Shorter leucocyte telomere length as a potential biomarker for nonalcoholic fatty liver disease-related advanced fibrosis in T2DM patients

Dong, Kun; Zhang, Ye; Huang, Jiaojiao; Xia, San-Shan; Yang, Yan

doi:10.21037/atm.2020.03.10

Cited by 8 publications

(7 citation statements)

References 38 publications

(42 reference statements)

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“…It has been reported that there is a significant association between telomere length and type 2 diabetes [71]. Moreover, in hTERC-deficient mice, insulin-producing pancreatic beta cells were found to be smaller and more likely to have impaired glucose tolerance, thus suggesting that telomerase dysfunction can lead to impaired regeneration of pancreatic beta cells and affect normal glucose metabolism [72,73].…”

Section: Telomerase In Metabolic Diseasesmentioning

confidence: 99%

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Telomerase: a key player in the pathogenesis of non-alcoholic fatty liver disease?

Tang

Zhang

Byrne

et al. 2021

Expert Review of Gastroenterology & Hepatology

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Introduction:Telomerase is a basic nuclear protein reverse transcriptase, which plays a key role in maintaining telomere stability, genome integrity, long-term cell activity and potential continued proliferation.Area covered: This narrative review discusses key research advances involving telomerase in the development and progression of non-alcoholic fatty liver disease (NAFLD). The review evaluates: a) whether the assessment of telomerase can be used as a non-invasive diagnostic tool; and b) whether modification of telomerase function might be a useful potential therapeutic target for treatment of NAFLD. Furthermore, the relationship between telomerase and other chronic metabolic diseases is evaluated.Expert opinion: Several experimental and preclinical studies have suggested that telomerase plays an important role in the development of NAFLD. However, further mechanistic studies are needed to prove a causal relationship and to better elucidate whether the measurement of telomerase has utility as a diagnostic tool or whether pharmacological manipulation of telomerase has therapeutic potential in NAFLD treatment.

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Section: Telomerase In Metabolic Diseasesmentioning

confidence: 99%

“…Leucocyte telomere length has been shown to be significantly associated with advanced liver fibrosis in patients with T2DM [71]. Moreover, telomerase could also be used as a new therapeutic target to treat NAFLD.…”

Section: Therapeutic Targeting Of Early Disease Severitymentioning

confidence: 99%

Telomerase: a key player in the pathogenesis of non-alcoholic fatty liver disease?

Tang

Zhang

Byrne

et al. 2021

Expert Review of Gastroenterology & Hepatology

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“…Hypothetically, liver function enzymes such as ALT and AST are not directly involved in the regulation of TL. Despite this, recent studies have shown that shorter leucocyte telomere length (LTL) is significantly correlated with advanced hepatic fibrosis and high levels of ALT and AST enzymes in T2DM patients (Dong et al 2020 ). The observation also suggests that shorter LTL may be used as a biomarker for advanced fibrosis in T2DM patients (Dong et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Despite this, recent studies have shown that shorter leucocyte telomere length (LTL) is significantly correlated with advanced hepatic fibrosis and high levels of ALT and AST enzymes in T2DM patients (Dong et al 2020 ). The observation also suggests that shorter LTL may be used as a biomarker for advanced fibrosis in T2DM patients (Dong et al 2020 ). Furthermore, it was recently confirmed that shorter telomeres were independently identified in elderly diagnosed with advanced liver disease (Rattan et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Enzymatic approaches against SARS-CoV-2 infection with an emphasis on the telomere-associated enzymes

Valdiani

Ofoghi

2023

Biotechnol Lett

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The pandemic phase of coronavirus disease 2019 (COVID-19) appears to be over in most countries. However, the unexpected behaviour and unstable nature of coronaviruses, including temporary hiatuses, re-emergence, emergence of new variants, and changing outbreak epicentres during the COVID-19 pandemic, have been frequently reported. The mentioned trend shows the fact that in addition to vaccine development, different strategies should be considered to deal effectively with this disease, in long term. In this regard, the role of enzymes in regulating immune responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has recently attracted much attention. Moreover, several reports confirm the association of short telomeres with sever COVID-19 symptoms. This review highlights the role of several enzymes involved in telomere length (TL) regulation and explains their relevance to SARS-CoV-2 infection. Apparently, inhibition of telomere shortening (TS) through inhibition and/or activation of these enzymes could be a potential target in the treatment of COVID-19, which may also lead to a reduction in disease severity.

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“…We reasoned that these short telomere-induced alterations could predispose hepatocytes to cell death, senescence, and fibrosis. Such a mechanism could not only be relevant for TBD patients but also for those with acquired conditions that are associated with short telomeres, including chronic hepatitis and fatty liver disease itself [ 42 , 43 ]. Our studies demonstrate that telomere shortening impairs the accumulation of TG in response to a fructose-rich diet in a p53-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Fructose Causes Liver Damage, Polyploidy, and Dysplasia in the Setting of Short Telomeres and p53 Loss

et al. 2021

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Studies in humans and model systems have established an important role of short telomeres in predisposing to liver fibrosis through pathways that are incompletely understood. Recent studies have shown that telomere dysfunction impairs cellular metabolism, but whether and how these metabolic alterations contribute to liver fibrosis is not well understood. Here, we investigated whether short telomeres change the hepatic response to metabolic stress induced by fructose, a sugar that is highly implicated in non-alcoholic fatty liver disease. We find that telomere shortening in telomerase knockout mice (TKO) imparts a pronounced susceptibility to fructose as reflected in the activation of p53, increased apoptosis, and senescence, despite lower hepatic fat accumulation in TKO mice compared to wild type mice with long telomeres. The decreased fat accumulation in TKO is mediated by p53 and deletion of p53 normalizes hepatic fat content but also causes polyploidy, polynuclearization, dysplasia, cell death, and liver damage. Together, these studies suggest that liver tissue with short telomers are highly susceptible to fructose and respond with p53 activation and liver damage that is further exacerbated when p53 is lost resulting in dysplastic changes.

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Shorter leucocyte telomere length as a potential biomarker for nonalcoholic fatty liver disease-related advanced fibrosis in T2DM patients

Cited by 8 publications

References 38 publications

Telomerase: a key player in the pathogenesis of non-alcoholic fatty liver disease?

Telomerase: a key player in the pathogenesis of non-alcoholic fatty liver disease?

Enzymatic approaches against SARS-CoV-2 infection with an emphasis on the telomere-associated enzymes

Fructose Causes Liver Damage, Polyploidy, and Dysplasia in the Setting of Short Telomeres and p53 Loss

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