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Hormone-sensitive lipase (Lipe): Sequence analysis of the 129Sv mouse Lipe gene

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Abstract

Hormone-sensitive lipase (Lipe) catalyzes both the release of fatty acids from storage triglycerides in adipocytes and the liberation of cholesterol from cholesterol esters in steroidogenic tissues. Lipe activity is regulated in a tissue-, development- and hormone-specific fashion, the latter in large part by serine phosphorylation. We cloned and sequenced the Lipe gene from the 129Sv strain mouse, including 2.7 kb of the 5′ nontranslated region. The primary transcript of the 129Sv Lipe locus spans 9.6 kb and contains 9 exons. We studied the curious hypervariable region immediately 5′ to the regulatory serine residues by aligning the peptide and nucleic acid sequences of mouse, human, and rat Lipe. We propose that much of the variability is attributable to differences in the copy number of a 12-nucleotide repeat that shifts the intron 7 acceptor splice site. Introns 1 and 7 contain B1 elements, which in intron 7 are immediately adjacent to a tetranucleotide repeat. The mouse Lipe promoter region contains numerous potential binding motifs for factors implicated in adipose tissue expression and hormone responsiveness including adipocyte determination- and differentiation-dependent factor 1 (ADD1/SREBP1).

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References

  • Arcot SS, Wang Z, Weber JL, Deininger PL, Batzer MA (1995) Alu repeats: a source for the genesis of primate microsatellites. Genomics 29, 136–144

    Article  PubMed  CAS  Google Scholar 

  • Chen J-Y, Waterman MR (1992) Two promoters in the bovine adrenodoxin gene and the role of associated, unique cAMP-responsive sequences. Biochemistry 31, 2400–2407

    Article  PubMed  CAS  Google Scholar 

  • Cheneval D, Christy RJ, Geiman D, Cornelius P, Lane D (1991) Cell-free transcription directed by the 422 adipose P2 gene promoter: Activation by the CCAAT/enhancer binding protein. Proc Natl Acad Sci USA 88, 8465–8469

    Article  PubMed  CAS  Google Scholar 

  • Cook KG, Yeaman SJ, Stralfors P, Fredrikson G, Beifrage P (1982) Direct evidence that cholesterol ester hydrolase from adrenal cortex is the same enzyme as hormone-sensitive lipase from adipose tissue. Eur J Biochem 125, 245–249

    Article  PubMed  CAS  Google Scholar 

  • Cooper DN, Krawczak M, Antonarakis SE (1995) The nature and mechanisms of human gene mutation. The Metabolic and Molecular Bases of Inherited Disease, CR Scriver, AL Beaudet, WS Sly, D Valle, eds., (New York, NY: McGraw Hill, Inc.), 7th ed., pp. 259–292

    Google Scholar 

  • Cornelius P, MacDougald OA, Lane MD (1994) Regulation of adipocyte development. Annu Rev Nutr 14, 99–129

    Article  PubMed  CAS  Google Scholar 

  • Egan JJ, Greenberg AS, Chang MK, Wek SA, Moos MC, Jr, Londos C (1992) Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormone-sensitive lipase to the lipid storage droplet. Proc Natl Acad Sci USA 89, 8537–8541

    Article  PubMed  CAS  Google Scholar 

  • Garton AJ, Yeaman SJ (1990) Identification and role of the basal phosphorylation site on hormone-sensitive lipase. Eur J Biochem 191, 245–250

    Article  PubMed  CAS  Google Scholar 

  • Hayashi S, Scott MP (1990) What determines the specificity of action of Drosophila homeodomain proteins? Cell 63, 883–894

    Article  PubMed  CAS  Google Scholar 

  • Holm C, Kirchgessner TG, Svenson KL, Fredrikson G, Nilsson S, Miller CG,Shively JE, Heinzmann C, Sparkes RS, Mohandas T, Lusis AJ, Belfrage P, Schotz M (1998a) Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-ql3.3. Science 241, 1503–1506

    Article  Google Scholar 

  • Holm C, Kirchgessner TG, Svenson KL, Lusis AJ, Belfrage P, Schotz MC (1988b) Nucleotide sequence of rat adipose hormone sensitive lipase cDNA. Nucleic Acids Res 16, 9879

    Article  PubMed  CAS  Google Scholar 

  • Holst LS, Langin D, Mulder H, Laurell H, Grober J, Bergh A, Mohrenweiser HW, Edgren G, Holm C (1996) Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase. Genomics 35, 441–447

    Article  PubMed  CAS  Google Scholar 

  • Hua X, Yokoyama C, Wu J, Briggs MR, Brown MS, Goldstein JL, Wang X (1993) SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Proc Natl Acad Sci USA 90, 11603–11607

    Article  PubMed  CAS  Google Scholar 

  • Hunt CR, Ro JH, Dobson DE, Min HY, Spiegelman BM (1986) Adipocyte P2 gene: developmental expression and homology of 5′-flanking sequences among fat cell-specific genes. Proc Natl Acad Sci USA 83, 3786–3792

    Article  PubMed  CAS  Google Scholar 

  • Kawamura M, Jensen DF, Wancewicz EV, Joy LL, Khoo JC, Steinberg D (1981) Hormone-sensitive lipase in differentiated 3T3-L1 cells and its activation by cyclic AMP-dependent protein kinase. Proc Natl Acad Sci USA 78, 732–736

    Article  PubMed  CAS  Google Scholar 

  • Khoo JC, Reue K, Steinberg D, Schotz MC (1993) Expression of hormone-sensitive lipase mRNA in macrophages. J Lipid Res 34, 1969–1974

    PubMed  CAS  Google Scholar 

  • Kim JB, Spotts GD, Halvorsen Y-D, Shih H-M, Ellenberger T, Towle, HC, Spiegelman BM (1995) Dual DNA binding specificity of ADD1/ SREBP1 controlled by a single amino acid in the basic helix-loop-helix domain. Mol Cell Biol 15, 2582–2588

    PubMed  CAS  Google Scholar 

  • Langin D, Laurell H, Holst LS, Belfrage P, Holm C (1993) Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antartic bacterium. Proc Natl Acad Sci USA 90, 4897–4901

    Article  PubMed  CAS  Google Scholar 

  • Levitt RC, Liu Z, Nouri N, Meyers DA, Brandriff B, Mohrenweiser HM (1995) Mapping of the gene for hormone sensitive lipase (LIPE) to chromosome 19q13.3 → q13.2. Cytogenet Cell Genet 69, 211–214

    Article  PubMed  CAS  Google Scholar 

  • Lewin B (1994) GENES V, (New York: Oxford University Press)

    Google Scholar 

  • Li Z, Sumida M, Birchbauer A, Schotz MC, Reue K (1994) Isolation and characterization of the gene for mouse hormone-sensitive lipase. Genomics 24, 259–265

    Article  PubMed  CAS  Google Scholar 

  • McGehee RE, Jr, Ron D, Braiser AR, Habener JF (1993) Differentiation-specific element: a cis-acting developmental switch required for the sustained transcriptional expression of the angiotensinogen gene during hormonal-induced differentiation of 3T3-L1 fibroblasts to adipocytes. Mol Endo 7, 551–560

    Article  CAS  Google Scholar 

  • NC.IUB, (1985) Nomenclature Committee of the International Union of Biochemistry (NC-IUB). Nomenclature of incompletely specified bases in nucleic acid sequences. Eur J Biochem 150, 1–5

    Article  Google Scholar 

  • Quentin Y (1989) Successive waves of fixation of B1 variants in rodent lineage history. J Mol Evol 28, 299–305

    Article  PubMed  CAS  Google Scholar 

  • Reynisdottir S, Ellerfeldt K, Wahrenberg H, Lithell H, Arner P (1994) Multiple lipolysis defects in the insulin resistance (metabolic) syndrome. J Clin Invest 93, 2590–2599

    Article  PubMed  CAS  Google Scholar 

  • Roesler WJ, Vanderbark GR, Hanson RW (1988) Cyclic AMP and the induction of eukaryotic gene transcription. J Biol Chem 263, 9063–9066

    PubMed  CAS  Google Scholar 

  • Ruvkun G, Finney, M (1991) Regulation of transcription and cell identity by POU domain proteins. Cell 64, 475–478

    Article  PubMed  CAS  Google Scholar 

  • Ryden TA, Beemon K (1989) Avian retroviral long terminal repeats bind CCAAT/enhancer-binding protein. Mol Cell Biol 9, 1155–1164

    PubMed  CAS  Google Scholar 

  • Shimura Y, Shimura H, Ohmori M, Ikuyama S, Kohn LD (1994) Identification of a novel insulin-responsive element in the rat thyrotropin receptor promoter. J Biol Chem 269, 31908–31914

    PubMed  CAS  Google Scholar 

  • Small CA, Garton AJ, Yeaman SJ (1989) The presence and role of hormone-sensitive lipase in heart muscle. Biochem J 258, 67–72

    PubMed  CAS  Google Scholar 

  • Stralfors P, Bjorgell P, Belfrage (1984) Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin. Proc Natl Acad Sci USA 81, 3317–3321

    Article  PubMed  CAS  Google Scholar 

  • Stralfors P, Olsson H, Belfrage P (1987). The Enzymes Vol XVIII. In: Hormone-Sensitive Lipase, PD, Boyer, EG Krass, eds. (New York: Academic Press), 18th ed., pp. 144–177

    Google Scholar 

  • Swick AG, Lane D (1992) Identification of a transcriptional repressor down-regulated during preadipocyte differentiation. Proc Natl Acad Sci USA 89, 7895–7899

    Article  PubMed  CAS  Google Scholar 

  • Tontonoz P, Kim JB, Graves RA, Spiegelman BM (1993) ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. Mol Cell Biol 13, 4753–1759

    PubMed  CAS  Google Scholar 

  • Wang S, Lapierre P, Robert M-F, Nadeau JH, Mitchell GA (1994) Hormone-sensitive lipase maps to proximal chromosome 7 in mice and is genetically distinct from the Ad and Tub loci. Genomics 24, 416–417

    Article  PubMed  CAS  Google Scholar 

  • Wang SP, Robert M-F, Gibson KM, Wanders RJA, Mitchell GA (1996) 3-Hydroxy-3-methylglutaryl-CoA lyase (HL): mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients. Genomics 33, 99–104

    Article  PubMed  CAS  Google Scholar 

  • Warden CH, Davis RC, Yoon MY, Hui DY, Svenson K, Xia YR, Diep A, He KY, Lusis AJ (1993) Chromosomal localization of lipolytic enzymes in the mouse: pancreatic lipase, colipase, hormone-sensitive lipase, hepatic lipase, and carboxyl ester lipase. J Lipid Res 34, 1451–1455

    PubMed  CAS  Google Scholar 

  • Yeaman SJ, Smith GM, Jepson CA, Wood SL, Emmison N (1994) The multifunctional role of hormone-sensitive lipase in lipid metabolism. Adv Enzyme Regul 34, 355–370

    Article  PubMed  CAS  Google Scholar 

  • Zanger UM, Kagawa N, Lund J, Waterman MR (1992) Distinct biochemical mechanisms for cAMP-dependent transcription of CYP17 and CYP21. FASEB J 6, 718–723

    Google Scholar 

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Authors and Affiliations

  1. Service de Génétique Médicale, Centre de Recherche, Hôpital Ste-Justine, 3175 chemin de la Côte Ste-Catherine, H3T1C5, Montreal, Quebec, Canada

    R. Sztrolovics, S. P. Wang, P. Lapierre, M -F. Robert & G. A. Mitchell

  2. Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada

    H. S. Chen

Authors
  1. R. Sztrolovics
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  2. S. P. Wang
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  3. P. Lapierre
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  4. H. S. Chen
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  5. M -F. Robert
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  6. G. A. Mitchell
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Additional information

The sequence described in this paper has been assigned GenBank accession No. U69543.

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Sztrolovics, R., Wang, S.P., Lapierre, P. et al. Hormone-sensitive lipase (Lipe): Sequence analysis of the 129Sv mouse Lipe gene. Mammalian Genome 8, 86–89 (1997). https://doi.org/10.1007/s003359900363

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  • DOI: https://doi.org/10.1007/s003359900363

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