1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Genetics
  4. Volume 49, 2015
  5. Article

Annual Review of Genetics

Volume 49, 2015

Neural Regulatory Pathways of Feeding and Fat in

Abstract

The compact nervous system of and its genetic tractability are features that make this organism highly suitable for investigating energy balance in an animal system. Here, we focus on molecular components and organizational principles emerging from the investigation of pathways that largely originate in the nervous system and regulate feeding behavior but also peripheral fat regulation through neuroendocrine signaling. We provide an overview of studies aimed at understanding how integrate internal and external cues in feeding behavior. We highlight some of the similarities and differences in energy balance between and mammals. We also provide our perspective on unresolved issues, both conceptual and technical, that we believe have hampered critical evaluation of findings relevant to fat regulation in .

Keyword(s): AMP-activated kinase, fasting, insulin, kynurenic, serotonin, TGF-β
Loading

Article metrics loading...

/content/journals/10.1146/annurev-genet-120213-092244
2015-11-23
2024-05-08
Loading full text...

Full text loading...

/deliver/fulltext/genet/49/1/annurev-genet-120213-092244.html?itemId=/content/journals/10.1146/annurev-genet-120213-092244&mimeType=html&fmt=ahah

Literature Cited

  1. Albertson DG, Thomson JN. 1.  1976. The pharynx of Caenorhabditis elegans. Philos. Trans. R. Soc. B 275:938299–325 [Google Scholar]
  2. Alkema MJ, Hunter-Ensor M, Ringstad N, Horvitz HR. 2.  2005. Tyramine functions independently of octopamine in the Caenorhabditis elegans nervous system. Neuron 46:2247–60 [Google Scholar]
  3. Ashrafi K, Chang FY, Watts JL, Fraser AG, Kamath RS. 3.  et al. 2003. Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421:6920268–72 [Google Scholar]
  4. Atkinson RL. 4.  2014. Current status of the field of obesity. Trends Endocrinol. Metab. 25:6283–84 [Google Scholar]
  5. Avery L. 5.  1993. The genetics of feeding in Caenorhabditis elegans. Genetics 133:4897–917 [Google Scholar]
  6. Avery L, Horvitz HR. 6.  1989. Pharyngeal pumping continues after laser killing of the pharyngeal nervous system of C. elegans. Neuron 3:4473–85 [Google Scholar]
  7. Avery L, Horvitz HR. 7.  1990. Effects of starvation and neuroactive drugs on feeding in Caenorhabditis elegans. J. Exp. Zool. 253:3263–70 [Google Scholar]
  8. Avery L, Shtonda BB. 8.  2003. Food transport in the C. elegans pharynx. J. Exp. Biol. 206:142441–57 [Google Scholar]
  9. Avery L, You Y-J. 9.  2012. C. elegans feeding. WormBook The C. elegans Research Community. http://www.wormbook.org/chapters/www_feeding/feeding.html
  10. Beets I, Janssen T, Meelkop E, Temmerman L, Suetens N. 10.  et al. 2012. Vasopressin/oxytocin-related signaling regulates gustatory associative learning in C. elegans. Science 338:6106543–45 [Google Scholar]
  11. Bendena WG, Boudreau JR, Papanicolaou T, Maltby M, Tobe SS, Chin-Sang ID. 11.  2008. A Caenorhabditis elegans allatostatin/galanin-like receptor NPR-9 inhibits local search behavior in response to feeding cues. PNAS 105:41339–42 [Google Scholar]
  12. Birch PJ, Grossman CJ, Hayes AG. 12.  1988. Kynurenic acid antagonises responses to NMDA via an action at the strychnine-insensitive glycine receptor. Eur. J. Pharmacol. 154:185–87 [Google Scholar]
  13. Blacque OE, Reardon MJ, Li C, McCarthy J, Mahjoub MR. 13.  et al. 2004. Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev. 18:131630–42 [Google Scholar]
  14. Blumenthal T, Squire M, Kirtland S, Cane J, Donegan M. 14.  et al. 1984. Cloning of a yolk protein gene family from Caenorhabditis elegans. J. Mol. Biol. 174:11–18 [Google Scholar]
  15. Brockie PJ, Madsen DM, Zheng Y, Mellem J, Maricq AV. 15.  2001. Differential expression of glutamate receptor subunits in the nervous system of Caenorhabditis elegans and their regulation by the homeodomain protein UNC-42. J. Neurosci. 21:51510–22 [Google Scholar]
  16. Brooks KK, Liang B, Watts JL. 16.  2009. The influence of bacterial diet on fat storage in C. elegans. PLOS ONE 4:10e7545 [Google Scholar]
  17. Burks DJ, de Mora JF, Schubert M, Withers DJ, Myers MG. 17.  et al. 2000. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature 407:6802377–82 [Google Scholar]
  18. Byerly L, Cassada RC, Russell RL. 18.  1976. The life cycle of the nematode Caenorhabditis elegans: I. Wild-type growth and reproduction. Dev. Biol. 51:123–33 [Google Scholar]
  19. Campbell EM, Fares H. 19.  2010. Roles of CUP-5, the Caenorhabditis elegans orthologue of human TRPML1, in lysosome and gut granule biogenesis. BMC Cell Biol. 11:140 [Google Scholar]
  20. Chakrabarti P, English T, Shi J, Smas CM, Kandror KV. 20.  2010. Mammalian target of rapamycin complex 1 suppresses lipolysis, stimulates lipogenesis, and promotes fat storage. Diabetes 59:4775–81 [Google Scholar]
  21. Chen J, Caswell-Chen EP. 21.  2003. Why Caenorhabditis elegans adults sacrifice their bodies to progeny. Nematology 5:4641–45 [Google Scholar]
  22. Cheong MC, Lee H-J, Na K, Joo H-J, Avery L. 22.  et al. 2012. NSBP-1 mediates the effects of cholesterol on insulin/IGF-1 signaling in Caenorhabditis elegans. Cell. Mol. Life Sci. 70:91623–36 [Google Scholar]
  23. Choi S, Jonak EM, Simpson L, Patil V, Fernstrom JD. 23.  2002. Intermittent, chronic fenfluramine administration to rats repeatedly suppresses food intake despite substantial brain serotonin reductions. Brain Res. 928:1–230–39 [Google Scholar]
  24. Cohen M, Reale V, Olofsson B, Knights A, Evans P, de Bono M. 24.  2009. Coordinated regulation of foraging and metabolism in C. elegans by RFamide neuropeptide signaling. Cell Metab. 9:4375–85 [Google Scholar]
  25. Cunningham KA, Bouagnon AD, Barros AG, Lin L, Malard L. 25.  et al. 2014. Loss of a neural AMP-activated kinase mimics the effects of elevated serotonin on fat, movement, and hormonal secretions. PLOS Genet 10:6e1004394 [Google Scholar]
  26. Cunningham KA, Hua Z, Srinivasan S, Liu J, Lee BH. 26.  et al. 2012. AMP-activated kinase links serotonergic signaling to glutamate release for regulation of feeding behavior in C. elegans. Cell Metab. 16:1113–21 [Google Scholar]
  27. Davenport JR, Watts AJ, Roper VC, Croyle MJ, van Groen T. 27.  et al. 2007. Disruption of intraflagellar transport in adult mice leads to obesity and slow-onset cystic kidney disease. Curr. Biol. 17:181586–94 [Google Scholar]
  28. de Almeida Barros AG, Bridi JC, de Souza BR, de Castro Júnior C, de Lima Torres KC. 28.  et al. 2014. Dopamine signaling regulates fat content through β-oxidation in Caenorhabditis elegans. PLOS ONE 9:1e85874 [Google Scholar]
  29. Deblon N, Bourgoin L, Veyrat-Durebex C, Peyrou M, Vinciguerra M. 29.  et al. 2012. Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. Br. J. Pharmacol. 165:72325–40 [Google Scholar]
  30. DePina AS, Iser WB, Park S-S, Maudsley S, Wilson MA, Wolkow CA. 30.  2011. Regulation of Caenorhabditis elegans vitellogenesis by DAF-2/IIS through separable transcriptional and posttranscriptional mechanisms. BMC Physiol. 11:111 [Google Scholar]
  31. Djouder N, Tuerk RD, Suter M, Salvioni P, Thali RF. 31.  et al. 2010. PKA phosphorylates and inactivates AMPKα to promote efficient lipolysis. EMBO J. 29:2469–81 [Google Scholar]
  32. Edmonds JW, Prasain JK, Dorand D, Yang Y, Hoang HD. 32.  et al. 2010. Insulin/FOXO signaling regulates ovarian prostaglandins critical for reproduction. Dev. Cell 19:6858–71 [Google Scholar]
  33. Even P, Nicolaidis S. 33.  1986. Dextrofenfluramine increases energy cost of muscular effort. Pharmacol. Biochem. Behav. 24:3647–55 [Google Scholar]
  34. Fang-Yen C, Avery L, Samuel ADT. 34.  2009. Two size-selective mechanisms specifically trap bacteria-sized food particles in Caenorhabditis elegans. PNAS 106:4720093–96 [Google Scholar]
  35. Farooqi IS, O'Rahilly S. 35.  2005. Monogenic obesity in humans. Annu. Rev. Med. 56:1443–58 [Google Scholar]
  36. Fernstrom JD, Choi S. 36.  2008. The development of tolerance to drugs that suppress food intake. Pharmacol. Ther. 117:1105–22 [Google Scholar]
  37. Fitzpatrick PF. 37.  1999. Tetrahydropterin-dependent amino acid hydroxylases. Annu. Rev. Biochem. 68:1355–81 [Google Scholar]
  38. Flegal KM, Graubard BI, Williamson DF, Gail MH. 38.  2008. Cause-specific excess deaths associated with underweight, overweight and obesity. JAMA 298:172028–37 [Google Scholar]
  39. Folick A, Oakley HD, Yu Y, Armstrong EH, Kumari M. 39.  et al. 2015. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans. Science 347:621783–86 [Google Scholar]
  40. Forsythe E, Beales PL. 40.  2013. Bardet-Biedl syndrome. Eur. J. Hum. Genet. 21:18–13 [Google Scholar]
  41. Gallagher T, Kim J, Oldenbroek M, Kerr R, You Y-J. 41.  2013. ASI regulates satiety quiescence in C. elegans. J. Neurosci. 33:239716–24 [Google Scholar]
  42. Gems D, Sutton AJ, Sundermeyer ML, Albert PS, King KV. 42.  et al. 1998. Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 150:1129–55 [Google Scholar]
  43. Grant B, Hirsh D. 43.  1999. Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte. Mol. Biol. Cell 10:124311–26 [Google Scholar]
  44. Greer ER, Pérez CL, Van Gilst MR, Lee BH, Ashrafi K. 44.  2008. Neural and molecular dissection of a C. elegans sensory circuit that regulates fat and feeding. Cell Metab. 8:2118–31 [Google Scholar]
  45. Gunther CV, Georgi LL, Riddle DL. 45.  2000. A Caenorhabditis elegans type I TGFβ receptor can function in the absence of type II kinase to promote larval development. Development 127:153337–47 [Google Scholar]
  46. Hardie DG, Ross FA, Hawley SA. 46.  2012. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13:4251–62 [Google Scholar]
  47. Harms M, Seale P. 47.  2013. Brown and beige fat: development, function and therapeutic potential. Nat. Med. 19:101252–63 [Google Scholar]
  48. Harris G, Korchnak A, Summers P, Hapiak V, Law WJ. 48.  et al. 2011. Dissecting the serotonergic food signal stimulating sensory-mediated aversive behavior in C. elegans. PLOS ONE 6:7e21897 [Google Scholar]
  49. Hermann GJ, Scavarda E, Weis AM, Saxton DS, Thomas LL. 49.  et al. 2012. C. elegans BLOC-1 functions in trafficking to lysosome-related gut granules. PLOS ONE 7:8e43043 [Google Scholar]
  50. Herndon LA, Crocker C, Hall DH, Altun Z. 50.  2012. Pharynx atlas. Worm Atlas http://www.wormatlas.org/pharynxatlas/pharynxatlas.html
  51. Hill AJ, Mansfield R, Lopez JMNG, Raizen DM, Van Buskirk C. 51.  2014. Cellular stress induces a protective sleep-like state in C. elegans. Curr. Biol. 24:202399–405 [Google Scholar]
  52. Hills T, Brockie PJ, Maricq AV. 52.  2004. Dopamine and glutamate control area-restricted search behavior in Caenorhabditis elegans. J. Neurosci. 24:51217–25 [Google Scholar]
  53. Hobson RJ, Hapiak VM, Xiao H, Buehrer KL, Komuniecki PR, Komuniecki RW. 53.  2006. SER-7, a Caenorhabditis elegans 5-HT7-like receptor, is essential for the 5-HT stimulation of pharyngeal pumping and egg laying. Genetics 172:1159–69 [Google Scholar]
  54. Horikawa M, Sakamoto K. 54.  2010. Polyunsaturated fatty acids are involved in regulatory mechanism of fatty acid homeostasis via daf-2/insulin signaling in Caenorhabditis elegans. Mol. Cell. Endocrinol. 323:2183–92 [Google Scholar]
  55. Horvitz HR, Chalfie M, Trent C, Sulston JE, Evans PD. 55.  1982. Serotonin and octopamine in the nematode Caenorhabditis elegans. Science 216:45491012–14 [Google Scholar]
  56. Janssen T, Meelkop E, Lindemans M, Verstraelen K, Husson SJ. 56.  et al. 2008. Discovery of a cholecystokinin-gastrin–like signaling system in nematodes. Endocrinology 149:62826–39 [Google Scholar]
  57. Jia K, Chen D, Riddle DL. 57.  2004. The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131:163897–906 [Google Scholar]
  58. Kang C, Avery L. 58.  2009. Systemic regulation of autophagy in Caenorhabditis elegans. Autophagy 5:4565–66 [Google Scholar]
  59. Kang C, Avery L. 59.  2009. Systemic regulation of starvation response in Caenorhabditis elegans. Genes Dev. 23:112–17 [Google Scholar]
  60. Kang C, You Y, Avery L. 60.  2007. Dual roles of autophagy in the survival of Caenorhabditis elegans during starvation. Genes Dev. 21:172161–71 [Google Scholar]
  61. Keane J, Avery L. 61.  2003. Mechanosensory inputs influence Caenorhabditis elegans pharyngeal activity via ivermectin sensitivity genes. Genetics 164:1153–62 [Google Scholar]
  62. Kimble J, Sharrock WJ. 62.  1983. Tissue-specific synthesis of yolk proteins in Caenorhabditis elegans. Dev. Biol. 96:1189–96 [Google Scholar]
  63. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G. 63.  1997. daf-2, an insulin receptor–like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:5328942–46 [Google Scholar]
  64. Klemm RW, Norton JP, Cole RA, Li CS, Park SH. 64.  et al. 2013. A conserved role for atlastin GTPases in regulating lipid droplet size. Cell Rep. 3:51465–75 [Google Scholar]
  65. Kopelman PG. 65.  2000. Obesity as a medical problem. Nature 404:6778635–43 [Google Scholar]
  66. Kubiak TM, Larsen MJ, Bowman JW, Geary TG, Lowery DE. 66.  2008. FMRFamide-like peptides encoded on the flp-18 precursor gene activate two isoforms of the orphan Caenorhabditis elegans G-protein–coupled receptor Y58G8A.4 heterologously expressed in mammalian cells. Pept. Sci. 90:3339–48 [Google Scholar]
  67. Lam DD, Heisler LK. 67.  2007. Serotonin and energy balance: molecular mechanisms and implications for type 2 diabetes. Expert Rev. Mol. Med. 9:51–24 [Google Scholar]
  68. Lam TKT, Schwartz GJ, Rossetti L. 68.  2005. Hypothalamic sensing of fatty acids. Nat. Neurosci. 8:5579–84 [Google Scholar]
  69. Lapierre LR, Gelino S, Meléndez A, Hansen M. 69.  2011. Autophagy and lipid metabolism coordinately modulate life span in germline-less C. elegans. Curr. Biol. 21:181507–14 [Google Scholar]
  70. Le Feuvre RA, Aisenthal L, Rothwell NJ. 70.  1991. Involvement of corticotrophin releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) and related compounds. Brain Res. 555:2245–50 [Google Scholar]
  71. Lee BH, Liu J, Wong D, Srinivasan S, Ashrafi K. 71.  2011. Hyperactive neuroendocrine secretion causes size, feeding, and metabolic defects of C. elegans Bardet-Biedl syndrome mutants. PLOS Biol. 9:12e1001219 [Google Scholar]
  72. Lee RYN, Sawin ER, Chalfie M, Horvitz HR, Avery L. 72.  1999. EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in Caenorhabditis elegans. J. Neurosci. 19:1159–67 [Google Scholar]
  73. Lemieux GA, Ashrafi K. 73.  2015. Insights and challenges in using C. elegans for investigation of fat metabolism. Crit. Rev. Biochem. Mol. Biol. 50:169–84 [Google Scholar]
  74. Lemieux GA, Cunningham KA, Lin L, Mayer F, Werb Z, Ashrafi K. 74.  2015. Kynurenic acid is a nutritional cue that enables behavioral plasticity. Cell 160:1–2119–31 [Google Scholar]
  75. Lemieux GA, Keiser MJ, Sassano MF, Laggner C, Mayer F. 75.  et al. 2013. In silico molecular comparisons of C. elegans and mammalian pharmacology identify distinct targets that regulate feeding. PLOS Biol. 11:11e1001712 [Google Scholar]
  76. Lewis GF, Carpentier A, Adeli K, Giacca A. 76.  2002. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr. Rev. 23:2201–29 [Google Scholar]
  77. Li Z, Li Y, Yi Y, Huang W, Yang S. 77.  et al. 2012. Dissecting a central flip-flop circuit that integrates contradictory sensory cues in C. elegans feeding regulation. Nat. Commun. 3:776 [Google Scholar]
  78. Lin X, Taguchi A, Park S, Kushner JA, Li F. 78.  et al. 2004. Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes. J. Clin. Investig. 114:7908–16 [Google Scholar]
  79. Lindblom TH, Dodd AK. 79.  2006. Xenobiotic detoxification in the nematode Caenorhabditis elegans. J. Exp. Zool. Part A 305A:9720–30 [Google Scholar]
  80. Ludewig AH, Kober-Eisermann C, Weitzel C, Bethke A, Neubert K. 80.  et al. 2004. A novel nuclear receptor/coregulator complex controls C. elegans lipid metabolism, larval development, and aging. Genes Dev. 18:172120–33 [Google Scholar]
  81. Mak HY, Nelson LS, Basson M, Johnson CD, Ruvkun G. 81.  2006. Polygenic control of Caenorhabditis elegans fat storage. Nat. Genet. 38:3363–68 [Google Scholar]
  82. McCormick M, Chen K, Ramaswamy P, Kenyon C. 82.  2012. New genes that extend Caenorhabditis elegans' lifespan in response to reproductive signals. Aging Cell 11:2192–202 [Google Scholar]
  83. McGhee J. 83.  2007. The C. elegans intestine. WormBook The C. elegans Research Community. http://www.wormbook.org/chapters/www_intestine/intestine.html
  84. Michaud JL, Boucher F, Melnyk A, Gauthier F, Goshu E. 84.  et al. 2001. Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus. Hum. Mol. Genet. 10:141465–73 [Google Scholar]
  85. Michaud JL, Rosenquist T, May NR, Fan C-M. 85.  1998. Development of neuroendocrine lineages requires the bHLH-PAS transcription factor SIM1. Genes Dev. 12:203264–75 [Google Scholar]
  86. Mukhopadhyay A, Deplancke B, Walhout AJM, Tissenbaum HA. 86.  2005. C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab. 2:135–42 [Google Scholar]
  87. Mukhopadhyay S, Jackson PK. 87.  2011. The tubby family proteins. Genome Biol. 12:6225 [Google Scholar]
  88. Murphy CT, Hu PJ. 88.  2013. Insulin/insulin-like growth factor signaling in C. elegans. WormBook The C. elegans Research Community. http://www.wormbook.org/chapters/www_insulingrowthsignal/insulingrowthsignal.html
  89. Murphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS. 89.  et al. 2003. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424:6946277–83 [Google Scholar]
  90. Nachury MV, Loktev AV, Zhang Q, Westlake CJ, Peränen J. 90.  et al. 2007. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 129:61201–13 [Google Scholar]
  91. Nagle CA, Klett EL, Coleman RA. 91.  2008. Hepatic triacylglycerol accumulation and insulin resistance. J. Lipid Res. 50:Suppl.S74–79 [Google Scholar]
  92. Nelson MD, Lee KH, Churgin MA, Hill AJ, Van Buskirk C. 92.  et al. 2014. FMRFamide-like FLP-13 neuropeptides promote quiescence following heat stress in Caenorhabditis elegans. Curr. Biol. 24:202406–10 [Google Scholar]
  93. Noble T, Stieglitz J, Srinivasan S. 93.  2013. An integrated serotonin and octopamine neuronal circuit directs the release of an endocrine signal to control C. elegans body fat. Cell Metab. 18:5672–84 [Google Scholar]
  94. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L. 94.  et al. 1997. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389:6654994–99 [Google Scholar]
  95. O'Rourke EJ, Soukas AA, Carr CE, Ruvkun G. 95.  2009. C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. Cell Metab. 10:5430–35 [Google Scholar]
  96. Ou G, Koga M, Blacque OE, Murayama T, Ohshima Y. 96.  et al. 2007. Sensory ciliogenesis in Caenorhabditis elegans: assignment of IFT components into distinct modules based on transport and phenotypic profiles. Mol. Biol. Cell 18:51554–69 [Google Scholar]
  97. Packham R, Walker RJ, Holden-Dye L. 97.  2010. The effect of a selective octopamine antagonist, epinastine, on pharyngeal pumping in Caenorhabditis elegans. Invertebr. Neurosci. 10:147–52 [Google Scholar]
  98. Patterson GI, Koweek A, Wong A, Liu Y, Ruvkun G. 98.  1997. The DAF-3 Smad protein antagonizes TGF-β–related receptor signaling in the Caenorhabditis elegans dauer pathway. Genes Dev. 11:202679–90 [Google Scholar]
  99. Pereira MJ, Palming J, Rizell M, Aureliano M, Carvalho E. 99.  et al. 2013. The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue. Mol. Cell. Endocrinol. 365:2260–69 [Google Scholar]
  100. Perez CL, Van Gilst MR. 100.  2008. A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans. Cell Metab. 8:3266–74 [Google Scholar]
  101. Polak P, Cybulski N, Feige JN, Auwerx J, Rüegg MA, Hall MN. 101.  2008. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab. 8:5399–410 [Google Scholar]
  102. Raizen DM, Avery L. 102.  1994. Electrical activity and behavior in the pharynx of Caenorhabditis elegans. Neuron 12:3483–95 [Google Scholar]
  103. Raizen DM, Cullison KM, Pack AI, Sundaram MV. 103.  2006. A novel gain-of-function mutant of the cyclic GMP–dependent protein kinase egl-4 affects multiple physiological processes in Caenorhabditis elegans. Genetics 173:1177–87 [Google Scholar]
  104. Raizen DM, Lee RY, Avery L. 104.  1995. Interacting genes required for pharyngeal excitation by motor neuron MC in Caenorhabditis elegans. Genetics 141:41365–82 [Google Scholar]
  105. Raizen DM, Zimmerman JE, Maycock MH, Ta UD, You Y. 105.  et al. 2008. Lethargus is a Caenorhabditis elegans sleep-like state. Nature 451:7178569–72 [Google Scholar]
  106. Ratnappan R, Amrit FRG, Chen S-W, Gill H, Holden K. 106.  et al. 2014. Germline signals deploy NHR-49 to modulate fatty-acid β-oxidation and desaturation in somatic tissues of C. elegans. PLOS Genet. 10:12e1004829 [Google Scholar]
  107. Reina A, Subramaniam AB, Laromaine A, Samuel ADT, Whitesides GM. 107.  2013. Shifts in the distribution of mass densities is a signature of caloric restriction in Caenorhabditis elegans. PLOS ONE 8:7e69651 [Google Scholar]
  108. Ren P, Lim C-S, Johnsen R, Albert PS, Pilgrim D, Riddle DL. 108.  1996. Control of C. elegans larval development by neuronal expression of a TGF-β homolog. Science 274:52911389–91 [Google Scholar]
  109. Rex E, Komuniecki RW. 109.  2002. Characterization of a tyramine receptor from Caenorhabditis elegans. J. Neurochem. 82:61352–59 [Google Scholar]
  110. Rex E, Molitor SC, Hapiak V, Xiao H, Henderson M, Komuniecki R. 110.  2004. Tyramine receptor (SER-2) isoforms are involved in the regulation of pharyngeal pumping and foraging behavior in Caenorhabditis elegans. J. Neurochem. 91:51104–15 [Google Scholar]
  111. Riddle DL, Swanson MM, Albert PS. 111.  1981. Interacting genes in nematode dauer larva formation. Nature 290:5808668–71 [Google Scholar]
  112. Roeder T. 112.  2005. Tyramine and octopamine: ruling behavior and metabolism. Annu. Rev. Entomol. 50:447–77 [Google Scholar]
  113. Rothwell NJ, Stock MJ. 113.  1987. Effect of diet and fenfluramine on thermogenesis in the rat: possible involvement of serotonergic mechanisms. Int. J. Obes. 11:4319–24 [Google Scholar]
  114. Rui L. 114.  2013. Brain regulation of energy balance and body weight. Rev. Endocr. Metab. Disord. 14:4387–407 [Google Scholar]
  115. Savage-Dunn C. 115.  2005. TGF-β signaling. WormBook The C. elegans Research Community. http://www.wormbook.org/chapters/www_tgfbsignal/tgfbsignal.html
  116. Sawin ER, Ranganathan R, Horvitz HR. 116.  2000. C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron 26:3619–31 [Google Scholar]
  117. Schackwitz WS, Inoue T, Thomas JH. 117.  1996. Chemosensory neurons function in parallel to mediate a pheromone response in C. elegans. Neuron 17:4719–28 [Google Scholar]
  118. Schafer W. 118.  2005. Egg-laying. WormBook The C. elegans Research Community. http://www.wormbook.org/chapters/www_egglaying/egglaying.html
  119. Schroeder LK, Kremer S, Kramer MJ, Currie E, Kwan E. 119.  et al. 2007. Function of the Caenorhabditis elegans ABC transporter PGP-2 in the biogenesis of a lysosome-related fat storage organelle. Mol. Biol. Cell 18:3995–1008 [Google Scholar]
  120. Schwarcz R, Bruno JP, Muchowski PJ, Wu H-Q. 120.  2012. Kynurenines in the mammalian brain: when physiology meets pathology. Nat. Rev. Neurosci. 13:7465–77 [Google Scholar]
  121. Seidel HS, Kimble J. 121.  2011. The oogenic germline starvation response in C. elegans. PLOS ONE 6:12e28074 [Google Scholar]
  122. Seo S, Guo D-F, Bugge K, Morgan DA, Rahmouni K, Sheffield VC. 122.  2009. Requirement of Bardet-Biedl syndrome proteins for leptin receptor signaling. Hum. Mol. Genet. 18:71323–31 [Google Scholar]
  123. Shtonda BB, Avery L. 123.  2006. Dietary choice behavior in Caenorhabditis elegans. J. Exp. Biol. 209:189–102 [Google Scholar]
  124. Song B, Avery L. 124.  2012. Serotonin activates overall feeding by activating two separate neural pathways in Caenorhabditis elegans. J. Neurosci. 32:61920–31 [Google Scholar]
  125. Song B-M, Faumont S, Lockery S, Avery L. 125.  2013. Recognition of familiar food activates feeding via an endocrine serotonin signal in Caenorhabditis elegans. eLife 2:0e00329 [Google Scholar]
  126. Soukas AA, Carr CE, Ruvkun G. 126.  2013. Genetic regulation of Caenorhabditis elegans lysosome related organelle function. PLOS Genet. 9:10e1003908 [Google Scholar]
  127. Soukas AA, Kane EA, Carr CE, Melo JA, Ruvkun G. 127.  2009. Rictor/TORC2 regulates fat metabolism, feeding, growth, and life span in Caenorhabditis elegans. Genes Dev. 23:4496–511 [Google Scholar]
  128. Srinivasan S. 128.  2015. Regulation of body fat in Caenorhabditis elegans. Annu. Rev. Physiol. 77:1161–78 [Google Scholar]
  129. Srinivasan S, Sadegh L, Elle IC, Christensen AGL, Faergeman NJ, Ashrafi K. 129.  2008. Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms. Cell Metab. 7:6533–44 [Google Scholar]
  130. Starich TA, Lee RY, Panzarella C, Avery L, Shaw JE. 130.  1996. eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling. J. Cell Biol. 134:2537–48 [Google Scholar]
  131. Sze JY, Victor M, Loer C, Shi Y, Ruvkun G. 131.  2000. Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant. Nature 403:6769560–64 [Google Scholar]
  132. Taubes G. 132.  2012. Treat obesity as physiology, not physics. Nature 492:7428155 [Google Scholar]
  133. Taubes G. 133.  2013. The science of obesity: What do we really know about what makes us fat?. BMJ 346:f1050 [Google Scholar]
  134. Trojanowski NF, Padovan-Merhar O, Raizen DM, Fang-Yen C. 134.  2014. Neural and genetic degeneracy underlies Caenorhabditis elegans feeding behavior. J. Neurophysiol. 112:4951–61 [Google Scholar]
  135. Vickers SP, Benwell KR, Porter RH, Bickerdike MJ, Kennett GA, Dourish CT. 135.  2000. Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity in rats. Br. J. Pharmacol. 130:61305–14 [Google Scholar]
  136. Voigt J-P, Fink H. 136.  2015. Serotonin controlling feeding and satiety. Behav. Brain Res. 277:14–31 [Google Scholar]
  137. Volkow ND, Wang G-J, Baler RD. 137.  2011. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn. Sci. 15:137–46 [Google Scholar]
  138. Wang MC, O'Rourke EJ, Ruvkun G. 138.  2008. Fat metabolism links germline stem cells and longevity in C. elegans. Science 322:5903957–60 [Google Scholar]
  139. Wei Q, Zhang Y, Li Y, Zhang Q, Ling K, Hu J. 139.  2012. The BBSome controls IFT assembly and turnaround in cilia. Nat. Cell Biol. 14:9950–57 [Google Scholar]
  140. Wolkow CA, Kimura KD, Lee M-S, Ruvkun G. 140.  2000. Regulation of C. elegans life-span by insulinlike signaling in the nervous system. Science 290:5489147–50 [Google Scholar]
  141. Yen K, Le TT, Bansal A, Narasimhan SD, Cheng J-X, Tissenbaum HA. 141.  2010. A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLOS ONE 5:9e12810 [Google Scholar]
  142. You Y, Kim J, Cobb M, Avery L. 142.  2006. Starvation activates map kinase through the muscarinic acetylcholine pathway in Caenorhabditis elegans pharynx. Cell Metab. 3:4237–45 [Google Scholar]
  143. You Y, Kim J, Raizen DM, Avery L. 143.  2008. Insulin, cGMP, and TGF-β signals regulate food intake and quiescence in C. elegans: a model for satiety. Cell Metab. 7:3249–57 [Google Scholar]
  144. Zaghloul NA, Katsanis N. 144.  2009. Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy. J. Clin. Investig. 119:3428–37 [Google Scholar]
  145. Zhang P, Na H, Liu Z, Zhang S, Xue P. 145.  et al. 2012. Proteomic study and marker protein identification of Caenorhabditis elegans lipid droplets. Mol. Cell. Proteomics 11:8317–28 [Google Scholar]
  146. Zhang SO, Trimble R, Guo F, Mak HY. 146.  2010. Lipid droplets as ubiquitous fat storage organelles in C. elegans. BMC Cell Biol. 11:96 [Google Scholar]
  147. Zhou Q-Y, Palmiter RD. 147.  1995. Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 83:71197–209 [Google Scholar]
/content/journals/10.1146/annurev-genet-120213-092244
Loading
Neural Regulatory Pathways of Feeding and Fat in Caenorhabditis elegans
Annual Review of Genetics 49, 413 (2015); https://doi.org/10.1146/annurev-genet-120213-092244
/content/journals/10.1146/annurev-genet-120213-092244
/content/journals/10.1146/annurev-genet-120213-092244
Loading

Data & Media loading...

Supplemental Material

Supplementary Data

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error