Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients

While improvement of mitochondrial function after bariatric surgery has been demonstrated, there is limited evidence about the effects of bariatric surgery on circulatory cell-free (cf) mitochondrial DNA (mtDNA) and intracellular mtDNA abundance. Plasma and peripheral blood mononuclear (PBM) cells w...

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Main Authors: Larysa V. Yuzefovych, Viktor M. Pastukh, Madhuri S. Mulekar, Kate Ledbetter, William O. Richards, Lyudmila I. Rachek
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/11/9/2514
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author Larysa V. Yuzefovych
Viktor M. Pastukh
Madhuri S. Mulekar
Kate Ledbetter
William O. Richards
Lyudmila I. Rachek
author_facet Larysa V. Yuzefovych
Viktor M. Pastukh
Madhuri S. Mulekar
Kate Ledbetter
William O. Richards
Lyudmila I. Rachek
author_sort Larysa V. Yuzefovych
collection DOAJ
description While improvement of mitochondrial function after bariatric surgery has been demonstrated, there is limited evidence about the effects of bariatric surgery on circulatory cell-free (cf) mitochondrial DNA (mtDNA) and intracellular mtDNA abundance. Plasma and peripheral blood mononuclear (PBM) cells were isolated from healthy controls (HC) and bariatric surgery patients before surgery and 2 weeks, 3 months, and 6 months after surgery. At baseline, the plasma level of short cf-mtDNA (<i>ND6</i>, ~100 bp) fragments was significantly higher in obese patients compared to HC. But there was no significant variation in mean <i>ND6</i> values post-surgery. A significant positive correlation was observed between preop plasma <i>ND6</i> levels and HgbA1c, <i>ND6</i> and HOMA-IR 2 weeks post-surgery, and mtDNA content 6 months post-surgery. Interestingly, plasma from both HC and obese groups at all time points post-surgery contains long (~8 kb) cf-mtDNA fragments, suggesting the presence of near-intact and/or whole mitochondrial genomes. No significant variation was observed in mtDNA content post-surgery compared to baseline data in both PBM and skeletal muscle samples. Overall, bariatric surgery improved insulin sensitivity and other metabolic parameters without significant changes in plasma short cf-mtDNA levels or cellular mtDNA content. Our study provides novel insights about possible molecular mechanisms underlying the metabolic effects of bariatric surgery and suggests the development of new generalized approaches to characterize cf-mtDNA.
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spelling doaj.art-d89f4872b4f34fdea77fe06447f0b1bf2023-11-19T09:42:24ZengMDPI AGBiomedicines2227-90592023-09-01119251410.3390/biomedicines11092514Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese PatientsLarysa V. Yuzefovych0Viktor M. Pastukh1Madhuri S. Mulekar2Kate Ledbetter3William O. Richards4Lyudmila I. Rachek5Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USADepartment of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USADepartment of Mathematics and Statistics, College of Art and Science, University of South Alabama, Mobile, AL 36688, USADepartment of Surgery, College of Medicine, University of South Alabama, Mobile, AL 36688, USADepartment of Surgery, College of Medicine, University of South Alabama, Mobile, AL 36688, USADepartment of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USAWhile improvement of mitochondrial function after bariatric surgery has been demonstrated, there is limited evidence about the effects of bariatric surgery on circulatory cell-free (cf) mitochondrial DNA (mtDNA) and intracellular mtDNA abundance. Plasma and peripheral blood mononuclear (PBM) cells were isolated from healthy controls (HC) and bariatric surgery patients before surgery and 2 weeks, 3 months, and 6 months after surgery. At baseline, the plasma level of short cf-mtDNA (<i>ND6</i>, ~100 bp) fragments was significantly higher in obese patients compared to HC. But there was no significant variation in mean <i>ND6</i> values post-surgery. A significant positive correlation was observed between preop plasma <i>ND6</i> levels and HgbA1c, <i>ND6</i> and HOMA-IR 2 weeks post-surgery, and mtDNA content 6 months post-surgery. Interestingly, plasma from both HC and obese groups at all time points post-surgery contains long (~8 kb) cf-mtDNA fragments, suggesting the presence of near-intact and/or whole mitochondrial genomes. No significant variation was observed in mtDNA content post-surgery compared to baseline data in both PBM and skeletal muscle samples. Overall, bariatric surgery improved insulin sensitivity and other metabolic parameters without significant changes in plasma short cf-mtDNA levels or cellular mtDNA content. Our study provides novel insights about possible molecular mechanisms underlying the metabolic effects of bariatric surgery and suggests the development of new generalized approaches to characterize cf-mtDNA.https://www.mdpi.com/2227-9059/11/9/2514circulating cell-free mitochondrial DNAobesityinsulin resistancetype 2 diabetes
spellingShingle Larysa V. Yuzefovych
Viktor M. Pastukh
Madhuri S. Mulekar
Kate Ledbetter
William O. Richards
Lyudmila I. Rachek
Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients
Biomedicines
circulating cell-free mitochondrial DNA
obesity
insulin resistance
type 2 diabetes
title Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients
title_full Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients
title_fullStr Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients
title_full_unstemmed Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients
title_short Effect of Bariatric Surgery on Plasma Cell-Free Mitochondrial DNA, Insulin Sensitivity and Metabolic Changes in Obese Patients
title_sort effect of bariatric surgery on plasma cell free mitochondrial dna insulin sensitivity and metabolic changes in obese patients
topic circulating cell-free mitochondrial DNA
obesity
insulin resistance
type 2 diabetes
url https://www.mdpi.com/2227-9059/11/9/2514
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