Perilipin-1

Perilipin, also known as lipid droplet-associated protein, Perilipin 1, or PLIN, is a protein that, in humans, is encoded by the PLIN gene.[1] The perilipins are a family of proteins that associate with the surface of lipid droplets. Phosphorylation of perilipin is essential for the mobilization of fats in adipose tissue.[2]

Function

Perilipin is a protein that coats lipid droplets in adipocytes,[3] the fat-storing cells in adipose tissue. Perilipin acts as a protective coating from the body’s natural lipases, such as hormone-sensitive lipase,[4] which break triglycerides into glycerol and free fatty acids for use in metabolism, a process called lipolysis.[2] In humans, perilipin is expressed in three different isoforms, A, B, and C, and perilipin A is the most abundant protein associated with the adipocyte lipid droplets.[5]

Perilipin is hyperphosphorylated by PKA following β-adrenergic receptor activation.[2] Phosphorylated perilipin changes conformation, exposing the stored lipids to hormone-sensitive lipase-mediated lipolysis. Although PKA also phosphorylates hormone-sensitive lipase, which can increase its activity, the more than 50-fold increase in fat mobilization (triggered by epinephrine) is primarily due to perilipin phosphorylation.

Clinical significance

Perilipin is an important regulator of lipid storage.[2] Perilipin expression is elevated in obese animals and humans. Perilipin-null mice eat more food than wild-type mice, but gain 1/3 less fat than wild-type mice on the same diet; perilipin-null mice are thinner, with more lean muscle mass.[6] Perilipin-null mice also exhibit enhanced leptin production and a greater tendency to develop insulin resistance than wild-type mice.

Polymorphisms in the human perilipin (PLIN) gene have been associated with variance in body-weight regulation and may be a genetic influence on obesity risk in humans.[7] In particular, variants 13041A>G and 14995A>T have been associated with increased risk of obesity in women and 11482G>A has been associated with decreased perilipin expression and increased lipolysis in women.[8][9]

Perilipin family of proteins

Perilipin
Identifiers
Symbol Perilipin
Pfam PF03036
InterPro IPR004279

Perilipin is part of a gene family with five currently-known members. In vertebrates, closely related genes include adipophilin (also known as adipose differentiation-related protein or Perilipin 2), TIP47 (Perilipin 3), Perilipin 4 and Perilipin 5 (also called MLDP, LSDP5, or OXPAT). Insects express related proteins, LSD1 and LSD2, in fat bodies.[5] The yeast Saccharomyces cerevisiae expresses PLN1 (formerly PET10), that stabilizes lipid droplets and aids in their assembly.[10]

References

  1. ↑ "Entrez Gene: PLIN perilipin".
  2. 1 2 3 4 Mobilization and Cellular Uptake of Stored Fats (with Animation)
  3. ↑ Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C (June 1991). "Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets". J. Biol. Chem. 266 (17): 11341–6. PMID 2040638.
  4. ↑ Wong K (2000-11-29). "Making Fat-proof Mice". Scientific American. Retrieved 2009-05-22.
  5. 1 2 Brasaemle DL, Subramanian V, Garcia A, Marcinkiewicz A, Rothenberg A (June 2009). "Perilipin A and the control of triacylglycerol metabolism". Mol. Cell. Biochem. 326 (1–2): 15–21. doi:10.1007/s11010-008-9998-8. PMID 19116774.
  6. ↑ telegraph.co.uk, 19 June 2001, Highfield, Roger (2000-11-29). "Couch potato mice discover the lazy way to stay slim". The Daily Telegraph. London. Retrieved 2008-09-03.
  7. ↑ Soenen S, Mariman EC, Vogels N, Bouwman FG, den Hoed M, Brown L, Westerterp-Plantenga MS (March 2009). "Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance". Physiol. Behav. 96 (4–5): 723–8. doi:10.1016/j.physbeh.2009.01.011. PMID 19385027.
  8. ↑ Qi L, Shen H, Larson I, Schaefer EJ, Greenberg AS, Tregouet DA, Corella D, Ordovas JM (November 2004). "Gender-specific association of a perilipin gene haplotype with obesity risk in a white population". Obes. Res. 12 (11): 1758–65. doi:10.1038/oby.2004.218. PMID 15601970.
  9. ↑ Corella D, Qi L, Sorlí JV, Godoy D, Portolés O, Coltell O, Greenberg AS, Ordovas JM (September 2005). "Obese subjects carrying the 11482G>A polymorphism at the perilipin locus are resistant to weight loss after dietary energy restriction". J. Clin. Endocrinol. Metab. 90 (9): 5121–6. doi:10.1210/jc.2005-0576. PMID 15985482.
  10. ↑ Gao, Qiang; Binns, Derk D.; Kinch, Lisa N.; Grishin, Nick V.; Ortiz, Natalie; Chen, Xiao; Goodman, Joel M. (2017-10-02). "Pet10p is a yeast perilipin that stabilizes lipid droplets and promotes their assembly". The Journal of Cell Biology. 216 (10): 3199–3217. doi:10.1083/jcb.201610013. ISSN 1540-8140. PMC 5626530. PMID 28801319.

Further reading

  • Brasaemle DL (December 2007). "Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis". J. Lipid Res. 48 (12): 2547–59. doi:10.1194/jlr.R700014-JLR200. PMID 17878492.
  • Tai ES, Ordovas JM (2007). "The role of perilipin in human obesity and insulin resistance". Curr. Opin. Lipidol. 18 (2): 152–6. doi:10.1097/MOL.0b013e328086aeab. PMID 17353663.
  • Nishiu J, Tanaka T, Nakamura Y (1998). "Isolation and chromosomal mapping of the human homolog of perilipin (PLIN), a rat adipose tissue-specific gene, by differential display method". Genomics. 48 (2): 254–7. doi:10.1006/geno.1997.5179. PMID 9521880.
  • Souza SC, Muliro KV, Liscum L, et al. (2002). "Modulation of hormone-sensitive lipase and protein kinase A-mediated lipolysis by perilipin A in an adenoviral reconstituted system". J. Biol. Chem. 277 (10): 8267–72. doi:10.1074/jbc.M108329200. PMID 11751901.
  • Hagström-Toft E, Qvisth V, Nennesmo I, et al. (2002). "Marked heterogeneity of human skeletal muscle lipolysis at rest". Diabetes. 51 (12): 3376–83. doi:10.2337/diabetes.51.12.3376. PMID 12453889.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Mottagui-Tabar S, Rydén M, Löfgren P, et al. (2004). "Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis". Diabetologia. 46 (6): 789–97. doi:10.1007/s00125-003-1112-x. PMID 12802495.
  • Wang Y, Sullivan S, Trujillo M, et al. (2004). "Perilipin expression in human adipose tissues: effects of severe obesity, gender, and depot". Obes. Res. 11 (8): 930–6. doi:10.1038/oby.2003.128. PMID 12917496.
  • Zhang HH, Souza SC, Muliro KV, et al. (2004). "Lipase-selective functional domains of perilipin A differentially regulate constitutive and protein kinase A-stimulated lipolysis". J. Biol. Chem. 278 (51): 51535–42. doi:10.1074/jbc.M309591200. PMID 14527948.
  • Kern PA, Di Gregorio G, Lu T, et al. (2004). "Perilipin expression in human adipose tissue is elevated with obesity". J. Clin. Endocrinol. Metab. 89 (3): 1352–8. doi:10.1210/jc.2003-031388. PMID 15001633.
  • Arvidsson E, Blomqvist L, Rydén M (2004). "Depot-specific differences in perilipin mRNA but not protein expression in obesity". J. Intern. Med. 255 (5): 595–601. doi:10.1111/j.1365-2796.2004.01314.x. PMID 15078502.
  • Dalen KT, Schoonjans K, Ulven SM, et al. (2004). "Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-gamma". Diabetes. 53 (5): 1243–52. doi:10.2337/diabetes.53.5.1243. PMID 15111493.
  • Qi L, Corella D, Sorlí JV, et al. (2005). "Genetic variation at the perilipin (PLIN) locus is associated with obesity-related phenotypes in White women". Clin. Genet. 66 (4): 299–310. doi:10.1111/j.1399-0004.2004.00309.x. PMID 15355432.
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
  • Yan W, Chen S, Huang J, et al. (2005). "Polymorphisms in PLIN and hypertension combined with obesity and lipid profiles in Han Chinese". Obes. Res. 12 (11): 1733–7. doi:10.1038/oby.2004.214. PMID 15601966.
  • Qi L, Shen H, Larson I, et al. (2005). "Gender-specific association of a perilipin gene haplotype with obesity risk in a white population". Obes. Res. 12 (11): 1758–65. doi:10.1038/oby.2004.218. PMID 15601970.
  • Qi L, Tai ES, Tan CE, et al. (2005). "Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population". J. Mol. Med. 83 (6): 448–56. doi:10.1007/s00109-004-0630-4. PMID 15770500.
  • Forcheron F, Legedz L, Chinetti G, et al. (2005). "Genes of cholesterol metabolism in human atheroma: overexpression of perilipin and genes promoting cholesterol storage and repression of ABCA1 expression". Arterioscler. Thromb. Vasc. Biol. 25 (8): 1711–7. doi:10.1161/01.ATV.0000174123.19103.52. PMID 15961705.
  • Corella D, Qi L, Sorlí JV, et al. (2005). "Obese subjects carrying the 11482G>A polymorphism at the perilipin locus are resistant to weight loss after dietary energy restriction". J. Clin. Endocrinol. Metab. 90 (9): 5121–6. doi:10.1210/jc.2005-0576. PMID 15985482.
  • Moore HP, Silver RB, Mottillo EP, et al. (2006). "Perilipin targets a novel pool of lipid droplets for lipolytic attack by hormone-sensitive lipase". J. Biol. Chem. 280 (52): 43109–20. doi:10.1074/jbc.M506336200. PMID 16243839.
  • Shimizu M, Akter MH, Emi Y, et al. (2007). "Peroxisome proliferator-activated receptor subtypes differentially cooperate with other transcription factors in selective transactivation of the perilipin/PEX11 alpha gene pair". J. Biochem. 139 (3): 563–73. doi:10.1093/jb/mvj053. PMID 16567422.
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