Asprosin

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. People with neonatal progeroid syndrome are deficient in asprosin, while people with insulin resistance and obesity have it in abundance.

Background

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] People with the congenital disease, neonatal progeroid syndrome, are deficient in asprosin, while people presenting the condition of insulin resistance and obesity produce it in abundance.[1][4]

Discovery and function

Asprosin was first identified by Dr. Atul Chopra and coworkers at Baylor as a C-terminal cleavage product of the FBN1 gene product profibrillin. They also found mutations in the FBN1 gene in two patients with NPS. 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). The authors concluded that NPS patients suffer from two distinct pathologies, Marfan syndrome due to the truncated fibrillin, and reduced hepatic glucose production due to reduced levels of asprosin.[1][5][6]

Therapeutic potential

In a test of pharmacologic asprosin depletion in animals, preliminary results raised the possibility of its use, therapeutically, in treating type 2 diabetes. Specifically, Chopra and coworkers observed that when antibodies targeting asprosin were injected into diabetic mice, blood glucose and insulin levels improved.[1][5]

References

  1. 1 2 3 4 Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton VR, Butte NF, Moore DD, Chopra AR (April 2016). "Asprosin, a Fasting-Induced Glucogenic Protein Hormone". Cell. 165 (3): 566–79. doi:10.1016/j.cell.2016.02.063. PMID 27087445.
  2. Levine R (1986). "Monosaccharides in Health and Disease". Annu. Rev. Nutr. 6: 211–224. 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. Retrieved 25 November 2016.
  4. Grens K (April 15, 2016). "Newly Discovered Hormone Explains Disease". The Scientist. Retrieved 18 April 2016.
  5. 1 2 Pathak, Dipali (Apr 14, 2016). "Discovery of Asprosin, New Hormone Could Have Potential Implications in Treatment of Diabetes". Houston, TX: Baylor College of Medicine. Retrieved 18 April 2016.
  6. Coghlan A (14 April 2016). "Newly discovered hormone could fight type 2 diabetes and obesity". New Scientist. Retrieved 20 April 2016.

Further reading

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