Pathophysiological Implication of Fetuin-A Glycoprotein in the Development of Metabolic Disorders: A Concise Review

Bourebaba, Lynda; Marycz, Krzysztof

doi:10.3390/jcm8122033

Cited by 79 publications

(61 citation statements)

References 112 publications

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“…Fetuin-A is a multifunctional glycoprotein that is predominately synthesized and secreted by hepatocytes (Bourebaba and Marycz, 2019) and associated with insulin action (Ochieng et al, 2018). To the best of our knowledge, fetuin-A has not been previously reported following bed rest and we report a significant increase in circulating fetuin-A following 60 days of HDT bed rest, irrespective of the experimental group.…”

Section: Discussionmentioning

confidence: 54%

“…An association between insulin sensitivity and fetuin-A has been well-established within the literature (Ochieng et al, 2018;Bourebaba and Marycz, 2019). In the current study, pre-to post-differences in insulin sensitivity and fetuin-A exhibited significant effects of time only, so to further explore the relationship between both variables additional subanalysis was conducted.…”

Section: In-depth Data Analysismentioning

confidence: 87%

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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: 54%

Section: In-depth Data Analysismentioning

confidence: 87%

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

et al. 2020

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“…The underlying mechanism likely involves insulin resistance caused by the impact of fetuin-A on diverse physiological processes, e.g. GLUT-4 translocation and protein kinase B (Akt) activation [60].…”

Section: Pathways Independently Associated With T2d or Chdmentioning

confidence: 99%

Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study

Huth

Bauer

Zierer

et al. 2020

Cardiovasc Diabetol

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Background: Biomarkers may contribute to our understanding of the pathophysiology of various diseases. Type 2 diabetes (T2D) and coronary heart disease (CHD) share many clinical and lifestyle risk factors and several biomarkers are associated with both diseases. The current analysis aims to assess the relevance of biomarkers combined to pathway groups for the development of T2D and CHD in the same cohort. Methods: Forty-seven serum biomarkers were measured in the MONICA/KORA case-cohort study using clinical chemistry assays and ultrasensitive molecular counting technology. The T2D (CHD) analyses included 689 (568) incident cases and 1850 (2004) non-cases from three population-based surveys. At baseline, the study participants were 35-74 years old. The median follow-up was 14 years. We computed Cox regression models for each biomarker, adjusted for age, sex, and survey. Additionally, we assigned the biomarkers to 19 etiological pathways based on information from literature. One age-, sex-, and survey-controlled average variable was built for each pathway. We used the R 2 PM coefficient of determination to assess the explained disease risk. Results: The associations of many biomarkers, such as several cytokines or the iron marker soluble transferrin receptor (sTfR), were similar in strength for T2D and CHD, but we also observed important differences. Lipoprotein (a) (Lp(a)) and N-terminal pro B-type natriuretic peptide (NT-proBNP) even demonstrated opposite effect directions. All pathway variables together explained 49% of the T2D risk and 21% of the CHD risk. The insulin-like growth factor binding protein 2 (IGFBP-2, IGF/IGFBP system pathway) best explained the T2D risk (about 9% explained risk, independent of all other pathway variables). For CHD, the myocardial-injury-and lipid-related-pathways were most important and both explained about 4% of the CHD risk. Conclusions: The biomarker-derived pathway variables explained a higher proportion of the T2D risk compared to CHD. The ranking of the pathways differed between the two diseases, with the IGF/IGFBP-system-pathway being most strongly associated with T2D and the myocardial-injury-and lipid-related-pathways with CHD. Our results help to better understand the pathophysiology of the two diseases, with the ultimate goal of pointing out targets for lifestyle intervention and drug development to ideally prevent both T2D and CHD development.

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“…Endocrine FGFs and fetuin-A regulate a broad spectrum of metabolic functions such as glucose, lipid metabolism, and energy homeostasis by regulating several signaling cascades that lead to altered insulin sensitivity (11,24). We hypothesized that disrupting glucose and lipid homeostasis by acute intralipid and insulin administration or via moderate exercise may differentially modulate circulating endocrine FGFs and fetuin-A in healthy women and women with PCOS.…”

Section: Discussionmentioning

confidence: 99%

“…In adipocytes, fetuin-A increases the accumulation of triacylglycerol and fatty acid uptake and enhances lipogenesis ( 10 ). Circulating fetuin-A levels are higher in obesity, T2D and non-alcoholic fatty liver disease (NAFLD) and is associated with impaired insulin sensitivity ( 11 ). Studies have shown that fetuin-A directly interacts with the insulin receptor and alters insulin signaling by disrupting insulin-stimulated phosphorylation of the insulin receptor and insulin receptor substrate-1 ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women

et al. 2020

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Background: The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS). Our study was designed to examine the response of endocrine FGFs and fetuin-A to an acute intralipid, insulin infusion and exercise in PCOS and healthy women. Subjects and Measurements: Ten healthy and 11 PCOS subjects underwent 5-h saline infusions with a hyperinsulinemic-euglycemic clamp (HIEC) performed during the final 2 h. One week later, intralipid infusions were undertaken with a HIEC performed during the final 2 h. After an 8 week of exercise intervention the saline, intralipid, and HIEC were repeated. Plasma levels of endocrine FGFs and fetuin-A were measured. Results: Baseline fetuin-A was higher in PCOS women but FGF19, FGF21, and FGF23 did not differ and were unaffected by exercise. Insulin administration elevated FGF21 in control and PCOS, suppressed FGF19 in controls, and had no effects on FGF23 and fetuin-A. Intralipid infusion suppressed FGF19 and increased FGF21. Insulin with intralipid synergistically increased FGF21 and did not have effects on lipid-mediated suppression of FGF19 in both groups. Conclusion: Our study provides evidence for insulin and lipid regulation of endocrine FGFs in healthy and PCOS women, suggesting that FGF family members play a role in lipid and glucose metabolism.

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Pathophysiological Implication of Fetuin-A Glycoprotein in the Development of Metabolic Disorders: A Concise Review

Cited by 79 publications

References 112 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

Biomarker-defined pathways for incident type 2 diabetes and coronary heart disease—a comparison in the MONICA/KORA study

Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women

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