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Sleeve Gastrektomi Uygulanmış Obezite Hastalarında Ghrelin, Obestatin, Leptin Ekspreyonları’nın Araştırılması

Year 2024, Volume: 1 Issue: 2, 80 - 98, 29.03.2024

Abstract

Sleeve Gastrektomi Uygulanmış Obezite Hastalarında Ghrelin, Obestatin, Leptin Ekspreyonları’nın Araştırılması
ÖZET
Amaç: Obezite, birçok hastalığın oluşmasına neden olduğu için tüm toplumu etkileyen önemli bir halk sağlığı problemi haline gelmiştir. Bu çalışmada, mideden salınan ghrelin, leptin ve obestatin hormonlarının ekspresyon oranı ile obezitenin diyabet ile olan ilişkisinin araştırılması amaçlanmıştır.
Araçlar ve Yöntem: Çalışmada, Sleeve gastrektomi ameliyatı olmuş obezite hastaları ile obezite dışı nedenlerle mide biyopsisi yapılmış toplam 126 hastanın mide dokuları ve hastaların klinik verileri incelendi. Vakaların histopatolojik değerlendirmesi için hematoksilen eozin boyama yöntemi kullanıldı. Mide dokusundaki ghrelin, leptin ve obestatin hormonlarının ekspresyon oranını belirlemek için immünohistokimya boyama yöntemi uygulandı. Ayrıca her iki gruptaki klinik bulgular incelendi. Çalışmadan elde edilen veriler istatistiksel olarak değerlendirildi.
Bulgular: Obez bireylerde ghrelin ve obestatin seviyesi daha düşük iken leptin seviyesi yüksek bulundu. Ayrıca, ghrelin ve obestatin ekspresyonunun yaş ilerledikçe azaldığı gözlendi. Obez kadınlarda ghrelin ekspresyonunun daha yüksek olduğu, obez olmayan erkeklerde leptin ekspresyonunun daha yüksek olduğu ve obez erkeklerde obestatin ekspresyonunun daha düşük olduğu gösterildi. Ayrıca, çalışmamızda diyabetik obez bireylerde ghrelin seviyesi daha düşük iken leptin ve obestatin seviyelerinin daha yüksek olduğu gözlendi.
Sonuç: Ghrelin, leptin ve obestatin hormonlarının ekspresyon düzeylerinin obezite ve obeziteye bağlı diyabet oluşumunda etkili olabileceği sonucuna varıldı.

Anahtar Kelimeler: Tüp mide ameliyatı, mide hormonları, immünohistokimya

Supporting Institution

Erciyes Üniversitesi Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir

Project Number

TDK-2018-8198

Thanks

Bu çalışma TDK-2018-8198 numaralı proje ile Erciyes Üniversitesi Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir. Katkılarından dolayı Dr. Öğretim Üyesi Münevver Baran’a teşekkür ederim.

References

  • 1.Monica B, Silvia G, Simone R, Alessendro A, Silke M, Federica D, at al. Multi-omics gut microbiome signatures in obese women: role of diet and uncontrolled eating behavior BMC Med.2022;20;500
  • 2.Cătoi AF, Pârvu AE, Mureşan A, Busetto L. Metabolic mechanisms in obesity and type 2 Diabetes: Insights from bariatric/metabolic surgery.Obes.Facts.2015;8:350–363.
  • 3.Cătoi AF, Busetto L. Metabolically healthy obesity and bariatric surgery. Obes. Surg. 2019
  • 4. Atila K. Morbid Obezitenin Cerrahi Tedavisi. Archives of Clinical Toxicology,2014;1(1), 23-27
  • 5. Samir AG, Elad H, Rachel BHS, Aya B, Hadar İ, Ayet H, at al. Sleeve Gastrectomy Improves Glycemia Independent of Weight Loss by Restoring Hepatic Insulin SensitivityDiabetes. 2018 Jun; 67(6):1079–1085.
  • 6.Foster-Schubert KE and Cummings DE (2006) Evolving therapeutic strategies for obesity. EndokrinRev.2006;27,779–793
  • 7.Nakahara T, Harada T, Yasuhara D, Shimada N, Amitani H, Sakoguchi T at al. Plasma obestatin concentrations are negatively correlated with body mass ındex, ınsulin resistance ındex, and plasma leptin concentrations in obesity and anorexia nervosa. Bıol Psychıatry 2008;64:252–255
  • 8.Ren AJ, Guo ZF, Wang YK, Lin L, Zheng X, Yuan WJ. Obestatin, obesity and diabetes. Peptides. 2009, 30(2):439-44.
  • 9.Demir G, Diyabetik Obez Kadınlarda Obeziteyi Etkileyen Süreçlerin Genel Olarak Değerlendirilmesi, Uzmanlık Tezi, Şişli Eftal Eğitim ve Araştırma Hastanesi 2.İç Hastalıkları Kliniği, İstanbul 2009:131
  • 10.Reilly JJ, El-Hamdouchi A, Diouf A, Monyeki A, A Somda S. Determining the worldwide prevalence of obesity. Lancet.2018;391773–1774.
  • 11. Akbalık, M. E. (2019). Keklik (Alectoris chukar) Barsağında Ghrelin, Leptin ve Obestatin Dağılımı. Dicle Üniversitesi Veteriner Fakültesi Dergisi, 12(2), 117-121. doi: 10.4149/BLL_2017_116.
  • 12. M Baran, O Canoz, H Altuntas, S Sivgin, M Cetin, A Yay, S Ketenci Immunohistochemical investigation of P16, P53 and Ki-67's prognostic values in diffuse large B-Cell lymphomas2017;118(10):602-608. DOI: 10.4149/BLL_2017_116
  • 13.Baştürk S. Sleeve gastrektomi’nin orta ve uzun dönem sonuçları, obeziteye eşlik eden komorbiditelere etkileri. Uzmanlık Tezi. Pamukkkale Üniversitesi Tıp Fakültesi Genel Cerrahi Anabilim Dalı.Denizli,2015.
  • 14.Vidal P, Ramon JM, Goday A, Benaiges D, Trillo L, Parri A, at al. Laparoscopic gastric bypass versus laparoscopic sleeve gastrectomy as a definitive surgical procedure for morbid obesity.Mid-term results, Obes Surg.2013;23:292–299.
  • 15.Dimitriadis E, Daskalakis M, Kampa M, Peppe A, Papadakis JA, Melissas J. Alterations in gut hormones after laparoscopic sleeve gastrectomy: a prospective clinical and laboratory investigational study.Ann Surg.2013;257(4):647–654.
  • 16.Iwona P, Siemowit M, Piotr D, Malgorzata K, Marta PO, Janine D. at al. Alterations in Small Intestine and Liver Morphology, Immunolocalization of Leptin, Ghrelin and Nesfatin-1 as Well as Immunoexpression of Tight Junction Proteins in Intestinal Mucosa after Gastrectomy in Rat Model J Clin Med.2021 Jan; 10(2):272.
  • 17.Kojima M. The discovery of ghrelin - A personal memory. Regulatory Peptides.2008, 145:2–6
  • 18.Guanya L, Gang J, Yang H, Li L, Qingchao J, Wenchao Z. at al. Reduced plasma ghrelin concentrations are associated with decreased brain reactivity to food cues after laparoscopic sleeve gastrectomyPsychoneuroendocrinology.2019 Feb;100:229–236.
  • 19.Tricia LM, Alan C, Stephen DR, Leptin's effect on taste bud calcium responses and transmitter secretion Chem Senses.2015 May;40(4):217-22.
  • 20.Karamanakos SN, Vagenas K, Kalfarentzos F, Alexandrides TK, Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind studyAnn Surg.2008 Mar;247(3):401-7.
  • 21.Abdemur A, Slone J, Berho M, Gianos M, Szomstein S, Rosenthal RJ. Morphology, localization, and patterns of ghrelin-producing cells in stomachs of a morbidly obese population.Surg Laparosc Endosc Percutan Tech.2014;24(2):122–126.
  • 22.Sato T, Nakamura Y, Shiimura Y, Ohgusu H, Kangawa K, Kojima M. Structure, regulation and function of ghrelin. J Biochem. 2012;151(2):119-128.
  • 23.Beasley JM, Ange BA, Anderson CAM, Miller ER, Holbrook JT, Appel LJ. Characteristics associated with fasting appetite hormones (obestatin, ghrelin, and leptin) Obesity. 2009;17:349–354.
  • 24.Soares JB, Leite-Moreira AF. Ghrelin, des-acylghrelin and obestatin: three pieces of the same puzzle. Peptides.2008 Jul;29(7):1255-70.
  • 25.Purnell JQ, Weigle DS, Breen PA,Cummings DE. Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 2003;88:5747-5752.
  • 26.Wilasco M, Goldani HAS, Dornelles CTL, Rafael LM, Carlos OK, Marilene P. at al. Ghrelin, leptin and insulin in healthy children: Relationship with anthropometry, gender, and age distribution Regul Pept. 2012 Jan 10;173(1-3):21-6.
  • 27.Khan M, Joseph F. Adipose Tissue and Adipokines: The Association with and Application of Adipokines in Obesity. Science.2014;2014:328-592.
  • 28.Valentina AG ,Rossella D, Giuseppe P, Cristina C, Angelo C, Annalisa N, at al. Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?2021 Jun; 22(12): 6445.
  • 29.Hekimoğlu A. Leptin ve fizyopatolojik olaylardaki rolü. Dicle Tıp Derg.2006;33(4):259-267.
  • 30.Gültürk S, Demirkazık A. Leptin ve diyabet. Cumhuriyet Üniversitesi Tıp Fakültesi Dergisi 2007;29(1):35-40.
  • 31. Pereira S, Cline DL, Glavas MM, Covey SD, Kieffer TJ. Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism. Endocr Rev.2021 Jan 28;42(1):1-28.
  • 32.Virsaladze D. Wide clinical implementation of insulin resistance syndrome? Metab Syndr Relat Disord. 2006 Fall;4(3):165-71.
  • 33.Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol.2003 Oct;149(4):331-5.
  • 34.Subasinghage AP, Green BD, Flatt PR, Irwin N, Hewage CM..Metabolic and structural properties of human obestatin {1-23} and two fragment peptides. Peptides. 2010 Sep;31(9):1697-705.
  • 35.Daniel V, Yu Z, Bingzhong X, Yuxiang S, Vincent CJ. De Boer, Academic Editor.,Diverse and Complementary Effects of Ghrelin and Obestatin. Biomolecules. 2022 Apr; 12(4): 517.
  • 36.Huda MSB, Durham BH, Wong SP, Derinak D, Kerrigan D, McCulloch at al. Plasma obestatin levels are lower in obese and postgastrectomy subjects, but do not change in response to a meal. International Journal of Obesity 2008;32:129–135.
  • 37.Hedayati M, Saghebjoo M, Ghanbari-Niaki A. Effects of circuit resistance training intensity on the plasma ghrelin to obestatin ratios in healthy young women. Int J Endocrinol Metab.Spring;2012;10(2):475-9.

Investigation of Ghrelin, Obestatin, Leptin Expressions in Obesity Patients Who Have Had Sleeve Gastrectomy

Year 2024, Volume: 1 Issue: 2, 80 - 98, 29.03.2024

Abstract

Investigation of Ghrelin, Obestatin, Leptin Expressions in Obesity Patients Who Have Had Sleeve Gastrectomy

ABSTRACT
Background: Obesity has become an important public health problem that affects the whole society because it causes many diseases. In this study, it was aimed to investigate the expression rate of ghrelin, leptin and obestatin hormones released from the stomach and the relationship between obesity and diabetes.
Materials and Methods: In the study, gastric tissues and clinical data of patients with obesity who underwent sleeve gastrectomy and 126 patients who underwent gastric biopsy for non-obesity reasons were examined. Hematoxylin-eosin staining method was used for the histopathological evaluation of the cases. To determine the expression rate of ghrelin, leptin and obestatin hormones in gastric tissue, immunohistochemistry staining method was applied. In addition, clinical findings in both groups were examined. The data obtained from the study were evaluated statistically.
Results: Ghrelin and obestatin levels were lower in obese individuals, while leptin levels were higher. In addition, it was observed that the expression of ghrelin and obestatin decreased with increasing age. It was shown that ghrelin expression is higher in obese women, leptin expression is higher in non-obese men, and obestatin expression is lower in obese men. In addition, in our study, while ghrelin levels were lower in diabetic obese individuals, leptin and obestatin levels were higher.
Conclusions: As a result, it was concluded that the expression levels of ghrelin, leptin and obestatin hormones may be effective in the formation of obesity and obesity-related diabetes.

Keywords: Gastric sleeve surgery, stomach hormones, immünohistochemistry

Project Number

TDK-2018-8198

References

  • 1.Monica B, Silvia G, Simone R, Alessendro A, Silke M, Federica D, at al. Multi-omics gut microbiome signatures in obese women: role of diet and uncontrolled eating behavior BMC Med.2022;20;500
  • 2.Cătoi AF, Pârvu AE, Mureşan A, Busetto L. Metabolic mechanisms in obesity and type 2 Diabetes: Insights from bariatric/metabolic surgery.Obes.Facts.2015;8:350–363.
  • 3.Cătoi AF, Busetto L. Metabolically healthy obesity and bariatric surgery. Obes. Surg. 2019
  • 4. Atila K. Morbid Obezitenin Cerrahi Tedavisi. Archives of Clinical Toxicology,2014;1(1), 23-27
  • 5. Samir AG, Elad H, Rachel BHS, Aya B, Hadar İ, Ayet H, at al. Sleeve Gastrectomy Improves Glycemia Independent of Weight Loss by Restoring Hepatic Insulin SensitivityDiabetes. 2018 Jun; 67(6):1079–1085.
  • 6.Foster-Schubert KE and Cummings DE (2006) Evolving therapeutic strategies for obesity. EndokrinRev.2006;27,779–793
  • 7.Nakahara T, Harada T, Yasuhara D, Shimada N, Amitani H, Sakoguchi T at al. Plasma obestatin concentrations are negatively correlated with body mass ındex, ınsulin resistance ındex, and plasma leptin concentrations in obesity and anorexia nervosa. Bıol Psychıatry 2008;64:252–255
  • 8.Ren AJ, Guo ZF, Wang YK, Lin L, Zheng X, Yuan WJ. Obestatin, obesity and diabetes. Peptides. 2009, 30(2):439-44.
  • 9.Demir G, Diyabetik Obez Kadınlarda Obeziteyi Etkileyen Süreçlerin Genel Olarak Değerlendirilmesi, Uzmanlık Tezi, Şişli Eftal Eğitim ve Araştırma Hastanesi 2.İç Hastalıkları Kliniği, İstanbul 2009:131
  • 10.Reilly JJ, El-Hamdouchi A, Diouf A, Monyeki A, A Somda S. Determining the worldwide prevalence of obesity. Lancet.2018;391773–1774.
  • 11. Akbalık, M. E. (2019). Keklik (Alectoris chukar) Barsağında Ghrelin, Leptin ve Obestatin Dağılımı. Dicle Üniversitesi Veteriner Fakültesi Dergisi, 12(2), 117-121. doi: 10.4149/BLL_2017_116.
  • 12. M Baran, O Canoz, H Altuntas, S Sivgin, M Cetin, A Yay, S Ketenci Immunohistochemical investigation of P16, P53 and Ki-67's prognostic values in diffuse large B-Cell lymphomas2017;118(10):602-608. DOI: 10.4149/BLL_2017_116
  • 13.Baştürk S. Sleeve gastrektomi’nin orta ve uzun dönem sonuçları, obeziteye eşlik eden komorbiditelere etkileri. Uzmanlık Tezi. Pamukkkale Üniversitesi Tıp Fakültesi Genel Cerrahi Anabilim Dalı.Denizli,2015.
  • 14.Vidal P, Ramon JM, Goday A, Benaiges D, Trillo L, Parri A, at al. Laparoscopic gastric bypass versus laparoscopic sleeve gastrectomy as a definitive surgical procedure for morbid obesity.Mid-term results, Obes Surg.2013;23:292–299.
  • 15.Dimitriadis E, Daskalakis M, Kampa M, Peppe A, Papadakis JA, Melissas J. Alterations in gut hormones after laparoscopic sleeve gastrectomy: a prospective clinical and laboratory investigational study.Ann Surg.2013;257(4):647–654.
  • 16.Iwona P, Siemowit M, Piotr D, Malgorzata K, Marta PO, Janine D. at al. Alterations in Small Intestine and Liver Morphology, Immunolocalization of Leptin, Ghrelin and Nesfatin-1 as Well as Immunoexpression of Tight Junction Proteins in Intestinal Mucosa after Gastrectomy in Rat Model J Clin Med.2021 Jan; 10(2):272.
  • 17.Kojima M. The discovery of ghrelin - A personal memory. Regulatory Peptides.2008, 145:2–6
  • 18.Guanya L, Gang J, Yang H, Li L, Qingchao J, Wenchao Z. at al. Reduced plasma ghrelin concentrations are associated with decreased brain reactivity to food cues after laparoscopic sleeve gastrectomyPsychoneuroendocrinology.2019 Feb;100:229–236.
  • 19.Tricia LM, Alan C, Stephen DR, Leptin's effect on taste bud calcium responses and transmitter secretion Chem Senses.2015 May;40(4):217-22.
  • 20.Karamanakos SN, Vagenas K, Kalfarentzos F, Alexandrides TK, Weight loss, appetite suppression, and changes in fasting and postprandial ghrelin and peptide-YY levels after Roux-en-Y gastric bypass and sleeve gastrectomy: a prospective, double blind studyAnn Surg.2008 Mar;247(3):401-7.
  • 21.Abdemur A, Slone J, Berho M, Gianos M, Szomstein S, Rosenthal RJ. Morphology, localization, and patterns of ghrelin-producing cells in stomachs of a morbidly obese population.Surg Laparosc Endosc Percutan Tech.2014;24(2):122–126.
  • 22.Sato T, Nakamura Y, Shiimura Y, Ohgusu H, Kangawa K, Kojima M. Structure, regulation and function of ghrelin. J Biochem. 2012;151(2):119-128.
  • 23.Beasley JM, Ange BA, Anderson CAM, Miller ER, Holbrook JT, Appel LJ. Characteristics associated with fasting appetite hormones (obestatin, ghrelin, and leptin) Obesity. 2009;17:349–354.
  • 24.Soares JB, Leite-Moreira AF. Ghrelin, des-acylghrelin and obestatin: three pieces of the same puzzle. Peptides.2008 Jul;29(7):1255-70.
  • 25.Purnell JQ, Weigle DS, Breen PA,Cummings DE. Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab 2003;88:5747-5752.
  • 26.Wilasco M, Goldani HAS, Dornelles CTL, Rafael LM, Carlos OK, Marilene P. at al. Ghrelin, leptin and insulin in healthy children: Relationship with anthropometry, gender, and age distribution Regul Pept. 2012 Jan 10;173(1-3):21-6.
  • 27.Khan M, Joseph F. Adipose Tissue and Adipokines: The Association with and Application of Adipokines in Obesity. Science.2014;2014:328-592.
  • 28.Valentina AG ,Rossella D, Giuseppe P, Cristina C, Angelo C, Annalisa N, at al. Impaired Leptin Signalling in Obesity: Is Leptin a New Thermolipokine?2021 Jun; 22(12): 6445.
  • 29.Hekimoğlu A. Leptin ve fizyopatolojik olaylardaki rolü. Dicle Tıp Derg.2006;33(4):259-267.
  • 30.Gültürk S, Demirkazık A. Leptin ve diyabet. Cumhuriyet Üniversitesi Tıp Fakültesi Dergisi 2007;29(1):35-40.
  • 31. Pereira S, Cline DL, Glavas MM, Covey SD, Kieffer TJ. Tissue-Specific Effects of Leptin on Glucose and Lipid Metabolism. Endocr Rev.2021 Jan 28;42(1):1-28.
  • 32.Virsaladze D. Wide clinical implementation of insulin resistance syndrome? Metab Syndr Relat Disord. 2006 Fall;4(3):165-71.
  • 33.Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol.2003 Oct;149(4):331-5.
  • 34.Subasinghage AP, Green BD, Flatt PR, Irwin N, Hewage CM..Metabolic and structural properties of human obestatin {1-23} and two fragment peptides. Peptides. 2010 Sep;31(9):1697-705.
  • 35.Daniel V, Yu Z, Bingzhong X, Yuxiang S, Vincent CJ. De Boer, Academic Editor.,Diverse and Complementary Effects of Ghrelin and Obestatin. Biomolecules. 2022 Apr; 12(4): 517.
  • 36.Huda MSB, Durham BH, Wong SP, Derinak D, Kerrigan D, McCulloch at al. Plasma obestatin levels are lower in obese and postgastrectomy subjects, but do not change in response to a meal. International Journal of Obesity 2008;32:129–135.
  • 37.Hedayati M, Saghebjoo M, Ghanbari-Niaki A. Effects of circuit resistance training intensity on the plasma ghrelin to obestatin ratios in healthy young women. Int J Endocrinol Metab.Spring;2012;10(2):475-9.
There are 37 citations in total.

Details

Primary Language Turkish
Subjects Pathology, Histology and Embryology
Journal Section Research Articles
Authors

Zeynep Ayvalı 0000-0002-8597-3607

Birkan Yakan 0000-0002-5456-4579

Kemal Deniz 0000-0001-7749-2152

Project Number TDK-2018-8198
Publication Date March 29, 2024
Submission Date January 22, 2024
Acceptance Date March 10, 2024
Published in Issue Year 2024 Volume: 1 Issue: 2

Cite

AMA Ayvalı Z, Yakan B, Deniz K. Sleeve Gastrektomi Uygulanmış Obezite Hastalarında Ghrelin, Obestatin, Leptin Ekspreyonları’nın Araştırılması. Tusad. March 2024;1(2):80-98.