Effect of bariatric surgery on circulating and urinary mitochondrial DNA copy numbers in obesity with or without diabetes

Abstract

IntroductionRecent studies have suggested that extracellular circulating and urinary mitochondrial DNA (mtDNA) are associated with mitochondrial dysfunction in obesity and type 2 diabetes mellitus (T2DM). However, the changes to cell-free serum and urinary mtDNA after bariatric surgery in patients with obesity with T2DM have not been investigated to date.Research design and methodsWe prospectively recruited patients with obesity (n=18), and with obesity and T2DM (n=14) who underwent bariatric surgery, along with healthy volunteers (HV) as a control group (n=22). Serum and urinary mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) copy numbers were measured using quantitative PCR (qPCR). The mtDNA copy numbers of patients with obesity (with and without T2DM) were followed up 6 months after surgery.ResultsThe copy numbers of urinary mtND-1 and mtCOX-3 in patients with obesity, with or without T2DM, were higher than those in the HVs. Moreover, urinary mtCOX-3 copy number increased in patients with obesity with T2DM compared with patients with obesity without T2DM (p=0.018). Meanwhile, serum mtCOX-3 copy numbers in HV were higher in both obesity patient groups (p=0.040). Bariatric surgery reduced urinary mtND-1 and mtCOX-3 copy numbers, as well as serum mtCOX-3 copy numbers only in patients with obesity with T2DM.ConclusionThese results suggest that T2DM induces greater kidney mitochondrial dysfunction in patients with obesity, which can be effectively restored with bariatric surgery.

Increased level of free‐circulating MtDNA in maintenance hemodialysis patients: Possible role in systemic inflammation

“…Indeed, by measuring the urinary MtDNA content in patients with residual urine, we found that although not statistically significant, there was a negative correlative trend between urine MtDNA and ccf‐MtDNA. The results of this study strongly support the idea that kidney is responsible for scavenging plasma MtDNA 25,33 . Previous studies proposed that circulating MtDNA is originated by passive leakage from broken mitochondria 7 .…”

“…The results of this study strongly support the idea that kidney is responsible for scavenging plasma MtDNA. 25,33 Previous studies proposed that circulating MtDNA is originated by passive leakage from broken mi-…”

Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents

“…This is in line with the observation that ecDNA correlates with body fat and inflammation but not with BMI (55). Similarly, bariatric surgery as the most effective treatment of obesity leads to a decrease of ecDNA but only in diabetic subjects (56).…”

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

“…For this reason, mtDNA methylation appears as a promising mediator between environmental exposure (i.e., diet) or metabolic conditions (i.e., obesity) and mitochondrial health. In addition, the blood level of mtDNA copy number (mtDNAcn) has emerged as a promising biomarker, especially in obesity [ 32 , 33 ], metabolic diseases (e.g., type 2 diabetes) [ 34 – 36 ], and CVD [ 37 , 38 ], and clinical interventions have been shown to modulate this parameter [ 39 ]. Despite the link between mtDNA, environmental exposures and complex diseases, and mtDNA's potential role as a biomarker, no previous research projects investigated mtDNAcn in people with increased body weight correlating it with the nutritional status, the abundance of 1CC intermediates, and with mtDNA methylation.…”