The hepatokines fetuin-A and fetuin-B are upregulated in the state of hepatic steatosis and may differently impact on glucose homeostasis in humans

Peter, Andreas; Kovarova, Marketa; Staiger, Harald; Machann, Jürgen; Schick, Fritz; Königsrainer, Alfred; Königsrainer, Ingmar; Schleicher, Erwin; Fritsche, Andreas; Häring, Hans‐Ulrich; Stefan, Norbert

doi:10.1152/ajpendo.00262.2017

Cited by 63 publications

(69 citation statements)

References 49 publications

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“…The regulation of hepatic fetuin-A secretion is incompletely understood (Haukeland et al, 2012). Previous research has reported that fetuin-A mRNA expression in the liver correlated positively with hepatic triglyceride content and homeostatic model of insulin resistance (HOMA-IR) and these associations remained significant after adjustment for BMI (Peter et al, 2018). These findings were supported by a cross-sectional study reporting higher fetuin-A in subjects with elevated liver fat content (Stefan et al, 2006).…”

Section: Discussionmentioning

confidence: 85%

Fetuin-A as a Potential Biomarker of Metabolic Variability Following 60 Days of Bed Rest

et al. 2020

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Background: Fetuin-A is a hepatokine linked to the development of insulin resistance. The purpose of this study was to determine if 60 days head-down-tilt (HDT) bed rest increased circulating fetuin-A and if it was linked to whole body insulin sensitivity (IS). Additionally, we examined whether reactive jump training (RJT) could alleviate the metabolic changes associated with bed rest. Methods: 23 young men (29 ± 6 years, 181 ± 6 cm, 77 ± 7 kg) were randomized to a control (CTRL, n = 11) or RJT group (JUMP, n = 12) and exposed to 60 days of bed rest. Before and after bed rest, body composition and V. O 2peak were measured and an oral glucose tolerance test was performed to estimate IS. Circulating lipids and fetuin-A were measured in fasting serum. Results: Body weight, lean mass, and V. O 2peak decreased in both groups following bed rest, with greater reductions in CTRL (p < 0.05). There was a main effect of time, but not the RJT intervention, for the increase in fetuin-A, triglycerides (TG), area under the curve for glucose (AUCG) and insulin (AUCI), and the decrease in Matsuda and tissue-specific IS (p < 0.05). Fetuin-A increased in participants who became less insulin sensitive (p = 0.019). In this subgroup, liver IS and adipose IS decreased (p < 0.05), while muscle IS was unchanged. In a subgroup, where IS did not decrease, fetuin-A did not change. Liver IS increased (p = 0.012), while muscle and adipose tissue IS remained unchanged. Conclusions: In this study, we report an increase in circulating fetuin-A following 60 days of bed rest, concomitant with reduced IS, which could not be mitigated by RJT. The amount of fetuin-A released from the liver may be an important determinant of changes in whole body IS. In this regard, it may also be a useful biomarker of individual variation due to inactivity or lifestyle interventions.

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Section: Discussionmentioning

confidence: 85%

Fetuin-A as a Potential Biomarker of Metabolic Variability Following 60 Days of Bed Rest

et al. 2020

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“…However, normal ranges reported among locations are variable, which complicates interpretation, and, more importantly, ALT values do not reliably differentiate NAFLD severity, or distinguish uncomplicated NAFLD from NASH in children or adults [ 13 , 15 , 16 ]. Several other potential circulating biomarkers have been proposed [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ] but few have been tested in children with biopsy-proven NAFLD, or tracked over the course of treatment or disease progression [ 13 , 16 , 25 ].…”

Section: Clinical Pathophysiologymentioning

confidence: 99%

Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms

et al. 2020

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Non-alcoholic fatty liver disease (NAFLD) is the number one chronic liver disease worldwide and is estimated to affect nearly 40% of obese youth and up to 10% of the general pediatric population without any obvious signs or symptoms. Although the early stages of NAFLD are reversible with diet and lifestyle modifications, detecting such stages is hindered by a lack of non-invasive methods of risk assessment and diagnosis. This absence of non-invasive means of diagnosis is directly related to the scarcity of long-term prospective studies of pediatric NAFLD in children and adolescents. In the majority of pediatric NAFLD cases, the mechanisms driving the origin and rapid progression of NAFLD remain unknown. The progression from NAFLD to non-alcoholic steatohepatitis (NASH) in youth is associated with unique histological features and possible immune processes and metabolic pathways that may reflect different mechanisms compared with adults. Recent data suggest that circulating microRNAs (miRNAs) are important new biomarkers underlying pathways of liver injury. Several factors may contribute to pediatric NAFLD development, including high-sugar diets, in utero exposures via epigenetic alterations, changes in the neonatal microbiome, and altered immune system development and mitochondrial function. This review focuses on the unique aspects of pediatric NAFLD and how nutritional exposures impact the immune system, mitochondria, and liver/gastrointestinal metabolic health. These factors highlight the need for answers to how NAFLD develops in children and for early stage-specific interventions.

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“…Fourth, we cannot preclude the possibility of reverse causality between serum Fetuin-B and atherosclerosis due to our crosssectional study design. Fifth, although Meex, Zhu and we all found significant association of serum Fetuin-B with liver steatosis 8,9,18) , Peter recently found serum Fetuin-B level did not correlate with liver fat content or insulin sensitivity 24) , therefore, more studies should be conducted in different populations before the consistent findings between Fetuin-B and liver steatosis has been reached. Sixth, we should acknowledge that although serum Fetuin-B is mainly from liver, it may also be from other organs, as Denecke et al suggested 25) .…”

Section: Discussionmentioning

confidence: 58%

Association of Fetuin-B with Subclinical Atherosclerosis in Obese Chinese Adults

Cai

Liu

et al. 2020

JAT

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We aimed to explore the independent associations of serum Fetuin-B and common genetic variants in FETUB locus with subclinical atherosclerosis. Methods: A cross-sectional study of 1,140 obese adults, who underwent serum Fetuin-B testing, hepatic ultrasonography scanning, genotyping on four tagging single nucleotide polymorphisms (SNPs) in FETUB locus and atherosclerosis detection, was conducted in Xiamen, China. Results: Increasing tertiles of brachial ankle pulse wave velocity (ba-PWV) were significantly associated with higher prevalence of nonalcoholic fatty liver disease (NAFLD) (48.8%, 61.5%, and 70.5% for tertiles of 1-3, respectively, p 0.001) and serum Fetuin-B (3.85 1.39, 4.09 1.40, and 4.27 1.46 µg/ml, p 0.047). Multivariable linear regression analyses with adjustment for potential confounding factors, even NAFLD per se, showed that serum Fetuin-B were significantly and positively associated with ba-PWV, with standardized regression coefficients () ranging from 0.055 to 0.075 (all p-values 0.05) in different models. However, the significant relationship between serum Fetuin-B and ba-PWV disappeared with further adjustment for insulin resistance. Serum Fetuin-B was not significantly associated with ankle-brachial index (ABI). All genotypes of the four tested FETUB tagging SNPs were not significantly associated with either ba-PWV or ABI with adjustment for potential confounding factors Conclusion: Serum Fetuin-B was positively associated with ba-PWV and may link liver fat accumulation to subclinical atherosclerosis via insulin resistance. diovascular disease (CVD) are not well known, although some hepatokines, such as fibroblast growth factors 21 (FGF21), Fetuin-A, and selenoprotein P are involved in liver steatosis and atherosclerosis crosstalk 4, 5). Fetuin-B is a member of the cystatin super Copyright©2019 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

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The hepatokines fetuin-A and fetuin-B are upregulated in the state of hepatic steatosis and may differently impact on glucose homeostasis in humans

Cited by 63 publications

References 49 publications

Fetuin-A as a Potential Biomarker of Metabolic Variability Following 60 Days of Bed Rest

Fetuin-A as a Potential Biomarker of Metabolic Variability Following 60 Days of Bed Rest

Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms

Association of Fetuin-B with Subclinical Atherosclerosis in Obese Chinese Adults

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