Abstract
The nematode Caenorhabditis elegans synthesizes a complex array of unsaturated fatty acids. The stearoyl-CoA desaturases (SCDs), which introduce the first double bond into a saturated fatty acid chain, are encoded by three genes. Two of these genes, fat-6 and fat-7, encode SCDs that introduce a double bond into stearic acid (18:0), generating oleic acid (18:1n-9). The third gene, fat-5, is a palmitoyl-CoA desaturase, which introduces a double bond into palmitic acid (16:0). Powerful molecular and genetic tools in C. elegans, combined with a relatively simple anatomy, make this an ideal model to study the roles and regulation of unsaturated fatty acids. This review summarizes the physiological roles of SCDs in C. elegans that have been determined by the analysis of SCD mutants. Studies examining the regulation of C. elegans SCDs by SREBP, nuclear hormone receptors, and other transcription factors are also highlighted in this chapter.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aarnio V, Storvik M, Lehtonen M, Asikainen S, Reisner K, Callaway J et al (2010) Fatty acid composition and gene expression profiles are altered in aryl hydrocarbon receptor-1 mutant Caenorhabditis elegans. Comp Biochem Physiol C Toxicol Pharmacol 151:318–324
Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C (2002) Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295:502–505
Arda HE, Taubert S, MacNeil LT, Conine CC, Tsuda B, Van Gilst M et al (2010) Functional modularity of nuclear hormone receptors in a Caenorhabditis elegans metabolic gene regulatory network. Mol Syst Biol 6:367
Barr MM (2003) Super models. Physiol Genomics 13:15–24
Blazek E, Mittler G, Meisterernst M (2005) The mediator of RNA polymerase II. Chromosoma 113:399–408
Brock TJ, Browse J, Watts JL (2006) Genetic regulation of unsaturated fatty acid composition in C. elegans. PLoS Genet 2:e108
Brock TJ, Browse J, Watts JL (2007) Fatty acid desaturation and the regulation of adiposity in Caenorhabditis elegans. Genetics 176:865–875
Brown MS, Goldstein JL (1997) The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89:331–340
Browse J, Xin Z (2001) Temperature sensing and cold acclimation. Curr Opin Plant Biol 4:241–246
Castro C, Sar F, Shaw WR, Mishima M, Miska EA, Griffin JL (2012) A metabolomic strategy defines the regulation of lipid content and global metabolism by Delta9 desaturases in Caenorhabditis elegans. BMC Genomics 13:36
Chirala SS, Wakil SJ (2004) Structure and function of animal fatty acid synthase. Lipids 39:1045–1053
Dobrzyn A, Ntambi JM (2005) Stearoyl-CoA desaturase as a new drug target for obesity treatment. Obes Rev 6:169–174
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391:806–811
Goudeau J, Bellemin S, Toselli-Mollereau E, Shamalnasab M, Chen Y, Aguilaniu H (2011) Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans. PLoS Biol 9:e1000599
Hamilton B, Dong Y, Shindo M, Liu W, Odell I, Ruvkun G et al (2005) A systematic RNAi screen for longevity genes in C. elegans. Genes Dev 19:1544–1555
Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11:1975–1980
Horikawa M, Sakamoto K (2009) Fatty-acid metabolism is involved in stress-resistance mechanisms of Caenorhabditis elegans. Biochem Biophys Res Commun 390:1402–1407
Horton JD, Bashmakov Y, Shimomura I, Shimano H (1998) Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. Proc Natl Acad Sci U S A 95:5987–5992
Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:362–366
Jeon TI, Osborne TF (2012) SREBPs: metabolic integrators in physiology and metabolism. Trends Endocrinol Metab 23:65–72
Kniazeva M, Crawford QT, Seiber M, Wang CY, Han M (2004) Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development. PLoS Biol 2:E257
Kniazeva M, Shen H, Euler T, Wang C, Han M (2012) Regulation of maternal phospholipid composition and IP(3)-dependent embryonic membrane dynamics by a specific fatty acid metabolic event in C. elegans. Genes Dev 26:554–566
Lapierre LR, Gelino S, Melendez A, Hansen M (2011) Autophagy and lipid metabolism coordinately modulate life span in germline-less C. elegans. Curr Biol 21:1507–1514
Li Y, Na K, Lee HJ, Lee EY, Paik YK (2011) Contribution of sams-1 and pmt-1 to lipid homoeostasis in adult Caenorhabditis elegans. J Biochem 149:529–538
Liang B, Ferguson K, Kadyk L, Watts JL (2010) The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans. PLoS One 5:e9869
Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278:1319–1322
Lin K, Hsin H, Libina N, Kenyon C (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28:139–145
McElwee J, Bubb K, Thomas JH (2003) Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16. Aging Cell 2:111–121
Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J et al (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424:277–283
Murray P, Hayward SA, Govan GG, Gracey AY, Cossins AR (2007) An explicit test of the phospholipid saturation hypothesis of acquired cold tolerance in Caenorhabditis elegans. Proc Natl Acad Sci U S A 104:5489–5494
O’Rourke EJ, Soukas AA, Carr CE, Ruvkun G (2009) C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. Cell Metab 10:430–435
Osborne TF, Espenshade PJ (2009) Evolutionary conservation and adaptation in the mechanism that regulates SREBP action: what a long, strange tRIP it’s been. Genes Dev 23:2578–2591
Palgunow D, Klapper M, Doring F (2012) Dietary restriction during development enlarges intestinal and hypodermal lipid droplets in Caenorhabditis elegans. PLoS One 7:e46198
Pathare PP, Lin A, Bornfeldt KE, Taubert S, Van Gilst MR (2012) Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships. PLoS Genet 8:e1002645
Perez CL, Van Gilst MR (2008) A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans. Cell Metab 8:266–274
Poole RJ, Bashllari E, Cochella L, Flowers EB, Hobert O (2011) A genome-wide RNAi screen for factors involved in neuronal specification in Caenorhabditis elegans. PLoS Genet 7:e1002109
Rappleye CA, Tagawa A, Le Bot N, Ahringer J, Aroian RV (2003) Involvement of fatty acid pathways and cortical interaction of the pronuclear complex in Caenorhabditis elegans embryonic polarity. BMC Dev Biol 3:8
Riddle DL, Blumenthal T, Meyer BJ, Priess JR (1997) Introduction to C. elegans. In: Riddle DL, Blumenthal T, Meyer BJ, Priess JR (eds) C. elegans, vol II. Cold Spring Harbor Laboratory Press, Plainview, pp 1–22
Robinson-Rechavi M, Maina CV, Gissendanner CR, Laudet V, Sluder A (2005) Explosive lineage-specific expansion of the orphan nuclear receptor HNF4 in nematodes. J Mol Evol 60:577–586
Savory FR, Sait SM, Hope IA (2011) DAF-16 and Delta9 desaturase genes promote cold tolerance in long-lived Caenorhabditis elegans age-1 mutants. PLoS One 6:e24550
Schuster E, McElwee JJ, Tullet JM, Doonan R, Matthijssens F, Reece-Hoyes JS et al (2010) DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. Mol Syst Biol 6:399
Sonnichsen B, Koski LB, Walsh A, Marschall P, Neumann B, Brehm M et al (2005) Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature 434:462–469
Sun LP, Seemann J, Goldstein JL, Brown MS (2007) Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proc Natl Acad Sci U S A 104:6519–6526
Taubert S, Van Gilst MR, Hansen M, Yamamoto KR (2006) A mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans. Genes Dev 20:1137–1149
Taubert S, Hansen M, Van Gilst MR, Cooper SB, Yamamoto KR (2008) The Mediator subunit MDT-15 confers metabolic adaptation to ingested material. PLoS Genet 4:e1000021
Taubert S, Ward JD, Yamamoto KR (2011) Nuclear hormone receptors in nematodes: evolution and function. Mol Cell Endocrinol 334:49–55
Tiku PE, Gracey AY, Macartney AI, Beynon RJ, Cossins AR (1996) Cold-induced expression of delta 9-desaturase in carp by transcriptional and posttranslational mechanisms. Science 271:815–818
Timmons L, Fire A (1998) Specific Interference by ingested dsRNA. Nature 395:854
Van Gilst MR, Hadjivassiliou H, Jolly A, Yamamoto KR (2005a) Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans. PLoS Biol 3:e53
Van Gilst MR, Hadjivassiliou H, Yamamoto KR (2005b) A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49. Proc Natl Acad Sci U S A 102:13496–13501
Vrablik TL, Watts JL (2012) Emerging roles for specific fatty acids in developmental processes. Genes Dev 26:631–637
Wakil SJ (1989) Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 28:4523–4530
Wakil SJ, Abu-Elheiga LA (2008) Fatty acid metabolism: target for metabolic syndrome. J Lipid Res 50(Suppl):S138–S143
Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A et al (2010) Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev 24:1403–1417
Walker AK, Jacobs RL, Watts JL, Rottiers V, Jiang K, Finnegan DM et al (2011) A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. Cell 147:840–852
Wallis JG, Watts JL, Browse J (2002) Polyunsaturated fatty acid synthesis: what will they think of next? Trends Biochem Sci 27:467
Wang MC, O’Rourke EJ, Ruvkun G (2008) Fat metabolism links germline stem cells and longevity in C. elegans. Science 322:957–960
Watts JL (2009) Fat synthesis and adiposity regulation in Caenorhabditis elegans. Trends Endocrinol Metab 20:58–65
Watts JL, Browse J (2000) A palmitoyl-CoA-specific delta9 fatty acid desaturase from Caenorhabditis elegans. Biochem Biophys Res Commun 272:263–269
Watts JL, Browse J (2002) Genetic dissection of polyunsaturated fatty acid synthesis in Caenorhabditis elegans. Proc Natl Acad Sci U S A 99:5854–5859
Yang T, Espenshade PJ, Wright ME, Yabe D, Gong Y, Aebersold R et al (2002) Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110:489–500
Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL et al (2006) An ARC/mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature 442:700–704
Zhang J, Bakheet R, Parhar RS, Huang CH, Hussain MM, Pan X et al (2011) Regulation of fat storage and reproduction by Kruppel-like transcription factor KLF3 and fat-associated genes in Caenorhabditis elegans. J Mol Biol 411:537–553
Acknowledgements
The author thanks the National Institutes of Health (R01-DK074114) for research support and Dr. Tracy Vrablik and Dr. Amy Walker for comments on the manuscript.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Watts, J.L. (2013). Physiological Functions and Regulation of C. elegans Stearoyl-CoA Desaturases. In: Ntambi, Ph.D., J. (eds) Stearoyl-CoA Desaturase Genes in Lipid Metabolism. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7969-7_14
Download citation
DOI: https://doi.org/10.1007/978-1-4614-7969-7_14
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-7968-0
Online ISBN: 978-1-4614-7969-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)