Asprosin

From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Fibrillin 1
Identifiers
Symbol FBN1
Entrez 2200
HUGO 3603
OMIM 134797
RefSeq NP_000129
UniProt P35555
Other data
Locus Chr. 15 q21.1

Asprosin is a protein hormone produced by mammals in their fatty (white adipose) tissues that stimulates the liver to release glucose into the blood stream. In these tissues, asprosin is encoded by the gene FBN1, which also encodes the protein fibrillin. In the liver, asprosin activates rapid glucose release via a cyclic adenosine monophosphate (cAMP) dependent pathway.

Background[edit]

Asprosin is a protein hormone that has been found to be produced by white adipose tissue in mammals; it is transported to the liver, where it stimulates the release of glucose into the blood stream, via a cAMP-dependent pathway.[1]

Glucose released by the liver into the blood stream is required for the normal function of the brain and other organs, as well as for survival during fasting and other aspects of mammalian function.[2][3] Individuals with Marfanoid–progeroid–lipodystrophy syndrome (MPL) are deficient in asprosin, while people presenting the condition of insulin resistance and obesity produce it in abundance.[1][4]

Discovery and function[edit]

Asprosin was first identified by Dr. Atul Chopra and coworkers at Baylor College of Medicine as a C-terminal cleavage product of the FBN1 gene product profibrillin. They found mutations in the FBN1 gene in two patients with congenital partial lipodystrophy and a progeroid appearance.[5] The two patients were Lizzie Velasquez and Abby Solomon.[6][7] Truncations of the FBN1 protein in these patients were seen to have two consequences for protein production: a mutant/truncated fibrillin protein and very low plasma asprosin levels (from a postulated dominant negative effect).[1][8][9] The condition has since been named Marfanoid–progeroid–lipodystrophy syndrome.

Therapeutic potential[edit]

In a test of pharmacologic asprosin depletion in animals, preliminary results raised the possibility of its use, therapeutically, in treating type 2 diabetes and obesity.[10] For instance, Chopra and coworkers observed that when antibodies targeting asprosin were injected into diabetic mice, blood glucose and insulin levels improved.[1][8]

Notes[edit]

  1. ^ a b c d Romere et al., 2016.
  2. ^ Levine R (1986). "Monosaccharides in Health and Disease". Annu. Rev. Nutr. 6: 211–224. doi:10.1146/annurev.nu.06.070186.001235. Retrieved 25 November 2016. 
  3. ^ Röder PV, Wu B, Liu Y, Han W (March 2016). "Pancreatic regulation of glucose homeostasis". Experimental & Molecular Medicine. 48 (3, March): e219. doi:10.1038/emm.2016.6. PMC 4892884Freely accessible. PMID 26964835. 
  4. ^ Grens K (April 15, 2016). "Newly Discovered Hormone Explains Disease". The Scientist. Retrieved 18 April 2016. 
  5. ^ Romere et al., 2016, describe two patients, whom they characterize as having "neonatal progeroid syndrome (NPS)", citing O'Neil et al., 2007. No additional clinical information was provided (see also the description of Romere et al. in OMIM entry *134797 FIBRILLIN 1 ). However, in a later paper (Garg & Xing 2013; not cited by Romere et al.) the two patients described by O'Neil et al. in 2007 as having NPS were re-examined and found to exhibit several features associated with Marfan syndrome, and were re-characterized as having "progeroid fibrillinopathy" based on the presence of mutations in the FBN1 gene. See also the description of Romere et al in OMIM entry #616914 - MARFAN LIPODYSTROPHY SYNDROME; MFLS; accessed 9 December 2016.
  6. ^ Kennedy, Pagan (25 Nov 2016). "The Thin Gene". The New York Times. Retrieved 22 May 2017. 
  7. ^ Bordo, Sara (Director); Campo, Michael (Writer); Velasquez, Lizzie (Star) (2015). A Brave Heart: The Lizzie Velasquez Story. Event occurs at 45:50 to 50:36. 
  8. ^ a b Pathak 2016.
  9. ^ Coghlan A (14 April 2016). "Newly discovered hormone could fight type 2 diabetes and obesity". New Scientist. Retrieved 20 April 2016. 
  10. ^ Greenhill C (2016). "Liver: Asprosin - new hormone involved in hepatic glucose release". Nat Rev Endocrinol. 12 (6): 312. doi:10.1038/nrendo.2016.66. PMID 27125501. 

References[edit]

Further reading[edit]