Thematic review series: Lipid droplet synthesis and metabolism: From yeast to man - Seipin: From human disease to molecular mechanism

Journal of Lipid Research

Volumn 53, Issue 6, 2012, Pages 1042-1055

  Cartwright, Bethany R ^a   Goodman, Joel M ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

Adipogenesis; Berardinelli Seip congenital lipodystrophy; Congenital generalized lipodystrophy; Lipid droplet; Lipodystrophy

Indexed keywords

AMINO ACID; ANTILIPEMIC AGENT; ANTIRETROVIRUS AGENT; FAT DROPLET; INSULIN; ISOPROTEIN; MEMBRANE PROTEIN; ORAL ANTIDIABETIC AGENT; SEIPIN; TROGLITAZONE; UNCLASSIFIED DRUG; BSCL2 PROTEIN, HUMAN; GUANINE NUCLEOTIDE BINDING PROTEIN GAMMA SUBUNIT;

ADIPOGENESIS; AGPAT2 GENE; BSCL2 GENE; CAV1 GENE; CAVIN 1 GENE; CONGENITAL GENERALIZED LIPODYSTROPHY; DIABETES MELLITUS; DIET RESTRICTION; DISEASE SEVERITY; GENE; GENE EXPRESSION; GENE IDENTIFICATION; GENE STRUCTURE; GENETIC DISORDER; GENETIC VARIABILITY; HOMEOSTASIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERLIPIDEMIA; HYPERTRIGLYCERIDEMIA; LIPID METABOLISM; LIPID STORAGE; LIPODYSTROPHY; LIPOGENESIS; MISSENSE MUTATION; MOLECULAR MECHANICS; MOLECULAR MODEL; MOLECULAR PROBE; MUSCLE HYPERTROPHY; NEUROLOGIC DISEASE; NEUROLOGICAL SEIPINOPATHY; NONHUMAN; OLIGOMERIZATION; PANCREATITIS; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DEFECT; PROTEIN DEPLETION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PTRF GENE; REVIEW; SEIPIN GENE; SYMPTOM; THEMATIC ANALYSIS; ANIMAL; CHEMISTRY; DISEASES; GENE EXPRESSION REGULATION; GENETICS; METABOLISM;

ANIMALS; DISEASE; GENE EXPRESSION REGULATION; GTP-BINDING PROTEIN GAMMA SUBUNITS; HUMANS; LIPODYSTROPHY, CONGENITAL GENERALIZED; NERVOUS SYSTEM DISEASES; PHENOTYPE;

EID: 84861432786     PISSN: 00222275     EISSN: 15397262     Source Type: Journal    
DOI: 10.1194/jlr.R023754     Document Type: Review

References (75)

1. Mitchell, S. W. 1885. Singular case of absence of adipose matter in the upper half of the body. Am. J. Med. Sci. 179: 105-106.
2. Garg, A. 2011. Lipodystrophies: genetic and acquired body fat disorders. J. Clin. Endocrinol. Metab. 96: 3313-3325.
3. Lawrence, R. D. 1946. Lipodystrophy and hepatomegaly, with diabetes, lipaemia, and other metabolic disturbances: a case throwing new light on the action of insulin. Lancet. 1: 724-731, 773-775.
4. Berardinelli, W. 1954. An undiagnosed endocrinometabolic syndrome: report of 2 cases. J. Clin. Endocrinol. Metab. 14: 193-204.
5. Seip, M. 1959. Lipodystrophy and gigantism with associated endocrine manifestations. A new diencephalic syndrome? Acta Paediatr. 48: 555-574.
6. Moller, D. E., and S. O'Rahilly. 1993. Syndromes of severe insulin resistance: clinical and pathophysiological features. In Insulin Resistance. D. E. Moller, editor. Wiley and Sons, New York. 49-81.
7. Agarwal, A. K., and A. Garg. 2006. Genetic basis of lipodystrophies and management of metabolic complications. Annu. Rev. Med. 57: 297-311. (Pubitemid 43261993)
8. Arioglu, E., J. Duncan-Morin, N. Sebring, K. I. Rother, N. Gottlieb, J. Lieberman, D. Herion, D. E. Kleiner, J. Reynolds, A. Premkumar, et al. 2000. Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann. Intern. Med. 133: 263-274. (Pubitemid 30660298)
9. Oral, E. A., V. Simha, E. Ruiz, A. Andewelt, A. Premkumar, P. Snell, A. J. Wagner, A. M. DePaoli, M. L. Reitman, S. I. Taylor, et al. 2002. Leptin-replacement therapy for lipodystrophy. N. Engl. J. Med. 346: 570-578. (Pubitemid 34438818)
10. Seip, M., and O. Trygstad. 1996. Generalized lipodystrophy, congenital and acquired (lipoatrophy). Acta Paediatr. Suppl. 413: 2-28. (Pubitemid 26189575)
11. Trygstad, O., M. Seip, and S. Oseid. 1977. Lipodystrophic diabetes treated with fenfluramine. Int. J. Obes. 1: 287-292.
12. Ebihara, K., T. Kusakabe, M. Hirata, H. Masuzaki, F. Miyanaga, N. Kobayashi, T. Tanaka, H. Chusho, T. Miyazawa, T. Hayashi, et al. 2007. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J. Clin. Endocrinol. Metab. 92: 532-541.
13. Tontonoz, P., E. Hu, and B. M. Spiegelman. 1994. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 79: 1147-1156.
14. Garg, A. 2004. Acquired and inherited lipodystrophies. N. Engl. J. Med. 350: 1220-1234. (Pubitemid 38339366)
15. Gomes, K. B., A. P. Fernandes, A. C. Ferreira, H. Pardini, A. Garg, J. Magre, and V. C. Pardini. 2004. Mutations in the seipin and AGPAT2 genes clustering in consanguineous families with Berardinelli-Seip congenital lipodystrophy from two separate geographical regions of Brazil. J. Clin. Endocrinol. Metab. 89: 357-361. (Pubitemid 38183904)
16. Magré, J., M. Delepine, E. Khallouf, T. Gedde-Dahl, Jr., L. Van Maldergem, E. Sobel, J. Papp, M. Meier, A. Megarbane, A. Bachy, et al. 2001. Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat. Genet. 28: 365-370. (Pubitemid 32702427)
17. Agarwal, A. K., E. Arioglu, S. De Almeida, N. Akkoc, S. I. Taylor, A. M. Bowcock, R. I. Barnes, and A. Garg. 2002. AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nat. Genet. 31: 21-23.
18. Garg, A., R. Wilson, R. Barnes, E. Arioglu, Z. Zaidi, F. Gurakan, N. Kocak, S. O'Rahilly, S. I. Taylor, S. B. Patel, et al. 1999. A gene for congenital generalized lipodystrophy maps to human chromosome 9q34. J. Clin. Endocrinol. Metab. 84: 3390-3394. (Pubitemid 30646973)
19. Leung, D. W. 2001. The structure and functions of human lysophosphatidic acid acyltransferases. Front. Biosci. 6: D944-953.
20. Takeuchi, K., and K. Reue. 2009. Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am. J. Physiol. Endocrinol. Metab. 296: E1195-E1209.
21. Agarwal, A. K., R. I. Barnes, and A. Garg. 2004. Genetic basis of congenital generalized lipodystrophy. Int. J. Obes. Relat. Metab. Dis. 28: 336-339. (Pubitemid 38228420)
22. Gale, S. E., A. Frolov, X. Han, P. E. Bickel, L. Cao, A. Bowcock, J. E. Schaffer, and D. S. Ory. 2006. A regulatory role for 1-acylglycerol-3-phosphate- O-acyltransferase 2 in adipocyte differentiation. J. Biol. Chem. 281: 11082-11089. (Pubitemid 43855532)
23. Cortés, V. A., D. E. Curtis, S. Sukumaran, X. Shao, V. Parameswara, S. Rashid, A. R. Smith, J. Ren, V. Esser, R. E. Hammer, et al. 2009. Molecular mechanisms of hepatic steatosis and insulin resistance in the AGPAT2-deficient mouse model of congenital generalized lipodystrophy. Cell Metab. 9: 165-176.
24. Hayashi, Y. K., C. Matsuda, M. Ogawa, K. Goto, K. Tominaga, S. Mitsuhashi, Y. E. Park, I. Nonaka, N. Hino-Fukuyo, K. Haginoya, et al. 2009. Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J. Clin. Invest. 119: 2623-2633.
25. Kim, C. A., M. Delepine, E. Boutet, H. El Mourabit, S. Le Lay, M. Meier, M. Nemani, E. Bridel, C. C. Leite, D. R. Bertola, et al. 2008. Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy. J. Clin. Endocrinol. Metab. 93: 1129-1134. (Pubitemid 351540679)
26. Fan, J. Y., J. L. Carpentier, E. van Obberghen, C. Grunfeld, P. Gorden, and L. Orci. 1983. Morphological changes of the 3T3-L1 fibroblast plasma membrane upon differentiation to the adipocyte form. J. Cell Sci. 61: 219-230. (Pubitemid 13064310)
27. Parton, R. G., and K. Simons. 2007. The multiple faces of caveolae. Nat. Rev. Mol. Cell Biol. 8: 185-194.
28. Simha, V., and A. Garg. 2003. Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes. J. Clin. Endocrinol. Metab. 88: 5433-5437. (Pubitemid 37452750)
29. Van Maldergem, L., J. Magre, T. E. Khallouf, T. Gedde-Dahl, Jr., M. Delepine, O. Trygstad, E. Seemanova, T. Stephenson, C. S. Albott, F. Bonnici, et al. 2002. Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy. J. Med. Genet. 39: 722-733. (Pubitemid 35178722)
30. Dwianingsih, E. K., Y. Takeshima, K. Itoh, Y. Yamauchi, H. Awano, R. G. Malueka, A. Nishida, M. Ota, M. Yagi, and M. Matsuo. 2010. A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4. Mol. Genet. Metab. 101: 233-237.
31. Rajab, A., V. Straub, L. J. McCann, D. Seelow, R. Varon, R. Barresi, A. Schulze, B. Lucke, S. Lutzkendorf, M. Karbasiyan, et al. 2010. Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet. 6: e1000874.
32. Shastry, S., M. R. Delgado, E. Dirik, M. Turkmen, A. K. Agarwal, and A. Garg. 2010. Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. Am. J. Med. Genet. A. 152A: 2245-2253.
33. Agarwal, A. K., V. Simha, E. A. Oral, S. A. Moran, P. Gorden, S. O'Rahilly, Z. Zaidi, F. Gurakan, S. A. Arslanian, A. Klar, et al. 2003. Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. J. Clin. Endocrinol. Metab. 88: 4840-4847. (Pubitemid 37357534)
34. Gomes, K. B., V. C. Pardini, A. C. Ferreira, and A. P. Fernandes. 2005. Phenotypic heterogeneity in biochemical parameters correlates with mutations in AGPAT2 or Seipin genes among Berardinelli- Seip congenital lipodystrophy patients. J. Inherit. Metab. Dis. 28: 1123-1131. (Pubitemid 43168949)
35. Rognum, T. O., K. S. Bjerve, M. Seip, O. Trygstad, and S. Oseid. 1978. Fat cell size and lipid content of subcutaneous tissue in congenital generalized lipodystrophy. Acta Endocrinol. (Copenh.). 88: 182-189. (Pubitemid 8333387)
36. Haque, W. A., I. Shimomura, Y. Matsuzawa, and A. Garg. 2002. Serum adiponectin and leptin levels in patients with lipodystrophies. J. Clin. Endocrinol. Metab. 87: 2395.
37. Pardini, V. C., I. M. Victoria, S. M. Rocha, D. G. Andrade, A. M. Rocha, F. B. Pieroni, G. Milagres, S. Purisch, and G. Velho. 1998. Leptin levels, beta-cell function, and insulin sensitivity in families with congenital and acquired generalized lipoatropic diabetes. J. Clin. Endocrinol. Metab. 83: 503-508. (Pubitemid 28496530)
38. Antuna-Puente, B., E. Boutet, C. Vigouroux, O. Lascols, L. Slama, M. Caron-Debarle, E. Khallouf, C. Levy-Marchal, J. Capeau, J. P. Bastard, et al. 2010. Higher adiponectin levels in patients with Berardinelli-Seip congenital lipodystrophy due to seipin as compared with 1-acylglycerol-3-phosphate-o- acyltransferase-2 defi- ciency. J. Clin. Endocrinol. Metab. 95: 1463-1468.
39. Bjørnstad, P. G., A. Foerster, and H. Ihlen. 1996. Cardiac findings in generalized lipodystrophy. Acta Paediatr. Suppl. 413: 39-43. (Pubitemid 26189577)
40. Ito, D., and N. Suzuki. 2009. Seipinopathy: a novel endoplasmic reticulum stress-associated disease. Brain. 132: 8-15.
41. Huang, H. H., T. H. Chen, H. P. Hsiao, C. T. Huang, C. C. Wang, Y. H. Shiau, and M. C. Chao. 2010. A Taiwanese boy with congenital generalized lipodystrophy caused by homozygous Ile262fs mutation in the BSCL2 gene. Kaohsiung J. Med. Sci. 26: 615-620.
42. Jin, J., L. Cao, Z. Zhao, S. Shen, W. Kiess, D. Zhi, R. Ye, R. Cheng, L. Chen, Y. Yang, et al. 2007. Novel BSCL2 gene mutation E189X in Chinese congenital generalized lipodystrophy child with early onset diabetes mellitus. Eur. J. Endocrinol. 157: 783-787.
43. Wu, Y. R., S. I. Hung, Y. C. Chang, S. T. Chen, Y. L. Lin, and W. H. Chung. 2009. Complementary mutations in seipin gene in a patient with Berardinelli-Seip congenital lipodystrophy and dystonia: phenotype variability suggests multiple roles of seipin gene. J. Neurol. Neurosurg. Psychiatry. 80: 1180-1181.
44. Fei, W., G. Shui, B. Gaeta, X. Du, L. Kuerschner, P. Li, A. J. Brown, M. R. Wenk, R. G. Parton, and H. Yang. 2008. Fld1p, a functional homologue of human seipin, regulates the size of lipid droplets in yeast. J. Cell Biol. 180: 473-482. (Pubitemid 351240697)
45. Szymanski, K. M., D. Binns, R. Bartz, N. V. Grishin, W. P. Li, A. K. Agarwal, A. Garg, R. G. Anderson, and J. M. Goodman. 2007. The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology. Proc. Natl. Acad. Sci. USA. 104: 20890-20895.
46. Miranda, D. M., B. L. Wajchenberg, M. R. Calsolari, M. J. Aguiar, J. M. Silva, M. G. Ribeiro, C. Fonseca, D. Amaral, W. L. Boson, B. A. Resende, et al. 2009. Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome. Clin. Endocrinol. (Oxf.). 71: 512-517.
47. Tian, Y., J. Bi, G. Shui, Z. Liu, Y. Xiang, Y. Liu, M. R. Wenk, H. Yang, and X. Huang. 2011. Tissue-autonomous function of Drosophila seipin in preventing ectopic lipid droplet formation. PLoS Genet. 7: e1001364.
48. Ebihara, K., T. Kusakabe, H. Masuzaki, N. Kobayashi, T. Tanaka, H. Chusho, F. Miyanaga, T. Miyazawa, T. Hayashi, K. Hosoda, et al. 2004. Gene and phenotype analysis of congenital generalized lipodystrophy in Japanese: a novel homozygous nonsense mutation in seipin gene. J. Clin. Endocrinol. Metab. 89: 2360-2364. (Pubitemid 38619876)
49. Lundin, C., R. Nordstrom, K. Wagner, C. Windpassinger, H. Andersson, G. von Heijne, and I. Nilsson. 2006. Membrane topology of the human seipin protein. FEBS Lett. 580: 2281-2284.
50. Windpassinger, C., M. Auer-Grumbach, J. Irobi, H. Patel, E. Petek, G. Horl, R. Malli, J. A. Reed, I. Dierick, N. Verpoorten, et al. 2004. Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat. Genet. 36: 271-276. (Pubitemid 38282752)
51. Binns, D., S. Lee, C. L. Hilton, Q. X. Jiang, and J. M. Goodman. 2010. Seipin is a discrete homooligomer. Biochemistry. 49: 10747-10755.
52. Ito, D., T. Fujisawa, H. Iida, and N. Suzuki. 2008. Characterization of seipin/BSCL2, a protein associated with spastic paraplegia 17. Neurobiol. Dis. 31: 266-277.
53. Ito, D., and N. Suzuki. 2007. Molecular pathogenesis of seipin/BSCL2-related motor neuron diseases. Ann. Neurol. 61: 237-250. (Pubitemid 46557348)
54. Chen, W., V. K. Yechoor, B. H. Chang, M. V. Li, K. L. March, and L. Chan. 2009. The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation. Endocrinology. 150: 4552-4561.
55. Lefterova, M. I., and M. A. Lazar. 2009. New developments in adipogenesis. Trends Endocrinol. Metab. 20: 107-114.
56. Rosen, E. D., and O. A. MacDougald. 2006. Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 7: 885-896. (Pubitemid 44871415)
57. Payne, V. A., N. Grimsey, A. Tuthill, S. Virtue, S. L. Gray, E. Dalla Nora, R. K. Semple, S. O'Rahilly, and J. J. Rochford. 2008. The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiation. Diabetes. 57: 2055-2060.
58. Kim, H., K. Melen, and G. von Heijne. 2003. Topology models for 37 Saccharomyces cerevisiae membrane proteins based on C-terminal reporter fusions and predictions. J. Biol. Chem. 278: 10208-10213. (Pubitemid 36800281)
59. Fei, W., H. Li, G. Shui, T. S. Kapterian, C. Bielby, X. Du, A. J. Brown, P. Li, M. R. Wenk, P. Liu, et al. 2011. Molecular characterization of seipin and its mutants: implications for seipin in triacylglycerol synthesis. J. Lipid Res. 52: 2136-2147.
60. Victoria, B., J. M. Cabezas-Agricola, B. Gonzalez-Mendez, G. Lattanzi, R. Del Coco, L. Loidi, F. Barreiro, C. Calvo, J. Lado-Abeal, and D. Araujo-Vilar. 2010. Reduced adipogenic gene expression in fibroblasts from a patient with type 2 congenital generalized lipodystrophy. Diabet. Med. 27: 1178-1187.
61. Cui, X., Y. Wang, Y. Tang, Y. Liu, L. Zhao, J. Deng, G. Xu, X. Peng, S. Ju, G. Liu, et al. 2011. Seipin ablation in mice results in severe generalized lipodystrophy. Hum. Mol. Genet. 20: 3022-3030.
62. Seale, P., B. Bjork, W. Yang, S. Kajimura, S. Chin, S. Kuang, A. Scime, S. Devarakonda, H. M. Conroe, H. Erdjument-Bromage, et al. 2008. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 454: 961-967.
63. Fei, W., X. Du, and H. Yang. 2011. Seipin, adipogenesis and lipid droplets. Trends Endocrinol. Metab. 22: 204-210.
64. Fei, W., G. Shui, Y. Zhang, N. Krahmer, C. Ferguson, T. S. Kapterian, R. C. Lin, I. W. Dawes, A. J. Brown, P. Li, et al. 2011. A role for phosphatidic acid in the formation of "supersized" lipid droplets. PLoS Genet. 7: e1002201.
65. Boutet, E., H. El Mourabit, M. Prot, M. Nemani, E. Khallouf, O. Colard, M. Maurice, A. M. Durand-Schneider, Y. Chretien, S. Gres, et al. 2009. Seipin deficiency alters fatty acid Delta9 desaturation and lipid droplet formation in Berardinelli-Seip congenital lipodystrophy. Biochimie. 91: 796-803.
66. de Craemer, D., L. Van Maldergem, and F. Roels. 1992. Hepatic ultrastructure in congenital total lipodystrophy with special reference to peroxisomes. Ultrastruct. Pathol. 16: 307-316.
67. Goodman, J. M. 2008. The gregarious lipid droplet. J. Biol. Chem. 283: 28005-28009.
68. Wolinski, H., D. Kolb, S. Hermann, R. I. Koning, and S. D. Kohlwein. 2011. A role for seipin in lipid droplet dynamics and inheritance in yeast. J. Cell Sci. 124: 3894-3904.
69. Fei, W., H. Wang, X. Fu, C. Bielby, and H. Yang. 2009. Conditions of endoplasmic reticulum stress stimulate lipid droplet formation in Saccharomyces cerevisiae. Biochem. J. 424: 61-67.
70. Ito, D., T. Yagi, M. Ikawa, and N. Suzuki. 2012. Characterization of inclusion bodies with cytoprotective properties formed by seipinopathy-linked mutant seipin. Hum. Mol. Genet. 21: 635-646.
71. Yagi, T., D. Ito, Y. Nihei, T. Ishihara, and N. Suzuki. 2011. N88S seipin mutant transgenic mice develop features of seipinopathy/BSCL2-related motor neuron disease via endoplasmic reticulum stress. Hum. Mol. Genet. 20: 3831-3840.
72. Adeyo, O., P. J. Horn, S. Lee, D. D. Binns, A. Chandrahas, K. D. Chapman, and J. M. Goodman. 2011. The yeast lipin orthologue Pah1p is important for biogenesis of lipid droplets. J. Cell Biol. 192: 1043-1055.
73. McFie, P. J., S. L. Banman, S. Kary, and S. J. Stone. 2011. Murine diacylglycerol acyltransferase-2 (DGAT2) can catalyze triacylglycerol synthesis and promote lipid droplet formation independent of its localization to the endoplasmic reticulum. J. Biol. Chem. 286: 28235-28246.
74. Jacquier, N., V. Choudhary, M. Mari, A. Toulmay, F. Reggiori, and R. Schneiter. 2011. Lipid droplets are functionally connected to the endoplasmic reticulum in Saccharomyces cerevisiae. J. Cell Sci. 124: 2424-2437.
75. Hamilton, J. A. 1989. Interactions of triglycerides with phospholipids: incorporation into the bilayer structure and formation of emulsions. Biochemistry. 28: 2514-2520. (Pubitemid 19094368)