Molecular and pathobiological involvement of fetuin-A in the pathogenesis of NAFLD

Sardana, Ojus; Goyal, Ravi; Bedi, Onkar

doi:10.1007/s10787-021-00837-4

Cited by 18 publications

(16 citation statements)

References 116 publications

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“…Fetuins are a family of a large group of proteins belonging to the cystatin superfamily of cysteine protease inhibitors of the metalloprotease, papain, calpain, cathepsin, and caspase families, possessing a domain of conserved cysteine residues responsible for their protease inhibitory activity ( Sardana et al, 2021 ). The cystatin superfamily comprises type 1 (mainly intracellular proteins), type 2 (mainly extracellular proteins), type 3 (plasma proteins), and unclassified cystatins ( Jahnen-Dechent et al, 2011 ).…”

Section: Overview Of the Fetuin Familymentioning

confidence: 99%

“…Along with the fetuin family, cystatins, histidine-rich glycoproteins, and kininogens are grouped under the type 3 cystatin family ( Brown and Dziegielewska, 1997 ). The fetuin family constitutes two paralogue proteins, which are homologous proteins encoded by duplicated genes, known as fetuin-A and fetuin-B ( Olivier et al, 2000 ; Sardana et al, 2021 ).…”

Section: Overview Of the Fetuin Familymentioning

confidence: 99%

“… Schematic representation of (A) Fetuin-A structure. The pre-fetuin-A contains 367 amino acids, including 18 amino acid size SS ( Pedersen, 1944 ; Brown et al, 1992 ; Dziegielewska and Brown, 1995 ; Brown and Dziegielewska, 1997 ; Olivier et al, 2000 ; Denecke et al, 2003 ; Kettler et al, 2003 ; Stefan et al, 2006a ; Häusler et al, 2009 ; Wojtysiak-Duma et al, 2010 ; Jahnen-Dechent et al, 2011 ; Mori et al, 2012 ; Dietzel et al, 2013 ; Cerdà‐Costa and Xavier Gomis‐Rüth, 2014 ; Stöcker et al, 2014 ; Floehr et al, 2016 ; Lin et al, 2018 ; Sardana et al, 2021 ); 282 amino acids A-chain (19–300), 40 amino acids CP (301–340), and 27 amino acids long B-chain (341–367). A-chain is composed of two cystatin-like domains (D1 and D2) and a variable non-cystatin domain, D3 (D3a and D3b).…”

Section: Structure and Biosynthesis Of Fetuin-amentioning

confidence: 99%

“…Besides, fetuin-A is involved in varieties of anti-inflammatory and inflammatory attributes, neutrophil and platelet degranulation, lymphocyte stimulation, keratinocyte migration, and carriers of metals and small molecules in the bloodstream by binding with fatty acids, thyroid hormones, phosphate, and calcium ions ( Dabrowska et al, 2015 ; Lin et al, 2018 ). Furthermore, fetuin-A plays a key role in the pathogenesis of several metabolic disorders such as IR, T2DM, NAFLD, CVDs, and autoimmune disorders; breast tumor cell proliferative signaling; brain disorders such as ischemic stroke and neurodegenerative disease and more recently, psoriasis ( Kettler et al, 2003 ; Wojtysiak-Duma et al, 2010 ; Mori et al, 2012 ; Sardana et al, 2021 ; Abebe et al, 2022 ). This part of the review comprehensively explores various biological roles of fetuin-A, with special emphasis on its physiological roles.…”

Section: Biological Roles Of Fetuin-amentioning

confidence: 99%

“…Besides, it acts as a protease inhibitor, inflammatory mediator, anti-inflammatory partner, atherogenic factor, and adipogenic factor, among several other moonlighting functions. Fetuin-A has also been found to have a key role in the development of various clinical conditions, such as insulin resistance (IR), type 2 diabetes mellitus (T2DM), metabolic disorders, nonalcoholic fatty liver disease (NAFLD), cardiovascular diseases (CVDs), tumors, and brain disorders ( Kettler et al, 2003 ; Wojtysiak-Duma et al, 2010 ; Mori et al, 2012 ; Sardana et al, 2021 ). This review article primarily aimed to explore the structure, biosynthesis, and biological roles of fetuin-A.…”

Section: Introductionmentioning

confidence: 99%

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The structure, biosynthesis, and biological roles of fetuin-A: A review

Abebe

Muche

T/Mariam

et al. 2022

Front. Cell Dev. Biol.

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Fetuin-A is a heterodimeric plasma glycoprotein containing an A-chain of 282 amino acids and a B-chain of 27 amino acid residues linked by a single inter-disulfide bond. It is predominantly expressed in embryonic cells and adult hepatocytes, and to a lesser extent in adipocytes and monocytes. Fetuin-A binds with a plethora of receptors and exhibits multifaceted physiological and pathological functions. It is involved in the regulation of calcium metabolism, osteogenesis, and the insulin signaling pathway. It also acts as an ectopic calcification inhibitor, protease inhibitor, inflammatory mediator, anti-inflammatory partner, atherogenic factor, and adipogenic factor, among other several moonlighting functions. Fetuin-A has also been demonstrated to play a crucial role in the pathogenesis of several disorders. This review mainly focuses on the structure, synthesis, and biological roles of fetuin-A. Information was gathered manually from various journals via electronic searches using PubMed, Google Scholar, HINARI, and Cochrane Library from inception to 2022. Studies written in English and cohort, case-control, cross-sectional, or experimental studies were considered in the review, otherwise excluded.

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Section: Overview Of the Fetuin Familymentioning

confidence: 99%

Section: Overview Of the Fetuin Familymentioning

confidence: 99%

Section: Structure and Biosynthesis Of Fetuin-amentioning

confidence: 99%

Section: Biological Roles Of Fetuin-amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The structure, biosynthesis, and biological roles of fetuin-A: A review

Abebe

Muche

T/Mariam

et al. 2022

Front. Cell Dev. Biol.

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Effect of rosuvastatin on sortilin and fetuin-A in type 2 diabetic patients: a randomized controlled trial

Werida,

Elattar,

Abdelghafour

et al. 2024

Int J Diabetes Dev Ctries

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Objective Rosuvastatin is a drug used for decreasing the risk of cardiovascular complications in type 2 diabetes mellitus (T2DM) patients. It is hypothesized that fetuin-A encourages lipid-induced insulin resistance and sortilin may increase the risk of atherosclerotic-related disorders. The aim of this study is to investigate the safety and efficacy of rosuvastatin co-treatment in T2DM patients and its effect on levels of sortilin and fetuin-A. Methods Seventy T2DM patients treated with glimepiride and metformin were randomly assigned to either co-treated with rosuvastatin 10 mg tablets (rosuvastatin group, n = 40), or placebo (placebo group, n = 30) daily for 3 months in a parallel, double-blind randomized controlled trial. Blood was collected for biochemical analysis. Serum sortilin and fetuin-A levels, glycemic and lipid profiles were measured before and 3 months after intervention. Results Fasting blood glucose (FBG, mg/dl) significantly decreased in placebo and rousvastatin groups from (104 ± 7.24 to 96.67 ± 7.14 vs 102.8 ± 6.43 to 93.0 ± 4.71), respectively, compared with baseline (p < 0.05). BMI and HbA1c decreased in placebo vs rosuvastatin group (29.20 ± 3.18 to 28.10 ± 3.08, p=0.08 vs 28.67 ± 3.56 to 27.66 ± 3.16, p = 0.27), and (6.59 ± 0.27 to 6.36 ± 0.27 vs 6.56 ± 0.26 to 6.29 ± 0.25), respectively, compared with baseline (p ≤ 0.001) with no significance difference between both groups (p = 0.58 and p = 0.25, respectively). Sortilin and fetuin-A levels significantly decreased in rosuvastatin vs placebo group from (1.77 ± 0.41 to 0.64 ± 0.37 vs 1.70 ± 0.36 to 1.65 ± 0.36) and from (295.33 ± 52.04 to 179.75 ± 60.22 vs 307.22 ± 50.11 to 288.94 ± 49.53), respectively, compared with baseline with significance difference between both groups (p < 0.001) compared with placebo. Significant positive correlation was found between sortilin with fetuin-A, low-density lipoprotein (LDL-C), and atherogenic index (p < 0.001). Significant positive correlation was observed between fetuin-A with FBG (p < 0.05) and atherogenic index (p < 0.001). Conclusion Rosuvastatin co-treatment in T2DM patients improves glycemic control and aids in decreasing the atherogenic biomarkers sortilin and fetuin-A levels, so it can be considered tolerable and efficient in improving lipid profile and atherogenic index. Trial registration ClinicalTrials.gov identifier (NCT number): NCT03907423, (The registration date: April 9, 2019). https://clinicaltrials.gov/ct2/show/NCT03907423.

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