A genome-wide landscape of mRNAs,lncRNAs,and circRNAs during subcutaneous adipogenesis in pigs
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摘要
Background: Preadipocyte differentiation plays a critical role in subcutaneous fat deposition in pigs.However,the roles of different RNAs,such as messenger RNAs(mRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs) in the differentiation process of subcutaneous preadipocytes,are still largely unclear.In the present study,a transcriptome analysis,including the analysis of mRNAs,lncRNAs,and circRNAs,during different differentiation stages,namely,day 0(D0),day 2(D2),day 4(D4),and day 8(D8),of subcutaneous preadipocytes from Chinese Erhualian pigs was performed.Results: A total of 1554,470,1344,1777,and 676 differentially expressed(DE) mRNAs,112,58,95,136,and 93 DE lncRNAs,and 902,787,710,932,and 850 DE circRNAs were identified between D2 and D0,between D4 and D2,between D8 and D4,between D4 and D0,and between D8 and D0,respectively.Furthermore,functional enrichment analysis showed that the common DE mRNAs during the entire differentiation process were mainly involved in lipid metabolic and cell differentiation processes.Additionally,co-expression network analysis identified the potential lncRNAs related to adipogenesis,e.g.,MSTRG.131380 and MSTRG.62128.Conclusions: Our study provides new insights of the expression changes of RNAs during adipogenic differentiation,which might contribute to the phenotype of subcutaneous adipogenesis.These results greatly improve our understanding of the molecular mechanisms regulating subcutaneous fat deposition in pigs.
Background: Preadipocyte differentiation plays a critical role in subcutaneous fat deposition in pigs.However,the roles of different RNAs,such as messenger RNAs(mRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs) in the differentiation process of subcutaneous preadipocytes,are still largely unclear.In the present study,a transcriptome analysis,including the analysis of mRNAs,lncRNAs,and circRNAs,during different differentiation stages,namely,day 0(D0),day 2(D2),day 4(D4),and day 8(D8),of subcutaneous preadipocytes from Chinese Erhualian pigs was performed.Results: A total of 1554,470,1344,1777,and 676 differentially expressed(DE) mRNAs,112,58,95,136,and 93 DE lncRNAs,and 902,787,710,932,and 850 DE circRNAs were identified between D2 and D0,between D4 and D2,between D8 and D4,between D4 and D0,and between D8 and D0,respectively.Furthermore,functional enrichment analysis showed that the common DE mRNAs during the entire differentiation process were mainly involved in lipid metabolic and cell differentiation processes.Additionally,co-expression network analysis identified the potential lncRNAs related to adipogenesis,e.g.,MSTRG.131380 and MSTRG.62128.Conclusions: Our study provides new insights of the expression changes of RNAs during adipogenic differentiation,which might contribute to the phenotype of subcutaneous adipogenesis.These results greatly improve our understanding of the molecular mechanisms regulating subcutaneous fat deposition in pigs.
Background: Preadipocyte differentiation plays a critical role in subcutaneous fat deposition in pigs.However,the roles of different RNAs,such as messenger RNAs(mRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs) in the differentiation process of subcutaneous preadipocytes,are still largely unclear.In the present study,a transcriptome analysis,including the analysis of mRNAs,lncRNAs,and circRNAs,during different differentiation stages,namely,day 0(D0),day 2(D2),day 4(D4),and day 8(D8),of subcutaneous preadipocytes from Chinese Erhualian pigs was performed.Results: A total of 1554,470,1344,1777,and 676 differentially expressed(DE) mRNAs,112,58,95,136,and 93 DE lncRNAs,and 902,787,710,932,and 850 DE circRNAs were identified between D2 and D0,between D4 and D2,between D8 and D4,between D4 and D0,and between D8 and D0,respectively.Furthermore,functional enrichment analysis showed that the common DE mRNAs during the entire differentiation process were mainly involved in lipid metabolic and cell differentiation processes.Additionally,co-expression network analysis identified the potential lncRNAs related to adipogenesis,e.g.,MSTRG.131380 and MSTRG.62128.Conclusions: Our study provides new insights of the expression changes of RNAs during adipogenic differentiation,which might contribute to the phenotype of subcutaneous adipogenesis.These results greatly improve our understanding of the molecular mechanisms regulating subcutaneous fat deposition in pigs.
引文
1.Bosi P,Russo V.The production of the heavy pig for high quality processed products.Ital J Anim Sci.2004;3:309-21.
2.Candek-Potokar M,Skrlep M.Factors in pig production that impact the quality of dry-cured ham:a review.Animal.2012;6:327-38.
3.Ros-Freixedes R,Reixach J,Bosch L,Tor M,Estany J.Genetic correlations of intramuscular fat content and fatty acid composition among muscles and with subcutaneous fat in Duroc pigs.J Anim Sci.2014;92:5417-25.
4.Gao J,Xu W,Wang J,Wang K,Li P.The role and molecular mechanism of non-coding RNAs in pathological cardiac remodeling.Int J Mol Sci.2017;18:608.
5.Jiang Q,Wang J,Wu X,Ma R,Zhang T,Jin S,et al.LncRNA2Target:a database for differentially expressed genes after lncRNA knockdown or overexpression.Nucleic Acids Res.2015;43:D193-6.
6.Kapranov P,Cheng J,Dike S,Nix DA,Duttagupta R,Willingham AT,et al.RNA maps reveal new RNA classes and a possible function for pervasive transcription.Science.2007;316:1484-8.
7.Chen J,Liu Y,Lu S,Yin L,Zong C,Cui S,et al.The role and possible mechanism of lncRNA U90926 in modulating 3T3-L1 preadipocyte differentiation.Int J Obes.2016;41:299-308.
8.Liu W,Ma C,Yang B,Yin C,Zhang B,Xiao Y.LncRNA Gm15290 sponges miR-27b to promote PPARγ-induced fat deposition and contribute to body weight gain in mice.Biochem Biophys Res Commun.2017;493:1168.
9.Nuermaimaiti N,Liu J,Liang X,Jiao Y,Zhang D,Liu L,et al.Effect of lncRNAHOXA11-AS1 on adipocyte differentiation in human adipose-derived stem cells.Biochem Biophys Res Commun.2018;495:1878-84.
10.Qu S,Yang X,Li X,Wang J,Gao Y,Shang R,et al.Circular RNA:a new star of noncoding RNAs.Cancer Lett.2015;365:141-8.
11.Ebbesen KK,Kjems J,Hansen TB.Circular RNAs:identification,biogenesis and function.Biochim Biophys Acta.2015;1859:163.
12.Legnini I,Di Timoteo G,Rossi F,Morlando M,Briganti F,Sthandier O,et al.Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis.Mol Cell.2017;66:22-37.
13.Li H,Yang J,Wei X,Song C,Dong D,Huang Y,et al.CircFUT10 reduces proliferation and facilitates differentiation of myoblasts by sponging miR-133a.J Cell Physiol.2017;233:4643-51.
14.Zambonelli P,Gaffo E,Zappaterra M,Bortoluzzi S,Davoli R.Transcriptional profiling of subcutaneous adipose tissue in Italian large white pigs divergent for backfat thickness.Anim Genet.2016;47:306-23.
15.Davoli R,Gaffo E,Zappaterra M,Bortoluzzi S,Zambonelli P.Identification of differentially expressed small RNAs and prediction of target genes in Italian Large White pigs with divergent backfat deposition.Anim Genet.2018;Epub ahead of print.
16.Jiang S,Wei H,Song T,Yang Y,Peng J,Jiang S.Transcriptome comparison between porcine subcutaneous and intramuscular stromal vascular cells during adipogenic differentiation.PLoS One.2013;8:e77094.
17.Yi F,Yang F,Liu X,Chen H,Ji T,Jiang L,et al.RNA-seq identified a super-long intergenic transcript functioning in adipogenesis.RNA Biol.2013;10:991-1001.
18.Wang J,Hua L,Chen J,Zhang J,Bai X,Gao B,et al.Identification and characterization of long non-coding RNAs in subcutaneous adipose tissue from castrated and intact full-sib pair Huainan male pigs.BMC Genomics.2017;18:542.
19.Kim D,Langmead B,Salzberg SL.HISAT:a fast spliced aligner with low memory requirements.Nat Methods.2015;12:357-60.
20.Li H.Aligning sequence reads,clone sequences and assembly contigs with BWA-MEM.arXiv preprint arXiv:1303.3997.2013.p.1-3.
21.Gao Y,Wang J,Zhao F.CIRI:an efficient and unbiased algorithm for de novo circular RNA identification.Genome Biol.2015;16:4.
22.Li Y,Zheng Q,Bao C,Li S,Guo W,Zhao J,et al.Circular RNA is enriched and stable in exosomes:a promising biomarker for cancer diagnosis.Cell Res.2015;25:981-4.
23.Wang L,Feng Z,Wang X,Wang X,Zhang X.DEGseq:an R package for identifying differentially expressed genes from RNA-seq data.Bioinformatics.2010;26:136-8.
24.Morris JH,Vijay D,Federowicz S,Pico AR,Ferrin TE.CyAnimator:simple animations of Cytoscape networks.F1000Res.2015;4:482.
25.Nakajima I,Muroya S,Chikuni K.Growth arrest by octanoate is required for porcine preadipocyte differentiation.Biochem Biophys Res Commun.2003;309:702-8.
26.Tang QQ,Otto TC,Lane MD.Mitotic clonal expansion:a synchronous process required for adipogenesis.Proc Natl Acad Sci U S A.2003;100:44-9.
27.Gregoire FM,Smas CM,Sul HS.Understanding adipocyte differentiation.Physiol Rev.1998;78:783-809.
28.Tontonoz P,Hu E,Spiegelman BM.Stimulation of adipogenesis in fibroblasts by PPAR gamma 2,a lipid-activated transcription factor.Cell.1994;79:1147-56.
29.Umek RM,Friedman AD,McKnight SL.CCAAT-enhancer binding protein:a component of a differentiation switch.Science.1991;251:288-92.
30.Altiok S,Xu M,Spiegelman BM.PPARgamma induces cell cycle withdrawal:inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A.Genes Dev.1997;11:1987-98.
31.Porse BT,Pedersen TA,Xu X,Lindberg B,Wewer UM,Friis-Hansen L,et al.E2F repression by C/EBPalpha is required for adipogenesis and granulopoiesis in vivo.Cell.2001;107:247-58.
32.Krawisz BR,Scott RE.Coupling of proadipocyte growth arrest and differentiation.I.Induction by heparinized medium containing human plasma.J Cell Biol.1982;94:394-9.
33.Ailhaud G,Dani C,Amri EZ,Djian P,Vannier C,Doglio A,et al.Coupling growth arrest and adipocyte differentiation.Environ Health Perspect.1989;80:17-23.
34.Marquez M,Alencastro F,Madrigal A,Jiminez J,Blanco G,Gureghian A,et al.The role of cellular proliferation in adipogenic differentiation of human mesenchymal stem cells.Stem Cells Dev.2017;26:1578-95.
35.Lim S,Kaldis P.Cdks,cyclins and CKIs:roles beyond cell cycle regulation.Development.2013;140:3079-93.
36.Kim HS,Hausman GJ,Hausman DB,Martin RJ,Dean RG.The expression of cyclin D1 during adipogenesis in pig primary stromal-vascular cultures.Obes Res.2001;9:572-8.
37.Wang C,Fu M,D'Amico M,Albanese C,Zhou JN,Brownlee M,et al.Inhibition of cellular proliferation through IkappaB kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin D1.Mol Cell Biol.2001;21:3057-70.
38.Morrison RF,Farmer SR.Role of PPARgamma in regulating a cascade expression of cyclin-dependent kinase inhibitors,p18(INK4c)and p21(Waf1/Cip1),during adipogenesis.J Biol Chem.1999;274:17088-97.
39.Qiu Z,Wei Y,Chen N,Jiang M,Wu J,Liao K.DNA synthesis and mitotic clonal expansion is not a required step for 3T3-L1 preadipocyte differentiation into adipocytes.J Biol Chem.2001;276:11988-95.
40.Ruehl M,Erben U,Schuppan D,Wagner C,Zeller A,Freise C,et al.The elongated first fibronectin type III domain of collagen XIV is an inducer of quiescence and differentiation in fibroblasts and preadipocytes.J Biol Chem2005;280:38537-43.
41.Vaittinen M,Kolehmainen M,Rydén M,Eskelinen M,Wabitsch M,Pihlajam?k J,et al.MFAP5 is related to obesity-associated adipose tissue and extracellular matrix remodeling and inflammation.Obesity(Silver Spring).2015;23:1371-8.
42.Verma S,Shewan AM,Scott JA,Helwani FM,den Elzen NR,Miki H,et al.Arp2/3 activity is necessary for efficient formation of E-cadherin adhesive contacts.J Biol Chem.2004;279:34062-70.
43.Zhou K,Sumigray KD,Lechler T.The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine.Mol Biol Cell.2015;26:1995-2004.
44.Yang W,Thein S,Lim CY,Ericksen RE,Sugii S,Xu F,et al.Arp2/3 complex regulates adipogenesis by controlling cortical actin remodelling.Biochem J.2014;464:179-92.
45.Chen L,Hu H,Qiu W,Shi K,Kassem M.Actin depolymerization enhances adipogenic differentiation in human stromal stem cells.Stem Cell Res.2018;29:76-83.
46.Padilla-Benavides T,Velez-Delvalle C,Marsch-Moreno M,Castro-Mu?ozledo F,Kuri-Harcuch W.Lipogenic enzymes complexes and cytoplasmic lipid droplet formation during adipogenesis.J Cell Biochem.2016;117:2315-26.
47.Haemmerle G,Zimmermann R,Zechner R.Letting lipids go:hormonesensitive lipase.Curr Opin Lipidol.2003;14:289-97.
48.Lass A,Zimmermann R,Haemmerle G,Riederer M,Schoiswohl G,Schweiger M,et al.Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman syndrome.Cell Metab.2006;3:309-19.
49.Smirnova E,Goldberg EB,Makarova KS,Lin L,Brown WJ,Jackson CL.ATGLhas a key role in lipid droplet/adiposome degradation in mammalian cells.EMBO Rep.2006;7:106-13.
50.Varanasi U,Chu R,Chu S,Espinosa R,LeBeau MM,Reddy JK.Isolation of the human peroxisomal acyl-CoA oxidase gene:organization,promoter analysis,and chromosomal localization.Proc Natl Acad Sci U S A.1994;91:3107-11.
2.Candek-Potokar M,Skrlep M.Factors in pig production that impact the quality of dry-cured ham:a review.Animal.2012;6:327-38.
3.Ros-Freixedes R,Reixach J,Bosch L,Tor M,Estany J.Genetic correlations of intramuscular fat content and fatty acid composition among muscles and with subcutaneous fat in Duroc pigs.J Anim Sci.2014;92:5417-25.
4.Gao J,Xu W,Wang J,Wang K,Li P.The role and molecular mechanism of non-coding RNAs in pathological cardiac remodeling.Int J Mol Sci.2017;18:608.
5.Jiang Q,Wang J,Wu X,Ma R,Zhang T,Jin S,et al.LncRNA2Target:a database for differentially expressed genes after lncRNA knockdown or overexpression.Nucleic Acids Res.2015;43:D193-6.
6.Kapranov P,Cheng J,Dike S,Nix DA,Duttagupta R,Willingham AT,et al.RNA maps reveal new RNA classes and a possible function for pervasive transcription.Science.2007;316:1484-8.
7.Chen J,Liu Y,Lu S,Yin L,Zong C,Cui S,et al.The role and possible mechanism of lncRNA U90926 in modulating 3T3-L1 preadipocyte differentiation.Int J Obes.2016;41:299-308.
8.Liu W,Ma C,Yang B,Yin C,Zhang B,Xiao Y.LncRNA Gm15290 sponges miR-27b to promote PPARγ-induced fat deposition and contribute to body weight gain in mice.Biochem Biophys Res Commun.2017;493:1168.
9.Nuermaimaiti N,Liu J,Liang X,Jiao Y,Zhang D,Liu L,et al.Effect of lncRNAHOXA11-AS1 on adipocyte differentiation in human adipose-derived stem cells.Biochem Biophys Res Commun.2018;495:1878-84.
10.Qu S,Yang X,Li X,Wang J,Gao Y,Shang R,et al.Circular RNA:a new star of noncoding RNAs.Cancer Lett.2015;365:141-8.
11.Ebbesen KK,Kjems J,Hansen TB.Circular RNAs:identification,biogenesis and function.Biochim Biophys Acta.2015;1859:163.
12.Legnini I,Di Timoteo G,Rossi F,Morlando M,Briganti F,Sthandier O,et al.Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis.Mol Cell.2017;66:22-37.
13.Li H,Yang J,Wei X,Song C,Dong D,Huang Y,et al.CircFUT10 reduces proliferation and facilitates differentiation of myoblasts by sponging miR-133a.J Cell Physiol.2017;233:4643-51.
14.Zambonelli P,Gaffo E,Zappaterra M,Bortoluzzi S,Davoli R.Transcriptional profiling of subcutaneous adipose tissue in Italian large white pigs divergent for backfat thickness.Anim Genet.2016;47:306-23.
15.Davoli R,Gaffo E,Zappaterra M,Bortoluzzi S,Zambonelli P.Identification of differentially expressed small RNAs and prediction of target genes in Italian Large White pigs with divergent backfat deposition.Anim Genet.2018;Epub ahead of print.
16.Jiang S,Wei H,Song T,Yang Y,Peng J,Jiang S.Transcriptome comparison between porcine subcutaneous and intramuscular stromal vascular cells during adipogenic differentiation.PLoS One.2013;8:e77094.
17.Yi F,Yang F,Liu X,Chen H,Ji T,Jiang L,et al.RNA-seq identified a super-long intergenic transcript functioning in adipogenesis.RNA Biol.2013;10:991-1001.
18.Wang J,Hua L,Chen J,Zhang J,Bai X,Gao B,et al.Identification and characterization of long non-coding RNAs in subcutaneous adipose tissue from castrated and intact full-sib pair Huainan male pigs.BMC Genomics.2017;18:542.
19.Kim D,Langmead B,Salzberg SL.HISAT:a fast spliced aligner with low memory requirements.Nat Methods.2015;12:357-60.
20.Li H.Aligning sequence reads,clone sequences and assembly contigs with BWA-MEM.arXiv preprint arXiv:1303.3997.2013.p.1-3.
21.Gao Y,Wang J,Zhao F.CIRI:an efficient and unbiased algorithm for de novo circular RNA identification.Genome Biol.2015;16:4.
22.Li Y,Zheng Q,Bao C,Li S,Guo W,Zhao J,et al.Circular RNA is enriched and stable in exosomes:a promising biomarker for cancer diagnosis.Cell Res.2015;25:981-4.
23.Wang L,Feng Z,Wang X,Wang X,Zhang X.DEGseq:an R package for identifying differentially expressed genes from RNA-seq data.Bioinformatics.2010;26:136-8.
24.Morris JH,Vijay D,Federowicz S,Pico AR,Ferrin TE.CyAnimator:simple animations of Cytoscape networks.F1000Res.2015;4:482.
25.Nakajima I,Muroya S,Chikuni K.Growth arrest by octanoate is required for porcine preadipocyte differentiation.Biochem Biophys Res Commun.2003;309:702-8.
26.Tang QQ,Otto TC,Lane MD.Mitotic clonal expansion:a synchronous process required for adipogenesis.Proc Natl Acad Sci U S A.2003;100:44-9.
27.Gregoire FM,Smas CM,Sul HS.Understanding adipocyte differentiation.Physiol Rev.1998;78:783-809.
28.Tontonoz P,Hu E,Spiegelman BM.Stimulation of adipogenesis in fibroblasts by PPAR gamma 2,a lipid-activated transcription factor.Cell.1994;79:1147-56.
29.Umek RM,Friedman AD,McKnight SL.CCAAT-enhancer binding protein:a component of a differentiation switch.Science.1991;251:288-92.
30.Altiok S,Xu M,Spiegelman BM.PPARgamma induces cell cycle withdrawal:inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A.Genes Dev.1997;11:1987-98.
31.Porse BT,Pedersen TA,Xu X,Lindberg B,Wewer UM,Friis-Hansen L,et al.E2F repression by C/EBPalpha is required for adipogenesis and granulopoiesis in vivo.Cell.2001;107:247-58.
32.Krawisz BR,Scott RE.Coupling of proadipocyte growth arrest and differentiation.I.Induction by heparinized medium containing human plasma.J Cell Biol.1982;94:394-9.
33.Ailhaud G,Dani C,Amri EZ,Djian P,Vannier C,Doglio A,et al.Coupling growth arrest and adipocyte differentiation.Environ Health Perspect.1989;80:17-23.
34.Marquez M,Alencastro F,Madrigal A,Jiminez J,Blanco G,Gureghian A,et al.The role of cellular proliferation in adipogenic differentiation of human mesenchymal stem cells.Stem Cells Dev.2017;26:1578-95.
35.Lim S,Kaldis P.Cdks,cyclins and CKIs:roles beyond cell cycle regulation.Development.2013;140:3079-93.
36.Kim HS,Hausman GJ,Hausman DB,Martin RJ,Dean RG.The expression of cyclin D1 during adipogenesis in pig primary stromal-vascular cultures.Obes Res.2001;9:572-8.
37.Wang C,Fu M,D'Amico M,Albanese C,Zhou JN,Brownlee M,et al.Inhibition of cellular proliferation through IkappaB kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin D1.Mol Cell Biol.2001;21:3057-70.
38.Morrison RF,Farmer SR.Role of PPARgamma in regulating a cascade expression of cyclin-dependent kinase inhibitors,p18(INK4c)and p21(Waf1/Cip1),during adipogenesis.J Biol Chem.1999;274:17088-97.
39.Qiu Z,Wei Y,Chen N,Jiang M,Wu J,Liao K.DNA synthesis and mitotic clonal expansion is not a required step for 3T3-L1 preadipocyte differentiation into adipocytes.J Biol Chem.2001;276:11988-95.
40.Ruehl M,Erben U,Schuppan D,Wagner C,Zeller A,Freise C,et al.The elongated first fibronectin type III domain of collagen XIV is an inducer of quiescence and differentiation in fibroblasts and preadipocytes.J Biol Chem2005;280:38537-43.
41.Vaittinen M,Kolehmainen M,Rydén M,Eskelinen M,Wabitsch M,Pihlajam?k J,et al.MFAP5 is related to obesity-associated adipose tissue and extracellular matrix remodeling and inflammation.Obesity(Silver Spring).2015;23:1371-8.
42.Verma S,Shewan AM,Scott JA,Helwani FM,den Elzen NR,Miki H,et al.Arp2/3 activity is necessary for efficient formation of E-cadherin adhesive contacts.J Biol Chem.2004;279:34062-70.
43.Zhou K,Sumigray KD,Lechler T.The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine.Mol Biol Cell.2015;26:1995-2004.
44.Yang W,Thein S,Lim CY,Ericksen RE,Sugii S,Xu F,et al.Arp2/3 complex regulates adipogenesis by controlling cortical actin remodelling.Biochem J.2014;464:179-92.
45.Chen L,Hu H,Qiu W,Shi K,Kassem M.Actin depolymerization enhances adipogenic differentiation in human stromal stem cells.Stem Cell Res.2018;29:76-83.
46.Padilla-Benavides T,Velez-Delvalle C,Marsch-Moreno M,Castro-Mu?ozledo F,Kuri-Harcuch W.Lipogenic enzymes complexes and cytoplasmic lipid droplet formation during adipogenesis.J Cell Biochem.2016;117:2315-26.
47.Haemmerle G,Zimmermann R,Zechner R.Letting lipids go:hormonesensitive lipase.Curr Opin Lipidol.2003;14:289-97.
48.Lass A,Zimmermann R,Haemmerle G,Riederer M,Schoiswohl G,Schweiger M,et al.Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman syndrome.Cell Metab.2006;3:309-19.
49.Smirnova E,Goldberg EB,Makarova KS,Lin L,Brown WJ,Jackson CL.ATGLhas a key role in lipid droplet/adiposome degradation in mammalian cells.EMBO Rep.2006;7:106-13.
50.Varanasi U,Chu R,Chu S,Espinosa R,LeBeau MM,Reddy JK.Isolation of the human peroxisomal acyl-CoA oxidase gene:organization,promoter analysis,and chromosomal localization.Proc Natl Acad Sci U S A.1994;91:3107-11.