Fetuin
Fetuins are
Family members
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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.
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]
References
Further reading
- Demetriou M, Binkert C, Sukhu B, Tenenbaum HC, Dennis JW (1996). "Fetuin/alpha2-HS glycoprotein is a transforming growth factor-beta type II receptor mimic and cytokine antagonist". J. Biol. Chem. 271 (22): 12755–61. PMID 8662721.
- Jahnen-Dechent W, Schäfer C, Ketteler M, McKee MD (2008). "Mineral chaperones: a role for fetuin-A and osteopontin in the inhibition and regression of pathologic calcification". J. Mol. Med. 86 (4): 379–89. S2CID 20960971.
- Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W (2003). "The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification". J. Clin. Invest. 112 (3): 357–66. PMID 12897203.
- Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Böhm R, Metzger T, Wanner C, Jahnen-Dechent W, Floege J (2003). "Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study". Lancet. 361 (9360): 827–33. S2CID 29188194.
- Heiss A, DuChesne A, Denecke B, Grötzinger J, Yamamoto K, Renné T, Jahnen-Dechent W (2003). "Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles". J. Biol. Chem. 278 (15): 13333–41. PMID 12556469.