Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1

Özçelik, Oğuz; Algül, Sermin

Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1

Sermin ALGÜL, (Fırat Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Elazığ, Türkiye)

Oğuz ÖZÇELİK (Fırat Üniversitesi, Tıp Fakültesi, Fizyoloji Anabilim Dalı, Elazığ, Türkiye)

Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi

10 3

Yıl: 2012 Cilt: 26 Sayı: 3 Sayfa Aralığı: 143 - 148 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1

Öz:

Obezite, diyabet, kalp krizi, hipertansiyon, kanser ve hatta erken ölüm gibi çeşitli hastalıklar için artmış bir risk faktörüdür. Hormonların, kilo alınımı ve hipotalamik fonksiyonlar arasındaki ilişki üzerine etkilerinin açıklanması obezitenin daha iyi anlaşılmasını sağlayacaktır. NEFA/nukleobindin2 (NUKB2)’den kaynaklanan nesfatin-1, hipotalamusta melanokortin yoluyla yemek alınımını baskılayan son zamanlarda keşfedilen bir hormondur. Intraserebroventriküler, subkutan ve intraperitonel enjeksiyon ya da burun sprey formunu içeren nesfatin-1 uygulamaları iştahı 3-14 saat arasında baskılamaktadır. Ek olarak, vücut kilo alımını azaltan nesfatin-1 yeni bir anoreksijenik faktör ve enerji dengesi modülatörü olarak önerilmektedir. Enerji-metabolizma düzenleyici etkisi yüzünden nesfatin-1 obezitenin gelişimine karşı önemli bir koruyucu rol oynayabilir. Son yıllarda beyinde ve periferal dokularda nesfatin-1’in lokalizasyonun belirlenmesinde büyük ilerlemeler olmuştur. Gelecek çalışmalarda, nesfatin-1’in anoreksijenik etkisini anlamak için; nesfatin-1 reseptörleri ile ilgili önemli moleküler mekanizmalar, NUKB2 basamaklarının düzenlenmesi, nesfatin-1’in salınmasının açıkça tanımlanması gerekmektedir. Son çalışmaların ışığında, nesfatin-1'in yakın gelecekte umut veren bir anti-obezite ilacı olabileceği düşünülmektedir.

Anahtar Kelime:

Konular: Cerrahi

A new promising pepdide for obesity treatment: Nesfatin-1

Öz:

Obesity is associated with increased risk of many diseases, inluding diabetes, heart attack, hypertension, cancer and even in early death. Identification of the association between weight gain and hypothalamic functions with respect to hormonal effects will provide a better understanding of obesity. Nesfatin-1, derived from NEFA/nucleobindin2 (NUCB2), is a recently introduced hormone that suppresses food intake via melanocortin system in hypothalamus. Nesfatin-1 administration, through intracerebroventricular, subcutaneous or intraperitoneal injections or even by nasal sprey, inhibited appetite from 3 to 14 hours. In addition, it reduces weight gain, suggesting a role as a new anorexigenic factor and modulator of energy balance. Due to these effetcs on energy metabolism homeostasis, nesfatin-1 could play an important role in protection against the development of obesity. In recent years, there is a great progress on the detection of localization of nesfatin-1 in the brain and peripheral tissues. In future studies, to understand the anorexic effect of nesfatin-1 the important molecular mechanisms related with the nesfatin-1 receptor and the regulation of NUCB2 processing and nesfatin-1 release should be clearly defined. In the light of recent studies, nesfatin-1 may be termed as a new and promising anti-obesity drug that can be used in the near future.

Anahtar Kelime:

Konular: Cerrahi

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Bellanger TM, Bray GA. Obesity related morbidity and mortality. J La State Med Soc 2005; 157: 42-49.
2. Overweight, obesity, and health risk. National Task Force on the Prevention and Treatment of Obesity. Arch Intern Med 2000; 160: 898-904.
3. WHO Physical Status: The use and interpretation of anthropometry Ceneva CH, Who Technical Report 854,World Health Organization, 1995.
4. Smith SC Jr, Haslam D. Abdominal obesity, waist circumference and cardio-metabolic risk: awareness among primary care physicians, the general population and patients at risk – the Shape of the Nations survey. Curr Med Res Opin 2007; 23: 29–47.
5. Hu FB. Obesity and mortality: watch your waist, not just your weight. Arch Intern Med 2007; 167: 875–876.
6. Molarius A, Seidell JC, Sans S, et al.Varying sensitivity of waist action levels to identify subjects with overweight or obesity in 19 populations of the WHO MONICA Project. Clin Epidemiol 1999; 52: 1213-1224.
7. Visscher TL, Seidell JC, Molarius A, et al. A comparison of body mass index, waist-hip ratio and waist circumference as predictors of all-cause mortality among the elderly: the Rotterdam study. Int J Obes Relat Metab Disord 2001; 25: 1730-1735.
8. Camhi SM, Bray GA, Bouchard C, et al. The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences. Obesity (Silver Spring) 2011; 19: 402-408.
9. Report of a WHO Consultation. Obesity: preventing and man-aging the global epidemic. World Health Organ Tech Rep Ser 2000; 894: i–xii, 1–253.
10. Visscher TL, Seidell JC. The public health impact of obesity. Annu Rev Publ Health 2001; 22: 355–375.
11. Seidell J, Rissanen A. Prevalence of obesity in adults: the global epidemic. In: Bray GA, Bouchard C (Editors). Handbook of Obesity: Etiology and Pathophysiology New York: Marcel Dekker Inc, 2004: 93–107.
12. Björntorp P. Do stress reactions cause abdominal obesity and comorbidities? Obes Rev 2001; 2: 73-86.
13. Challis BG, Yeo GS. Past, present and future strategies to study the genetics of body weight regulation. Brief Funct Genomic Proteomic 2002; 1: 290-304.
14. Swinburn BA, Caterson I, Seidell JC, James WP. Diet, nutrition and the prevention of excess weight gain and obesity. Public Health Nutr 2004; 7: 123-146.
15. Rodgers RJ, Tschöp MH,. Wilding JPH. Anti-obesity drugs: past, present and future. Dis Model Mech 2012; 5: 621- 626.
16. Kennett GA, Clifton PG. New approaches to the pharmacological treatment of obesity: Can they break through the efficacy barrier? Pharmacol Biochem Behav 2010; 97: 63–83.
17. Juge-Aubry CE, Somm E, Giusti V, Pernin A, et al. Adipose tissue is a major source of interleukin-1 receptor antagonist: upregulation in obesity and inflammation. Diabetes 2003; 52: 1104–1110.
18. Williams LM. Hypothalamic dysfunction in obesity. Proc Nutr Soc 2012; 6: 1-13.
19. Spiegelman BM, Fliers JS. Obesity and the regulation of energy balance. Cell 2001; 104: 531–543.
20. Richard D, Baraboi D. Circuitries involved in the control of energy homeostasis and the hypothalamic-pituitary-adrenal axis activity. Treat Endocrinol 2004; 3: 269-277.
21. King PJ. The hypothalamus and obesity. Curr Drug Targets 2005; 6: 225-240.
22. Havel PJ. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 2004; 53: 143-151.
23. Bray GA. Afferent signals regulating food intake. Proc Nutr Soc 2000; 59: 373-384.
24. Morley JE, Levine AS, Yim GK, Lowy MT. Opioid modulation of appetite. Neurosci Biobehav Rev 1983; 7: 281–305.
25. Akabayashi A, Koenig JI, Watanabe Y, et al. Galanincontaining neurons in the paraventricular nucleus: a neurochemical marker for fat ingestion and body weight gain. Proc Natl Acad Sci USA 1994; 91: 10375-10379.
26. Kappeler L, Zizzari P, Grouselle D, et al. Plasma and hypothalamic peptide-hormone levels regulating somatotroph function and energy balance in fed and fasted states: a comparative study in four strains of rats. J Neuroendocrinol 2004; 16: 980-988.
27. Geiselman PJ. Control of food intake. A physiologically complex, motivated behavioral system. Endoc Metab Clin North Am 1996; 25: 815-829.
28. Valassi E, Scacchi M, Cavagnini F. Neuroendocrine control of food intake. Nutr Metab Cardiovasc Dis 2008; 18: 158- 168.
29. Tritos NA, Maratos-Flier E. Two important systems in energy homeostasis: melanocortins and melaninconcentrating hormone. Neuropeptides 1999; 33: 339-349.
30. Trayhurn P. Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol 2005; 184: 285–293.
31. Trayhurn P, Bing C. Appetite and energy balance signals from adipocytes. Philos Trans R Soc Lond B Biol Sci 2006; 36: 1237-1249.
32. Hauner H. Secretory factors from human adipose tissue and their functional role. Proc Nutr Soc. 2005; 64: 163-169.
33. York DA. Lessons from animal models of obesity. Clin Endoc Metab North America 1996; 25: 781-800.
34. Jéquier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci 2002; 967: 379-388.
35. Havel PJ. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 2002; 13: 51– 59.
36. Shimizu H, Inoue K, Mori M. The leptin-dependent andindependent melanocortin signaling system: regulation of feeding and energy expenditure. J Endocrinol 2007; 193: 1–9.
37. Lee YS. The role of leptin-melanocortin system and human weight regulation: lessons from experiments of nature. Ann Acad Med Singapore 2009; 38: 34-11.
38. Steiner J, LaPaglia N, Kirsteins L, et al. The response of the hypothalamic-pituitary-gonadal axis to fasting is modulated by leptin. Endocr Res 2003 29: 107-117.
39. Cameron JL, Helmreich DL, Schreihofer DA. Modulation of reproductive hormone secretion by nutritional intake: stress signals versus metabolic signals. Hum Reprod 1993; 8: 162–167.
40. Blundell JE. Apetite regulation and obesity treatment, International Textbook of Obesity Edited by Björntorp John Willey Section: 8, 2001; 113-124.
41. Stengel A, Taché Y. Nesfatin-1 role as possible new potent regulator of food intake. Regul Pept 2010; 163: 18-23.
42. Oh-I S, Shimizu H, Satoh T, Okada S, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 2006; 443: 709–712.
43. 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: 330-336.
44. 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: 662-671.
45. Stengel A, Goebel-Stengel M, Wang L, et al. Nesfatin-1 (30-59) but not the N- and C-terminal fragments, nesfatin-1 (1-29) and nesfatin-1 (60-82) injected tracerebroventricularly decreases dark phase food intake by increasing inter-meal intervals in mice. Peptides 2012; 35: 143-148.
46. 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: e15201.
47. 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– 1301.
48. Goebel M, Stengel A, Wang L, et al. Nesfatin-1 immunoreactivity in rat brain and spinal cord autonomic nuclei. Neurosci Lett 2009; 452: 241–246.
49. Inchoff 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: 257–262.
50. 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: 232–238.
51. Zhang AQ, Li XL, Jiang CY, et al. Expression of nesfatin- 1/NUCB2 in rodent digestive system. World J Gastroentero 2010; 16: 1735–1741.
52. 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.
53. Foo K, Brismar H, Broberger C. Distribution and neuropeptide coexistence of nucleobindin-2 mRNA/nesfatin-like immunoreactivity in the rat CNS. Neuroscience 2008; 156: 563–579.
54. Beckers S, Zegers D, Van Gaal LF, Van Hul W. The role of the leptin-melanocortin signalling pathway in the control of food intake. Crit Rev Eukaryot Gene Expr 2009; 19: 267- 287.
55. Stengel A, Taché Y. Minireview: nesfatin-1 an emerging new player in the brain-gut, endocrine, and metabolic axis. Endocrinology 2011; 152: 4033-4038.
56. Kerbel B, Unniappan S. Nesfatin-1 suppresses energy intake, co-localises ghrelin in the brain and gut, and alters ghrelin, cholecystokinin and orexin mRNA expression in goldfish. J Neuroendocrinol 2012; 24: 366-377.
57. Cui H, Sohn JW, Gautron L, et al. Neuroanatomy of melanocortin-4 receptor pathway in the lateral hypothalamic area. J Comp Neurol 2012; 520: 4168-4183.
58. Takahashi T. Toward molecular neuroeconomics of obesity. Med Hypotheses 2010; 75: 393–396.
59. William F. Colmers less fat with nesfatin-1. Trends Endocrin Metab 2007; 18: 131-132.
60. Stengel A, Goebel M, Wang L, et al. Central nesfatin-1 reduces dark-phase food ıntake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor. Endocrinology. 2009; 150: 4911-4919.
61. Ogiso K, Asakawa A, Amitani H, et al. Plasma nesfatin-1 concentrations in restricting-type anorexia nervosa. Peptides 2011; 32; 150-153.
62. 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: 355-365.
63. Tsuchiya T, Shimizu H, Yamada M, et al. Fasting concentrations of nesfatin-1 are negatively correlated with body mass index in non-obese males. Clin Endocrinol 2010; 73: 484–490.
64. Su Y, Zhang J, Tang Y, et al. The novel function of nesfatin-1: Anti-hyperglycemia. Biochem Biophys Res Co 2010; 391: 1039–1042.
65. Yosten GLC, 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: 330-336.
66. Li QC, Wang HY, Chen X, et al. Fasting plasma levels of nesfatin-1 in patients with type 1 and type 2 diabetes mellitus and the nutrient-related fluctuation of nesfatin-1 level in normal humans. Regul Peptides 2010; 159: 72–77.
67. Merali Z, Cayer C, Kent P, Anisman H. Nesfatin-1 increases anxiety- and fear-related behaviors in the rat. Psychopharmacology 2008; 201: 115–123.
68. Pan W, Hsuchou H, Kastin AJ. Nesfatin-1 crosses the blood–brain barrier without saturation. Peptides 2007; 28: 2223–2228.

APA	Algül S, Özçelik O (2012). Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. , 143 - 148.
Chicago	Algül Sermin,Özçelik Oğuz Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. (2012): 143 - 148.
MLA	Algül Sermin,Özçelik Oğuz Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. , 2012, ss.143 - 148.
AMA	Algül S,Özçelik O Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. . 2012; 143 - 148.
Vancouver	Algül S,Özçelik O Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. . 2012; 143 - 148.
IEEE	Algül S,Özçelik O "Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1." , ss.143 - 148, 2012.
ISNAD	Algül, Sermin - Özçelik, Oğuz. "Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1". (2012), 143-148.

APA	Algül S, Özçelik O (2012). Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi, 26(3), 143 - 148.
Chicago	Algül Sermin,Özçelik Oğuz Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi 26, no.3 (2012): 143 - 148.
MLA	Algül Sermin,Özçelik Oğuz Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi, vol.26, no.3, 2012, ss.143 - 148.
AMA	Algül S,Özçelik O Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi. 2012; 26(3): 143 - 148.
Vancouver	Algül S,Özçelik O Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi. 2012; 26(3): 143 - 148.
IEEE	Algül S,Özçelik O "Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1." Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi, 26, ss.143 - 148, 2012.
ISNAD	Algül, Sermin - Özçelik, Oğuz. "Obezite tedavisi için umut verici yeni bir peptid: Nesfatin-1". Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi 26/3 (2012), 143-148.