title: Fat-specific protein 27 inhibits lipolysis by facilitating the inhibitory effect of transcription factor Egr1 on transcription of adipose triglyceride lipase.
abstract: Lipolysis in fat tissue represents a major source of circulating fatty acids. Previously, we have found that lipolysis in adipocytes is controlled by early growth response transcription factor Egr1 that directly inhibits transcription of adipose triglyceride lipase, ATGL (Chakrabarti, P., Kim, J. Y., Singh, M., Shin, Y. K., Kim, J., Kumbrink, J., Wu, Y., Lee, M. J., Kirsch, K. H., Fried, S. K., and Kandror, K. V. (2013) Mol. Cell. Biol. 33, 3659-3666). Here we demonstrate that knockdown of the lipid droplet protein FSP27 (a.k.a. CIDEC) in human adipocytes increases expression of ATGL at the level of transcription, whereas overexpression of FSP27 has the opposite effect. FSP27 suppresses the activity of the ATGL promoter in vitro, and the proximal Egr1 binding site is responsible for this effect. FSP27 co-immunoprecipitates with Egr1 and increases its association with and inhibition of the ATGL promoter. Knockdown of Egr1 attenuates the inhibitory effect of FSP27. These results provide a new model of transcriptional regulation of ATGL.
authors.affiliation: From the Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Maneet
authors.initials: M
authors.lastname: Singh
authors.affiliation: From the Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Rajween
authors.initials: R
authors.lastname: Kaur
authors.affiliation: From the Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Mi-Jeong
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: From the Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: R Taylor
authors.initials: RT
authors.lastname: Pickering
authors.affiliation: From the Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Vishva Mitra
authors.initials: VM
authors.lastname: Sharma
authors.affiliation: From the Boston University School of Medicine, Boston, Massachusetts 02118 vpuri@bu.edu.
authors.forename: Vishwajeet
authors.initials: V
authors.lastname: Puri
authors.affiliation: From the Boston University School of Medicine, Boston, Massachusetts 02118 kkandror@bu.edu.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Kandror
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000235:genetics; D051379:Mice; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000217:Acyltransferases
chemical_list: D051017:Apoptosis Regulatory Proteins; D051766:Early Growth Response Protein 1; D008049:Lipase; D011506:Proteins; C472088:CIDEC protein, human; C497325:EGR1 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases
keywords: Adipocyte; Adipose Triglyceride Lipase (ATGL); Early Growth Response Protein 1 (EGR1); Lipid Droplets; Lipolysis
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