A whole-organism screen identifies new regulators of fat storage

Nature Chemical Biology

Volumn 7, Issue 4, 2011, Pages 206-213

  Lemieux, George A ^a   Liu, Jason ^b   Mayer, Nasima ^a   Bainton, Roland J ^a   Ashrafi, Kaveh ^b   Werb, Zena ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE PHOSPHATE; TRANSCRIPTION FACTOR;

ARTICLE; CAENORHABDITIS ELEGANS; CONTROLLED STUDY; ENZYME ACTIVE SITE; FAT CONTENT; FEEDING; FUNGUS GROWTH; GENETIC ANALYSIS; HOMEOSTASIS; INSECT CELL CULTURE; LIPID STORAGE; NONHUMAN; PRIORITY JOURNAL; REPRODUCTION;

ANIMALIA; CAENORHABDITIS ELEGANS; HEXAPODA; MAMMALIA;

EID: 79952971308     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio.534     Document Type: Article

References (50)

1. Spiegelman, B.M. & Flier, J.S. Obesity and the regulation of energy balance. Cell 104, 531-543 (2001). (Pubitemid 32201948)
2. Kopelman, P.G. Obesity as a medical problem. Nature 404, 635-643 (2000). (Pubitemid 30205068)
3. Knight, Z.A. & Shokat, K.M. Chemical genetics: Where genetics and pharmacology meet. Cell 128, 425-430 (2007). (Pubitemid 46198904)
4. Stelling, J. et al. Robustness of cellular functions. Cell 118, 675-685 (2004). (Pubitemid 39221728)
5. Wheeler, G.N. & Brandli, A.W. Simple vertebrate models for chemical genetics and drug discovery screens: Lessons from zebrafish and Xenopus. Dev. Dyn. 238, 1287-1308 (2009).
6. Moy, T.I. et al. High-throughput screen for novel antimicrobials using a whole animal infection model. ACS Chem. Biol. 4, 527-533 (2009).
7. Petrascheck, M., Ye, X. & Buck, L.B. An antidepressant that extends lifespan in adult Caenorhabditis elegans. Nature 450, 553-556 (2007). (Pubitemid 350190239)
8. Kwok, T.C. et al. A small-molecule screen in C. elegans yields a new calcium channel antagonist. Nature 441, 91-95 (2006).
9. Jones, A.K., Buckingham, S.D. & Sattelle, D.B. Chemistry-to-gene screens in Caenorhabditis elegans. Nat. Rev. Drug Discov. 4, 321-330 (2005). (Pubitemid 41130945)
10. Schafer, W.R., Sanchez, B.M. & Kenyon, C.J. Genes affecting sensitivity to serotonin in Caenorhabditis elegans. Genetics 143, 1219-1230 (1996).
11. Weinshenker, D., Garriga, G. & Thomas, J.H. Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans. J. Neurosci. 15, 6975-6985 (1995).
12. Watts, J.L. Fat synthesis and adiposity regulation in Caenorhabditis elegans. Trends Endocrinol. Metab. 20, 58-65 (2009).
13. Perez, C.L. & Van Gilst, M.R. A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans. Cell Metab. 8, 266-274 (2008).
14. Jones, K.T. & Ashrafi, K. Caenorhabditis elegans as an emerging model for studying the basic biology of obesity. Dis. Model. Mech. 2, 224-229 (2009).
15. McKay, R.M. et al. C. elegans: A model for exploring the genetics of fat storage. Dev. Cell 4, 131-142 (2003). (Pubitemid 36105339)
16. Jia, K., Chen, D. & Riddle, D.L. The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131, 3897-3906 (2004). (Pubitemid 39232150)
17. Kimura, K.D. et al. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942-946 (1997). (Pubitemid 27366677)
18. Srinivasan, S. et al. Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms. Cell Metab. 7, 533-544 (2008). (Pubitemid 351729208)
19. de Bono, M. & Bargmann, C.I. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans. Cell 94, 679-689 (1998). (Pubitemid 28427586)
20. Suo, S., Culotti, J.G. & Van Tol, H.H. Dopamine counteracts octopamine signalling in a neural circuit mediating food response in C. elegans. EMBO J. 28, 2437-2448 (2009).
21. Ashrafi, K. et al. Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421, 268-272 (2003). (Pubitemid 36139130)
22. Greenspan, P., Mayer, E.P. & Fowler, S.D. Nile red: A selective fluorescent stain for intracellular lipid droplets. J. Cell Biol. 100, 965-973 (1985). (Pubitemid 15135357)
23. Van Gilst, M.R. et al. Nuclear hormone receptor NHR-49 controls fat consumption and fatty acid composition in C. elegans. PLoS Biol. 3, e53 (2005).
24. Jones, K.S. et al. A high throughput live transparent animal bioassay to identify non-toxic small molecules or genes that regulate vertebrate fat metabolism for obesity drug development. Nutr. Metab. (Lond) 5, 23 (2008).
25. Sullivan, J.E. et al. Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett. 353, 33-36 (1994). (Pubitemid 24312538)
26. Watts, J.L. & Browse, J. A palmitoyl-CoA-specific delta9 fatty acid desaturase from Caenorhabditis elegans. Biochem. Biophys. Res. Commun. 272, 263-269 (2000). (Pubitemid 30444932)
27. Van Gilst, M.R., Hadjivassiliou, H. & Yamamoto, K.R. A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49. Proc. Natl. Acad. Sci. USA 102, 13496-13501 (2005). (Pubitemid 41420876)
28. Yang, F. et al. An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature 442, 700-704 (2006). (Pubitemid 44215326)
29. MacDougald, O.A. & Lane, M.D. Transcriptional regulation of gene expression during adipocyte differentiation. Annu. Rev. Biochem. 64, 345-373 (1995).
30. Guo, Y. et al. Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature 453, 657-661 (2008). (Pubitemid 351769298)
31. Horton, J.D. et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc. Natl. Acad. Sci. USA 100, 12027-12032 (2003). (Pubitemid 37271509)
32. Kniazeva, M. et al. Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development. PLoS Biol. 2, E257 (2004).
33. Shiri-Sverdlov, R. et al. Identification of TUB as a novel candidate gene influencing body weight in humans. Diabetes 55, 385-389 (2006). (Pubitemid 43343267)
34. Goldstone, A.P. & Beales, P.L. Genetic obesity syndromes. Front. Horm. Res. 36, 37-60 (2008).
35. Ogg, S. et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994-999 (1997). (Pubitemid 27485694)
36. Steinberg, G.R. & Kemp, B.E. AMPK in health and disease. Physiol. Rev. 89, 1025-1078 (2009).
37. Apfeld, J. et al. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev. 18, 3004-3009 (2004). (Pubitemid 39658169)
38. Narbonne, P. & Roy, R. Caenorhabditis elegans dauers need LKB1/AMPK to ration lipid reserves and ensure long-term survival. Nature 457, 210-214 (2009).
39. Dobrzyn, P. et al. Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc. Natl. Acad. Sci. USA 101, 6409-6414 (2004). (Pubitemid 38585987)
40. Corton, J.M. et al. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur. J. Biochem. 229, 558-565 (1995).
41. Owen, M.R., Doran, E. & Halestrap, A.P. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348, 607-614 (2000). (Pubitemid 30410251)
42. Cool, B. et al. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab. 3, 403-416 (2006). (Pubitemid 43811782)
43. Wang, X., Jia, H. & Chamberlin, H.M. The bZip proteins CES-2 and ATF-2 alter the timing of transcription for a cell-specific target gene in C. elegans. Dev. Biol. 289, 456-465 (2006). (Pubitemid 43049947)
44. Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167-1174 (2001). (Pubitemid 32995375)
45. Davies, S.P., Sim, A.T. & Hardie, D.G. Location and function of three sites phosphorylated on rat acetyl-CoA carboxylase by the AMP-activated protein kinase. Eur. J. Biochem. 187, 183-190 (1990). (Pubitemid 20040376)
46. O'Rourke, E.J. et al. C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. Cell Metab. 10, 430-435 (2009).
47. Brooks, K.K., Liang, B. & Watts, J.L. The influence of bacterial diet on fat storage in C. elegans. PLoS ONE 4, e7545 (2009).
48. Mörck, C. et al. Statins inhibit protein lipidation and induce the unfolded protein response in the non-sterol producing nematode Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 106, 18285-18290 (2009).
49. Kodiha, M. et al. Localization of AMP kinase is regulated by stress, cell density, and signaling through the MEK?ERK1/2 pathway. Am. J. Physiol. Cell Physiol. 293, C1427-C1436 (2007). (Pubitemid 350085641)
50. MacRae, C.A. & Peterson, R.T. Zebrafish-based small molecule discovery. Chem. Biol. 10, 901-908 (2003). (Pubitemid 37316907)