Perilipin
| Perilipin 1 | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | PLIN1; FPLD4; PERI; PLIN | ||||||||||||
| External IDs | OMIM: 170290 MGI: 1890505 HomoloGene: 2001 ChEMBL: 1741164 GeneCards: PLIN1 Gene | ||||||||||||
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| RNA expression pattern | |||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 5346 | 103968 | |||||||||||
| Ensembl | ENSG00000166819 | ENSMUSG00000030546 | |||||||||||
| UniProt | O60240 | Q8CGN5 | |||||||||||
| RefSeq (mRNA) | NM_001145311 | NM_001113471 | |||||||||||
| RefSeq (protein) | NP_001138783 | NP_001106942 | |||||||||||
| Location (UCSC) | Chr 15: 90.21 – 90.22 Mb | Chr 7: 79.72 – 79.73 Mb | |||||||||||
| PubMed search | |||||||||||||
Perilipin, also known as lipid droplet-associated protein 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 | |||||||||
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| Identifiers | |||||||||
| Symbol | Perilipin | ||||||||
| Pfam | PF03036 | ||||||||
| InterPro | IPR004279 | ||||||||
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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), TIP47, and LSDP5 (also called MLDP and OXPAT). Insects express related proteins, LSD1 and LSD2, in fat bodies.[5]
References
- ↑ "Entrez Gene: PLIN perilipin".
- ↑ 2.0 2.1 2.2 2.3 Mobilization and Cellular Uptake of Stored Fats (with Animation)
- ↑ 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.
- ↑ Wong K (2000-11-29). "Making Fat-proof Mice". Scientific American. Retrieved 2009-05-22.
- ↑ 5.0 5.1 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
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.