Fetuin

fetuin-B
fetuin-B
Identifiers
Symbol	FETUB
Alt. symbols	16G2, Gugu
NCBI gene	26998
HGNC	3658
OMIM	605954
RefSeq	NM_014375
UniProt	Q9UGM5
Other data
Locus	Chr. 3 q27.3
Structures
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Structures	Swiss-model
Domains	InterPro

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Structures	Swiss-model
Domains	InterPro

Α2-HS-glycoprotein
Α2-HS-glycoprotein
Identifiers
Symbol	AHSG
Alt. symbols	FETUA, A2HS, HSGA
NCBI gene	197
HGNC	349
OMIM	138680
RefSeq	NM_001622
UniProt	P02765
Other data
Locus	Chr. 3 q27.3
Structures
Search for
Structures	Swiss-model
Domains	InterPro

Last updated July 29, 2023

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. FetuinAKnockout.jpg — 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 that are made in the liver and secreted into the bloodstream. They belong to a large group of binding proteins mediating the transport and availability of a wide variety of cargo substances in the bloodstream.^[1] Fetuin-A is a major carrier protein of free fatty acids in the circulation.^[1] The best known representative of carrier proteins is serum albumin,^{[ citation needed ]} the most abundant protein in the blood plasma of adult animals. 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 fetuin is synonymous with α2-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, also exists in the human, rat, and mouse genomes. Like fetuin-A, fetuin-B is made predominantly by the liver and to a lesser extent by a number of secretory tissues. Fetuins exist in all vertebrate genomes including fish and reptiles. Fetuins are members of a family of proteins that evolved from the protein cystatin by gene duplication and exchange of gene segments. Fetuins thus belong to the cystatin superfamily of proteins. Fetuin relatives within this superfamily are the histidine-rich glycoprotein (HRG) and kininogen (KNG).

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-rich diet to fetuin-A-deficient mice resulted in widespread calcification (ectopic mineralization) of lung, heart, and kidneys 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 cause Fetuin-A overexpression by increasing the pro-inflammatory protein NF-κB.^[1] Fetuin-A has been shown to facilitate the binding of free fatty acids to TLR4 receptors, thereby inducing insulin resistance in mice.^[1]

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.^[2]^{[ unreliable medical source ]} Obese persons have elevated circulating Fetuin-A, which can be reduced by metformin, exercise, or weight loss. ^[3] 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.^[4]

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, Crohn's disease, and ulcerative colitis. Differential effects on different toll like receptors in different tissues and organ systems may explain these paradoxical effects in different systems.^[5]^{[ unreliable medical source ]}

Related Research Articles

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Lipolysis is the metabolic pathway through which lipid triglycerides are hydrolyzed into a glycerol and free fatty acids. It is used to mobilize stored energy during fasting or exercise, and usually occurs in fat adipocytes. The most important regulatory hormone in lipolysis is insulin; lipolysis can only occur when insulin action falls to low levels, as occurs during fasting. Other hormones that affect lipolysis include glucagon, epinephrine, norepinephrine, growth hormone, atrial natriuretic peptide, brain natriuretic peptide, and cortisol.

Transferrins are glycoproteins found in vertebrates which bind and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe³⁺ ions. Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein.

Adiponectin is a protein hormone and adipokine, which is involved in regulating glucose levels and fatty acid breakdown. In humans, it is encoded by the ADIPOQ gene and is produced primarily in adipose tissue, but also in muscle and even in the brain.

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Serum albumin, often referred to simply as blood albumin, is an albumin found in vertebrate blood. Human serum albumin is encoded by the ALB gene. Other mammalian forms, such as bovine serum albumin, are chemically similar.

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alpha-2-HS-glycoprotein also known as fetuin-A is a protein that in humans is encoded by the AHSG gene. Fetuin-A belongs to the fetuin class of plasma binding proteins and is more abundant in fetal than adult blood.

FABP1 is a human gene coding for the protein product FABP1. It is also frequently known as liver-type fatty acid-binding protein (LFABP).

Leukocyte cell-derived chemotaxin-2 (LECT2) is a protein first described in 1996 as a chemotactic factor for neutrophils, i.e. it stimulated human neutrophils to move directionally in an in vitro assay system. The protein was detected in and purified from cultures of Phytohaemagglutinin-activated human T-cell leukemia SKW-3 cells. Subsequent studies have defined LECT2 as a hepatokine, i.e. a substance made and released into the circulation by liver hepatocyte cells that regulates the function of other cells: it is a hepatocyte-derived, hormone-like, signaling protein.

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Fetuin-B is a protein that in humans is encoded by the FETUB gene.

The liver plays the major role in producing proteins that are secreted into the blood, including major plasma proteins, factors in hemostasis and fibrinolysis, carrier proteins, hormones, prohormones and apolipoprotein:

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References

1 2 3 4 Pal D, Dasgupta S, Kundu R, Maitra S, Das G, Mukhopadhyay S, Ray S, Majumdar SS, Bhattacharya S (2012). "Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance" (PDF). Nature Medicine . 18 (8): 1279–1285. doi:10.1038/nm.2851. PMID 22842477. S2CID 888828.
↑ Dutta D, Mondal SA, Kumar M, Hasanoor Reza AH, Biswas D, Singh P, Chakrabarti S, Mukhopadhyay S (2014). "Serum fetuin-A concentration predicts glycaemic outcomes in people with prediabetes: a prospective study from eastern India". Diabet. Med. 31 (12): 1594–9. doi:10.1111/dme.12539. PMID 24975463. S2CID 8532064.
↑ Trepanowski JF, Mey J, Varady KA (2015). "Fetuin-A: a novel link between obesity and related complications". International Journal of Obesity . 39 (5): 734–741. doi:10.1038/ijo.2014.203. PMID 25468829. S2CID 24089111.
↑ Nascimbeni F, Romagnoli D, Ballestri S, Baldelli E, Lugari S, Sirotti V, Giampaoli V, Lonardo A (2018). "Do Nonalcoholic Fatty Liver Disease and Fetuin-A Play Different Roles in Symptomatic Coronary Artery Disease and Peripheral Arterial Disease?". Diseases. 6 (1): E17. doi: 10.3390/diseases6010017 . PMC 5871963 . PMID 29462898.
↑ Mukhopadhyay S, Mondal SA, Kumar M, Dutta D (2014). "Proinflammatory and antiinflammatory attributes of fetuin-a: a novel hepatokine modulating cardiovascular and glycemic outcomes in metabolic syndrome". Endocr Pract. 20 (12): 1345–51. doi:10.4158/EP14421.RA. PMID 25370330.