Abstract

The purpose of this review is to summarize the role of fetuin-A in disease processes prevalent in postmenopausal women and synthesize effective interventions in obtaining healthy fetuin-A levels. A review of databases for articles related to fetuin-A and diseases associated with postmenopausal women was conducted. Articles were limited to full-text access, published in English since 1944. High fetuin-A levels are closely associated with decreased bone mineral density, increased cardiovascular disease risks, impairment of insulin signaling and disruption of adipocyte functioning. Postmenopausal women have increased risk of osteoporosis, cardiovascular disease, insulin-resistance, intra-abdominal fat accumulation and vascular calcification. Low-levels of fetuin-A have been shown to be protective against the latter. The role of fetuin-A is multi-factorial and the mechanisms in which it is involved in each of these processes are vast. The present body of literature is inconsistent in defining high versus low levels of fetuin-A and their association with healthy-matched controls. The diseases associated with high levels of fetuin-A mimic diseases most prevalent in postmenopausal women. In addition, there is no research, to date, exploring fetuin-A levels in postmenopausal women and the associations it may or may not have in related diseases.Key words: fetuin-A; Alpha2-Heremans-Schmid glycoprotein; cardiovascular disease; and elderly, insulin-resistance, intra-abdominal fat, metabolic syndrome, exercise, weight-loss, calorie restriction and postmenopausal.Resumen. El propósito de esta revisión es sintetizar el papel de la fetuina A en los procesos de enfermedad prevalentes en mujeres posmenopáusicas y resumir las intervenciones efectivas que permiten obtener niveles saludables de fetuina A. Para ello, se revisaron bases de datos con artículos relacionados con fetuina A y las enfermedades asociadas con mujeres posmenopáusicas. La búsqueda de artículos se limitó a aquellos de texto completo publicados en el idioma inglés desde el año 1944. Se encontró que altos niveles de fetuina A están íntimamente relacionados con una reducción de la densidad mineral ósea, un aumento en el riesgo de enfermedad cardiovascular, deterioro de la señalización de la insulina y la alteración del funcionamiento de los adipocitos. Las mujeres posmenopáusicas tienen un mayor riesgo de osteoporosis, enfermedad cardiovascular, resistencia a la insulina, acumulación de grasa intra abdominal y calcificación vascular. Se ha demostrado que niveles bajos de fetuina A son protectores contra esta última condición. El papel de fetuina A es multifactorial y los mecanismos en los que está involucrado en cada uno de estos procesos son muy amplios. El estado actual de la literatura no es consistente en la definición de niveles de fetuina A altos versus bajos y su asociación con controles sanos. Las enfermedades asociadas con altos niveles de fetuina A asemejan las enfermedades más prevalentes en mujeres posmenopáusicas. Además, no existen investigaciones, hasta la fecha, en las que se exploren los niveles de fetuina A en mujeres posmenopáusicas y las asociaciones que puede o no puede tener en las enfermedades relacionadas.Palabras claves: fetuina A, glicoproteína Alpha2-Heremans-Schmid, enfermedad cardiovascular, adulto mayor, resistencia a la insulina, grasa intra abdominal, síndrome metabólico, ejercicio, pérdida de peso, restricción calórica, posmenopausia.

Highlights

  • Fetuin-A is a circulating glycoprotein that plays a critical role in bone homeostasis (Price, Toroian, & Lim, 2009), prevention of vascular calcification (Schäfer et al, 2003), impairment of insulin signaling (Goustin & Abou-Samra, 2011) and disruption of adipocyte functioning (Rasul, Wagner, & Kautzky-Willer, 2012)

  • High levels of fetuin-A have been associated with diseases such as type-2 diabetes mellitus (T2DM), obesity (Schultes, Frick, Ernst, Stefan, & Fritsche, 2010) and metabolic syndrome (Ix et al, 2006).An increase in myocardial infarction and stroke are positively correlated with increased fetuin-A blood concentrations (Ix, Wassel & Kanaya et al, 2008)

  • It is apparent that postmenopausal women are at increased risk for insulin resistance, hyperinsulinemia, metabolic syndrome and cardiovascular disease (CVD)

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Summary

Introduction

1993; Sutton-Tyrrell et al, 2005). A decrease in ovarian production of estrogen and progesterone has been linked to an increase in insulin resistance (Sathya Bhama, Balaji & Seethalakshmi, 2012), intra-abdominal fat (Tchernof, Calles-Escandon, Sites, & Poehlman, 1998) and increased inflammatory markers (Hennige et al, 2008), all of which are associated with metabolic syndrome and/or cardiovascular disease. The purpose of this review is to summarize the role of fetuin-A in disease processes prevalent in postmenopausal women and synthesize effective interventions in obtaining healthy fetuin-A levels. Search terms included: fetuin-AorAlpha2-Heremans-Schmid glycoprotein in combination with: cardiovascular disease and elderly, insulin-resistance, intra-abdominal fat, metabolic syndrome, exercise, weight-loss, calorie restriction and postmenopausal. The human form of fetuin is known as Alpha2-HeremansSchmid glycoprotein (AHSG) This glycoprotein has binding sites for hydroxyapatite (Heiss et al, 2003) and transforming growth factor-Beta (TGF-Beta) (Demetriou, Binkert, Sukhu, Tenenbaum, & Dennis, 1996), which help to partially explain fetuin-A’s role in bone homeostasis and inflammation. Perhaps a more definitive concentration of what is considered healthy-normal and observed normal levels of fetuin-A would be better understood This would help to strengthen the definition of high and low fetuin-Alevels in studies without healthy, non-diseased counterparts. Fetuin-A levels reported in va rious diseases and conditions

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