Association between serum netrin-1 level and obesity-related markers in obese subjects

Year 2022, Volume: 10 Issue: 2, 108 - 115, 26.08.2022

Çiğdem Aydın Acar , Niyazi Aydın , Suray Pehlivanoğlu , Mehmet Kök

https://doi.org/10.24998/maeusabed.1130028

Abstract

Netrins are important signaling proteins that guide both neural and vascular development. Netrin-1 regulates many physiological processes such as cell proliferation, adhesion and migration. The aim of this study was to determine the association between serum netrin-1 level and biochemical parameters in obese subjects. Serum samples were collected from obese (n=15) and control (n=30) subjects. The serum netrin-1 levels were evaluated by ELISA. Variable data were compared by Mann Whitney U test and correlation was estimated by Spearman correlation analyses. The level of circulating netrin-1 protein was determined to be significantly lower in obese group compared to controls. The median value was 844.0 pg/mL in the control group and 338 pg/mL in the obese group (p<0.0001). Serum netrin-1 level was negatively correlated with HbA1c, LDL, cholesterol and triglyceride (P< 0.01). In addition, ROC curve analysis indicated that netrin-1 level could define the presence of obesity with AUC value of 0.8667 (95% Cl=0.7249-1.000; P<0.0001). Our study suggests that netrin-1 secretions are significantly reduced in obese subjects and negatively correlated with obesity markers. Therefore, netrin-1 can be evaluated as a possible potential biomarker for obesity.

Keywords

Obesity, Netrin-1, ELISA, Biomarker

Supporting Institution

Burdur Mehmet Akif Ersoy University Scientific Research Rrojects Unit

Project Number

0648-YL-20

Thanks

This work was supported by the Burdur Mehmet Akif Ersoy University Scientific Research Rrojects Unit [Project number: 0648-YL-20].

Obez bireylerde serum netrin-1 düzeyi ve obezite ile ilgili belirteçler arasındaki ilişki

Abstract

Netrinler, hem nöral hem de vasküler gelişime rehberlik eden önemli sinyal proteinleridir. Netrin-1 hücre çoğalması, yapışması ve göçü gibi birçok fizyolojik süreci düzenler. Bu çalışmanın amacı obez bireylerde serum netrin-1 düzeyi ile biyokimyasal parametreler arasındaki ilişkiyi belirlemektir. Obez (n=15) ve kontrol (n=30) bireylerden serum örnekleri alındı. Serum netrin-1 seviyeleri ELISA ile değerlendirildi. Değişken veriler Mann Whitney U testi ile karşılaştırıldı ve korelasyon Spearman korelasyon analizleri ile belirlendi. Obez grupta serumda netrin-1 protein seviyesinin kontrollere göre anlamlı derecede düşük olduğu belirlendi. Ortanca değer kontrol grubunda 844,0 pg/mL ve obez grupta 338 pg/mL idi (p<0,0001). Serum netrin-1 düzeyi HbA1c, LDL, kolesterol ve trigliserit ile negatif korelasyon gösterdi (P< 0.01). Ayrıca, ROC eğrisi analizi, netrin-1 seviyesinin 0.8667 AUC değeri ile obezite varlığını tanımlayabildiğini gösterdi (%95 Cl=0.7249-1.000; P<0.0001). Çalışmamız, netrin-1 salınımının obez bireylerde önemli ölçüde azaldığını ve obezite belirteçleri ile negatif korele olduğunu göstermektedir. Bu nedenle netrin-1, obezite için olası bir potansiyel biyobelirteç olarak değerlendirilebilir.

Keywords

Obezite, Netrin-1, ELISA, Biyobelirteç

Project Number

0648-YL-20

References

• Ay, E., Marakoglu, K., Kizmaz, M., Unlu, A., 2016. Evaluation of Netrin-1 Levels and Albuminuria in Patients With Diabetes. J Clin Lab Anal 30(6), 972-977.
• Aydin Acar, C., Pehlivanoglu, S., Kok, M., Yilmaz, G., 2021. Evaluation of serum levels of Netrin-1 as a potential biomarker for early prediction of prediabetes. Turkish Journal of Health Science and Life 4(2), 70-76.
• Bakhshi, E., Eshraghian, M.R., Mohammad, K., Foroushani, A.R., Zeraati, H., Fotouhi A et al. (2008). Sociodemographic and smoking associated with obesity in adult women in Iran: results from the National Health Survey. J Public Health (Oxf) 30(4), 429-35.
• Cayir, A., Atak, N., Kose, S.K., (2011). Assessment of Obesity Frequency and Related Factors on Individuals Attending to the Department of Nutrition and Dietetics. Ankara Üniversitesi Tıp Fakültesi Mecmuası 64(1), 13-19.
• Deepa, M., Farooq, S., Deepa, R., Manjula, D., Mohan, V., (2009). Prevalence and significance of generalized and central body obesity in an urban Asian Indian population in Chennai, India (CURES: 47). Eur J Clin Nutr 63(2), 259-67.
• Gorur, A., Unal, A. D., Tamer, L., (2018). Role of Netrin-1 in Cardiovascular Diseases. Archives Medical Review Journal 27(4), 440-458.
• Liu, C., Ke, X., Wang, Y., Feng, X., Li, Q., Zhang, Y., Zhu, J., Li, Q., (2016). The level of netrin-1 is decreased in newly diagnosed type 2 diabetes mellitus patients. BMC Endocr Disord 16(1), 33.
• Lu, X., Le Noble, F., Yuan, L., Jiang, Q., De Lafarge, B., Sugiyama, D., Bréant, C., Claes , F., De Smet, F., Thomas, J.L., Autiero, M., Carmeliet, P., Tessier-Lavigne, M., Eichmann, A., (2004). The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 432(7014), 179-86.
• Mayoral, L.P., Andrade, G.M., Mayoral, E.P., Huerta, T.H., Canseco, S.P., Rodal Canales, F.J., Cabrera-Fuentes, H.A., Cruz, M.M., Pérez Santiago, A.D., Alpuche, J.J., Zenteno, E., Ruíz, H.M., Cruz, R.M., Jeronimo, J.H., Perez-Campos, E., (2020). Obesity subtypes, related biomarkers & heterogeneity. Indian J Med Res 151(1), 11-21.
• Mehlen, P., Furne, C., (2005). Netrin-1: when a neuronal guidance cue turns out to be a regulator of tumorigenesis. Cell Mol Life Sci 62(22), 2599-616.
• Moore, K.J., Fisher, E.A., (2012). Macrophages, atherosclerosis and the potential of netrin-1 as a novel target for future therapeutic intervention. Future Cardiol 8(3), 349-52.
• Nedeva, I., Gateva, A., Assyov, Y., Karamfilova, V., Velikova, T., Kamenov, Z., (2020). Relationship between circulating netrin-1 levels, obesity, prediabetes and newly diagnosed type 2 diabetes. Arch Physiol Biochem. 2020, 1-6.
• Ovunc Hacihamdioglu, D., Hacihamdioglu, B., Altun, D., Muftuoglu, T., Karademir, F., Suleymanoglu, S., (2016). Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children. J Clin Res Pediatr Endocrinol 8(3), 282-7.
• Park, K.W., Crouse, D., Lee, M., Karnik, S.K., Sorensen, L.K., Murphy, K.J., Kuo, C.J., Li, D.Y., (2004). The axonal attractant Netrin-1 is an angiogenic factor. Proc Natl Acad Sci U S A. 101(46), 16210-5.
• Rajasekharan, S., Kennedy, T.E., (2009). The netrin protein family. Genome Biol 10(9), 239.
• Ramesh, G., Berg, A., Jayakumar, C., (2011). Plasma netrin-1 is a diagnostic biomarker of human cancers. Biomarkers 16(2), 172-80.
• Ramesh, G., (2012). Role of Netrin-1 Beyond the Brain: From Biomarker of Tissue Injury to Therapy for Inflammatory Diseases. Recent Pat Biomark 2(3), 202-208.
• Wang, W., Reeves, W.B., Pays, L., Mehlen, P., Ramesh, G., (2009). Netrin-1 overexpression protects kidney from ischemia reperfusion injury by suppressing apoptosis. Am J Pathol 175(3), 1010-8.
• Wang, W., Reeves, W.B., Ramesh, G., (2008). Netrin-1 and kidney injury. I. Netrin-1 protects against ischemia-reperfusion injury of the kidney. Am J Physiol Renal Physiol 294, F739–F747.
• Yim, J., Kim, G., Lee, B.W., Kang, E.S., Cha, B.S., Kim, J.H., Cho, J.W., Lee, S.G., Lee, Y.H., (2018). Relationship Between Circulating Netrin-1 Concentration, Impaired Fasting Glucose, and Newly Diagnosed Type 2 Diabetes. Front Endocrinol (Lausanne) 9, 691.