery are unclear. We hypothesized that microRNAs (miRNAs) mediate at least some of the regulatory processes driving such mechanisms. Consequently, this work aimed at profiling plasma miRNAs in participants of the Physical Activity Following Surgery Induced Weight Loss study (clinicaltrials.gov identifier: NCT00692367), to assess whether miRNA levels track with improvements in SI and cardiometabolic risk factors. SUBJECTS/ METHODS: Ninety-four miRNAs implicated in metabolism were profiled in plasma samples from 22 severely obese subjects who were recruited 1-3 months after RYGB surgery and followed for 6 months of RYGB surgery-induced weight loss, with (exercise program (EX), N=11) or without (CON, N=11) an exercise training intervention. The subjects were selected, considering a priori sample size calculations, among the participants in the parent study. Mixed-effect modeling for repeated measures and partial correlation analysis was implemented in the R environment for statistical analysis. RESULTS: Mirroring results in the parent trial, both groups experienced significant weight loss and improvements in cardiometabolic risk. In the CON group, weight loss significantly altered the pattern of circulating miR-7, miR-15a, miR-34a, miR-106a, miR-122 and miR-221. In the EX group, a distinct miRNA signature was altered: miR-15a, miR-34a, miR-122, miR-135b, miR-144, miR-149 and miR-206. Several miRNAs were significantly associated with improvements in acute insulin response, SI, and other cardiometabolic risk factors. CONCLUSIONS: These findings present novel insights into the RYGB surgery-induced molecular changes and the effects of mild exercise to facilitate and/or maintain the benefits of a 'comprehensive' weight-loss intervention with concomitant improvements in cardiometabolic functions. Notably, we show a predictive value for miR-7, miR-15a, miR-106b and miR-135b.
RCT Entities:
BACKGROUND/ OBJECTIVES: Roux-en-Y gastric bypass (RYGB) surgery improves insulin sensitivity (SI) and β-cell function in obese non-diabetic subjects. Exercise also improves SI and may be an effective adjunct therapy to RYGB surgery. However, the mechanisms by which exercise or weight loss improve peripheral SI after RYGB surgery are unclear. We hypothesized that microRNAs (miRNAs) mediate at least some of the regulatory processes driving such mechanisms. Consequently, this work aimed at profiling plasma miRNAs in participants of the Physical Activity Following Surgery Induced Weight Loss study (clinicaltrials.gov identifier: NCT00692367), to assess whether miRNA levels track with improvements in SI and cardiometabolic risk factors. SUBJECTS/ METHODS: Ninety-four miRNAs implicated in metabolism were profiled in plasma samples from 22 severely obese subjects who were recruited 1-3 months after RYGB surgery and followed for 6 months of RYGB surgery-induced weight loss, with (exercise program (EX), N=11) or without (CON, N=11) an exercise training intervention. The subjects were selected, considering a priori sample size calculations, among the participants in the parent study. Mixed-effect modeling for repeated measures and partial correlation analysis was implemented in the R environment for statistical analysis. RESULTS: Mirroring results in the parent trial, both groups experienced significant weight loss and improvements in cardiometabolic risk. In the CON group, weight loss significantly altered the pattern of circulating miR-7, miR-15a, miR-34a, miR-106a, miR-122 and miR-221. In the EX group, a distinct miRNA signature was altered: miR-15a, miR-34a, miR-122, miR-135b, miR-144, miR-149 and miR-206. Several miRNAs were significantly associated with improvements in acute insulin response, SI, and other cardiometabolic risk factors. CONCLUSIONS: These findings present novel insights into the RYGB surgery-induced molecular changes and the effects of mild exercise to facilitate and/or maintain the benefits of a 'comprehensive' weight-loss intervention with concomitant improvements in cardiometabolic functions. Notably, we show a predictive value for miR-7, miR-15a, miR-106b and miR-135b.
Authors: C Dirksen; N B Jørgensen; K N Bojsen-Møller; S H Jacobsen; D L Hansen; D Worm; J J Holst; S Madsbad Journal: Diabetologia Date: 2012-04-27 Impact factor: 10.122
Authors: Clarissa P C Gomes; Getúlio P Oliveira; Bibiano Madrid; Jeeser A Almeida; Octávio L Franco; Rinaldo W Pereira Journal: Biomarkers Date: 2014-08-22 Impact factor: 2.658
Authors: Paul M Coen; Charles J Tanner; Nicole L Helbling; Gabriel S Dubis; Kazanna C Hames; Hui Xie; George M Eid; Maja Stefanovic-Racic; Frederico G S Toledo; John M Jakicic; Joseph A Houmard; Bret H Goodpaster Journal: J Clin Invest Date: 2014-12-01 Impact factor: 14.808
Authors: Chasity B Coleman; Daniel J Lightell; Stephanie C Moss; Michael Bates; Patrick E Parrino; T Cooper Woods Journal: Mol Cell Endocrinol Date: 2013-05-03 Impact factor: 4.102
Authors: Dwi Setyowati Karolina; Arunmozhiarasi Armugam; Subramaniam Tavintharan; Michael T K Wong; Su Chi Lim; Chee Fang Sum; Kandiah Jeyaseelan Journal: PLoS One Date: 2011-08-01 Impact factor: 3.240
Authors: Md Sayed Ali Sheikh; Ke Xia; Fei Li; Xu Deng; Umme Salma; Hai Deng; Liu Wei Wei; Tian-Lun Yang; Jun Peng Journal: Biomed Res Int Date: 2015-01-15 Impact factor: 3.411
Authors: Alejandro Carretero-Ruiz; María Del Carmen Olvera-Porcel; Iván Cavero-Redondo; Celia Álvarez-Bueno; Vicente Martínez-Vizcaíno; Manuel Ferrer-Márquez; Alberto Soriano-Maldonado; Enrique G Arter Journal: Obes Surg Date: 2019-10 Impact factor: 4.129
Authors: Yury O Nunez Lopez; Ravi Retnakaran; Bernard Zinman; Richard E Pratley; Attila A Seyhan Journal: Mol Metab Date: 2018-11-16 Impact factor: 7.422
Authors: G Catanzaro; T Filardi; C Sabato; A Vacca; S Migliaccio; S Morano; E Ferretti Journal: J Endocrinol Invest Date: 2020-10-28 Impact factor: 4.256