Review
BibTex RIS Cite

OBEZİTE AŞISI

Year 2018, Volume: 51 Issue: 1, 70 - 76, 30.03.2018

Abstract

Obezite
çağımızın önemli halk sağlığı problemlerinden biri olup tedavi opsiyonları
oldukça sınırlıdır. Son zamanlarda bu heyecan verici araştırma sahasında bazı
tedavi hedefleri ortaya çıkmaya başlamıştır. Ufuktaki enteresan stratejilerden
biri, aşıların kullanımı sayesinde enerji dengesinin regülasyonu ile ilgili
moleküler faktörlere yönelik çalışmalardır.

Gıda
alımını azaltmak, enerji kullanımını arttırmak, negatif enerji dengesini
sağlamak ve kilo kaybına yol açmak açılarından etkili olabilecek alternatif
obezite tedavileri arasında oreksijenik bir hormon olan ghrelin değişik
nötralizasyon yöntemlerinin ortaya atılması ile dikkat çekmektedir. Ne yazık ki
bir anti-obezite ajanı olarak insan ve hayvanlarda ghrelin aşısının kullanımı halen
beklentilerimizi karşılamış değildir. ghrelinin gıda tüketilmesi
regülasyonundaki rolü bazal iştah ve gıda alımını sağlamaktan çok, açlık ve
düşük enerji üretimine adaptif davranış cevabını kapsar. Çoğu obez hastada ghrelin
seviyesi yüksek değildir. Sonuçta diet bağlantılı ghrelin artışı olmayan bir
durumda, bir aşının etkili olmasını beklemek çok akıllıca gibi durmamaktadır. Bu
çeşit terapötik yaklaşımlardan faydalanabilecek hastalar ghrelin seviyelerinin
yüksek saptandığı Prader-Willi sendromuna sahip olanlar olabilir.

Ghrelin
dışında adipöz doku antijenleri, somatostatin, glukoz bağımlı insülinotropik
polipeptid, adenovirüs tip 36, p62 gibi hedefler ve aP2 kullanılarak denenen
obezite aşıları üzerinde halen çalışılmaktadır, ama umut vaad edici sonuçlara
henüz ulaşılamamıştır.







Sonuç
olarak obezite tedavisinde sadece tek bir sinyal yolunun antagonize edilmesinin
enerji homeostazisinde ve vücut kilosunun regülasyonunda efektif olamayabileceğini,
muhtemelen multipl yolların inhibe edilmesinin gerekebileceğini düşünüyoruz.    

References

  • 1-Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord. 1992;16: 397-415.2- Padwal RS, Majumdar SR. Drug treatments for obesity:orlistat,sibutramine and rimonabant. Lancet.2007; 369: 71-7. 3-Sjostrom L, Narbo K, Sjostrom CD etal. Effects of bariatric surgery on mortality on swedish obese subjects. N Eng J Med. 2007; 357: 741-52. 4-Bourinbair AS, Jirathitikal V. Effect of oral immunisation with pooled antigens derived from adipose tissue on atherosclerosis and obesity indices. Vaccine. 2010; 28:2763-8. 5- Haffer KN. Effects of novel vaccines on weight loss in diet induced obese mice. J Anim Sci Biotechnol. 2012; 3:21-4. 6- Hansotin T, Maida A, Flock G et al. Extrapancreatic incretin receptors modulate glucose homeostasis, body weight and energy expenditure.J Clin Invest. 2007;117:143-52. 7- Wortley KE, del Rincon JP, Murray JD et al. Absence of ghrelin protects against early-onset obesity. J Clin Invest. 2005; 115:3573-8. 8- Lu SC, Xu J, Chinookoswong N et al. An acyl-ghrelin-specific neutralizing antibody inhibits the acute ghrelin-mediated orexigenic effects in mice. Mol Pharmacol. 2009; 75:901- 7. 9- Zakhari JS, Zorrilla EP, Zhou B, Mayorov AV, Janda KD. Oligoclonal antibody targeting ghrelin increases energy expenditure and reduces food intake in fasted mice. Mol Pharm. 2012; 9:281-9. 10- Jerry R Colca. Discontinued drugs in 2006: renal, endocrine and metabolic drugs. Expert Opin Inv Drug. 2007;16:1517-23.11- Moran TH, Dailey MJ. Gut peptides: targets for anti-obesity drug development? Endocrinology. 2009;150:2526-30. 12- Vizcarra JA, Kirby JD, Kim SK, Galyean ML. Active immunization against ghrelin decreases weight gain and alters plasma concentrations of growth hormone in growing pigs. Domest Anim Endocrinol. 2007; 33:176-89. 13- . Zorrilla EP, Iwasaki S, Moss JA et al. Vaccination against weight gain. Proc Natl Acad Sci. 2006; 103:13226-31.14- Kellokoski E, Kummu O, Serpi R et al. Ghrelin vaccination decreases plasma MCP-1 level in LDLR(-/-)- mice. Peptides 2009; 30:2292-300.15- Jennings GT, Bachmann MF. Immunodrugs: therapeutic VLP-based vaccines for chronic diseases. Annu Rev Pharmacol Toxicol. 2009; 49:303-26.16- Brown MJ. Therapeutic potential of vaccines in the management of hypertension. Drugs. 2008;68:2557-60.17- Bachmann MF, Jennings GT. Therapeutic vaccines for chronic diseases: successes and technical challanges. Philos Trans R Soc Lond Biol Sci. 2011;366:2815-22.18- Andrade S, Pinho F, Ribeiro AM et al. Immunization against active ghrelin using virus-like particles for obesity treatment. Curr Pharm Des. 2013; 19:6551-8.19- Phase I/IIa Clinical Trial with Obese Individuals Shows no Effect of CYT009-GhrQb on Weight Loss. [(accessed on 3 January 2015)]; Available online: http://www.evaluategroup.com/Universal/View.aspx.20- Campitelli MA, Rosella LC, Kwong JC. The association between obesity and outpatient visits for acute respiratory infections in ontario, Canada. Int J Obes. 2014; 38: 113–9. 21- Mullen JT, Moorman DW, Davenport DL. The obesity paradox: Body mass index and outcomes in patients undergoing nonbariatric general surgery. Ann Surg. 2009; 250: 166-72.22- Arslan E, Atilgan H, Yavasoglu I. The prevalence of helicobacter pylori in obese subjects. Eur J Intern Med. 2009; 20: 695-7. 23- Uberos J, Molina-Carballo A, Fernandez-Puentes V, Rodriguez-Belmonte R, Munoz-Hoyos A. Overweight and obesity as risk factors for the asymptomatic carrier state of neisseria meningitidis among a paediatric population. Eur J Clin Microbiol Infect Dis. 2010; 29: 333-4.24- Morgan OW, Bramley A, Fowlkes A et al. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza a(h1n1) disease. PLoS ONE 2010; 5: e9694. 25- Dhurandhar NV. Insulin sparing action of adenovirus 36 and its e4orf1 protein. J Diabetes Complicat. 2013; 27: 191-9. 26-Ponterio E, Gnessi L. Adenovirus 36 and Obesity: An Overview. Viruses. 2015; 7:3719-40.27- Ergin S, Altan E, Pilanci O et al. The role of adenovirus 36 as a risk factor in obesity: The first clinical study made in the fatty tissues of adults in Turkey. Microb Pathog. 2015; 80: 57-62. 28- Karamese M, Altoparlak U, Turgut A, Aydogdu S, Karamese SA. The relationship between adenovirus-36 seropositivity, obesity and metabolic profile in Turkish children and adults. Epidemiol Infect. 2015; 16:1-7. 29- Wang ZQ, Cefalu WT, Zhang XH et al. Human adenovirus type 36 enhances glucose uptake in diabetic and nondiabetic human skeletal muscle cells independent of insulin signaling. Diabetes. 2008; 57:1805-13. 30- Na HN, Nam JH. Adenovirus 36 as an obesity agent maintains the obesity state by increasing mcp-1 and inducing inflammation. J Infect Dis 2012; 205:914-22. 31- Pasarica M, Loiler S, Dhurandhar NV. Acute effect of infection by adipogenic human adenovirus ad36. Arch Virol 2008: 153: 2097-102. 32- Na HN, Nam JH. Proof-of-concept for a virus-induced obesity vaccine; vaccination against the obesity agent adenovirus 36. Int J Obes. 2014; 38: 1470-4. 33- Börgeson E, Johnson AM, Lee YS et al. Lipoxin A4 attenuates obesity-induced adipose inflammation and associated liver and kidney disease. Cell Metabolism. 2015;22:125-37. 34- Rodriguez A, Durán A, Selloum M et al. Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62. Cell Metabolism. 2006;3:211-22. 35- Halenova T, Savchuk O, Ostapchenko L et al. P62 plasmid can alleviate diet-induced obesity and metabolic dysfunctions. Oncotarget. 2017; 8: 56030-40.36- Hotamisligil GS, Johnson RS, Distel RJ et al. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science. 1996; 274: 1377-9.
Year 2018, Volume: 51 Issue: 1, 70 - 76, 30.03.2018

Abstract

References

  • 1-Goldstein DJ. Beneficial health effects of modest weight loss. Int J Obes Relat Metab Disord. 1992;16: 397-415.2- Padwal RS, Majumdar SR. Drug treatments for obesity:orlistat,sibutramine and rimonabant. Lancet.2007; 369: 71-7. 3-Sjostrom L, Narbo K, Sjostrom CD etal. Effects of bariatric surgery on mortality on swedish obese subjects. N Eng J Med. 2007; 357: 741-52. 4-Bourinbair AS, Jirathitikal V. Effect of oral immunisation with pooled antigens derived from adipose tissue on atherosclerosis and obesity indices. Vaccine. 2010; 28:2763-8. 5- Haffer KN. Effects of novel vaccines on weight loss in diet induced obese mice. J Anim Sci Biotechnol. 2012; 3:21-4. 6- Hansotin T, Maida A, Flock G et al. Extrapancreatic incretin receptors modulate glucose homeostasis, body weight and energy expenditure.J Clin Invest. 2007;117:143-52. 7- Wortley KE, del Rincon JP, Murray JD et al. Absence of ghrelin protects against early-onset obesity. J Clin Invest. 2005; 115:3573-8. 8- Lu SC, Xu J, Chinookoswong N et al. An acyl-ghrelin-specific neutralizing antibody inhibits the acute ghrelin-mediated orexigenic effects in mice. Mol Pharmacol. 2009; 75:901- 7. 9- Zakhari JS, Zorrilla EP, Zhou B, Mayorov AV, Janda KD. Oligoclonal antibody targeting ghrelin increases energy expenditure and reduces food intake in fasted mice. Mol Pharm. 2012; 9:281-9. 10- Jerry R Colca. Discontinued drugs in 2006: renal, endocrine and metabolic drugs. Expert Opin Inv Drug. 2007;16:1517-23.11- Moran TH, Dailey MJ. Gut peptides: targets for anti-obesity drug development? Endocrinology. 2009;150:2526-30. 12- Vizcarra JA, Kirby JD, Kim SK, Galyean ML. Active immunization against ghrelin decreases weight gain and alters plasma concentrations of growth hormone in growing pigs. Domest Anim Endocrinol. 2007; 33:176-89. 13- . Zorrilla EP, Iwasaki S, Moss JA et al. Vaccination against weight gain. Proc Natl Acad Sci. 2006; 103:13226-31.14- Kellokoski E, Kummu O, Serpi R et al. Ghrelin vaccination decreases plasma MCP-1 level in LDLR(-/-)- mice. Peptides 2009; 30:2292-300.15- Jennings GT, Bachmann MF. Immunodrugs: therapeutic VLP-based vaccines for chronic diseases. Annu Rev Pharmacol Toxicol. 2009; 49:303-26.16- Brown MJ. Therapeutic potential of vaccines in the management of hypertension. Drugs. 2008;68:2557-60.17- Bachmann MF, Jennings GT. Therapeutic vaccines for chronic diseases: successes and technical challanges. Philos Trans R Soc Lond Biol Sci. 2011;366:2815-22.18- Andrade S, Pinho F, Ribeiro AM et al. Immunization against active ghrelin using virus-like particles for obesity treatment. Curr Pharm Des. 2013; 19:6551-8.19- Phase I/IIa Clinical Trial with Obese Individuals Shows no Effect of CYT009-GhrQb on Weight Loss. [(accessed on 3 January 2015)]; Available online: http://www.evaluategroup.com/Universal/View.aspx.20- Campitelli MA, Rosella LC, Kwong JC. The association between obesity and outpatient visits for acute respiratory infections in ontario, Canada. Int J Obes. 2014; 38: 113–9. 21- Mullen JT, Moorman DW, Davenport DL. The obesity paradox: Body mass index and outcomes in patients undergoing nonbariatric general surgery. Ann Surg. 2009; 250: 166-72.22- Arslan E, Atilgan H, Yavasoglu I. The prevalence of helicobacter pylori in obese subjects. Eur J Intern Med. 2009; 20: 695-7. 23- Uberos J, Molina-Carballo A, Fernandez-Puentes V, Rodriguez-Belmonte R, Munoz-Hoyos A. Overweight and obesity as risk factors for the asymptomatic carrier state of neisseria meningitidis among a paediatric population. Eur J Clin Microbiol Infect Dis. 2010; 29: 333-4.24- Morgan OW, Bramley A, Fowlkes A et al. Morbid obesity as a risk factor for hospitalization and death due to 2009 pandemic influenza a(h1n1) disease. PLoS ONE 2010; 5: e9694. 25- Dhurandhar NV. Insulin sparing action of adenovirus 36 and its e4orf1 protein. J Diabetes Complicat. 2013; 27: 191-9. 26-Ponterio E, Gnessi L. Adenovirus 36 and Obesity: An Overview. Viruses. 2015; 7:3719-40.27- Ergin S, Altan E, Pilanci O et al. The role of adenovirus 36 as a risk factor in obesity: The first clinical study made in the fatty tissues of adults in Turkey. Microb Pathog. 2015; 80: 57-62. 28- Karamese M, Altoparlak U, Turgut A, Aydogdu S, Karamese SA. The relationship between adenovirus-36 seropositivity, obesity and metabolic profile in Turkish children and adults. Epidemiol Infect. 2015; 16:1-7. 29- Wang ZQ, Cefalu WT, Zhang XH et al. Human adenovirus type 36 enhances glucose uptake in diabetic and nondiabetic human skeletal muscle cells independent of insulin signaling. Diabetes. 2008; 57:1805-13. 30- Na HN, Nam JH. Adenovirus 36 as an obesity agent maintains the obesity state by increasing mcp-1 and inducing inflammation. J Infect Dis 2012; 205:914-22. 31- Pasarica M, Loiler S, Dhurandhar NV. Acute effect of infection by adipogenic human adenovirus ad36. Arch Virol 2008: 153: 2097-102. 32- Na HN, Nam JH. Proof-of-concept for a virus-induced obesity vaccine; vaccination against the obesity agent adenovirus 36. Int J Obes. 2014; 38: 1470-4. 33- Börgeson E, Johnson AM, Lee YS et al. Lipoxin A4 attenuates obesity-induced adipose inflammation and associated liver and kidney disease. Cell Metabolism. 2015;22:125-37. 34- Rodriguez A, Durán A, Selloum M et al. Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62. Cell Metabolism. 2006;3:211-22. 35- Halenova T, Savchuk O, Ostapchenko L et al. P62 plasmid can alleviate diet-induced obesity and metabolic dysfunctions. Oncotarget. 2017; 8: 56030-40.36- Hotamisligil GS, Johnson RS, Distel RJ et al. Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science. 1996; 274: 1377-9.
There are 1 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Review
Authors

Gül Gürsoy

Eray Atalay

Publication Date March 30, 2018
Submission Date April 20, 2018
Published in Issue Year 2018 Volume: 51 Issue: 1

Cite

AMA Gürsoy G, Atalay E. OBEZİTE AŞISI. Ankara Eğitim ve Araştırma Hastanesi Tıp Dergisi. March 2018;51(1):70-76.