Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery

IntroductionRoux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) that can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscl...

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Main Authors: Matthew D. Barberio, G. Lynis Dohm, Walter J. Pories, Natalie A. Gadaleta, Joseph A. Houmard, Evan P. Nadler, Monica J. Hubal
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Endocrinology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2021.728593/full
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author Matthew D. Barberio
Matthew D. Barberio
G. Lynis Dohm
Walter J. Pories
Natalie A. Gadaleta
Joseph A. Houmard
Evan P. Nadler
Monica J. Hubal
Monica J. Hubal
author_facet Matthew D. Barberio
Matthew D. Barberio
G. Lynis Dohm
Walter J. Pories
Natalie A. Gadaleta
Joseph A. Houmard
Evan P. Nadler
Monica J. Hubal
Monica J. Hubal
author_sort Matthew D. Barberio
collection DOAJ
description IntroductionRoux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) that can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscle transcriptome changes.MethodsVastus lateralis biopsy transcriptomes were generated pre- and 1-year post-RYGB in black adult females with (T2D; n = 5, age = 51 ± 6 years, BMI = 53.0 ± 5.8 kg/m2) and without (CON; n = 7, 43 ± 6 years, 51.0 ± 9.2 kg/m2) T2DM. Insulin, glucose, and HOMA-IR were measured in blood at the same time points. ANCOVA detected differentially expressed genes (p < 0.01, fold change < |1.2|), which were used to identify enriched biological pathways.ResultsPre-RYGB, 95 probes were downregulated with T2D including subunits of mitochondrial complex I. Post-RYGB, the T2D group had normalized gene expression when compared to their non-diabetic counterparts with only three probes remaining significantly different. In the T2D, we identified 52 probes upregulated from pre- to post-RYGB, including NDFUB7 and NDFUA1.ConclusionBlack females with T2DM show extensive downregulation of genes across aerobic metabolism pathways prior to RYGB, which resolves 1 year post-RYGB and is related to improvements in clinical markers. These data support efficacy of RYGB for improving skeletal muscle health, especially in patients with T2DM.
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spelling doaj.art-edc5e5204f1746b99e3ade645fa2ad222022-12-21T23:11:36ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-10-011210.3389/fendo.2021.728593728593Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass SurgeryMatthew D. Barberio0Matthew D. Barberio1G. Lynis Dohm2Walter J. Pories3Natalie A. Gadaleta4Joseph A. Houmard5Evan P. Nadler6Monica J. Hubal7Monica J. Hubal8Center for Genetic Medicine Research, Children’s National Research Institute, Washington, DC, United StatesDepartment of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, United StatesDepartment of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United StatesDepartment of Surgery, Brody School of Medicine, East Carolina University, Greenville, NC, United StatesDepartment of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, United StatesHuman Performance Laboratory, Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC, United StatesDivision of Pediatric Surgery, Children’s National Hospital, Washington, DC, United StatesCenter for Genetic Medicine Research, Children’s National Research Institute, Washington, DC, United StatesDepartment of Kinesiology, Indiana University Purdue University Indianapolis, Indianapolis, IN, United StatesIntroductionRoux-en-Y gastric bypass (RYGB) is an effective treatment for type 2 diabetes mellitus (T2DM) that can result in remission of clinical symptoms, yet mechanisms for improved skeletal muscle health are poorly understood. We sought to define the impact of existing T2DM on RYGB-induced muscle transcriptome changes.MethodsVastus lateralis biopsy transcriptomes were generated pre- and 1-year post-RYGB in black adult females with (T2D; n = 5, age = 51 ± 6 years, BMI = 53.0 ± 5.8 kg/m2) and without (CON; n = 7, 43 ± 6 years, 51.0 ± 9.2 kg/m2) T2DM. Insulin, glucose, and HOMA-IR were measured in blood at the same time points. ANCOVA detected differentially expressed genes (p < 0.01, fold change < |1.2|), which were used to identify enriched biological pathways.ResultsPre-RYGB, 95 probes were downregulated with T2D including subunits of mitochondrial complex I. Post-RYGB, the T2D group had normalized gene expression when compared to their non-diabetic counterparts with only three probes remaining significantly different. In the T2D, we identified 52 probes upregulated from pre- to post-RYGB, including NDFUB7 and NDFUA1.ConclusionBlack females with T2DM show extensive downregulation of genes across aerobic metabolism pathways prior to RYGB, which resolves 1 year post-RYGB and is related to improvements in clinical markers. These data support efficacy of RYGB for improving skeletal muscle health, especially in patients with T2DM.https://www.frontiersin.org/articles/10.3389/fendo.2021.728593/fullskeletal musclebariatric (weight-loss) surgerytype 2 diabetes (T2D)gene expressionmetabolism
spellingShingle Matthew D. Barberio
Matthew D. Barberio
G. Lynis Dohm
Walter J. Pories
Natalie A. Gadaleta
Joseph A. Houmard
Evan P. Nadler
Monica J. Hubal
Monica J. Hubal
Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery
Frontiers in Endocrinology
skeletal muscle
bariatric (weight-loss) surgery
type 2 diabetes (T2D)
gene expression
metabolism
title Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery
title_full Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery
title_fullStr Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery
title_full_unstemmed Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery
title_short Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery
title_sort type 2 diabetes modifies skeletal muscle gene expression response to gastric bypass surgery
topic skeletal muscle
bariatric (weight-loss) surgery
type 2 diabetes (T2D)
gene expression
metabolism
url https://www.frontiersin.org/articles/10.3389/fendo.2021.728593/full
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