PLIN2
Identifiers
AliasesPLIN2, ADFP, ADRP, Adipose differentiation-related protein, perilipin 2
External IDsOMIM: 103195 MGI: 87920 HomoloGene: 872 GeneCards: PLIN2
Orthologs
SpeciesHumanMouse
Entrez

123

11520

Ensembl

ENSG00000147872

ENSMUSG00000028494

UniProt

Q99541

P43883

RefSeq (mRNA)

NM_001122

NM_007408

RefSeq (protein)

NP_001113

Location (UCSC)Chr 9: 19.11 – 19.15 MbChr 4: 86.65 – 86.67 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Adipose differentiation-related protein, also known as perilipin 2, ADRP or adipophilin, is a protein which belongs to the perilipin (PAT) family of cytoplasmic lipid droplet (CLD)–binding proteins.[5] In humans it is encoded by the ADFP gene.[6] This protein surrounds the lipid droplet along with phospholipids and is involved in assisting the storage of neutral lipids within the lipid droplets.[7]

Discovery

The adipose differentiation related protein (ADRP) was first characterized as an mRNA molecule that express early in adipocyte differentiation.[8] The full length cDNA was cloned by rapid amplification of cDNA ends method and sequence analysis results in a protein with 425 amino acids that is unique and similar sequences had not previously been reported.[8]

Gene location

In humans, the gene for adipose differentiation related protein is located at short p arm of chromosome 9 at region 22 band 1 from base pair 19108391 to 19127606 (GRCh38.p7) (map).[9]

Protein structure

The proposed models for adipose differentiation related protein (perilipin 2) is maintained by the protein model portal.[10] It is based on homology modelling and no models were found with greater than 90 percent homology. Perlipin 2 has three different functional domains . 1-115 amino acid sequences at N-terminal is highly similar with other perlipin family proteins and is required for stabilization of lipid droplets, 103-215 mid- region is needed for binding at lipid droplets while the C-terminal sequence from 220-437 forms four helix bundles.[11]

Function

Perilipin 2 was thought to be expressed only in adipose tissues previously.[12] However, later on it was found to be expressed in all types of cells including many non-adipose tissues.[12] The function of perilipin 2 involves the formation of lipid droplets, formation of fatty liver by increasing uptake of fatty acids etc. Decreased expression of perilipin 2 decreases the fatty liver while increase expression of perilipin is associated with several metabolic diseases like type 2 diabetes, insulin resistance, heart diseases. Moreover, its expression was also found to be linked with other age related diseases.[7] This protein is associated with the globule surface membrane material and is major constituent of the globule surface. Increase in mRNA levels is one of the earliest indications of adipocyte differentiation.[6]

Pre-adipocytes are undifferentiated fibroblasts that can be stimulated to form adipocytes. Studies have shed light into potential molecular mechanisms in the fate determination of pre-adipocytes although the exact lineage of adipocyte is still unclear.[13]

Mutation

In humans, a substitution mutation at the C-terminal region of perlipin 2 was shown to affect both the structure and function of the protein.[11] At 251 position , serine residue was substituted by proline which results in the disruption of predicted alpha helical structure of the protein as well as reduction in the plasma triglycerides and lipolysis.[14] Thus, mutation in perlipin 2 may influence the development of different human metabolic diseases.

In vitro and animal studies

Metabolic disorders and liver diseases

Conditions like obesity, type 2 diabetes are related with metabolic disorders. It involves increase accumulation of lipid due to impaired fatty acid metabolism. Alcoholic liver diseases and non-alcoholic fatty liver disease are two types of conditions associated with liver lipid accumulation.[15] Obesity is related with increase accumulation of lipid droplets in non-adipose tissues causing lipotoxicity. The expression of perlipin 2 at normal level appears necessary to induce obesity in mouse model. Increased activity of perlipin 2 increases the resistance to insulin thereby promoting type 2 diabetes.[15]

Cardiovascular diseases

Age related diseases like atherosclerosis, hypertension accounts many deaths in elderly people.[16] Accumulation of lipid droplets induce the modification of macrophages to foam cells. Lysis of foam cells resulted in Atherosclerotic plaques and such plaques rupture and blocked the thrombotic vessel.[16] Perlipin 2 protein around the macrophages and foam cells was found to play important role in formation of atheroma. Downregulation of perlipin 2 inhibits the lipid droplet accumulation and decreases the likelihood to convert macrophages to foam cells.[17]

Cancer

Another factor which increases the risk for cancer is aging process.[18] Analysis of body fluids like urine and blood from circulation from different types of cancer for example colorectal cancer, Burkitt cancer, lung adenocarcinoma showed increase level of Perlipin 2.[19] Perlipin 2 can also serve as a biomarker for early detection of some type of cancer.[20]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000147872 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028494 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Orlicky DJ, Degala G, Greenwood C, Bales ES, Russell TD, McManaman JL (September 2008). "Multiple functions encoded by the N-terminal PAT domain of adipophilin". Journal of Cell Science. 121 (Pt 17): 2921–9. doi:10.1242/jcs.026153. PMC 3139108. PMID 18697835.
  6. 1 2 "Entrez Gene: ADFP adipose differentiation-related protein".
  7. 1 2 Conte M, Franceschi C, Sandri M, Salvioli S (September 2016). "Perilipin 2 and Age-Related Metabolic Diseases: A New Perspective". Trends in Endocrinology and Metabolism. 27 (12): 893–903. doi:10.1016/j.tem.2016.09.001. PMID 27659144. S2CID 3651182.
  8. 1 2 Jiang HP, Serrero G (September 1992). "Isolation and characterization of a full-length cDNA coding for an adipose differentiation-related protein". Proceedings of the National Academy of Sciences of the United States of America. 89 (17): 7856–60. Bibcode:1992PNAS...89.7856J. doi:10.1073/pnas.89.17.7856. PMC 49813. PMID 1518805.
  9. ↑ "Homo sapiens (human) Annotation Release 107 (Current)". NCBI map viewer.
  10. ↑ "Q99541". UniProt.
  11. 1 2 Magné J, Aminoff A, Perman Sundelin J, Mannila MN, Gustafsson P, Hultenby K, et al. (August 2013). "The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an α-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans". FASEB J. 27 (8): 3090–9. doi:10.1096/fj.13-228759. PMID 23603836. S2CID 205370787.
  12. 1 2 Brasaemle DL, Barber T, Wolins NE, Serrero G, Blanchette-Mackie EJ, Londos C (November 1997). "Adipose differentiation-related protein is an ubiquitously expressed lipid storage droplet-associated protein". Journal of Lipid Research. 38 (11): 2249–63. doi:10.1016/S0022-2275(20)34939-7. PMID 9392423.
  13. ↑ Coskun H, Summerfield TL, Kniss DA, Friedman A (July 2010). "Mathematical modeling of preadipocyte fate determination". Journal of Theoretical Biology. 265 (1): 87–94. Bibcode:2010JThBi.265...87C. doi:10.1016/j.jtbi.2010.03.047. PMID 20385145.
  14. ↑ Sentinelli F, Capoccia D, Incani M, Bertoccini L, Severino A, Pani MG, Manconi E, Cossu E, Leonetti F, Baroni MG (September 2016). "The perilipin 2 (PLIN2) gene Ser251Pro missense mutation is associated with reduced insulin secretion and increased insulin sensitivity in Italian obese subjects". Diabetes Metab. Res. Rev. 32 (6): 550–6. doi:10.1002/dmrr.2751. PMID 26443937. S2CID 5256380.
  15. 1 2 Carr RM, Peralta G, Yin X, Ahima RS (2014). "Absence of perilipin 2 prevents hepatic steatosis, glucose intolerance and ceramide accumulation in alcohol-fed mice". PLOS ONE. 9 (5): e97118. Bibcode:2014PLoSO...997118C. doi:10.1371/journal.pone.0097118. PMC 4022498. PMID 24831094.
  16. 1 2 Son SH, Goo YH, Choi M, Saha PK, Oka K, Chan LC, Paul A (February 2016). "Enhanced atheroprotection and lesion remodelling by targeting the foam cell and increasing plasma cholesterol acceptors". Cardiovascular Research. 109 (2): 294–304. doi:10.1093/cvr/cvv241. PMC 4724936. PMID 26487692.
  17. ↑ Larigauderie G, Cuaz-Pérolin C, Younes AB, Furman C, Lasselin C, Copin C, Jaye M, Fruchart JC, Rouis M (August 2006). "Adipophilin increases triglyceride storage in human macrophages by stimulation of biosynthesis and inhibition of beta-oxidation". FEBS J. 273 (15): 3498–510. doi:10.1111/j.1742-4658.2006.05357.x. PMID 16884492. S2CID 27830334.
  18. ↑ Matsubara J, Honda K, Ono M, Sekine S, Tanaka Y, Kobayashi M, Jung G, Sakuma T, Nakamori S, Sata N, Nagai H, Ioka T, Okusaka T, Kosuge T, Tsuchida A, Shimahara M, Yasunami Y, Chiba T, Yamada T (October 2011). "Identification of adipophilin as a potential plasma biomarker for colorectal cancer using label-free quantitative mass spectrometry and protein microarray". Cancer Epidemiology, Biomarkers & Prevention. 20 (10): 2195–203. doi:10.1158/1055-9965.EPI-11-0400. hdl:2433/197220. PMID 21828233.
  19. ↑ Zhang XD, Li W, Zhang N, Hou YL, Niu ZQ, Zhong YJ, Zhang YP, Yang SY (2014). "Identification of adipophilin as a potential diagnostic tumor marker for lung adenocarcinoma". International Journal of Clinical and Experimental Medicine. 7 (4): 1190–6. PMC 4057887. PMID 24955208.
  20. ↑ Prieto DA, Johann DJ, Wei BR, Ye X, Chan KC, Nissley DV, Simpson RM, Citrin DE, Mackall CL, Linehan WM, Blonder J (2014). "Mass spectrometry in cancer biomarker research: a case for immunodepletion of abundant blood-derived proteins from clinical tissue specimens". Biomarkers in Medicine. 8 (2): 269–86. doi:10.2217/bmm.13.101. PMC 4201940. PMID 24521024.

Further reading

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