Plasma mitochondrial DNA is elevated in obese type 2 diabetes mellitus patients and correlates positively with insulin resistance

Yuzefovych, Larysa V.; Pastukh, Viktor M.; Ruchko, Mykhaylo V.; Simmons, Jon D.; Richards, William O.; Rachek, Lyudmila I.

doi:10.1371/journal.pone.0222278

Cited by 43 publications

(34 citation statements)

References 47 publications

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“…Due to the damage to mitochondrial biology, the amount of mtDNA in tissues (such as heart, liver, pancreas, and kidney) in the DM model decreased, while the amount of mtDNA in peripheral blood increased in patients with DM. Early increase in mtDNA copy number is closely related to insulin resistance and increased inflammatory factors [22,24,32]. Al-Kafaji et al observed similar reductions in mtDNA copy number in peripheral blood in clinical trials.…”

Section: Change Of Mtdna In Bloodmentioning

confidence: 93%

Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease

Huang

Chi

Wei

et al. 2020

International Journal of Endocrinology

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Diabetic kidney disease (DKD) is a common cause of end-stage renal disease, and diagnosis and treatment in time can help delay its progress. At present, there are more and more studies on the pathogenesis of DKD; mitochondrial dysfunction plays an important role in DKD. The occurrence and development of DKD is closely related to epigenetic changes and the interaction between mtDNA, ROS, inflammatory factors, and endothelial damage, which continuously aggravates kidney. The change of mtDNA is both the cause of DKD and the result of DKD. It is of great significance to incorporate the change of mtDNA into the monitoring of patients with diabetes. Existing evidence indicates that changes in mtDNA copy number in blood and urine reflect mitochondrial dysfunction and the severity of DKD. However, large-scale, long-term follow-up clinical trials are still needed to determine the threshold range. By the time, mitochondrial-targeted antioxidants will become a new method for the treatment of DKD and other diabetic complications; mtDNA also can be a therapeutic target for them.

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Section: Change Of Mtdna In Bloodmentioning

confidence: 93%

Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease

Huang

Chi

Wei

et al. 2020

International Journal of Endocrinology

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“…The DNA released by WAT explants was associated with high mobility group box 1 (HMGB1), a nuclear protein that was previously shown to be an endogenous DAMP and increases the inflammatory potential of self-DNA ( 19 ). Importantly, systemic levels of these cfDNA and HMGB1 positively correlated with the severity of metabolic syndrome induced by obesity including the extent of visceral fat tissue, insulin resistance, and liver injury ( 14 , 15 , 20 , 21 ).…”

Section: Sources and Forms Of Nucleic Acids That Accumulate During Obmentioning

confidence: 99%

Self-Nucleic Acid Sensing: A Novel Crucial Pathway Involved in Obesity-Mediated Metaflammation and Metabolic Syndrome

et al. 2021

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Obesity and overweight are a global health problem affecting almost one third of the world population. There are multiple complications associated with obesity including metabolic syndrome that commonly lead to development of type II diabetes and non-alcoholic fatty liver disease. The development of metabolic syndrome and severe complications associated with obesity is attributed to the chronic low-grade inflammation that occurs in metabolic tissues such as the liver and the white adipose tissue. In recent years, nucleic acids (mostly DNA), which accumulate systemically in obese individuals, were shown to aberrantly activate innate immune responses and thus to contribute to metabolic tissue inflammation. This minireview will focus on (i) the main sources and forms of nucleic acids that accumulate during obesity, (ii) the sensing pathways required for their detection, and (iii) the key cellular players involved in this process. Fully elucidating the role of nucleic acids in the induction of inflammation induced by obesity would promote the identification of new and long-awaited therapeutic approaches to limit obesity-mediated complications.

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“…The study of Revelo furthermore confirmed that HFD-fed mice lacking TLR9, show reduced metabolic inflammation and treatment of HFD-fed mice with a TLR7/9 antagonist improved metabolic disease. A more recent study from Yuzefovych et al, showed that plasma mtDNA is elevated in obese type 2 diabetes mellitus patients and is associated with oxidative stress in skeletal muscle and correlates with insulin resistance ( Yuzefovych et al, 2019 ). TLR9 message and protein expression levels which are higher in diabetic wounds compared to control wounds have been linked to impaired wound healing in type 2 diabetes mellitus (T2DM) cases via the induction of pro-inflammatory S100A8 and IL-8 ( Singh et al, 2016 ).…”

Section: Multidisciplinary Clues That Reason the Proposed Role For Tlmentioning

confidence: 99%

TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target

Bezemer

Garssen

2021

Front. Pharmacol.

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By mapping the clinical pathophysiology of the novel coronavirus disease 2019 (COVID-19) against insights from virology, immunology, genomics, epidemiology and pharmacology, it is here proposed that the pathogen recognition receptor called toll like receptor 9 (TLR9) might have a pivotal role in the pathogenesis of COVID-19. Severe Acute Respiratory Syndrome Coronavirus 2, is causing the greatest global social and economic disruption since world war II. Lack of a vaccine, lack of successful treatment and limitations of the healthcare workforce and resources needed to safeguard patients with severe COVID-19 on the edge of life, demands radical preventive measures. It is urgently needed to identify biomarkers and drug candidates so that vulnerable individuals can be recognized early and severe multi-organ complications can be prevented or dampened. The TLR9 COVID-19 hypothesis describes a mechanism of action that could explain a wide spectrum of manifestations observed in patients with severe COVID-19. The introduced hypothesis proposes biomarkers for identification of vulnerable individuals and positions TLR9 as a promising multifaceted intervention target for prevention and/or treatment of COVID-19. TLR9 agonists might have value as prophylactic vaccine adjuvants and therapeutic immune stimulators at the early onset of disease. Additionally, in this current manuscript it is proposed for the first time that TLR9 could be considered as a target of “inhibition” aimed to dampen hyperinflammation and thrombotic complications in vulnerable patients that are at risk of developing late stages of COVID-19. The readily availability of TLR9 modulating drug candidates that have reached clinical testing for other disorders could favor a fast track development scenario, an important advantage under the current high unmet medical need circumstances regarding COVID-19.

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Plasma mitochondrial DNA is elevated in obese type 2 diabetes mellitus patients and correlates positively with insulin resistance

Cited by 43 publications

References 47 publications

Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease

Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease

Self-Nucleic Acid Sensing: A Novel Crucial Pathway Involved in Obesity-Mediated Metaflammation and Metabolic Syndrome

TLR9 and COVID-19: A Multidisciplinary Theory of a Multifaceted Therapeutic Target

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