# Fetuin > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Fetuin > Markdown URL: https://mediated.wiki/source/Fetuin.md > Source: https://en.wikipedia.org/wiki/Fetuin > Source revision: 1259004816 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{Short description|Blood proteins made in the liver and secreted into the bloodstream}} thumb|250px|right|X-ray picture of a Fetuin-A knockout mouse (-/-) compared to a wildtype mouse (+/+). The bright dots in the fetuin-A deficient mouse indicate calcified lesions throughout the body. '''Fetuins''' are [blood proteins](/source/blood_proteins) that are made in the [liver](/source/liver) and secreted into the [bloodstream](/source/bloodstream). They belong to a large group of binding [protein](/source/protein)s mediating the transport and availability of a wide variety of cargo substances in the bloodstream.{{cite journal | vauthors=Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, Ray S, Majumdar SS, Bhattacharya S | title=Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance | journal=[Nature Medicine](/source/Nature_Medicine) | volume=18 | issue=8 | pages=1279–1285 | year=2012 | url=http://basicmed.med.ncku.edu.tw/public/project/1216-1348566288-1.pdf | doi=10.1038/nm.2851 | pmid=22842477 | s2cid=888828 | access-date=2018-09-07 | archive-date=2018-09-07 | archive-url=https://web.archive.org/web/20180907221449/http://basicmed.med.ncku.edu.tw/public/project/1216-1348566288-1.pdf | url-status=dead }} [Fetuin-A](/source/alpha-2-HS-glycoprotein) is a major carrier protein of [free fatty acids](/source/Fatty_acid) in the circulation. The best known representative of carrier proteins is [serum albumin](/source/serum_albumin),{{Citation needed|date=September 2018}} the most abundant protein in the [blood plasma](/source/blood_plasma) of adult [animal](/source/animal)s. Fetuin is more abundant in fetal blood, hence the name "fetuin" (from Latin, ''fetus''). Fetal bovine serum contains more fetuin than albumin, while adult serum contains more albumin than fetuin. == Family members == [Human](/source/Human) fetuin is synonymous with [α2-HS-glycoprotein](/source/%CE%B12-HS-glycoprotein) (genetic symbol AHSG), α2-HS, A2HS, AHS, HSGA, and fetuin-A. Fetuin-A exists as a single-copy gene in the human and mouse genomes. A closely related gene, [fetuin-B](/source/fetuin-B), also exists in the human, [rat](/source/rat), and [mouse](/source/mouse) [genome](/source/genome)s. Like fetuin-A, fetuin-B is made predominantly by the liver and to a lesser extent by a number of secretory [tissues](/source/Biological_tissue). Fetuins exist in all vertebrate genomes including [fish](/source/fish) and [reptile](/source/reptile)s. Fetuins are members of a family of proteins that evolved from the protein [cystatin](/source/cystatin) by [gene](/source/gene) duplication and exchange of gene segments. Fetuins thus belong to the cystatin superfamily of proteins. Fetuin relatives within this superfamily are the [histidine](/source/histidine)-rich glycoprotein (HRG) and [kininogen](/source/kininogen) (KNG). {| |{{infobox protein | Name = [Α2-HS-glycoprotein](/source/%CE%912-HS-glycoprotein) | caption = | image = | width = | HGNCid = 349 | Symbol = [AHSG](/source/%CE%912-HS-glycoprotein) | AltSymbols = FETUA, A2HS, HSGA | EntrezGene = 197 | OMIM = 138680 | RefSeq = NM_001622 | UniProt = P02765 | PDB = | ECnumber = | Chromosome = 3 | Arm = q | Band = 27.3 | LocusSupplementaryData = }} |{{infobox protein | Name = [fetuin-B](/source/fetuin-B) | caption = | image = | width = | HGNCid = 3658 | Symbol = [FETUB](/source/fetuin-B) | AltSymbols = 16G2, Gugu | EntrezGene = 26998 | OMIM = 605954 | RefSeq = NM_014375 | UniProt = Q9UGM5 | PDB = | ECnumber = | Chromosome = 3 | Arm = q | Band = 27.3 | LocusSupplementaryData = }} |} == Animal studies == The function of Fetuin-A in the body was determined by gene knockout technology in mice. Knocking out the gene for fetuin-A rendered the mice completely fetuin-A deficient. Feeding a [mineral](/source/mineral)-rich [diet](/source/diet_(nutrition)) to fetuin-A-deficient mice resulted in widespread calcification (ectopic mineralization) of [lung](/source/lung), [heart](/source/heart), and [kidney](/source/kidney)s in these mice. The calcification became drastically exacerbated when the fetuin-A knockout was combined with the genetic background DBA/2. The mouse strain DBA/2 is known for its proneness to calcify damaged tissues, a process called "dystrophic calcification". Fetuin-A deficiency dramatically increased the calcification proneness of these mice in that all mice spontaneously calcified throughout their body even without a mineral-rich diet or surgical tissue trauma. Fetuin-A is therefore regarded as a potent inhibitor of systemic calcification. [Free fatty acids](/source/Fatty_acid) cause Fetuin-A [overexpression](/source/Gene_expression) by increasing the pro-inflammatory protein [NF-κB](/source/NF-%CE%BAB). Fetuin-A has been shown to facilitate the binding of free fatty acids to [TLR4](/source/TLR4) receptors, thereby inducing [insulin resistance](/source/insulin_resistance) in mice. == Human studies == Fetuin-A was originally discovered to be an inhibitor of vascular calcification in early 1990s. Since then many more roles have been attributed to fetuin-A. Fetuin-A has been demonstrated to play an important role in free fatty acid induced insulin resistance in the liver. Increased fetuin-A in patients with pre-diabetes is associated with increased progression to diabetes and decreased reversal to normoglycemia. Hence fetuin-A is a predictor of adverse glycemic outcomes in pre-diabetes.{{cite journal | vauthors = Dutta D, Mondal SA, Kumar M, Hasanoor Reza AH, Biswas D, Singh P, Chakrabarti S, Mukhopadhyay S | title = Serum fetuin-A concentration predicts glycaemic outcomes in people with prediabetes: a prospective study from eastern India | journal = Diabet. Med. | volume = 31 | issue = 12 | pages = 1594–9 | year = 2014 | pmid = 24975463 | doi = 10.1111/dme.12539 | s2cid = 8532064 | doi-access = free }}{{Unreliable medical source|date=January 2015|sure=y}} Obese persons have elevated circulating Fetuin-A, which can be reduced by [metformin](/source/metformin), exercise, or weight loss. {{cite journal | vauthors=Trepanowski JF, Mey J, Varady KA | title=Fetuin-A: a novel link between obesity and related complications | journal= [International Journal of Obesity](/source/International_Journal_of_Obesity) | volume=39 |issue=5 | pages=734–741 | year=2015 | doi=10.1038/ijo.2014.203 | pmid = 25468829 | s2cid=24089111 }} Increased fetuin-A has also been linked to increased occurrence of non-alcoholic fatty liver disease and cardiovascular events, believed to be due to its proinflammatory effects.{{cite journal | vauthors=Nascimbeni F, Romagnoli D, Ballestri S, Baldelli E, Lugari S, Sirotti V, Giampaoli V, Lonardo A | title=Do Nonalcoholic Fatty Liver Disease and Fetuin-A Play Different Roles in Symptomatic Coronary Artery Disease and Peripheral Arterial Disease? | journal= Diseases | volume=6 |issue=1 | pages=E17 | year=2018 | doi=10.3390/diseases6010017 | pmc=5871963 | pmid = 29462898 | doi-access=free }} Fetuin-A in contrast has also been demonstrated to have anti-inflammatory properties. It is a negative acute-phase reactant in sepsis and endotoxemia, promotes wound healing, and is neuroprotective in Alzheimer's disease. Decreased fetuin-A is a predictor of increased disease activity in [obstructive lung disease](/source/obstructive_lung_disease), [Crohn's disease](/source/Crohn's_disease), and [ulcerative colitis](/source/ulcerative_colitis). Differential effects on different toll like receptors in different tissues and organ systems may explain these paradoxical effects in different systems.{{cite journal | vauthors = Mukhopadhyay S, Mondal SA, Kumar M, Dutta D | title = Proinflammatory and antiinflammatory attributes of fetuin-a: a novel hepatokine modulating cardiovascular and glycemic outcomes in metabolic syndrome | journal = Endocr Pract | volume = 20 | issue = 12 | pages = 1345–51 | year = 2014 | pmid = 25370330 | doi = 10.4158/EP14421.RA }}{{Unreliable medical source|date=January 2015|sure=y}} == References == {{Reflist}} == Further reading == {{refbegin}} * {{cite journal | vauthors = Demetriou M, Binkert C, Sukhu B, Tenenbaum HC, Dennis JW | title = Fetuin/alpha2-HS glycoprotein is a transforming growth factor-beta type II receptor mimic and cytokine antagonist | journal = J. Biol. Chem. | volume = 271 | issue = 22 | pages = 12755–61 | year = 1996 | pmid = 8662721 | doi = 10.1074/jbc.271.22.12755 | doi-access = free | url = https://escholarship.org/content/qt59r439q2/qt59r439q2.pdf?t=pnjbkq }} * {{cite journal | vauthors = Jahnen-Dechent W, Schäfer C, Ketteler M, McKee MD | title = Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification | journal = J. Mol. Med. | volume = 86 | issue = 4 | pages = 379–89 | year = 2008 | pmid = 18080808 | doi = 10.1007/s00109-007-0294-y | s2cid = 20960971 }} * {{cite journal | vauthors = Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W | title = The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification | journal = J. Clin. Invest. | volume = 112 | issue = 3 | pages = 357–66 | year = 2003 | pmid = 12897203 | pmc = 166290 | doi = 10.1172/JCI17202 }} * {{cite journal | vauthors = Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Böhm R, Metzger T, Wanner C, Jahnen-Dechent W, Floege J | title = Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study | journal = Lancet | volume = 361 | issue = 9360 | pages = 827–33 | year = 2003 | pmid = 12642050 | doi = 10.1016/S0140-6736(03)12710-9 | s2cid = 29188194 }} * {{cite journal | vauthors = Heiss A, DuChesne A, Denecke B, Grötzinger J, Yamamoto K, Renné T, Jahnen-Dechent W | title = Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles | journal = J. Biol. Chem. | volume = 278 | issue = 15 | pages = 13333–41 | year = 2003 | pmid = 12556469 | doi = 10.1074/jbc.M210868200 | doi-access = free | url = http://pdfs.semanticscholar.org/495e/041a5b5b24c77026b8ee74eaedd704c1a1e4.pdf }} {{refend}} Category:Blood proteins --- Adapted from the Wikipedia article [Fetuin](https://en.wikipedia.org/wiki/Fetuin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Fetuin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.