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Caenorhabditis elegans as a model for obesity research

International Journal of Obesity volume 36, pages 186–194 (2012)Cite this article

Abstract

Caenorhabditis elegans (C. elegans) is a small nematode that conserves 65% of the genes associated with human disease, has a 21-day lifespan, reproductive cycles of 3 days, large brood sizes, lives in an agar dish and does not require committee approvals for experimentation. Research using C. elegans is encouraged and a Caenorhabditis Genetics Center (CGC, Minnesota) is funded by the National Institutes of Health–National Center for Research Resources. Many genetically manipulated strains of C. elegans are available at nominal cost from the CGC. Studies using the C. elegans model have explored insulin signaling, response to dietary glucose, the influence of serotonin on obesity, satiety, feeding and hypoxia-associated illnesses. C. elegans has also been used as a model to evaluate potential obesity therapeutics, explore the mechanisms behind single gene mutations related to obesity and to define the mechanistic details of fat metabolism. Obesity now affects a third of the US population and is becoming a progressively more expensive public health problem. Faster and less expensive methods to reach more effective treatments are clearly needed. We present this review hoping to stimulate interest in using the C. elegans model as a vehicle to advance the understanding and future treatment of obesity.

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References

  1. World Health Organization. Obesity: Preventing and Managing the Global Epidemic. World Health Organization: Geneva, Switzerland, 1997.

  2. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM . Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 2006; 295: 1549–1555.

    Article  CAS  Google Scholar 

  3. Bray GA . Obesity: a time bomb to be defused. Lancet 1998; 352: 160–161.

    Article  CAS  Google Scholar 

  4. Wolf AM, Colditz GA . Current estimates of the economic cost of obesity in the United States. Obes Res 1998; 6: 97–106.

    Article  CAS  Google Scholar 

  5. Hogan P, Dall T, Nikolov P, American Diabetes A . Economic costs of diabetes in the US in 2002. Diabetes Care 2003; 26: 917–932.

    Article  Google Scholar 

  6. C. elegans Sequencing Consortium. Genome sequence of the nematode C. elegans: a platform for investigating, 1998; 282: 2012–2018.

  7. Baumeister R, Ge L . The worm in us—Caenorhabditis elegans as a model of human disease. Trends Biotechnol 2002; 20: 147–148.

    Article  CAS  Google Scholar 

  8. Li H, Black PN, DiRusso CC . A live-cell high-throughput screening assay for identification of fatty acid uptake inhibitors. Anal Biochem 2005; 336: 11–19.

    Article  CAS  Google Scholar 

  9. Ashrafi K, Chang FY, Watts JL, Fraser AG, Kamath RS, Ahringer J et al. Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 2003; 421: 268–272.

    Article  CAS  Google Scholar 

  10. Hirsch D, Stahl A, Lodish HF . A family of fatty acid transporters conserved from mycobacterium to man. Proc Natl Acad Sci USA 1998; 95: 8625–8629.

    Article  CAS  Google Scholar 

  11. Yen K, Le TT, Bansal A, Narasimhan SD, Cheng JX, Tissenbaum HA . A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLoS One 2010; 5: e12810.

    Article  Google Scholar 

  12. Liu LX, Spoerke JM, Mulligan EL, Chen J, Reardon B, Westlund B et al. High-throughput isolation of Caenorhabditis elegans deletion mutants. Genome Res 1999; 9: 859–867.

    Article  CAS  Google Scholar 

  13. Brooks KK, Liang B, Watts JL . The influence of bacterial diet on fat storage in C. elegans. PLoS One 2009; 4: e7545.

    Article  Google Scholar 

  14. Jeong PY, Kwon MS, Joo HJ, Paik YK . Molecular time-course and the metabolic basis of entry into dauer in Caenorhabditis elegans. PLoS One 2009; 4: e4162.

    Article  Google Scholar 

  15. Atherton HJ, Jones OA, Malik S, Miska EA, Griffin JL . A comparative metabolomic study of NHR-49 in Caenorhabditis elegans and PPAR-alpha in the mouse. FEBS Lett 2008; 582: 1661–1666.

    Article  CAS  Google Scholar 

  16. Lakowski B, Hekimi S . The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci USA 1998; 95: 13091–13096.

    Article  CAS  Google Scholar 

  17. Sze JY, Victor M, Loer C, Shi Y, Ruvkun G . Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant. Nature 2000; 403: 560–564.

    Article  CAS  Google Scholar 

  18. Watts JL . Fat synthesis and adiposity regulation in Caenorhabditis elegans. Trends Endocrinol Metab 2009; 20: 58–65.

    Article  CAS  Google Scholar 

  19. You YJ, Kim J, Raizen DM, Avery L . Insulin, cGMP, and TGF-beta signals regulate food intake and quiescence in C. elegans: a model for satiety. Cell Metab 2008; 7: 249–257.

    Article  CAS  Google Scholar 

  20. Jones KT, Ashrafi K . Caenorhabditis elegans as an emerging model for studying the basic biology of obesity. Dis Model Mech 2009; 2: 224–229.

    Article  CAS  Google Scholar 

  21. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 1997; 389: 994–999.

    Article  CAS  Google Scholar 

  22. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G . daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 1997; 277: 942–946.

    Article  CAS  Google Scholar 

  23. Das UN . GLUT-4, tumor necrosis factor, essential fatty acids and daf-genes and their role in insulin resistance and non-insulin dependent diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 1999; 60: 13–20.

    Article  CAS  Google Scholar 

  24. Kramer JM, Davidge JT, Lockyer JM, Staveley BE . Expression of Drosophila FOXO regulates growth and can phenocopy starvation. BMC Dev Biol 2003; 3: 5.

    Article  Google Scholar 

  25. Hertweck M, Gobel C, Baumeister R . C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 2004; 6: 577–588.

    Article  CAS  Google Scholar 

  26. Tissenbaum HA, Ruvkun G . An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. Genetics 1998; 148: 703–717.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Burks DJ, Font de Mora J, Schubert M, Withers DJ, Myers MG, Towery HH et al. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature 2000; 407: 377–382.

    Article  CAS  Google Scholar 

  28. Porte Jr D, Baskin DG, Schwartz MW . Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans. Diabetes 2005; 54: 1264–1276.

    Article  CAS  Google Scholar 

  29. Laron Z . The GH–IGF1 axis and longevity. The paradigm of IGF1 deficiency. Hormones (Athens) 2008; 7: 24–27.

    Article  Google Scholar 

  30. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R . A C. elegans mutant that lives twice as long as wild type. Nature 1993; 366: 461–464.

    Article  CAS  Google Scholar 

  31. Kloting N, Bluher M . Extended longevity and insulin signaling in adipose tissue. Exp Gerontol 2005; 40: 878–883.

    Article  Google Scholar 

  32. Lee SJ, Murphy CT, Kenyon C . Glucose shortens the life span of C. elegans by downregulating DAF-16/FOXO activity and aquaporin gene expression. Cell Metab 2009; 10: 379–391.

    Article  CAS  Google Scholar 

  33. Hibuse T, Maeda N, Funahashi T, Yamamoto K, Nagasawa A, Mizunoya W et al. Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase. Proc Natl Acad Sci USA 2005; 102: 10993–10998.

    Article  CAS  Google Scholar 

  34. Ceperuelo-Mallafre V, Miranda M, Chacon MR, Vilarrasa N, Megia A, Gutierrez C et al. Adipose tissue expression of the glycerol channel aquaporin-7 gene is altered in severe obesity but not in type 2 diabetes. J Clin Endocrinol Metab 2007; 92: 3640–3645.

    Article  CAS  Google Scholar 

  35. Prudente S, Flex E, Morini E, Turchi F, Capponi D, De Cosmo S et al. A functional variant of the adipocyte glycerol channel aquaporin 7 gene is associated with obesity and related metabolic abnormalities. Diabetes 2007; 56: 1468–1474.

    Article  CAS  Google Scholar 

  36. Garattini S, Bizzi A, Caccia S, Mennini T, Samanin R . Progress in assessing the role of serotonin in the control of food intake. Clin Neuropharmacol 1988; 11 (Suppl 1): S8–S32.

    CAS  PubMed  Google Scholar 

  37. Zarse K, Ristow M . Antidepressants of the serotonin-antagonist type increase body fat and decrease lifespan of adult Caenorhabditis elegans. PLoS One 2008; 3: e4062.

    Article  Google Scholar 

  38. Srinivasan S, Sadegh L, Elle IC, Christensen AG, Faergeman NJ, Ashrafi K . Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms. Cell Metab 2008; 7: 533–544.

    Article  CAS  Google Scholar 

  39. Laurence JZ, Moon RC . Four cases of ‘retinitis pigmentosa’ occurring in the same family, and accompanied by general imperfections of development. 1866. Obes Res 1995; 3: 400–403.

    Article  CAS  Google Scholar 

  40. Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC et al. Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome. Nature 2003; 425: 628–633.

    Article  CAS  Google Scholar 

  41. Pan J, Wang Q, Snell WJ . Cilium-generated signaling and cilia-related disorders. Lab Invest 2005; 85: 452–463.

    Article  CAS  Google Scholar 

  42. Fan Y, Esmail MA, Ansley SJ, Blacque OE, Boroevich K, Ross AJ et al. Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet–Biedl syndrome. Nat Genet 2004; 36: 989–993.

    Article  CAS  Google Scholar 

  43. Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA . C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab 2005; 2: 35–42.

    Article  CAS  Google Scholar 

  44. Mak HY, Nelson LS, Basson M, Johnson CD, Ruvkun G . Polygenic control of Caenorhabditis elegans fat storage. Nat Genet 2006; 38: 363–368.

    Article  CAS  Google Scholar 

  45. Mukhopadhyay A, Pan X, Lambright DG, Tissenbaum HA . An endocytic pathway as a target of tubby for regulation of fat storage. EMBO Rep 2007; 8: 931–938.

    Article  CAS  Google Scholar 

  46. Suh JM, Zeve D, McKay R, Seo J, Salo Z, Li R et al. Adipose is a conserved dosage-sensitive antiobesity gene. Cell Metab 2007; 6: 195–207.

    Article  CAS  Google Scholar 

  47. Korotkova N, Chistoserdova L, Kuksa V, Lidstrom ME . Glyoxylate regeneration pathway in the methylotroph Methylobacterium extorquens AM1. J Bacteriol 2002; 184: 1750–1758.

    Article  CAS  Google Scholar 

  48. Perez CL, Van Gilst MR . A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans. Cell Metab 2008; 8: 266–274.

    Article  CAS  Google Scholar 

  49. Brey CW, Nelder MP, Hailemariam T, Gaugler R, Hashmi S . Kruppel-like family of transcription factors: an emerging new frontier in fat biology. Int J Biol Sci 2009; 5: 622–636.

    Article  CAS  Google Scholar 

  50. Raghow R, Yellaturu C, Deng X, Park EA, Elam MB . SREBPs: the crossroads of physiological and pathological lipid homeostasis. Trends Endocrinol Metab 2008; 19: 65–73.

    Article  CAS  Google Scholar 

  51. Nomura T, Horikawa M, Shimamura S, Hashimoto T, Sakamoto K . Fat accumulation in Caenorhabditis elegans is mediated by SREBP homolog SBP-1. Genes Nutr 2010; 5: 17–27.

    Article  CAS  Google Scholar 

  52. Ntambi JM, Miyazaki M, Stoehr JP, Lan H, Kendziorski CM, Yandell BS et al. Loss of stearoyl-CoA desaturase-1 function protects mice against adiposity. Proc Natl Acad Sci USA 2002; 99: 11482–11486.

    Article  CAS  Google Scholar 

  53. Ashrafi K . Obesity and the regulation of fat metabolism. WormBook 2007; 9: 1–20.

    Google Scholar 

  54. Van Gilst MR, Hadjivassiliou H, Jolly A, Yamamoto KR . Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans. PLoS Biol 2005; 3: e53.

    Article  Google Scholar 

  55. Golden A, Liu J, Cohen-Fix O . Inactivation of the C. elegans lipin homolog leads to ER disorganization and to defects in the breakdown and reassembly of the nuclear envelope. J Cell Sci 2009; 122: 1970–1978.

    Article  CAS  Google Scholar 

  56. Elle IC, Olsen LC, Pultz D, Rodkaer SV, Faergeman NJ . Something worth dyeing for: molecular tools for the dissection of lipid metabolism in Caenorhabditis elegans. FEBS Lett 2010; 584: 2183–2193.

    Article  CAS  Google Scholar 

  57. Singh SP, Niemczyk M, Zimniak L, Zimniak P . Fat accumulation in Caenorhabditis elegans triggered by the electrophilic lipid peroxidation product 4-hydroxynonenal (4-HNE). Aging (Albany NY) 2009; 1: 68–80.

    Article  CAS  Google Scholar 

  58. Meissner B, Boll M, Daniel H, Baumeister R . Deletion of the intestinal peptide transporter affects insulin and TOR signaling in Caenorhabditis elegans. J Biol Chem 2004; 279: 36739–36745.

    Article  CAS  Google Scholar 

  59. Spanier B, Lasch K, Marsch S, Benner J, Liao W, Hu H et al. How the intestinal peptide transporter PEPT-1 contributes to an obesity phenotype in Caenorhabditis elegans. PLoS One 2009; 4: e6279.

    Article  Google Scholar 

  60. McClean KM, Kee F, Young IS, Elborn JS . Obesity and the lung: 1. Epidemiology. Thorax 2008; 63: 649–654.

    Article  CAS  Google Scholar 

  61. Mohanna S, Baracco R, Seclen S . Lipid profile, waist circumference, and body mass index in a high altitude population. High Alt Med Biol 2006; 7: 245–255.

    Article  CAS  Google Scholar 

  62. Taghibiglou C, Martin HG, Rose JK, Ivanova N, Lin CH, Lau HL et al. Essential role of SBP-1 activation in oxygen deprivation induced lipid accumulation and increase in body width/length ratio in Caenorhabditis elegans. FEBS Lett 2009; 583: 831–834.

    Article  CAS  Google Scholar 

  63. Dwyer DS, Donohoe D, Lu XH, Aamodt EJ . Mechanistic connections between glucose/lipid disturbances and weight gain induced by antipsychotic drugs. Int Rev Neurobiol 2005; 65: 211–247.

    Article  CAS  Google Scholar 

  64. Crossley NA, Constante M, McGuire P, Power P . Efficacy of atypical v. typical antipsychotics in the treatment of early psychosis: meta-analysis. Br J Psychiatry 2010; 196: 434–439.

    Article  Google Scholar 

  65. Zheng J, Enright F, Keenan M, Finley J, Zhou J, Ye J et al. Resistant starch, fermented resistant starch, and short-chain fatty acids reduce intestinal fat deposition in Caenorhabditis elegans. J Agric Food Chem 2010; 58: 4744–4748.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Louisiana State University Agricultural Center, Department of Veterinary Science, Baton Rouge, Louisiana, USA

    J Zheng

  2. Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, Louisiana, USA

    F L Greenway

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  1. J Zheng
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Correspondence to F L Greenway.

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Zheng, J., Greenway, F. Caenorhabditis elegans as a model for obesity research. Int J Obes 36, 186–194 (2012). https://doi.org/10.1038/ijo.2011.93

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