Leptin and NUCB2/Nesfatin-1 in Acute Appendicitis
Author(s)
Unal Bakal1,
Mehmet Saraç1,
Harun Ciftci2,
Tugay Tartar1,
Ahmet Kazez1,
Suleyman Aydin3,4*
Affiliation(s)
1 Department of Pediatric Surgery, School of Medicine, Firat University, Elazig, Turkey. 2 Department of Medical Biochemistry, Ahievran University, Kirsehir, Turkey. 3 Department of Medical Biochemistry (Firat Hormones Research Group), School of Medicine, Firat University, Elazig, Turkey. 4 Illinois Institute of Technology, Chicago, IL, USA.
1 Department of Pediatric Surgery, School of Medicine, Firat University, Elazig, Turkey. 2 Department of Medical Biochemistry, Ahievran University, Kirsehir, Turkey. 3 Department of Medical Biochemistry (Firat Hormones Research Group), School of Medicine, Firat University, Elazig, Turkey. 4 Illinois Institute of Technology, Chicago, IL, USA.
ABSTRACT
Objective: Appetite loss is seen in 90% to 95% of patients with acute appendicitis; however, the cause of this symptom remains unknown. This study is performed to determine whether changes in the blood levels of two anorexigenic hormones, leptin and NUCB2/nesfatin-1, can help to diagnose acute appendicitis in children and whether these two parameters can distinguish acute appendicitis from abdominal pain. Methods: Sixty children with comparable ages and body mass indices are divided into three groups of 20 children each: those with acute appendicitis, those with abdominal pain, and controls. The blood sample with acute appendicitis is taken preoperatively (T1), and subsequent samples are taken 24 hrs postoperatively (T2) and 3 days postoperatively (T3). The blood sample with abdominal pain subjects is also taken in the corresponding times with those with acute appendicitis while blood sample from controls is only taken in the T1 corresponding time. Leptin and NUCB2/nesfatin-1 levels are measured by enzyme-linked immunosorbent assay. Results: The serum leptin levels are significantly higher preoperatively than postoperatively in all three groups. The NUCB2/nesfatin-1 levels at T1 in acute appendicitis are significantly higher than those at T2 in all three groups, but are restored at T3 to levels similar to those of controls. Neutrophil percentage has a sensitivity of 100%, and specificity of 76.32%, NUCB2/nesfatin-1 level has a sensitivity of 47% and specificity of 95%, and the leptin level has a sensitivity of 64% and specificity of 51% in the diagnosis of acute appendicitis. Conclusions: High preoperative leptin and NUCB2/nesfatin-1 levels may be a causative factor for appetite suppression observed in patients with acute appendicitis. High preoperative and low postoperative serum leptin and NUCB2/nesfatin-1 concentrations may serve as new candidate biomarkers that help to distinguish acute appendicitis from abdominal pain in children in addition to high CRP concentration, high WBC count, and neutrophilia.
Objective: Appetite loss is seen in 90% to 95% of patients with acute appendicitis; however, the cause of this symptom remains unknown. This study is performed to determine whether changes in the blood levels of two anorexigenic hormones, leptin and NUCB2/nesfatin-1, can help to diagnose acute appendicitis in children and whether these two parameters can distinguish acute appendicitis from abdominal pain. Methods: Sixty children with comparable ages and body mass indices are divided into three groups of 20 children each: those with acute appendicitis, those with abdominal pain, and controls. The blood sample with acute appendicitis is taken preoperatively (T1), and subsequent samples are taken 24 hrs postoperatively (T2) and 3 days postoperatively (T3). The blood sample with abdominal pain subjects is also taken in the corresponding times with those with acute appendicitis while blood sample from controls is only taken in the T1 corresponding time. Leptin and NUCB2/nesfatin-1 levels are measured by enzyme-linked immunosorbent assay. Results: The serum leptin levels are significantly higher preoperatively than postoperatively in all three groups. The NUCB2/nesfatin-1 levels at T1 in acute appendicitis are significantly higher than those at T2 in all three groups, but are restored at T3 to levels similar to those of controls. Neutrophil percentage has a sensitivity of 100%, and specificity of 76.32%, NUCB2/nesfatin-1 level has a sensitivity of 47% and specificity of 95%, and the leptin level has a sensitivity of 64% and specificity of 51% in the diagnosis of acute appendicitis. Conclusions: High preoperative leptin and NUCB2/nesfatin-1 levels may be a causative factor for appetite suppression observed in patients with acute appendicitis. High preoperative and low postoperative serum leptin and NUCB2/nesfatin-1 concentrations may serve as new candidate biomarkers that help to distinguish acute appendicitis from abdominal pain in children in addition to high CRP concentration, high WBC count, and neutrophilia.
Cite this paper
Bakal, U. , Saraç, M. , Ciftci, H. , Tartar, T. , Kazez, A. , Aydin, S. (2015) Leptin and NUCB2/Nesfatin-1 in Acute Appendicitis. International Journal of Clinical Medicine, 6, 919-927. doi: 10.4236/ijcm.2015.612120.
Bakal, U. , Saraç, M. , Ciftci, H. , Tartar, T. , Kazez, A. , Aydin, S. (2015) Leptin and NUCB2/Nesfatin-1 in Acute Appendicitis. International Journal of Clinical Medicine, 6, 919-927. doi: 10.4236/ijcm.2015.612120.
References
[1] Nance, M.L., Adamson, W.T. and Hedrick, H.L. (2000) Appendicitis in the Young Child: A Continuing Diagnostic Challenge. Pediatric Emergency Care, 16, 160-162.
http://dx.doi.org/10.1097/00006565-200006000-00005 [2] Alvarado, A. (1986) A Practical Score for the Early Diagnosis of Acute Appendicitis. Annals of Emergency Medicine, 15, 557-564.
http://dx.doi.org/10.1016/S0196-0644(86)80993-3 [3] Apak, S., Kazez, A., Ozel, S.K., Ustundag, B., Akpolat, N. and Kizirgil, A. (2005) Spot Urine 5-Hydroxyindoleacetic Acid Levels in the Early Diagnosis of Acute Appendicitis. Journal of Pediatric Surgery, 40, 1436-1439.
http://dx.doi.org/10.1016/j.jpedsurg.2005.05.042 [4] Bakal, U., Sarac, M., Ciftci, H., Tartar, T. and Kazez, A. (2014) Neutrophil Gelatinase-Associated Lipocalin (NGAL) May Be Support in the Diagnosis of Acute Appendicitis. 32nd National Congress of Pediatric Surgery in Trabzon, Turkey, 17-20 September 2012, 138. [5] Branescu, C., Serban, C., Savlovschi, C., Dascalu, A.M. and Kraft, A. (2012) Lipopolysaccharide Binding Protein (L.B.P.)—An Inflammatory Marker of Prognosis in the Acute Appendicitis. Journal of Medicine and Life, 5, 342-347. [6] Rodriguez-Sanjuan, J.C., Martin-Parra, J.I., Seco, I., Garcia-Castrillo, L. and Naranjo, A. (1999) C-Reactive Protein and Leukocyte in the Diagnosis of Acute Appendicitis in Children. Diseases of the Colon & Rectum, 42, 1325-1329.
http://dx.doi.org/10.1007/BF02234223 [7] Flum, D.R. and Koepsell, T. (2002) The Clinical and Economic Correlates of Misdiagnosed Appendicitis: Nationwide Analysis. Archives of Surgery, 137, 799-804.
http://dx.doi.org/10.1001/archsurg.137.7.799 [8] Cetinkaya, Z., Aydin, S., Cerrahoglu, Y.Z., Ayten, R., Erman, F. and Aygen, E. (2009) Changes in Appetite Hormone (Ghrelin) Levels of Saliva and Serum in Acute Appendicitis Cases before and after Operation. Appetite, 52, 104-107.
http://dx.doi.org/10.1016/j.appet.2008.09.001 [9] Sand, M., Trullen, X.V., Bechara, F.G., Pala, X.F., Sand, D., Landgrafe, G. and Mann, B. (2009) A Prospective Bicenter Study Investigating the Diagnostic Value of Procalcitonin in Patients with Acute Appendicitis. European Surgical Research, 43, 291-297.
http://dx.doi.org/10.1159/000232939 [10] Ahima, R.S. and Flier, J.S. (2000) Leptin. Annual Review of Physiology, 62, 413-437.
http://dx.doi.org/10.1146/annurev.physiol.62.1.413 [11] Mc Conway, M.G., Johnson, D., Kelly, A., Griffin, D., Smith, J. and Wallace, A.M. (2000) Differences in Circulating Concentrations of Total, Free and Bound Leptin Relate to Gender and Body Composition in Adult Humans. Annals of Clinical Biochemistry, 37, 717-723.
http://dx.doi.org/10.1258/0004563001899771 [12] Farr, O.M., Gavrieli, A. and Mantzoros, C.S. (2015) Leptin Applications in 2015: What Have We Learned about Leptin and Obesity? Current Opinion in Endocrinology, Diabetes and Obesity, 22, 353-359.
http://dx.doi.org/10.1097/MED.0000000000000184 [13] Aydin, S. (2013) Multi-Functional Peptide Hormone NUCB2/Nesfatin-1. Endocrine, 44, 312-325.
http://dx.doi.org/10.1007/s12020-013-9923-0 [14] Oh, I., Shimizu, H., Satoh, T., Okada, S., Adachi, S., Inoue, K., Eguchi, H., Yamamoto, M., Imaki, T., Hashimoto, K., Tsuchiya, T., Monden, T., Horiguchi, K., Yamada, M. and Mori, M. (2006) Identification of Nesfatin-1 as a Satiety Molecule in the Hypothalamus. Nature, 443, 709-712.
http://dx.doi.org/10.1038/nature05162 [15] Mohebbi, H., Nourshahi, M., Ghasemikaram, M. and Safarimosavi, S. (2015) Effects of Exercise at Individual Anaerobic Threshold and Maximal Fat Oxidation Intensities on Plasma Levels of Nesfatin-1 and Metabolic Health Biomarkers. Journal of Physiology and Biochemistry, 71, 79-88.
http://dx.doi.org/10.1007/s13105-015-0383-2 [16] Aydin, S., Dag, E., Ozkan, Y., Arslan, O., Koc, G., Bek, S., Kirbas, S., Kasikci, T., Abasli, D., Gokcil, Z., Odabasi, Z. and Catak, Z. (2011) Time-Dependent Changes in the Serum Levels of Prolactin, Nesfatin-1 and Ghrelin as a Marker of Epileptic Attacks Young Male Patients. Peptides, 32, 1276-1280.
http://dx.doi.org/10.1016/j.peptides.2011.04.021 [17] Caglayan, F., Cakmak, M., Caglayan, O. and Cavusoglu, T. (2003) Plasma D-Lactate Levels in Diagnosis of Appendicitis. Journal of Investigative Surgery, 16, 233-237.
http://dx.doi.org/10.1080/08941930390215033 [18] Gavela, T., Cabeza, B., Serrano, A. and Casado-Flores, J. (2012) C-Reactive Protein and Procalcitonin Are Predictors of the Severity of Acute Appendicitis in Children. Pediatric Emergency Care, 28, 416-419.
http://dx.doi.org/10.1097/PEC.0b013e318252d875 [19] Groselj-Grenc, M., Repse, S., Dolenc-Strazar, Z., Hojker, S. and Derganc, M. (2007) Interleukin-6 and Lipopolysaccharide-Binding Protein in Acute Appendicitis in Children. Scandinavian Journal of Clinical and Laboratory Investigation, 67, 197-206.
http://dx.doi.org/10.1080/00365510601010397 [20] Huckins, D.S., Simon, H.K., Copeland, K., Spiro, D.M., Gogain, J. and Wandell, M. (2013) A Novel Biomarker Panel to Rule out Acute Appendicitis in Pediatric Patients with Abdominal Pain. American Journal of Emergency Medicine, 3, 1368-1375.
http://dx.doi.org/10.1016/j.ajem.2013.06.016 [21] Kanat, B.H., Ayten, R., Aydin, S., Girgin, M., Cetinkaya, Z., Ilhan, Y.S., Yur, M. and Catak, Z. (2014) Significance of Appetite Hormone Ghrelin and Obestatin Levels in the Assessment of the Severity of Acute Pancreatitis. Turkish Journal of Gastroenterology, 25, 309-313.
http://dx.doi.org/10.5152/tjg.2014.4081 [22] Brailoiu, G.C., Dun, S.L., Brailoiu, E., Inan, S., Yang, J., Chang, J.K. and Dun, N.J. (2007) Nesfatin-1: Distribution and Interaction with a G Protein-Coupled Receptor in the Rat Brain. Endocrinology, 148, 5088-5094.
http://dx.doi.org/10.1210/en.2007-0701 [23] Stengel, A., Goebel-Stengel, M., Jawien, J., Kobelt, P., Taché, Y. and Lambrecht, N.W. (2011) Lipopolysaccharide Increases Gastric and Circulating NUCB2/Nesfatin-1 Concentrations in Rats. Peptides, 32, 1942-1947.
http://dx.doi.org/10.1016/j.peptides.2011.07.006 [24] Stengel, A., Goebel-Stengel, M., Wang, L., Shaikh, A., Lambrecht, N.W., Rivier, J. and Tache, Y. (2011) Abdominal Surgery Inhibits Circulating Acyl Ghrelin and Ghrelin-O-Acyl Transferase Levels in Rats: Role of the Somatostatin Receptor Subtype 2. American Journal of Physiology—Gastrointestinal and Liver Physiology, 301, G239-G248.
http://dx.doi.org/10.1152/ajpgi.00018.2011
[1] Nance, M.L., Adamson, W.T. and Hedrick, H.L. (2000) Appendicitis in the Young Child: A Continuing Diagnostic Challenge. Pediatric Emergency Care, 16, 160-162.
http://dx.doi.org/10.1097/00006565-200006000-00005 [2] Alvarado, A. (1986) A Practical Score for the Early Diagnosis of Acute Appendicitis. Annals of Emergency Medicine, 15, 557-564.
http://dx.doi.org/10.1016/S0196-0644(86)80993-3 [3] Apak, S., Kazez, A., Ozel, S.K., Ustundag, B., Akpolat, N. and Kizirgil, A. (2005) Spot Urine 5-Hydroxyindoleacetic Acid Levels in the Early Diagnosis of Acute Appendicitis. Journal of Pediatric Surgery, 40, 1436-1439.
http://dx.doi.org/10.1016/j.jpedsurg.2005.05.042 [4] Bakal, U., Sarac, M., Ciftci, H., Tartar, T. and Kazez, A. (2014) Neutrophil Gelatinase-Associated Lipocalin (NGAL) May Be Support in the Diagnosis of Acute Appendicitis. 32nd National Congress of Pediatric Surgery in Trabzon, Turkey, 17-20 September 2012, 138. [5] Branescu, C., Serban, C., Savlovschi, C., Dascalu, A.M. and Kraft, A. (2012) Lipopolysaccharide Binding Protein (L.B.P.)—An Inflammatory Marker of Prognosis in the Acute Appendicitis. Journal of Medicine and Life, 5, 342-347. [6] Rodriguez-Sanjuan, J.C., Martin-Parra, J.I., Seco, I., Garcia-Castrillo, L. and Naranjo, A. (1999) C-Reactive Protein and Leukocyte in the Diagnosis of Acute Appendicitis in Children. Diseases of the Colon & Rectum, 42, 1325-1329.
http://dx.doi.org/10.1007/BF02234223 [7] Flum, D.R. and Koepsell, T. (2002) The Clinical and Economic Correlates of Misdiagnosed Appendicitis: Nationwide Analysis. Archives of Surgery, 137, 799-804.
http://dx.doi.org/10.1001/archsurg.137.7.799 [8] Cetinkaya, Z., Aydin, S., Cerrahoglu, Y.Z., Ayten, R., Erman, F. and Aygen, E. (2009) Changes in Appetite Hormone (Ghrelin) Levels of Saliva and Serum in Acute Appendicitis Cases before and after Operation. Appetite, 52, 104-107.
http://dx.doi.org/10.1016/j.appet.2008.09.001 [9] Sand, M., Trullen, X.V., Bechara, F.G., Pala, X.F., Sand, D., Landgrafe, G. and Mann, B. (2009) A Prospective Bicenter Study Investigating the Diagnostic Value of Procalcitonin in Patients with Acute Appendicitis. European Surgical Research, 43, 291-297.
http://dx.doi.org/10.1159/000232939 [10] Ahima, R.S. and Flier, J.S. (2000) Leptin. Annual Review of Physiology, 62, 413-437.
http://dx.doi.org/10.1146/annurev.physiol.62.1.413 [11] Mc Conway, M.G., Johnson, D., Kelly, A., Griffin, D., Smith, J. and Wallace, A.M. (2000) Differences in Circulating Concentrations of Total, Free and Bound Leptin Relate to Gender and Body Composition in Adult Humans. Annals of Clinical Biochemistry, 37, 717-723.
http://dx.doi.org/10.1258/0004563001899771 [12] Farr, O.M., Gavrieli, A. and Mantzoros, C.S. (2015) Leptin Applications in 2015: What Have We Learned about Leptin and Obesity? Current Opinion in Endocrinology, Diabetes and Obesity, 22, 353-359.
http://dx.doi.org/10.1097/MED.0000000000000184 [13] Aydin, S. (2013) Multi-Functional Peptide Hormone NUCB2/Nesfatin-1. Endocrine, 44, 312-325.
http://dx.doi.org/10.1007/s12020-013-9923-0 [14] Oh, I., Shimizu, H., Satoh, T., Okada, S., Adachi, S., Inoue, K., Eguchi, H., Yamamoto, M., Imaki, T., Hashimoto, K., Tsuchiya, T., Monden, T., Horiguchi, K., Yamada, M. and Mori, M. (2006) Identification of Nesfatin-1 as a Satiety Molecule in the Hypothalamus. Nature, 443, 709-712.
http://dx.doi.org/10.1038/nature05162 [15] Mohebbi, H., Nourshahi, M., Ghasemikaram, M. and Safarimosavi, S. (2015) Effects of Exercise at Individual Anaerobic Threshold and Maximal Fat Oxidation Intensities on Plasma Levels of Nesfatin-1 and Metabolic Health Biomarkers. Journal of Physiology and Biochemistry, 71, 79-88.
http://dx.doi.org/10.1007/s13105-015-0383-2 [16] Aydin, S., Dag, E., Ozkan, Y., Arslan, O., Koc, G., Bek, S., Kirbas, S., Kasikci, T., Abasli, D., Gokcil, Z., Odabasi, Z. and Catak, Z. (2011) Time-Dependent Changes in the Serum Levels of Prolactin, Nesfatin-1 and Ghrelin as a Marker of Epileptic Attacks Young Male Patients. Peptides, 32, 1276-1280.
http://dx.doi.org/10.1016/j.peptides.2011.04.021 [17] Caglayan, F., Cakmak, M., Caglayan, O. and Cavusoglu, T. (2003) Plasma D-Lactate Levels in Diagnosis of Appendicitis. Journal of Investigative Surgery, 16, 233-237.
http://dx.doi.org/10.1080/08941930390215033 [18] Gavela, T., Cabeza, B., Serrano, A. and Casado-Flores, J. (2012) C-Reactive Protein and Procalcitonin Are Predictors of the Severity of Acute Appendicitis in Children. Pediatric Emergency Care, 28, 416-419.
http://dx.doi.org/10.1097/PEC.0b013e318252d875 [19] Groselj-Grenc, M., Repse, S., Dolenc-Strazar, Z., Hojker, S. and Derganc, M. (2007) Interleukin-6 and Lipopolysaccharide-Binding Protein in Acute Appendicitis in Children. Scandinavian Journal of Clinical and Laboratory Investigation, 67, 197-206.
http://dx.doi.org/10.1080/00365510601010397 [20] Huckins, D.S., Simon, H.K., Copeland, K., Spiro, D.M., Gogain, J. and Wandell, M. (2013) A Novel Biomarker Panel to Rule out Acute Appendicitis in Pediatric Patients with Abdominal Pain. American Journal of Emergency Medicine, 3, 1368-1375.
http://dx.doi.org/10.1016/j.ajem.2013.06.016 [21] Kanat, B.H., Ayten, R., Aydin, S., Girgin, M., Cetinkaya, Z., Ilhan, Y.S., Yur, M. and Catak, Z. (2014) Significance of Appetite Hormone Ghrelin and Obestatin Levels in the Assessment of the Severity of Acute Pancreatitis. Turkish Journal of Gastroenterology, 25, 309-313.
http://dx.doi.org/10.5152/tjg.2014.4081 [22] Brailoiu, G.C., Dun, S.L., Brailoiu, E., Inan, S., Yang, J., Chang, J.K. and Dun, N.J. (2007) Nesfatin-1: Distribution and Interaction with a G Protein-Coupled Receptor in the Rat Brain. Endocrinology, 148, 5088-5094.
http://dx.doi.org/10.1210/en.2007-0701 [23] Stengel, A., Goebel-Stengel, M., Jawien, J., Kobelt, P., Taché, Y. and Lambrecht, N.W. (2011) Lipopolysaccharide Increases Gastric and Circulating NUCB2/Nesfatin-1 Concentrations in Rats. Peptides, 32, 1942-1947.
http://dx.doi.org/10.1016/j.peptides.2011.07.006 [24] Stengel, A., Goebel-Stengel, M., Wang, L., Shaikh, A., Lambrecht, N.W., Rivier, J. and Tache, Y. (2011) Abdominal Surgery Inhibits Circulating Acyl Ghrelin and Ghrelin-O-Acyl Transferase Levels in Rats: Role of the Somatostatin Receptor Subtype 2. American Journal of Physiology—Gastrointestinal and Liver Physiology, 301, G239-G248.
http://dx.doi.org/10.1152/ajpgi.00018.2011