Investigation of serum neprilysin levels in overweight and normal weight young women

Abstract

Background: In this study we aimed to evaluate biochemical, lipid and glycemic parameters and to compare serum neprilysin levels between overweight (OW) and normal weight (NW) young women who are more prone to gain weight. Material and Methods: A total of 28 overweight/obese women aged between 22-34 years and 34 age matched normal-weight women were included in this cross-sectional study on voluntary basis. of the subjects were performed, Participants’ anthropometric measurements, hormone profiles, glycemic parameters and insulin resistance, and serum neprilysin levels were recorded and analyzed. Patients were evaluated in two groups as Group OW and Group NW. Results: The mean ALT, TSH and uric acid values were statistically significantly higher in Group OW compared to Group NW (for all, p<0.05). The mean HDL-c was statistically significantly lower in Group OW than in Group NW (p<0.01), while the mean triglyceride level was significantly higher in Group OW than in Group NW (p=0.002). The mean fasting blood glucose, insulin, HOMA, HbA1c and triglyceride values were statistically significantly higher in Group OW compared to Group NW (for all, p<0.001). The mean neprilysin (NEP) value was found as 1123.44±1327.60 mmol/L in Group NW and 1229.39±1315.17 mmol/L in Group OW with no statistically significant difference between the groups. No significant correlation was found between NEP and BMI values. Conclusions: In this study, no significant difference was found between serum neprilysin levels of overweight/obese and normal weight women, suggesting that neprilysin does not play a role in the pathogenesis of obesity, insulin resistance or diabetes.

Keywords

• Obesity
• Neprilysin
• insulin resistance
• diabetes
• lipid profile

References

1. Sand AS, Emaus N, Lian O. Overweight and obesity in young adult women: A matter of health or appearance? The Tromsø study: Fit futures. Int J Qual Stud Health Well-being. 2015 Sep 22;10:29026. doi: 10.3402/qhw.v10.29026.
2. Tan HS, Habib AS. Obesity in women: anaesthetic implications for peri-operative and peripartum management. Anaesthesia. 2021 Apr;76 Suppl 4:108-117. doi: 10.1111/anae.15403.
3. Wondmkun YT. Obesity, insulin resistance, and type 2 diabetes: Associations and therapeutic implications. Diabetes Metab Syndr Obes. 2020 Oct 9;13:3611-6. doi: 10.2147/DMSO. S275898.
4. Wane S, van Uffelen JG, Brown W. Determinants of weight gain in young women: a review of the literature. J Womens Health (Larchmt). 2010 Jul;19(7):1327-40. doi: 10.1089/jwh.2009.1738.
5. Turner AJ. Neprilysin. In: Barret AJ, Rawlings ND, Woessner JF, eds. Handbook of Proteolytic Enzymes. Amsterdam: Elsevier; 2004;419-26.
6. Standeven KF, Hess K, Carter AM, Rice GI, Cordell PA, Balmforth AJ, Lu B, Scott DJ, Turner AJ, Hooper NM, Grant PJ. Neprilysin, obesity and the metabolic syndrome. Int J Obes (Lond). 2011 Aug;35(8):1031-40. doi: 10.1038/ijo.2010.227.
7. Moro C. Targeting cardiac natriuretic peptides in the therapy of diabetes and obesity. Expert Opin Ther Targets. 2016 Dec;20(12):1445-52. doi: 10.1080/14728222.2016.1254198.
8. Schling P, Schäfer T. Human adipose tissue cells keep tight control on the angiotensin II levels in their vicinity. J Biol Chem. 2002 Dec 13;277(50):48066-75. doi: 10.1074/jbc.M204058200.

9. Arbin V, Claperon N, Fournié-Zaluski MC, Roques BP, Peyroux J. Effects of dual angiotensin-converting enzyme and neutral endopeptidase 24-11 chronic inhibition by mixanpril on insulin sensitivity in lean and obese Zucker rats. J Cardiovasc Pharmacol. 2003 Feb;41(2):254-64. doi: 10.1097/00005344- 200302000-00015.
10. Wang CH, Leung N, Lapointe N, Szeto L, Uffelman KD, Giacca A, Rouleau JL, Lewis GF. Vasopeptidase inhibitor omapatrilat induces profound insulin sensitization and increases myocardial glucose uptake in Zucker fatty rats: Studies comparing a vasopeptidase inhibitor, angiotensin-converting enzyme inhibitor, and angiotensin II type I receptor blocker. Circulation. 2003 Apr 15;107(14):1923-9. doi: 10.1161/01. CIR.0000062646.09566.CC.
11. Rice GI, Jones AL, Grant PJ, Carter AM, Turner AJ, Hooper NM. Circulating activities of angiotensin-converting enzyme, its homolog, angiotensin-converting enzyme 2, and neprilysin in a family study. Hypertension. 2006 Nov;48(5):914-20. doi: 10.1161/01.HYP.0000244543.91937.79.
12. Jordan J, Stinkens R, Jax T, Engeli S, Blaak EE, May M, Havekes B, Schindler C, Albrecht D, Pal P, Heise T, Goossens GH, Langenickel TH. Improved insulin sensitivity with angiotensin receptor neprilysin inhibition in individuals with obesity and hypertension. Clin Pharmacol Ther. 2017 Feb;101(2):254-63. doi: 10.1002/cpt.455.
13. Willard JR, Barrow BM, Zraika S. Improved glycaemia in high- fat-fed neprilysin-deficient mice is associated with reduced DPP-4 activity and increased active GLP-1 levels. Diabetologia. 2017 Apr;60(4):701-8. doi: 10.1007/s00125-016-4172-4.
14. Link DG. Obesity in women: Paying a high price. Nurs Clin North Am. 2021 Dec;56(4):609-17. doi: 10.1016/j. cnur.2021.07.005.
15. Kulie T, Slattengren A, Redmer J, Counts H, Eglash A, Schrager S. Obesity and women’s health: an evidence-based review. J Am Board Fam Med. 2011 Jan-Feb;24(1):75-85. doi: 10.3122/ jabfm.2011.01.100076.
16. Faulkner JL. Obesity-associated cardiovascular risk in women: hypertension and heart failure. Clin Sci (Lond). 2021 Jun 25;135(12):1523-44. doi: 10.1042/CS20210384.
17. Jönsson J, Renault KM, García-Calzón S, et al. Lifestyle intervention in pregnant women with obesity impacts cord blood DNA methylation, Which associates with body composition in the offspring. Diabetes. 2021;70(4):854-66. doi:10.2337/db20- 0487.
18. Stranges S, Dorn JM, Muti P, Freudenheim JL, Farinaro E, Russell M, Nochajski TH, Trevisan M. Body fat distribution, relative weight, and liver enzyme levels: a population-based study. Hepatology. 2004 Mar;39(3):754-63. doi: 10.1002/ hep.20149.
19. Kim J, Jo I. Relationship between body mass index and alanine aminotransferase concentration in non-diabetic Korean adults. Eur J Clin Nutr. 2010 Feb;64(2):169-75. doi: 10.1038/ ejcn.2009.131.
20. Choi HK, Mount DB, Reginato AM; American College of Physicians; American Physiological Society. Pathogenesis of gout. Ann Intern Med. 2005 Oct 4;143(7):499-516. doi: 10.7326/0003-4819-143-7-200510040-00009.
21. Duan Y, Liang W, Zhu L, Zhang T, Wang L, Nie Z, Chen Y, He L, Jin Y, Yao Y. Association between serum uric acid levels and obesity among university students (China). Nutr Hosp. 2015 Jun 1;31(6):2407-11. doi: 10.3305/nh.2015.31.6.8734.
22. Ciarla S, Struglia M, Giorgini P, Striuli R, Necozione S, Properzi G, Ferri C. Serum uric acid levels and metabolic syndrome. Arch Physiol Biochem. 2014 Jul;120(3):119-22. doi: 10.3109/13813455.2014.924145.
23. de Oliveira A, Hermsdorff HHM, Guedes Cocate P, Bressan J, Azevedo Novello A, Cardoso dos Santos E, José Natali A. The impact of serum uric acid on the diagnostic of metabolic syndrome in apparently healthy brazilian middle-aged men. Nutr Hosp. 2014 Sep 1;30(3):562-9. doi: 10.3305/nh.2014.30.3.7540.
24. Walczak K, Sieminska L. Obesity and Thyroid Axis. Int J Environ Res Public Health. 2021 Sep 7;18(18):9434. doi: 10.3390/ijerph18189434.