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

ABSTRACT

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 nonalcoholic fatty liver disease (NAFLD). The review evaluates 9a) whether the assessment of telomerase can be used as a noninvasive 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.

KEYWORDS:

• Telomerase
• nonalcoholic fatty liver disease
• liver fibrosis
• lipid metabolism
• hepatocellular carcinoma
• metabolic disorders
• therapeutic targets

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Article highlights

• The specific role of telomerase function in hepatocytes is discussed.

• Fatty degeneration, cellular inflammation, oxidative stress, mitochondrial dysfunction, as well as fibrosis and increased susceptibility to cancer in the liver are considered to be pathological changes potentially induced by telomerase dysfunction.

• A novel therapeutic strategy to regulate telomere length by improving telomerase function in NAFLD is also considered.

Additional information

Funding

This paper was funded by grants from the National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) and Project of New Century 551 Talent Nurturing in Wenzhou. G Targher is supported in part by grants from the School of Medicine, University of Verona, Verona, Italy. C D Byrne is supported in part by the Southampton NIHR Biomedical Research Centre(IS-BRC-20004), UK.This paper was funded by grants from the National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) and Project of New Century 551 Talent Nurturing in Wenzhou. G Targher, is supported in part by grants from the School of Medicine, University of Verona, Verona, Italy. C D Byrne is supported in part by the Southampton NIHR Biomedical Research Centre (IS-BRC-20004), UK.