Anorexigenic Peptide in the Control of Food Intake: Nesfatin-1

Abstract

The sensations of hunger and fullness during the regulation of the energy homeostasis are regulated through a complex process. This process consists of many anorexigenic factors’ combination that inhibit food intake as well as appetite-stimulating (orexigenic) factor. In the last decade, many neuropeptides have been identified that alter food intake and energy expenditure. Nesfatin-1 peptide derived from the NEFA/nucleobindin2 precursor have emerged as a hypothalamic neuropeptide suppressing the food intake. Nesfatin-1 was first identified in the hypothalamus and solitary tract neurons (NTS). The expression profiles in the brain areas of NUCB2/Nesfatin-1 neurons, their effect on physiological mechanisms, and their co-localizations with other neuropeptides are topics still studied. In the studies carried out in our laboratory, we also have identified the location of nesfatin-1 in the hypothalamic nuclei. In this review, in addition to the localization of nesfatin neurons, recent literature knowledge on the physiology and functions of nesfatin-1 peptide are included.

Keywords

• NUCB2,Nesfatin-1,Hypothalamic nuclei,Feeding

Besin Alımının Kontrolündeki Anoreksijenik Peptit: Nesfatin-1

Abstract

Enerji homeostazının regülasyonunda yer alan açlık ve tokluğun fizyolojik mekanizması, besin alımını uyarıcı oreksijenik faktörlerle inhibe edici anoreksijenik çoğu faktörün birleşiminden oluşan kompleks bir süreçle düzenlenir. Son on yılda, besin alımı ve enerji harcanmasını değiştiren pek çok nöropeptit tanımlanmıştır. NEFA/Nükleobindin2 prekürsöründen türeyen nesfatin-1 peptiti besin alımını baskılayan hipotalamik nöropeptit olarak karşımıza çıkar. Nesfatin-1 ilk defa hipotalamus ve soliter traktusta (NTS) yerleşik nöronlarda belirlenmiştir. Nesfatin-1 nöronlarının beyin alanlarındaki ekspresyon profilleri, fizyolojik mekanizmalar üzerindeki etkisi ve de diğer nöropeptitlerle olan kolokalizasyonları hala üzerinde çalışılmakta olan konulardandır. Laboratuvarımızda yürütülen çalışmalarda bizde nesfatin-1’in hipotalamik çekirdeklerdeki lokalizasyonunu belirledik. Bu derleme makalede, nesfatin nöronlarının lokalizasyonunun yanı sıra, nesfatin-1 peptitinin fizyolojisi ile fonksiyonlarına ait, bugüne kadar literatürde yer alan bilgilere yer verilmiştir.

Keywords

• NUCB2,Nesfatin-1,Hipotalamik çekirdekler,Beslenme

References

1. Oh-I S, Shimizu H, Satoh T. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 2006;443:709-12.
2. Stengel A, Tache Y. Nesfatin-1-Role as possible new potent regulator of food intake. Regulatory Peptides 2010;163:18-23.
3. Stengel A, Goebel M, Wang L, Tache Y. Ghrelin, desacyl ghrelin and nesfatin-1 in gastric X/A-like cells: role as regulators of food intake and body weight. Peptides 2010;31:357-69.
4. Shimizu H, Ohsaki A, Oh-I S, Okada S, Mori M. A new anorexigenic protein, nesfatin-1. Peptides 2009;30:995-98.
5. Palasz A, Krzystanek M, Worthington J, et al. Nesfatin-1, a unique regulatory neuropeptide of the brain. Neuropeptides 2012;46:105-12.
6. Stengel A. Nesfatin-1-More than a food intake regulatory peptide. Peptides 2015;72:175-83.
7. Crespo CS, Cachero AP, Jimenez LP, Barrios V, Ferreiro EA. Peptides and food intake. Front Endocrinol (Lausanne) 2014;5:58-62.
8. Shimizu H, Oh-I S, Hashimoto K, et al. Peripheral administration of nesfatin-1 reduces food intake in mice: the leptin-independent mechanism. Endocrinology. 2009;150:662-71.

9. Garcia-Galiano D, Navarro VM, Gaytan F, Tena-Sempere M. Expanding roles of NUCB2/nesfatin-1 in neuroendocrine regulation. J Mol Endocrinol 2010;45:281-90.
10. Ishida E, Hashimoto K, Shimizu H, et al. Nesfatin-1 induces the phosphorylation levels of cAMP response element-binding protein for intracellular signaling in a neural cell line. PLoS One 2012;7:e50918.
11. Prinz P, Goebel-Stengel M, Teuffel P, et al. Peripheral and central localization of the nesfatin-1 receptor using autoradiography in rats. Biochem Biophys Res Commun 2016;470:521-27.
12. Dore R, Levata L, Lehnert H, Schulz C. Nesfatin-1: functions and physiology of a novel regulatory peptide. J Endocrinol 2017;232:R45-65.
13. Nakata M, Manaka K, Yamamoto S, Mori M, Yada T. Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca(2+) influx through L-type channels in mouse islet beta-cells. Endocr J 2011;58:305-13.
14. Brailoiu GC, Dun SL, Brailoiu E, et al. Nesfatin-1: distribution and interaction with a G protein-coupled receptor in the rat brain. Endocrinology 2007;148:5088-94.
15. Brailoiu GC, Deliu E, Tica AA, et al. Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguus and elicits bradycardia in conscious rats. J Neurochem 2013;126:739-48.
16. Iwasaki Y, Nakabayashi H, Kakei M, et al. Nesfatin-1 evokes Ca2+ signaling in isolated vagal afferent neurons via Ca2+ influx through N-type channels. Biochem Biophys Res Commun 2009;390:958-62.
17. Maejima Y, Sedbazar U, Suyama S, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causesanorexia through a leptin-independent melanocortin pathway. Cell Metab 2009;10:355-65.
18. Foo KS, Brismar H, Broberger C. Distribution and neuropeptide coexistence of nucleobindin-2 mRNA/nesfatin-like immunoreactivity in the rat CNS. Neuroscience 2008;156: 563-79.
19. Fort P, Salvert D, Hanriot L, et al. The satiety molecule nesfatin-1 is co-expressed with melanin concentrating hormone in tuberal hypothalamic neurons of the rat. Neuroscience 2008;155:174-81.
20. Goebel M, Stengel A, Wang L, Lambrecht NW, Tache Y, et al. Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei. Neurosci Lett 2009;452:241-46.
21. Inhoff T, Mönnikes H, Noetzel S, et al. Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats. Peptides 2008;29:2159-68.
22. Inhoff T, Stengel A, Peter L, et al. Novel insight in distribution of nesfatin-1 and phospho-mTOR in the arcuate nucleus of the hypothalamus of rats. Peptides 2010;31:257-62.
23. Kohno D, Nakata M, Maejima Y, et al. Nesfatin-1 neurons in paraventricular and supraoptic nuclei of the rat hypothalamus coexpress oxytocin and vasopressin and are activated by refeeding. Endocrinology 2008;149:1295-301.
24. Goebel-Stengel M, Wang L, Stengel A, Tache Y. Localization of nesfatin-1 neurons in the mouse brain and functional implication. Brain Res 2011;1396:20-34.
25. Maejima Y, Sedbazar U, Suyama S, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway. Cell Metab 2009;10:355-65.
26. Okere B, Xu L, Roubos EW, Sonetti D, Kozicz T. Restraint stress alters the secretory activity of neurons co-expressing urocortin-1, cocaine- and amphetamine-regulated transcript peptide and nesfatin-1 in the mouse Edinger-Westphal nucleus. Brain Res 2010;1317:92-9.
27. Feijoo-Bandin S, Rodriguez-Penas D, Garcia-Rua V, et al. Nesfatin-1 in human and murine cardiomyocytes: synthesis, secretion and mobilization of Glut-4. Endocrinology 2013;154:4757-67.
28. Foo KS, Brauner H, Ostenson CG, Broberger C. Nucleobindin-2/nesfatin in the endocrine pancreas: distribution and relationship to glycaemic state. J Endocrinol 2010;204:255-63.
29. Gonzalez R, Tiwari A, Unniappan S. Pancreatic beta cells colocalize insülin and pronesfatin immunoreactivity in rodents. Biochem Biophys Res Commun 2009;381:643-48.
30. Gonzalez R, Kerbel B, Chun A, Unniappan S. Molecular, cellular and physiological evidences for the anorexigenic actions of nesfatin-1 in goldfish. PLoS One 2010;5(12):e15201.
31. Ramanjaneya M, Chen J, Brown JE, et al. Identification of nesfatin-1 in human and murine adipose tissue: a novel depot-specific adipokine with increased levels in obesity. Endocrinology 2010;151:3169-80.
32. Stengel A, Goebel M, Yakubov I, et al. Identification and characterization of nesfatin-1 immunoreactivity in endocrine cell types of the rat gastric oxyntic mucosa. Endocrinology 2009;150:232-38.
33. Atsuchi K, Asakawa A, Ushikai M, et al. Centrally administered nesfatin-1 inhibits feeding behaviour and gastroduodenal motility in mice. Neuroreport 2010;21:1008-11.
34. Goebel M, Stengel A, Wang L, Tache Y. Central nesfatin-1 reduces the nocturnal food intake in mice by reducing meal size and increasing inter-meal intervals. Peptides 2011;32:36-43.
35. Chen X, Dong J, Jiang ZY. Nesfatin-1 influences the excitability of glucosensing neurons in the hypothalamic nuclei and inhibits the food intake. Regul Pept 2012;177:21-6.
36. Dong J, Guan HZ, Jiang ZY, Chen X. Nesfatin-1 influences the excitability of glucosensing neurons in the dorsal vagal complex and inhibits food intake. PLoS One 2014;9(6):e98967.
37. Moreau JM, Ciriello J. Nesfatin-1 induces Fos expression and elicits dipsogenic responses in subfornical organ. Behav Brain Res 2013;250:343-50.
38. Kerbel B, Unniappan S. Nesfatin-1 suppresses energy intake, co-localisesghrelin in the brain and gut, and alters ghrelin, cholecystokinin and orexin mRNA expression in goldfish. J Neuroendocrinol 2012;24:366-77.
39. Stengel A, Taché Y. Role of NUCB2/Nesfatin-1 in the Hypothalamic Control of Energy Homeostasis. Horm Metab Res 2013;45:975-79.
40. Konczol K, Pinter O, Ferenczi S, et al. Nesfatin-1 exerts long-term effect on food intake and body temperature. Int J Obes 2012;36:1514-21.
41. Stengel A, Goebel M, Wang L, et al. Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor. Endocrinology 2009;150:4911-19.
42. Merali Z, Cayer C, Kent P, Anisman H. Nesfatin-1 increases anxiety- and fear-related behaviors in the rat. Psychopharmacology (Berl) 2008;201:115-123.
43. Chen X, Dong J, Jiang ZY. Nesfatin-1 influences the excitability of glucosensing neurons in the hypothalamic nuclei and inhibits the food intake. Regul Pept 2012;177:21-6.
44. Maejima Y, Sedbazar U, Suyama S, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin independent melanocortin pathway. Cell Metab 2009;10:355-65.
45. Garcia-Galiano D, Navarro VM, Roa J, et al. The anorexigenic neuropeptide, nesfatin-1 is indispensable for normal puberty onset in the female rat. J Neurosci 2010;30:7783-92.
46. Sedbazar U, Maejima Y, Nakata M, Mori M, Yada T. Paraventricular NUCB2/nesfatin-1 rises in synchrony with feeding suppression during early light phase in rats. Biochem Biophys Res Commun 2013;434:434-38.
47. Mohan H, Unniappan S. Ontogenic pattern of nucleobindin-2/nesfatin-1 expression in the gastroenteropancreatic tissues and serum of sprague dawley rats. Regul Pept 2012;175:61-9.
48. Zhang Z, Li L, Yang M. Increased plasma levels of nesfatin-1 in patients with newly diagnosed type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2012:120;91-5.
49. Zhang AQ, Li XL, Jiang CY, et al. Expression of nesfatin-1/NUCB2 in rodent digestive system. World J Gastroenterol 2010:16;1735-41.
50. Gonzalez R, Perry RL, Gao X, et al. Nutrient responsive nesfatin-1 regulates energy balance and induces glucose-stimulated insulin secretion in rats. Endocrinology 2011;152:3628-37.
51. Pan WH, Hung HC, Kastin AJ. Nesfatin-1 crosses the blood brain barrier without saturation. Peptides 2007;28:2223-8.
52. Price TO, Samson WK, Niehoff ML, Banks WA. Permeability of the blood-brain barrier to a novel satiety molecule nesfatin-1. Peptides 2007;28:2372-81.
53. Colmers WF. Less fat with nesfatin. Trends Endocrinol Metab 2007;18:131-32.
54. Wernecke K, Lamprecht I, Johren O, Lehnert H, Schulz C. Nesfatin-1 increases energy expenditure and reduces food intake in rats. Obesity 2014;22:1662-68.
55. Price CJ, Hoyda TD, Samson WK, Ferguson AV. Nesfatin-1 influences the excitability of paraventricular nucleus neurones. J Neuroendocrinol 2008;20:245-50.
56. Price CJ, Samson WK, Ferguson AV. Nesfatin-1 inhibits NPY neurons in the arcuate nucleus. Brain Res 2008;1230:99-106.
57. Gotoh K, Masaki T, Chiba S, et al. Nesfatin-1, corticotropin-releasing hormone, thyrotropin-releasing hormone, and neuronal histamine interact in the hypothalamus to regulate feeding behavior. J Neurochem 2013;124:90-99.
58. Noetzel S, Stengel A, Inhoff T, et al. CCK-8S activates c-Fos in a dose-dependent manner in nesfatin-1 immunoreactive neurons in the paraventricular nucleus of the hypothalamus and in the nucleus of the solitary tract of the brainstem. Regul Pept 2009;157: 84-91.
59. Goebel M, Stengel A, Wang L, Tache Y. Restraint stress activates nesfatin-1-immunoreactive brain nuclei in rats. Brain Res 2009;1300:114-24.
60. Yosten GL, Samson WK. Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. Am J Physiol Regul Integr Comp Physiol 2009;297:R330-36.
61. Tanida M, Gotoh H, Yamamoto N, et al. Hypothalamic nesfatin-1 stimulates sympathetic nerve activity via hypothalamic ERK signaling. Diabetes 2015;64:3725-36.
62. Nakamura A, Johns EJ. Renal nerves, renin and angiotensinogen gene expression in spontaneously hypertensive rats. Hypertension 1995;25:581-86.
63. Tanida M, Mori M. Nesfatin-1 stimulates renal sympathetic nerve activity in rats. Neuroreport 2011;22:309-12.
64. Mimee A, Smith PM, Ferguson AV. Nesfatin-1 influences the excitability of neurons in the nucleus of the solitary tract and regulates cardiovascular function. Am J Physiol Regul Integr Comp Physiol 2012;302:R1297-1304.
65. Cone RD Anatomy and regulation of the central melanocortin system. Nat Neurosci 2005;8:571-78.
66. da Silva AA, do Carmo JM, Hall JE. Role of leptin and central nervous system melanocortins in obesity hypertension. Curr Opin Nephrol Hypertens 2013;22:135-40.
67. Yosten GL, Samson WK. Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin. Am J Physiol Regul Integr Comp Physiol 2014;306:R722-27.
68. Yoshida N, Maejima Y, Sedbazar U, et al. Stressor-responsive central nesfatin-1 activates corticotropin-releasing hormone, noradrenaline and serotonin neurons and evokes hypothalamic-pituitary-adrenal axis. Aging 2010;2:775-84.
69. Xu YY, Ge JF, Qin G, et al. Acute, but not chronic, stress increased the plasma concentration and hypothalamic mRNA expression of NUCB2/nesfatin-1 in rats. Neuropeptides 2015;54:47-53.
70. Xu L, Bloem B, Gaszner B. Stress-related changes in the activity of cocaine- and amphetamine-regulated transcript and nesfatin neurons in the midbrain non-preganglionic Edinger-Westphal nucleus in the rat. Neuroscience 2010;170:478-88.
71. Ari M, Ozturk OH, Bez Y, Oktar S, Erduran D. High plasma nesfatin-1 level in patients with major depressive disorder. Prog NeuroPsychopharmacol Biol Psychiatry 2011;35:497-500.
72. Garcia-Galiano D, Tena-Sempere M. Emerging roles of NUCB2/nesfatin-1 in the metabolic control of reproduction. Curr Pharm Des 2013;19:6966-72.
73. Navarro VM, Kaiser UB. Metabolic influences on neuroendocrine regulation of reproduction. Curr Opin Endocrinol Diabetes Obes 2013;20:335-41.
74. Tadross JA, Patterson M, Wynne KJ, et al. Nesfatin suppresses feeding and stimulates the hypothalamo-pituitary-gonadal axis. 14th International Congress of Endocrinology 2010:S442.
75. Patterson M, Wynne K, Patel S, et al. Nesfatin stimulates the hypothalamic-pituitary-gonadal axis in male rats. Endocrine Abstracts 2011;25: P279.
76. Gao X, Zhang K, Song M, et al. Role of nesfatin-1 in the reproductive axis of male rat. Sci Rep 2016;6:32877.
77. Aydin S, Dag E, Ozkan Y, et al. Nesfatin-1 and ghrelin levels in serum and saliva of epileptic patients: hormonal changes can have a major effect on seizure disorders. Mol Cell Biochem 2009;328: 49-56.
78. Aydin S, Dag E, Ozkan Y, et al. Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients. Peptides 2011;32:1276-80.
79. Papp RS, Palkovits M. Brainstem projections of neurons located in various subdivisions of the dorsolateral hypothalamic area-an anterograde tract-tracing study. Front Neuroanat 2014;8:34.
80. Vas S, Adori C, Konczol K, et al. Nesfatin-1/NUCB2 as a potential new element of sleep regulation in rats. PLoS One 2013;8:e59809.
81. Jego S, Salvert D, Renouard L, et al. Tuberal hypothalamic neurons secreting the satiety molecule nesfatin-1 are critically involved in paradoxical (REM) sleep homeostasis. PLoS One 2012;7:e52525.