مطالعه سطح سرمی Angiopoietin-like protein 4 در زنان مبتلا به سندرم تخمدان پلی‌کیستیک با توده بدنی نرمال

نوع مقاله : اصیل پژوهشی

نویسندگان

1 دانشیار گروه زنان و مامایی، دانشکده پزشکی، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران.

2 دانشیار گروه بیوشیمی بالینی، دانشکده پزشکی، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران.

3 دانشجوی پزشکی، دانشکده پزشکی، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران.

4 دانشیار گروه پزشکی اجتماعی، دانشکده پزشکی، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران.

5 کارشناس علوم آزمایشگاهی، مرکز تحقیقات طب گرمسیری خلیج فارس، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران.

6 دانشجوی کارشناسی ارشد بیوشیمی، دانشکده پزشکی، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران.

7 کارشناس ارشد فیزیولوژی پزشکی، مرکز تحقیقات طب گرمسیری خلیج فارس، دانشگاه علوم پزشکی بوشهر، بوشهر، ایران.

چکیده

مقدمه: سندرم تخمدان پلی‌کیستیک (PCOS) یک بیماری اندوکرین پیچیده در زنان می‌باشد و تقریباً 75% از زنان PCOS دچار افزایش وزن هستند. Angiopoietin-like protein 4 (ANGPTL4) مهار‌کننده قوی آنزیم لیپوپروتئین ‌لیپاز (LPL) می‌باشد. این پروتئین تعیین‌کننده غلظت و کلیرانس تری‌گلیسرید ‌پلاسما می‌باشد. مطالعه حاضر با هدف بررسی سطح سرمی ANGPTL4 در زنان PCOS با شاخص توده بدنی نرمال انجام شد.
روش‌‌کار: این مطالعه مورد- شاهدی در سال 95-1394 بر روی 47 زن مراجعه کننده به درمانگاه ابوالفضل وابسته به دانشگاه علوم پزشکی بوشهر انجام شد. در این مطالعه 25 زن  PCOSبه روش غیر‌احتمالی آسان و بر اساس معیار‌های تشخیصی روتردام (2003) به عنوان گروه مورد و 22 زن سالم به عنوان گروه شاهد انتخاب شدند. سطح سرمی تمام هورمون‌ها به کمک تکنیک الایزا و پارامترهای بیوشیمیایی نیز به کمک اتوآنالیزر اندازه‌گیری شد. تجزیه و تحلیل داده‌ها با استفاده از نرم‌افزار آماری  SPSS(نسخه 16) و آزمون‌های تی مستقل، من ویتنی و رگرسیون خطی انجام شد. میزان p‌ کمتر از 05/0 معنادار در نظر گرفته شد.
یافته‌ها: نتایج این مطالعه افزایش معناداری در میزان LH (003/0=p)،  LH/FSH(007/0=p)، FBS (03/0=p)، تستوسترون (02/0=p) و پرولاکتین (005/0=p) در گروه مورد نشان داد. تفاوت معناداری در میزان ANGPTL4، انسولین، HOMA-IR، لیپوپروتئین‌های با چگالی پایین (LDL)، HDL، HOMA-B و کراتینین در گروه مورد نسبت به گروه شاهد مشاهده نشد. ارتباط معکوس و معناداری بین سطح سرمی ANGPTL4 با لگاریتم انسولین (002/0=p)، FBS (006/0=p)، لگاریتم HOMA-IR (001/0=p) و شاخص توده بدنی (03/0=p) وجود داشت، اما ارتباطی بین ANGPTL4 و پارامترهای لیپیدی مشاهده نشد.
نتیجه‌گیری: در مطالعه حاضر تفاوت معناداری در سطح سرمی ANGPTL4 در زنان مبتلا به تخمدان پلی‌کیستیک با توده بدنی نرمال در مقایسه با گروه شاهد مشاهده نشد.

کلیدواژه‌ها

عنوان مقاله [English]

Serum levels of angiopoietin-like protein 4 in polycystic ovary syndrome women with normal body mass index

نویسندگان [English]

  • Elham Rahmani 1
  • Samad Akbarzadeh 2
  • Abdollah Nazari 3
  • Niloofar Motamed 4
  • Soraya Ghodrati 5
  • Anahita Abasi Fard 6
  • Marzieh Zohrabi 7
1 Associate Professor, Department of Obstetrics and Gynecology, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
2 Associate Professor, Department of Clinical Biochemistry, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
3 Medical Student, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
4 Associate Professor, Department of Social Medicine, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
5 B.Sc. in Laboratory Sciences, Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran.
6 M.Sc. Student of Clinical Biochemistry, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
7 M.Sc. in Medical Physiology, Gulf Tropical Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran.
چکیده [English]

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women, and approximately 75% of women affected by PCOS are overweight. Angiopoietin-like protein 4 (ANGPTL4) is a potent inhibitor of lipoprotein lipase (LPL) enzyme. This protein is a determinant of plasma concentration and clearance of triglyceride. In this study, we aimed to evaluate the serum levels of ANGPTL4 in PCOS women with normal body mass index (BMI).
Methods: A case-control study of 47 women visiting Abolfazle Clinic, affiliated to Bushehr University of Medical Sciences, was performed during 2015-2016. In this study, 25 PCOS women were assigned to the case group through simple non-probable sampling based on the Rotterdam 2003 criteria. Further, 22 healthy women were selected for the control group. Serum levels of all hormones were measured by the ELISA technique, and biochemical parameters were evaluated by an autoanalyser. The obtained data were analyzed using independent samples t-test, Mann-Whitney U test, and linear regression test in SPSS, version 16. P-values less than 0.05 were considered statistically significant.
Results: The results of this study showed a significant increase in LH (P=0.003), LH/FSH (P= 0.007), FBS (P= 0.03), testosterone (P= 0.02), and prolactin (P= 0.005) levels in the case group. There was no significant difference in the levels of ANGPTL4, insulin, HOMA-IR, low-density lipoprotein (LDL), HDL, HOMA-B, and creatinine between the groups. There was a significant negative correlation between serum level of ANGPTL4 and insulin logarithm (P=0.002), FBS (P=0.006), HOMA-IR logarithm (P=0.001), and BMI (P=0.03), but no correlation was found between ANGPTL4 and lipid parameters.
Conclusion: We found no significant difference between the PCOS women with normal BMI and the controls regarding serum levels of ANGPTL4.

کلیدواژه‌ها [English]

  • Polycystic ovary syndrome (PCOS)
  • Angiopoietin-like protein 4 (ANGPTL4)
  • Lipoprotein lipase (LPL)
  • Normal BMI

مراجع

  1. Lord J, Wilkin T. Polycystic ovary syndrome and fat distribution: the central issue? Hum Fertil (Camb) 2002; 5(2):67-71.
  2. Kirchengast S, Huber J. Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 2001; 16(6):1255-60.
  3. Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19(1):41-7.
  4. Franks S, McCarthy MI, Hardy K. Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int J Androl 2006; 29(1):278-85.
  5. Akbarzadeh S, Ghasemi S, Kalantarhormozi M, Nabipour I, Abbasi F, Aminfar A, et al. Relationship among plasma adipokines, insulin and androgens level as well as biochemical glycemic and lipidemic markers with incidence of PCOS in women with normal BMI. Gynecol Endocrinol 2012; 28(7):521-4.
  6. Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB. Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1985; 61(5):946-51.
  7. Jalilian N, Haghnazari L, Rasolinia S. Leptin and body mass index in polycystic ovary Syndrome. Indian J Endocrinol Metab 2016; 20(3):324-8.
  8. Minooee S, Ramezani Tehrani F, Mirmiran P, Azizi F. Low birth weight may increase body fat mass in adult women with polycystic ovarian syndrome. Int J Reprod Biomed 2016; 14(5):335-40.
  9. La Paglia L, Listì A, Caruso S, Amodeo V, Passiglia F, Bazan V, et al. Potential role of ANGPTL4 in the cross talk between metabolism and cancer through PPAR signaling pathway. PPAR Res 2017; 2017:8187235.
  10. Mandard S, Zandbergen F, Van Straten E, Wahli W, Kuipers F, Muller M, et al. The fasting-induced adipose factor/angiopoietin-like protein 4 is physically associated with lipoproteins and governs plasma lipid levels and adiposity. J Biol Chem 2006; 281(2):934-44.
  11. Jonker JT, Smit JW, Hammer S, Snel M, van der Meer RW, Lamb HJ, et al. Dietary modulation of plasma angiopoietin-like protein 4 concentrations in healthy volunteers and in patients with type 2 diabetes. Am J Clin Nutr 2013; 97(2):255-60.
  12. Ortega-Senovilla H, Schaefer-Graf U, Meitzner K, Abou-Dakn M, Herrera E. Decreased concentrations of the lipoprotein lipase inhibitor angiopoietin-like protein 4 and increased serum triacylglycerol are associated with increased neonatal fat mass in pregnant women with gestational diabetes mellitus. J Clin Endocrinol Metab 2013; 98(8):3430-7.
  13. Adachi H, Kondo T, Koh GY, Nagy A, Oike Y, Araki E. Angptl4 deficiency decreases serum triglyceride concentrations in low-density lipoprotein receptor knockout mice and streptozotocin-induced diabetic mice. Biochem Biophys Res Commun 2011; 409(2):177-80.
  14. Kersten S. Regulation of lipid metabolism via angiopoietin- like proteins. Biochem Soc Trans 2005; 33(Pt 5):1059-62.
  15. Sukonina V, Lookene A, Olivecrona T, Olivecrona G. Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue. Proc Natl Acad Sci U S A 2006; 103(46):17450-5.
  16. Brands M, Sauerwein HP, Ackermans MT, Kersten S, Serlie MJ. Omega-3 long-chain fatty acids strongly induce angiopoietin-like 4 in humans. J Lipid Res 2013; 54(3):615-21.
  17. van der Kolk BW, Goossens GH, Jocken JW, Kersten S, Blaak EE. Angiopoietin-like protein 4 and postprandial skeletal muscle lipid metabolism in overweight and obese prediabetics. J Clin Endocrinol Metab 2016; 101(6):2332-9.
  18. Glintborg D, Andersen M. An update on the pathogenesis, inflammation, and metabolism in hirsutism and polycystic ovary syndrome. Gynecol Endocrinol 2010; 4:281-96.
  19. Tjeerdema N, Georgiadi A, Jonker JT, van Glabbeek M, Alizadeh Dehnavi R, Tamsma JT, et al. Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes. BMJ Open Diabetes Res Care 2014; 2(1):e000034.
  20. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18(6):499-502.
  21. Chutia H, Lynrah KG. Association of serum magnesium deficiency with insulin resistance in type 2 diabetes mellitus. J Lab Physicians 2015; 7(2):75-8.
  22. Nasrat H, Patra SK, Goswami B, Jain A, Raghunandan C. Study of association of leptin and insulin resistance markers in patients of PCOS. Indian J Clin Biochem 2016; 31(1):104-7.
  23. Chen MJ, Chou CH, Chen SU, Yang WS, Yang YS, Ho HN. The effect of androgens on ovarian follicle maturation: dihydrotestosterone suppress FSH-stimulated granulosa cell proliferation by upregulating PPARγ-dependent PTEN expression. Sci Rep 2015; 5:18319.
  24. Morin-Papunen LC, Vauhkonen I, Koivunen RM, Ruokonen A, Tapanainen JS. Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovarian syndrome. Hum Reprod 2000; 15(6):1266-74.
  25. Bonakdaran S, Barazandeh Ahmadabadi F. Assessment of insulin resistance in idiopathic hirsutism in comparison with polycystic ovary syndrome (PCOS) patients and healthy individuals. Med J Mashhad Univ Med Sci 2014; 56(6):340-6. (Persian).
  26. Sheehan MT. Polycystic ovarian syndrome: diagnosis and management. Clin Med Res 2004; 2(1):13-27.
  27. Eftekhar M, Dehghani Firouzabadi R, Karimi H, Rahmani E. Outcome of cryopreserved-thawed embryo transfer in the GnRH agonist versus antagonist protocol. Iran J Reprod Med 2012; 10(4):297-302.
  28. Szosland K, Pawlowicz P, Lewiński A. Prolactin secretion in polycystic ovary syndrome (PCOS). Neuro Endocrinol Lett 2015; 36(1):53-8.
  29. Gupta N, Radhakrishnan G, Madhu SV, Radhika AG. Comparison of metabolic and endocrinal parameters in obese and nonobese women of polycystic ovarian syndrome with normal controls. Fertil Sci Res 2015; 2(1):19-23.
  30. Banaszewska B, Spaczyński RZ, Pelesz M, Pawelczyk L. Incidence of elevated LH/FSH ratio in polycystic ovary syndrome women with normo- and hyperinsulinemia. Rocz Akad Med Bialymst 2003; 48:131-4.
  31. Mizutani N, Ozaki N, Seino Y, Fukami A, Sakamoto E, Fukuyama T, et al. Reduction of insulin signaling upregulates angiopoietin-like protein 4 through elevated free fatty acids in diabetic mice. Exp Clin Endocrinol Diabetes 2012; 120(3):139-44.
  32. Yoshida K, Shimizugawa T, Ono M, Furukawa H. Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase. J Lipid Res 2002; 43(11):1770-2.
  33. Koster A, Chao YB, Mosior M, Ford A, Gonzalez-De Whitt PA, Hale JE, et al. Transgenic angiopoietin-like (angptl)4 overexpression and targeted disruption of angptl4 and angptl3: regulation of triglyceride metabolism. Endocrinology 2005; 146(11):4943-50.
  34. Kersten S, Mandard S, Tan NS, Escher P, Metzger D, Chambon P, et al. Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J Biol Chem 2000; 275(37):28488-93.
  35. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395(6704):763-70.
  36. Robciuc MR, Naukkarinen J, Ortega-Alonso A, Tyynismaa H, Raivio T, Rissanen A, et al. Serum angiopoietin-like 4 protein levels and expression in adipose tissue are inversely correlated with obesity in monozygotic twins. J Lipid Res 2011; 52(8):1575-82.
  37. Xu A, Lam MC, Chan KW, Wang Y, Zhang J, Hoo RL, et al. Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice. Proc Natl Acad Sci U S A 2005; 102(17):6086-91.
Ruge T, Sukonina V, Kroupa O, Makoveichuk E, Lundgren M, Svensson MK, et al. Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipopro-tein binding protein 1 in subjects with and without type 2 diabetes mellitus. Metabolism 2012; 61(5):652-60.
مجله زنان، مامایی و نازایی ایران

دوره 21، شماره 2
اردیبهشت 1397
صفحه 1-8

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