Molecular characterization of seipin and its mutants: implications for seipin in triacylglycerol synthesis

Abstract

The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin has been implicated in adipocyte differentiation, lipid droplet (LD) formation, and motor neuron development. However, the molecular function of seipin and its disease-causing mutants remains to be elucidated. Here, we characterize seipin and its mis-sense mutants: N88S/S90L (both linked to motoneuron disorders) and A212P (linked to lipodystrophy) in cultured mammalian cells. Knocking down seipin significantly increases oleate incorporation into triacylglycerol (TAG) and the steady state level of TAG, and induces the proliferation and clustering of small LDs. By contrast, overexpression of seipin reduces TAG synthesis, leading to decreased formation of LDs. Expression of the A212P mutant, however, had little effect on LD biogenesis. Surprisingly, expression of N88S or S90L causes the formation of many small LDs reminiscent of seipin deficient cells. This dominant-negative effect may be due to the N88S/S90L-induced formation of inclusions where wild-type seipin can be trapped. Importantly, coexpression of wild-type seipin and the N88S or S90L mutant can significantly reduce the formation of inclusions. Finally, we demonstrate that seipin can interact with itself and its mutant forms. Our results provide important insights into the biochemical characteristics of seipin and its mis-sense mutants, and suggest that seipin may function to inhibit lipogenesis. The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin has been implicated in adipocyte differentiation, lipid droplet (LD) formation, and motor neuron development. However, the molecular function of seipin and its disease-causing mutants remains to be elucidated. Here, we characterize seipin and its mis-sense mutants: N88S/S90L (both linked to motoneuron disorders) and A212P (linked to lipodystrophy) in cultured mammalian cells. Knocking down seipin significantly increases oleate incorporation into triacylglycerol (TAG) and the steady state level of TAG, and induces the proliferation and clustering of small LDs. By contrast, overexpression of seipin reduces TAG synthesis, leading to decreased formation of LDs. Expression of the A212P mutant, however, had little effect on LD biogenesis. Surprisingly, expression of N88S or S90L causes the formation of many small LDs reminiscent of seipin deficient cells. This dominant-negative effect may be due to the N88S/S90L-induced formation of inclusions where wild-type seipin can be trapped. Importantly, coexpression of wild-type seipin and the N88S or S90L mutant can significantly reduce the formation of inclusions. Finally, we demonstrate that seipin can interact with itself and its mutant forms. Our results provide important insights into the biochemical characteristics of seipin and its mis-sense mutants, and suggest that seipin may function to inhibit lipogenesis. Obesity is characterized by the accumulation of fully differentiated adipocytes loaded with lipid droplets (LDs) (1.Farese Jr, R.V. Walther T.C. Lipid droplets finally get a little R-E-S-P-E-C-T.Cell. 2009; 139: 855-860Abstract Full Text Full Text PDF PubMed Scopus (691) Google Scholar, 2.Park K.W. Halperin D.S. Tontonoz P. Before they were fat: adipocyte progenitors.Cell Metab. 2008; 8: 454-457Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar). The increasing prevalence of obesity and its related disorders in both developed and developing countries demands a better understanding of the molecular mechanisms underlying fat storage and adipogenesis (adipocyte differentiation) (2.Park K.W. Halperin D.S. Tontonoz P. Before they were fat: adipocyte progenitors.Cell Metab. 2008; 8: 454-457Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 3.Gesta S. Tseng Y.H. Kahn C.R. Developmental origin of fat: tracking obesity to its source.Cell. 2007; 131: 242-256Abstract Full Text Full Text PDF PubMed Scopus (1085) Google Scholar). Of particular relevance to adipogenesis is the rare genetic disease, congenital generalized lipodystrophy (CGL, also known as Berardinelli-Seip congenital lipodystrophy, or BSCL), an autosomal recessive disorder that is characterized by a near total loss of adipose tissue, severe insulin resistance, hypertriglyceridemia, and fatty liver (4.Agarwal A.K. Garg A. Genetic basis of lipodystrophies and management of metabolic complications.Annu. Rev. Med. 2006; 57: 297-311Crossref PubMed Scopus (119) Google Scholar). Genome-wide linkage analyses have identified two loci for CGL: CGL type 1 (CGL1) is caused by mutations in the 1-acylglycerol-3-phosphate-O-acyl transferase 2 (AGPAT2) gene and CGL2 by mutations in the BSCL2 gene, which encodes seipin (5.Magré J. Delepine M. Khallouf E. Gedde-Dahl Jr, T. Van Maldergem L. Sobel E. Papp J. Meier M. Megarbane A. Bachy A. et al.Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.Nat. Genet. 2001; 28: 365-370Crossref PubMed Scopus (567) Google Scholar, 6.Agarwal A.K. Arioglu E. De Almeida S. Akkoc N. Taylor S.I. Bowcock A.M. Barnes R.I. Garg A. AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34.Nat. Genet. 2002; 31: 21-23Crossref PubMed Scopus (419) Google Scholar). Recently, a homozygous nonsense mutation in caveolin-1 has been linked to CGL in a candidate gene approach, and the malfunction of cavin/PTRF can cause CGL through its effect on caveolins (7.Kim C.A. Delepine M. Boutet E. El Mourabit H. Le Lay S. Meier M. Nemani M. Bridel E. Leite C.C. Bertola D.R. et al.Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy.J. Clin. Endocrinol. Metab. 2008; 93: 1129-1134Crossref PubMed Scopus (304) Google Scholar, 8.Hayashi Y.K. Matsuda C. Ogawa M. Goto K. Tominaga K. Mitsuhashi S. Park Y.E. Nonaka I. Hino-Fukuyo N. Haginoya K. et al.Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy.J. Clin. Invest. 2009; 119: 2623-2633Crossref PubMed Scopus (308) Google Scholar, 9.Liu L. Brown D. McKee M. Lebrasseur N.K. Yang D. Albrecht K.H. Ravid K. Pilch P.F. Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance.Cell Metab. 2008; 8: 310-317Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar). Both AGPAT2 and caveolin-1/cavin have clear cellular functions: AGPAT2 catalyzes the formation of phosphatidic acid and appears to control adipogenesis through modulating the synthesis of phospholipids, and caveolin-1/cavin has a defined role in caveolae formation. In contrast, little is known about the molecular function of seipin, despite the fact that CGL2/BSCL2 patients demonstrate the most severe form of fat loss (4.Agarwal A.K. Garg A. Genetic basis of lipodystrophies and management of metabolic complications.Annu. Rev. Med. 2006; 57: 297-311Crossref PubMed Scopus (119) Google Scholar). The human BSCL2/seipin gene has three transcripts: 1.6kb, 1.8kb, and 2.2kb C. K. C. H. I. of the human seipin 2006; PubMed Scopus Google Scholar). The is in the and the two C. M. J. H. E. I. N. et mutations in BSCL2 with motor and Genet. PubMed Scopus Google Scholar). has been that seipin is in adipose and is adipocyte N. A. S. E. S. The human lipodystrophy gene BSCL2/seipin may be for adipocyte 2008; 57: PubMed Scopus Google Scholar, L. The human lipodystrophy gene product BSCL2/seipin a role in adipocyte 2009; PubMed Scopus Google Scholar). The role of seipin in adipogenesis has been in cultured and L. J. S. et in results in severe generalized Genet. PubMed Scopus Google Scholar, J. Yang H. function of seipin in lipid droplet Genet. PubMed Scopus Google Scholar). is that both seipin and the seipin a role in the cellular of LDs E. El Mourabit H. M. Nemani M. Khallouf E. M. A.M. S. et deficiency fatty acid and lipid droplet formation in Berardinelli-Seip congenital 2009; PubMed Scopus Google Scholar, L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar, D. A.K. Garg A. The lipodystrophy seipin is lipid droplet and is important for droplet 2007; PubMed Scopus Google Scholar). has been that may the of fatty the of the molecular function of seipin remains to be D. S. is a PubMed Scopus Google Scholar, Yang H. adipogenesis and lipid Endocrinol. Metab. Full Text Full Text PDF PubMed Scopus Google Scholar, N. C. Brown P. et role for phosphatidic acid in the formation of lipid Genet. PubMed Scopus Google Scholar). is to the with both and in the and a C. K. C. H. I. of the human seipin 2006; PubMed Scopus Google Scholar, D. T. H. N. of a with 2008; 31: PubMed Scopus Google Scholar). to the human can be or in with the an the mutations in the linked to autosomal motoneuron disorders and and also to the recessive CGL C. M. J. H. E. I. N. et mutations in BSCL2 with motor and Genet. PubMed Scopus Google Scholar, A.K. Garg A. a Med. Full Text Full Text PDF PubMed Scopus Google Scholar). is that the N88S and S90L mutations the of seipin, and D. T. H. N. of a with 2008; 31: PubMed Scopus Google Scholar, D. N. of motor neuron 2007; PubMed Scopus Google Scholar). The A212P mutation to a or loss of seipin as most seipin mutations with CGL cause of seipin (5.Magré J. Delepine M. Khallouf E. Gedde-Dahl Jr, T. Van Maldergem L. Sobel E. Papp J. Meier M. Megarbane A. Bachy A. et al.Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.Nat. Genet. 2001; 28: 365-370Crossref PubMed Scopus (567) Google Scholar). In the of A212P the D. S. is a PubMed Scopus Google Scholar). the important role of seipin in both LD formation and adipocyte differentiation, the molecular and cellular function of seipin remains to be elucidated. Here, we to characterize wild-type seipin and its three mis-sense mutants and in cultured seipin is and the of is to mutations of seipin Knocking down seipin increases triacylglycerol (TAG) synthesis overexpression of seipin TAG synthesis and reduces LD formation. overexpression of N88S or S90L A212P dominant-negative on LD formation. Our results provide important and insights into seipin and its and for and and were and in and were a of and of with and for and for and and for and were in with of were the were the to and and human were and in I. TAG synthesis and LD formation, were with oleate of oleate to and a with an were with a and a with a a and a and with a a and a of were with 2 and with the were with were with a to the and were by for 2 and were as H. C. Yang H. of lipid droplet formation in J. 2009; PubMed Scopus Google Scholar). of TAG and were in an for and the of TAG and were to of cellular as L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar). the of fatty acid by and its incorporation into TAG, were with 2 and for 1 or by with the the of cellular TAG into by a were for TAG formation in the of oleate for by of and of the of incorporation of acid into TAG and were with acid for 2 were by and by were to a for The the The of to TAG and were the and to as with S. P. E. T. Jr, R.V. of a mammalian and related 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). were in of in and were for and were by for the of and and and were with A. J. Brown acid in PubMed Scopus Google Scholar). were through a by for 1 and by for The were by for 1 with of were with of with of The resulting were three with 1 of in of for and to and were with and with for by with in for 1 were with in for 1 by with the secondary for 1 were with and through a and by for were to to and to with were by the to with wild-type or mutant of or seipin were with by for were loaded for and seipin were with and were in The results as for that in TAG synthesis L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar). in also that seipin caused TAG accumulation in the in a J. Yang H. function of seipin in lipid droplet Genet. PubMed Scopus Google Scholar). However, the role of seipin in TAG is in mammalian a in TAG synthesis in a E. El Mourabit H. M. Nemani M. Khallouf E. M. A.M. S. et deficiency fatty acid and lipid droplet formation in Berardinelli-Seip congenital 2009; PubMed Scopus Google proliferation of LDs in seipin deficient D. A.K. Garg A. The lipodystrophy seipin is lipid droplet and is important for droplet 2007; PubMed Scopus Google Scholar). to the role of seipin in lipid cultured mammalian to down expression in cells. that seipin level by which in a in TAG formation In with oleate a in oleate incorporation into TAG which down seipin expression by also TAG synthesis, to a seipin by in also in the proliferation and clustering of small LDs be that the proliferation and clustering of LDs has been in human and and also in for the gene seipin E. El Mourabit H. M. Nemani M. Khallouf E. M. A.M. S. et deficiency fatty acid and lipid droplet formation in Berardinelli-Seip congenital 2009; PubMed Scopus Google Scholar, L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar, D. A.K. Garg A. The lipodystrophy seipin is lipid droplet and is important for droplet 2007; PubMed Scopus Google Scholar). results that in cultured mammalian seipin to inhibit TAG synthesis with and J. Yang H. function of seipin in lipid droplet Genet. PubMed Scopus Google Scholar). the effect of seipin in a the that were to and down seipin expression by and in Knocking down seipin TAG synthesis by to and oleate incorporation into TAG by Our that cellular TAG synthesis with the level of seipin, an important role of seipin in TAG to the clustering of LDs in two seipin the of by in with that seipin by the N. A. S. E. S. The human lipodystrophy gene BSCL2/seipin may be for adipocyte 2008; 57: PubMed Scopus Google Scholar, L. The human lipodystrophy gene product BSCL2/seipin a role in adipocyte 2009; PubMed Scopus Google Scholar). demonstrate that seipin has a clear role in cellular TAG to the of seipin results have been on the overexpression of of The that seipin N88S and S90L to to inclusions by of seipin were by C. M. J. H. E. I. N. et mutations in BSCL2 with motor and Genet. PubMed Scopus Google Scholar). however, to the of seipin and that wild-type seipin may overexpression N. A. S. E. S. The human lipodystrophy gene BSCL2/seipin may be for adipocyte 2008; 57: PubMed Scopus Google Scholar, L. The human lipodystrophy gene product BSCL2/seipin a role in adipocyte 2009; PubMed Scopus Google Scholar). better the biochemical and of seipin, we or seipin the or and cells. in for the of human seipin both the of and the of a of which with the the of human seipin a of In contrast, of to the to the an a of about for both and two as they in and of and of reminiscent of This be the by the three and The most the and the and to be the of near the of with the fact that can also a due to In the of the of the demonstrate that seipin, can be and by and suggest that seipin form due to the results and the we and by and the and of seipin were to N. A. S. E. S. The human lipodystrophy gene BSCL2/seipin may be for adipocyte 2008; 57: PubMed Scopus Google Scholar, L. The human lipodystrophy gene product BSCL2/seipin a role in adipocyte 2009; PubMed Scopus Google Scholar). with were loaded for of seipin were for both and in contrast, the were for and seipin as a the is that both and also as that of causes the of seipin, which be as by the of seipin may in and the is due to of the seipin and with that the lipodystrophy mutant A212P and the motor neuron mutants N88S and S90L by in The expression of mutants by with the that seipin has a the N88S and S90L mutants The in that both the and the of seipin seipin TAG synthesis and LD proliferation we the effect of seipin overexpression on TAG synthesis and LD formation. the of seipin for for the have the seipin is The seipin to the The human seipin can in deficient the is L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar, D. A.K. Garg A. The lipodystrophy seipin is lipid droplet and is important for droplet 2007; PubMed Scopus Google and both and seipin to the effect of the were with and and with of TAG that seipin overexpression TAG to the about of TAG to control In contrast, overexpression of to in cellular of TAG synthesis seipin overexpression to its effect on LD biogenesis. in overexpression of wild-type seipin, both the and the formation of LDs in both and cells. In contrast, the expression of by the the formation of that the effect of overexpression on LD synthesis seipin the that the may the and cellular function of seipin, TAG synthesis and LD formation, we also with and Our that overexpression of both and LD formation which that the of TAG and LD formation is caused by overexpression of the effect of seipin is we also an expression with the of a Expression M. S. H. by in mammalian PubMed Scopus Google to the level of seipin expression a level to significantly inhibit LD formation and most be that the effect on LD formation in wild-type seipin, which is a recessive mis-sense mutation with congenital generalized lipodystrophy (5.Magré J. Delepine M. Khallouf E. Gedde-Dahl Jr, T. Van Maldergem L. Sobel E. Papp J. Meier M. Megarbane A. Bachy A. et al.Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.Nat. Genet. 2001; 28: 365-370Crossref PubMed Scopus (567) Google Scholar). The and expression of wild-type seipin and A212P and the effect of wild-type seipin is an overexpression is that a acid that TAG synthesis and droplet formation be due to decreased fatty acid the and incorporation into LDs of a fatty overexpression the of of in LDs in results a role of seipin on TAG synthesis and LD formation. The in TAG and LD formation in seipin be to synthesis of However, is the of with or Expression of both the and of seipin significantly the that seipin overexpression TAG synthesis TAG In with in oleate incorporation that oleate incorporation into TAG to about of control This due to cellular of its incorporation into in the of in TAG synthesis and of to that of control that seipin expression inhibit the the of for TAG The of in TAG synthesis and were also by and were seipin has a we that the of the of seipin mutant for gene L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar). overexpression of also inhibit LD formation. to the also significantly LD formation The mis-sense mutations of seipin linked to autosomal motoneuron disorders and and the autosomal recessive CGL However, on cellular lipid has been in wild-type seipin, overexpression of seipin A212P significantly the formation of LDs and of mutant to a in as in in N. A. S. E. S. The human lipodystrophy gene BSCL2/seipin may be for adipocyte 2008; 57: PubMed Scopus Google Scholar). Surprisingly, the or which both and small N88S or S90L mutants many small and clustering LDs reminiscent of the LD in seipin or deficient E. El Mourabit H. M. Nemani M. Khallouf E. M. A.M. S. et deficiency fatty acid and lipid droplet formation in Berardinelli-Seip congenital 2009; PubMed Scopus Google Scholar, D. A.K. Garg A. The lipodystrophy seipin is lipid droplet and is important for droplet 2007; PubMed Scopus Google Scholar). results suggest that the N88S or S90L mutant may dominant-negative on lipid were to TAG in the mutants as of due to D. T. H. N. of a with 2008; 31: PubMed Scopus Google Scholar). has been that human and many LDs with E. El Mourabit H. M. Nemani M. Khallouf E. M. A.M. S. et deficiency fatty acid and lipid droplet formation in Berardinelli-Seip congenital 2009; PubMed Scopus Google Scholar, D. A.K. Garg A. The lipodystrophy seipin is lipid droplet and is important for droplet 2007; PubMed Scopus Google which in cultured mammalian in Our that overexpression of the N88S and S90L seipin mutants caused to and LDs to that mutants may the wild-type seipin into resulting in a seipin of we the of seipin mis-sense mutants and that and to to the identified by C. M. J. H. E. I. N. et mutations in BSCL2 with motor and Genet. PubMed Scopus Google Scholar, D. T. H. N. of a with 2008; 31: PubMed Scopus Google Scholar). By to the to were with and N88S or a of the with the N88S or S90L In contrast, with or to the results that N88S and S90L can wild-type seipin to the the wild-type with or mutants, significantly the of N88S and S90L mutants were with the N88S or S90L about of and decreased to By contrast, the coexpression of reduce the of seipin N88S and results that the N88S and S90L mutants the wild-type seipin into the wild-type seipin also that can form D. S. is a PubMed Scopus Google Scholar). on the and the results we that mammalian seipin interact with itself and N88S or were with with wild-type or mutant of and with and with Our results that wild-type seipin can interact with and both of mutant seipin and S90L also with seipin a and two with seipin the of wild-type and mutant seipin in were by and seipin and its mutants were by wild-type or A212P N88S or S90L that seipin and its mutant in in seipin with motoneuron disorders and the most severe form of human lipodystrophy (5.Magré J. Delepine M. Khallouf E. Gedde-Dahl Jr, T. Van Maldergem L. Sobel E. Papp J. Meier M. Megarbane A. Bachy A. et al.Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13.Nat. Genet. 2001; 28: 365-370Crossref PubMed Scopus (567) Google Scholar, C. M. J. H. E. I. N. et mutations in BSCL2 with motor and Genet. PubMed Scopus Google Scholar). and its have also been to the cellular of the storage form of E. El Mourabit H. M. Nemani M. Khallouf E. M. A.M. S. et deficiency fatty acid and lipid droplet formation in Berardinelli-Seip congenital 2009; PubMed Scopus Google Scholar, L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar, D. A.K. Garg A. The lipodystrophy seipin is lipid droplet and is important for droplet 2007; PubMed Scopus Google Scholar). little is known about the biochemical and cellular function of seipin, which in the through two C. K. C. H. I. of the human seipin 2006; PubMed Scopus Google Scholar, A.K. Garg A. a Med. Full Text Full Text PDF PubMed Scopus Google Scholar). Here, we an important role for seipin in TAG in cultured mammalian by and overexpression also demonstrate that seipin can interact with itself and its mutant forms. of N88S or appears to dominant-negative by seipin in inclusions. Finally, we provide a to the of Our results important insights into the biochemical characteristics and cellular of seipin and its The role of seipin in adipogenesis has been however, its function in and its molecular function have been elucidated. Here, a role for seipin in TAG has been in cultured mammalian down seipin significantly TAG synthesis seipin had an effect results the with in and the overexpression were by the of a seipin a seipin and to the of overexpression to the level in we results seipin overexpression to be for the overexpression of or seipin, the TAG synthesis, which the that particular may seipin expression of wild-type seipin the mis-sense and form TAG synthesis both the and of seipin and its A212P mutant were a level the effect of wild-type seipin on TAG synthesis is to be an seipin a level by a also in LD formation the effect of seipin overexpression is to that of seipin the and human seipin can in deficient the is L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar). Finally, three the of seipin overexpression N. A. S. E. S. The human lipodystrophy gene BSCL2/seipin may be for adipocyte 2008; 57: PubMed Scopus Google Scholar, L. The human lipodystrophy gene product BSCL2/seipin a role in adipocyte 2009; PubMed Scopus Google Scholar, D. T. H. N. of a with 2008; 31: PubMed Scopus Google results that seipin can be on analyses that of caused seipin to and seipin as a on in The has also been by role in TAG synthesis, which be in is that seipin can interact with itself and the A212P and N88S/S90L mutants the of has been D. S. is a PubMed Scopus Google Scholar). is that N88S or S90L A212P appears to a dominant-negative effect on LD N88S and S90L have been linked to motoneuron disorders and role in lipid has been Our for the suggest that N88S/S90L may have an on LD formation N88S and S90L have been to form inclusions D. N. of motor neuron 2007; PubMed Scopus Google they may wild-type seipin into inclusions overexpression to with seipin function and cause a dominant-negative This may in the level of N88S/S90L be to with seipin patients N88S/S90L motoneuron The mutant, to the in seipin function and LD is that the A212P can seipin in the seipin may be the A212P mutant may be a of seipin, which In down seipin expression by can adipogenesis in L. The human lipodystrophy gene product BSCL2/seipin a role in adipocyte 2009; PubMed Scopus Google Scholar). Knocking down seipin increases TAG synthesis in and the of into adipocytes and lipid storage in adipose the loss of seipin function on on the inhibit adipogenesis and fat results the provide the most to deficient in an TAG synthesis is that and C.A. M. Yang K. N. et for triacylglycerol synthesis and lipid droplets in Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). The of lipid storage in adipose seipin is due to a in the in lipogenesis. lipid accumulation is in the liver and of BSCL2 The role of seipin on cellular is by that TAG in the mutant and in seipin deficient of and that LDs in J. Yang H. function of seipin in lipid droplet Genet. PubMed Scopus Google Scholar, L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar, D. A.K. Garg A. The lipodystrophy seipin is lipid droplet and is important for droplet 2007; PubMed Scopus Google Scholar). with results the seipin has also been implicated in and fatty acid E. El Mourabit H. M. Nemani M. Khallouf E. M. A.M. S. et deficiency fatty acid and lipid droplet formation in Berardinelli-Seip congenital 2009; PubMed Scopus Google Scholar, L. P. Brown Yang H. a of human seipin, the of lipid droplets in 2008; PubMed Scopus Google Scholar). may function in fatty acid and TAG however, the effect of seipin on fatty may be secondary as the level and of phospholipids, as can have a on lipid to Yang H. adipogenesis and lipid Endocrinol. Metab. Full Text Full Text PDF PubMed Scopus Google Scholar, of and its for lipid in 2007; PubMed Scopus Google Scholar). the effect of seipin on be as seipin may cellular as which is known to TAG synthesis H. C. Yang H. of lipid droplet formation in J. 2009; PubMed Scopus Google Scholar). analyses with better to the molecular function of In we have for the that seipin is in TAG synthesis in cultured mammalian and we have important biochemical characteristics of seipin and its results of the important seipin Yang H. adipogenesis and lipid Endocrinol. Metab. Full Text Full Text PDF PubMed Scopus Google Scholar, A.K. Garg A. a Med. Full Text Full Text PDF PubMed Scopus Google Scholar). and of the Yang for also for with 1-acylglycerol-3-phosphate-O-acyl transferase 2 Berardinelli-Seip congenital lipodystrophy 2 congenital generalized lipodystrophy lipid droplet small triacylglycerol