Fetuin-B, a second member of the fetuin family in mammals

Abstract

A set of orthologous plasma proteins found in human, sheep, pig, cow and rodents, now collectively designated fetuin-A, constitutes the fetuin family. Fetuin-A has been identified as a major protein during fetal life and is also involved in important functions such as inhibition of the insulin receptor tyrosine kinase activity, protease inhibitory activities and development-associated regulation of calcium metabolism and osteogenesis. Furthermore, fetuin-A is a key partner in the recovery phase of an acute inflammatory response. We now describe a second protein of the fetuin family, called fetuin-B, which is found at least in human and rodents. On grounds of domain homology, overall conservation of cysteine residues and chromosomal assignments of the corresponding genes in these species, fetuin-B is unambiguously a paralogue of fetuin-A. Yet, fetuin-A and fetuin-B exhibit significant differences at the amino acid sequence level, notably including variations with respect to the archetypal fetuin-specific signature. Differences and similarities in terms of gene regulation were also observed. Indeed, studies performed during development in rat and mouse showed for the first time high expression of a member of the fetuin family in adulthood, as shown with the fetuin-B mRNA in rat. However, like its fetuin-A counterpart, the fetuin-B mRNA level is down-regulated during the acute phase of experimentally induced inflammation in rat.

Increased fetuin-B levels are associated with carotid intima media thickness and hormonal-metabolic disturbances in women with polycystic ovary syndrome

“…For this reason, many biomarkers have been identified to predict risk of cardiovascular events in women with PCOS [22,23]. CIMT is a good indicator of cardiovascular risk and is strongly associated with conventional cardiovascular risk factors [5,6]. In the present study, we found that CIMT was increased in PCOS subjects compared to controls.…”

“…Fetuin-B is a novel pluripotent peptide hormone which is a member of the cystatin super family of cysteine protease [5]. It is secreted from various tissues such as liver and adipose tissue [6]. Growing evidence suggest that fetuin-B plays a crucial role in glucose metabolism.…”

Increased serum fetuin-B concentration is associated with HOMA-β and indices of liver steatosis in women with polycystic ovary syndrome: a pilot study

“…Fetuin-B is a member of the fetuin family, part of the cystatin superfamily of cysteine protease inhibitors (7) and is predominantly expressed in the liver (8, 9), but also, to a lesser extent, in other tissues, such as placenta (10), white adipose tissue and heart (8). It has been shown that fetuin-B could be activated by agonists of farnesoid X receptor, which is a key factor in the regulation of lipid and carbohydrate metabolism (11).…”

Diabetes, Insulin Resistance, Fetuin-B and Exercise Training

“…In addition to impaired insulin secretion from pancreatic cells, a reduced insulin sensitivity is found to play a predominant role in the pathogenesis of the disease (2). Several circulating proteins are involved in the regulation of insulin sensitivity; such as, adiponectin, retinol binding protein 4, and fetuin-A (3). The fetuin family consists of a set of orthologous plasma proteins found in humans, sheep, pigs, cows and rodents.…”

“…Fetuin-B was discovered in mice prone to diabetes. Based on domain homology, overall conservation of cysteine residues and chromosomal assignments of the corresponding genes in these species, fetuin-B is a unambiguously paralogue of fetuin-A (3, 4). Recently, fetuin-B has also been identified as a novel adipokine/hepatokine which is significantly increased in hepatic steatosis and which mediates impaired insulin action, as well as glucose intolerance (4).…”