PMID- 34690929 OWN - NLM STAT- MEDLINE DCOM- 20220214 LR - 20220214 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 12 DP - 2021 TI - Type 2 Diabetes Modifies Skeletal Muscle Gene Expression Response to Gastric Bypass Surgery. PG - 728593 LID - 10.3389/fendo.2021.728593 [doi] LID - 728593 AB - INTRODUCTION: Roux-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. METHODS: Vastus 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/m(2)) and without (CON; n = 7, 43 +/- 6 years, 51.0 +/- 9.2 kg/m(2)) 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. RESULTS: Pre-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. CONCLUSION: Black 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. CI - Copyright (c) 2021 Barberio, Dohm, Pories, Gadaleta, Houmard, Nadler and Hubal. FAU - Barberio, Matthew D AU - Barberio MD AD - Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, United States. AD - Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, United States. FAU - Dohm, G Lynis AU - Dohm GL AD - Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, United States. FAU - Pories, Walter J AU - Pories WJ AD - Department of Surgery, Brody School of Medicine, East Carolina University, Greenville, NC, United States. FAU - Gadaleta, Natalie A AU - Gadaleta NA AD - Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, United States. FAU - Houmard, Joseph A AU - Houmard JA AD - Human Performance Laboratory, Department of Kinesiology, College of Health and Human Performance, East Carolina University, Greenville, NC, United States. FAU - Nadler, Evan P AU - Nadler EP AD - Division of Pediatric Surgery, Children's National Hospital, Washington, DC, United States. FAU - Hubal, Monica J AU - Hubal MJ AD - Center for Genetic Medicine Research, Children's National Research Institute, Washington, DC, United States. AD - Department of Kinesiology, Indiana University Purdue University Indianapolis, Indianapolis, IN, United States. LA - eng GR - UL1 TR000075/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20211006 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 SB - IM MH - Adult MH - Biopsy MH - Case-Control Studies MH - Diabetes Mellitus, Type 2/complications/genetics/pathology/*surgery MH - Female MH - *Gastric Bypass MH - Gene Expression MH - Gene Expression Profiling MH - Humans MH - Middle Aged MH - Muscle, Skeletal/*metabolism/pathology MH - Obesity/complications/genetics/pathology/surgery MH - *Transcriptome MH - Treatment Outcome MH - United States PMC - PMC8526857 OTO - NOTNLM OT - bariatric (weight-loss) surgery OT - gene expression OT - metabolism OT - skeletal muscle OT - type 2 diabetes (T2D) COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/10/26 06:00 MHDA- 2022/02/15 06:00 PMCR- 2021/01/01 CRDT- 2021/10/25 06:24 PHST- 2021/06/21 00:00 [received] PHST- 2021/09/13 00:00 [accepted] PHST- 2021/10/25 06:24 [entrez] PHST- 2021/10/26 06:00 [pubmed] PHST- 2022/02/15 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2021.728593 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2021 Oct 6;12:728593. doi: 10.3389/fendo.2021.728593. eCollection 2021.