Journal of Steroid Biochemistry and Molecular Biology, https://doi.org/10.1016/j.jsbmb.2018.04.009
Gillian E. Walkera, , , Antonia Follenzia, Valentina Bruscaggina, Marcello Manfredib, Simonetta Bellonea, c, Emilio Marengob, Luigi Maiuria, c, Flavia Prodama, c, Gianni Bonaa, c
This is the first mention of Fetuin B in VitaminDWiki
Fetuin A is mentioned on 40 web pages as of April 2018
- Fetuin-A: a novel link between obesity and related complications - PubMed 2015
- Serum fetuin-A levels in obese and non-obese subjects with and without type 2 diabetes mellitus - PubMed Jan 2018
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- https://en.wikipedia.org/wiki/Fetuin-B shows it is generated in the Liver
•Via proteomics, FETUB was identified/confirmed to be higher in VDD obese children.
•VD can directly downregulate hepatocellular FETUB synthesis in vitro.
•VDR silencing in vitro releases FETUB, suggesting VDR is a negative regulator.
•VD-supplementation to juvenile mice for 6 weeks, reduced circulating FETUB in vivo.
•Plasma FETUB levels likely depend on other VD-responsive tissues, with the liver.
Vitamin D (VD) deficiency (VDD) correlates to obesity, with VD a recognized mediator of metabolic diseases. From a previous proteomic study identifying adiponectin as a link between VDD and pediatric obesity, herein we analysed another protein (SSP2301) increased with VDD. A focused 2D-electrophoretic analysis identified 4 corresponding plasma proteins, with one predicted to be fetuin B (FETUB). FETUB was studied due to its emerging role in metabolic diseases and cytogenetic location (3q27.3) with adiponectin.
Results were confirmed in obese children, where plasma FETUB was higher with VDD. A direct effect by 1α,25-(OH)2D3 on hepatocellular FETUB synthesis was observed, with a time and dose dependent reduction. Further, we demonstrated the VD-receptor (VDR) is key, with FETUB “released” with VDR silencing. Finally, VD supplementation (6 weeks) to juvenile mice fed a standard diet, reduced plasma FETUB. Only at 22 weeks did liver FETUB correspond to plasma FETUB, highlighting the contribution of other VD-responsive tissues. Overall, FETUB is a key protein linking VDD to pediatric obesity. With an emerging role in metabolic diseases, we demonstrate that VD/VDR directly regulate FETUB.
Fetuin B as a potential link between obesity and VDD, can be supported by several very important characteristics. Human FETUB is structurally related to fetuin A (FETUA), both of which are members of the cystatin superfamily comprising of structurally related protease inhibitors (Lee et al., 2009). Fetuins have diverse functions including the regulation of osteogenesis, mineralization and systemic inflammation (Denecke et al., 2003; Szweras et al., 2002; Ombrellino et al., 2001). Circulating FETUA levels are increased in NAFLD independent of obesity (Stefan et al., 2006), while it also considered an independent risk factor for type 2 diabetes mellitus in adults and children (Stefan N et al., 2008), and a potent cardiovascular risk factor (Fiore CE et al., 2007). Only now is data emerging on the importance of FETUB, with the levels of FETUB increased in
- liver steatosis and type 2 diabetes mellitus (Meex RC et al., 2015),
- patients with chronic obstructive pulmonary disease (COPD; Diao et al., 2016),
- coronary artery disease (Zhu et al., 2017),
- as well as the demonstration of its functional involvement in the development of acute myocardial infarction and (Jung et al., 2015).
At the cellular level, treatment with FETUB in hepatoyctes and myocytes in vitro results in insulin resistance, supported by the observation of glucose intolerance following FETUB administration to lean mice (Meex et al., 2015). Another interesting observation is that human FETUB is found on chromosome 3q27.3, the identical cytogenetic band in which adiponectin is located (Rankinen et al., 2006). As described, adiponectin has been demonstrated to be significantly reduced in VDD pediatric obese subjects and to be directly upregulated by VD administration (Walker et al., 2014; Mai et al., 2017). These findings also highlight that 3q27.3 could be an important regulatory region for VD actions.