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Obesity-Linked Homologues and Establish Meal Frequency in


The size of individual meals and feeding frequency are important for homeostatic control. Due to the complex neuroendocrine system regulating human food intake it is difficult to uncover the mechanisms underlying eating disorders. The genetically tractable model system Drosophila melanogaster has a comparatively simple brain; yet, similar to humans, its eating behavior can adapt to respond to nutritional needs. Our study describes how the obesity-linked homologues TfAP-2 (human TFAP2B) and Tiwaz (human KCTD15) regulate a unique feedback system involving noradrenalin-like octopamine and the CCK homolog Dsk, that exert positive and negative effects on Drosophila feeding behavior. Our findings provide insight into how two conserved obesity-linked genes regulate feeding behavior in order to maintain metabolic balance.


Vyšlo v časopise: Obesity-Linked Homologues and Establish Meal Frequency in. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004499
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004499

Souhrn

The size of individual meals and feeding frequency are important for homeostatic control. Due to the complex neuroendocrine system regulating human food intake it is difficult to uncover the mechanisms underlying eating disorders. The genetically tractable model system Drosophila melanogaster has a comparatively simple brain; yet, similar to humans, its eating behavior can adapt to respond to nutritional needs. Our study describes how the obesity-linked homologues TfAP-2 (human TFAP2B) and Tiwaz (human KCTD15) regulate a unique feedback system involving noradrenalin-like octopamine and the CCK homolog Dsk, that exert positive and negative effects on Drosophila feeding behavior. Our findings provide insight into how two conserved obesity-linked genes regulate feeding behavior in order to maintain metabolic balance.


Zdroje

1. ZhaoJ, BradfieldJP, LiM, WangK, ZhangH, et al. (2009) The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Obesity 17: 2254–2257.

2. WillerCJ, SpeliotesEK, LoosRJ, LiS, LindgrenCM, et al. (2009) Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41: 25–34.

3. RenstromF, PayneF, NordstromA, BritoEC, RolandssonO, et al. (2009) Replication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden. Hum Mol Genet 18: 1489–1496.

4. BauerF, ElbersCC, AdanRA, LoosRJ, Onland-MoretNC, et al. (2009) Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr 90: 951–959.

5. MongeI, KrishnamurthyR, SimsD, HirtF, SpenglerM, et al. (2001) Drosophila transcription factor AP-2 in proboscis, leg and brain central complex development. Development 128: 1239–1252.

6. WilliamsMJ, GoergenP, RajendranJ, KlockarsA, KasagiannisA, et al. (2014) Regulation of aggression by obesity-linked genes TfAP-2 and Twz through octopamine signaling in Drosophila. Genetics 196: 349–362.

7. WilliamsM, AlménM, FredrikssonR, SchiöthH (2012) What model organisms and interactomics can reveal about the genetics of human obesity. Cell Mol Life Sci 69: 3819–3834.

8. ZarelliVE, DawidIB (2013) Inhibition of neural crest formation by Kctd15 involves regulation of transcription factor AP-2. Proc Natl Acad Sci U S A 110: 2870–2875.

9. GiotL, BaderJS, BrouwerC, ChaudhuriA, KuangB, et al. (2003) A protein interaction map of Drosophila melanogaster. Science 302: 1727–1736.

10. WankS, PisegnaJ, de WeerthA (1994) Cholecystokinin receptor family. Molecular cloning, structure, and functional expression in rat, guinea pig, and human. Ann N Y Acad Sci 713: 49–66.

11. MönnikesH, LauerG, ArnoldR (1997) Peripheral administration of cholecystokinin activates c-fos expression in the locus coeruleus/subcoeruleus nucleus, dorsal vagal complex and paraventricular nucleus via capsaicin-sensitive vagal afferents and CCK-A receptors in the rat. Brain Res 770: 277–288.

12. SöderbergJ, CarlssonM, NässelD (2012) Insulin-Producing Cells in the Drosophila Brain also Express Satiety-Inducing Cholecystokinin-Like Peptide, Drosulfakinin. Front Endocrinol 3: 109.

13. ZhangT, BranchA, ShenP (2013) Octopamine-mediated circuit mechanism underlying controlled appetite for palatable food in Drosophila. Proc Natl Acad Sci U S A 110: 15431–15436.

14. Al-AnziB, ArmandE, NagameiP, OlszewskiM, SapinV, et al. (2010) The Leucokinin Pathway and Its Neurons Regulate Meal Size in Drosophila. Curr Biol 20: 969–978.

15. JaWW, CarvalhoGB, MakEM, de la RosaNN, FangAY, et al. (2007) Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci U S A 104: 8253–8256.

16. LuanH, LemonWC, PeabodyNC, PohlJB, ZelenskyPK, et al. (2006) Functional dissection of a neuronal network required for cuticle tanning and wing expansion in Drosophila. J Neurosci 26: 573–584.

17. PonceletM, ArnoneM, HeaulmeM, GonalonsN, GueudetC, et al. (1993) Neurobehavioral effects of SR 27897, a selective cholecystokinin type A (CCK-A) receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol 348: 102–107.

18. GullyD, FrehelD, MarcyC, SpinazzeA, LespyL, et al. (1993) Peripheral biological activity of SR 27897: a new potent non-peptide antagonist of CCKA receptors. Eur J Pharmacol 232: 13–19.

19. ChenX, PetersonJ, NachmanR, GanetzkyB (2012) Drosulfakinin activates CCKLR-17D1 and promotes larval locomotion and escape response in Drosophila. Fly 6: 290–297.

20. ChenX, GanetzkyB (2012) A neuropeptide signaling pathway regulates synaptic growth in Drosophila. J Cell Biol 196: 529–543.

21. GoodmanA (2008) Neurobiology of addiction. An integrative review. Biochem Pharmacol 75: 266–322.

22. NarayananN, GuarnieriD, DiLeoneR (2010) Metabolic hormones, dopamine circuits, and feeding. Frontier Neuroendocrinol 31: 104–112.

23. GuJ, PolakJ, TapiaF, MarangosP, PearseA (1981) Neuron-specific enolase in the Merkel cells of mammalian skin. The use of specific antibody as a simple and reliable histologic marker. Am J Pathol 104: 63–68.

24. ReevesS, HelmanL, AllisonA, IsraelM (1989) Molecular cloning and primary structure of human glial fibrillary acidic protein. Proc Natl Acad Sci U S A 86: 5178–5182.

25. SöderbergO, GullbergM, JarviusM, RidderstråleK, LeuchowiusK-J, et al. (2006) Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat Methods 3: 995–1995.

26. ElorantaJJ, HurstHC (2002) Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo. J Biol Chem 277: 30798–30804.

27. CaoJ, NiJ, MaW, ShiuV, MillaLA, et al. (2014) Insight into Insulin Secretion from Transcriptome and Genetic Analysis of Insulin-Producing Cells of Drosophila. Genetics 197: 175–192.

28. MeyerAH, LanghansW, ScharrerE (1989) Vasopressin reduces food intake in goats. Q J Exp Physiol 74: 465–473.

29. MortonGJ, ThatcherBS, ReidelbergerRD, OgimotoK, Wolden-HansonT, et al. (2012) Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. Am J Physiol Endocrinol Metab 302: E134–144.

30. BlevinsJE, HoJM (2013) Role of oxytocin signaling in the regulation of body weight. Rev Endocr Metab Disord 14: 311–329.

31. WuQ, ZhaoZ, ShenP (2005) Regulation of aversion to noxious food by Drosophila neuropeptide Y- and insulin-like systems. Nat Neurosci 8: 1350–1355.

32. WangY, PuY, ShenP (2013) Neuropeptide-gated perception of appetitive olfactory inputs in Drosophila larvae. Cell Rep 3: 820–830.

33. ShimazuT, NomaM, SaitoM (1986) Chronic infusion of norepinephrine into the ventromedial hypothalamus induces obesity in rats. Brain Res 369: 215–223.

34. CincottaAH, LuoS, ZhangY, LiangY, BinaKG, et al. (2000) Chronic infusion of norepinephrine into the VMH of normal rats induces the obese glucose-intolerant state. Am J Physiol Regul Integr Comp Physiol 278: R435–444.

35. WangCX, YangH, PerrottCJ, GietzenDW (1999) Inhibition of norepinephrine release in the rat ventromedial hypothalamic nucleus in essential amino acid deficiency. Neurosci Lett 259: 53–55.

36. BerghC, SjöstedtS, HellersG, ZandianM, SöderstenP (2003) Meal size, satiety and cholecystokinin in gastrectomized humans. Physiol Behav 78: 143–147.

37. RitterR, CovasaM, MatsonC (1999) Cholecystokinin: proofs and prospects for involvement in control of food intake and body weight. Neuropeptides 33: 387–399.

38. Burton-FreemanB, GietzenD, SchneemanB (1999) Cholecystokinin and serotonin receptors in the regulation of fat-induced satiety in rats. Am J Physiol 276: 34.

39. MoranT, KatzL, Plata-SalamanC, SchwartzG (1998) Disordered food intake and obesity in rats lacking cholecystokinin A receptors. Am J Physiol 274: 25.

40. VoigtJ, FinkH, MarsdenC (1995) Evidence for the involvement of the 5-HT1A receptor in CCK induced satiety in rats. Naunyn Schmiedebergs Arch Pharmacol 351: 217–220.

41. GreenbergD (1993) Is cholecystokinin the peptide that controls fat intake? Nutr Rev 51: 181–183.

42. MyersRD, SwartzwelderHS, PeinadoJM, LeeTF, HeplerJR, et al. (1986) CCK and other peptides modulate hypothalamic norepinephrine release in the rat: dependence on hunger or satiety. Brain Res Bull 17: 583–597.

43. BayonY, TrinidadAG, de la PuertaML, Del Carmen RodriguezM, BogetzJ, et al. (2008) KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases. FEBS J 275: 3900–3910.

44. CorrealeS, PironeL, Di MarcotullioL, De SmaeleE, GrecoA, et al. (2011) Molecular organization of the cullin E3 ligase adaptor KCTD11. Biochimie 93: 715–724.

45. WangS, TulinaN, CarlinDL, RulifsonEJ (2007) The origin of islet-like cells in Drosophila identifies parallels to the vertebrate endocrine axis. Proc Natl Acad Sci U S A 104: 19873–19878.

46. DudaiY (1982) High-affinity octopamine receptors revealed in Drosophila by binding or [3H]octopamine. Neurosci Lett 28: 163–170.

47. ChomczynskiP, SacchiN (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159.

48. LindblomJ, JohanssonA, HolmgrenA, GrandinE, NedergårdC, et al. (2006) Increased mRNA levels of tyrosine hydroxylase and dopamine transporter in the VTA of male rats after chronic food restriction. Eur J Neurosci 23: 180–186.

49. RamakersC, RuijterJ, DeprezR, MoormanA (2003) Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett 339: 62–66.

50. VandesompeleJ, De PreterK, PattynF, PoppeB, Van RoyN, et al. (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3: RESEARCH0034.

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Genetika Reprodukčná medicína

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PLOS Genetics


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