Horm Metab Res 2017; 49(06): 446-451
DOI: 10.1055/s-0042-122782
Endocrine Care

The Effects of Omega-3 Fatty Acids Supplementation on Gene Expression Involved in the Insulin and Lipid Signaling Pathway in Patients with Polycystic Ovary Syndrome

Khadijeh Nasri
1   Maternal-Fetal & Neonatal Research Center and Breast Feeding Research Center, Tehran University of Medical Sciences, Tehran, Iran
2   Department of Gynecology and Obstetrics, Endocrinology and Metabolism Research Center, School of Medicine, Arak University of Medical Sciences, Arak, Iran
,
Sedigheh Hantoushzadeh
1   Maternal-Fetal & Neonatal Research Center and Breast Feeding Research Center, Tehran University of Medical Sciences, Tehran, Iran
,
Esmat Aghadavod
3   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
,
Mohsen Taghizadeh
3   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
,
Zatollah Asemi
3   Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
› Author Affiliations

Abstract

Limited data are available evaluating the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid-signaling pathway in women with polycystic ovary syndrome (PCOS). This study was conducted to evaluate the effects of omega-3 fatty acids supplementation on gene expression involved in the insulin and lipid signaling pathway in women with PCOS. This randomized double blind, placebo-controlled trial was done among 60 women aged 18–40 years old and diagnosed with PCOS according to the Rotterdam criteria. Participants were randomly assigned into 2 groups to receive either 1 000 mg omega-3 fatty acids from flaxseed oil containing 400 mg α-linolenic acid (n=30) or placebo (n=30) twice a day for 12 weeks. Gene expressions involved in the insulin and lipid-signaling pathway were quantified in blood samples of PCOS women with RT-PCR method. Quantitative results of RT-PCR demonstrated that compared with the placebo, omega-3 fatty acids supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) mRNA (p=0.005) in peripheral blood mononuclear cells of women with PCOS. In addition, compared to the placebo, omega-3 fatty acids supplementation downregulated expressed levels of oxidized low-density lipoprotein receptor (LDLR) mRNA (p=0.002) in peripheral blood mononuclear cells of women with PCOS. We did not observe any significant effect of omega-3 fatty acids supplementation on expressed levels of glucose transporter 1 (GLUT-1) and lipoprotein(a) [Lp(a)] genes in peripheral blood mononuclear cells. Overall, omega-3 fatty acids supplementation for 12 weeks in PCOS women significantly improved gene expression of PPAR-γ and LDLR.

Supporting Information



Publication History

Received: 27 July 2016

Accepted: 24 November 2016

Article published online:
24 February 2017

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Azziz R. Introduction: Determinants of polycystic ovary syndrome. Fertil Steril 2016; 106: 4-5
  • 2 Barber TM, Dimitriadis GK, Andreou A, Franks S. Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance. Clin Med (Lond) 2016; 16: 262-266
  • 3 Jamil AS, Alalaf SK, Al-Tawil NG, Al-Shawaf T. A case-control observational study of insulin resistance and metabolic syndrome among the 4 phenotypes of polycystic ovary syndrome based on Rotterdam criteria. Reprod Health 2015; 12: 7
  • 4 Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012; 33: 981-1030
  • 5 Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 2001; 111: 607-613
  • 6 Karakas SE, Perroud B, Kind T, Palazoglu M, Fiehn O. Changes in plasma metabolites and glucose homeostasis during omega-3 polyunsaturated fatty acid supplementation in women with polycystic ovary syndrome. BBA Clin 2016; 5: 179-185
  • 7 Derosa G, Cicero AF, D’Angelo A, Borghi C, Maffioli P. Effects of n-3 pufas on fasting plasma glucose and insulin resistance in patients with impaired fasting glucose or impaired glucose tolerance. Biofactors 2016; 42: 316-322
  • 8 Soleimani A, Taghizadeh M, Bahmani F, Badroj N, Asemi Z. Metabolic response to omega-3 fatty acid supplementation in patients with diabetic nephropathy: A randomized, double-blind, placebo-controlled trial. Clin Nutr 2015; Nov 11. pii: S0261-5614(15)00274-5
  • 9 Mohammadi E, Rafraf M, Farzadi L, Asghari-Jafarabadi M, Sabour S. Effects of omega-3 fatty acids supplementation on serum adiponectin levels and some metabolic risk factors in women with polycystic ovary syndrome. Asia Pac J Clin Nutr 2012; 21: 511-518
  • 10 Phelan N, O’Connor A, Kyaw Tun T, Correia N, Boran G, Roche HM, Gibney J. Hormonal and metabolic effects of polyunsaturated fatty acids in young women with polycystic ovary syndrome: results from a cross-sectional analysis and a randomized, placebo-controlled, crossover trial. Am J Clin Nutr 2011; 93: 652-662
  • 11 Zaree M, Shahnazi V, Fayezi S, Darabi M, Mehrzad-Sadaghiani M, Khani S, Khani S, Nouri M. Expression Levels of PPARgamma and CYP-19 in Polycystic Ovarian Syndrome Primary Granulosa Cells: Influence of omega-3 Fatty Acid. Int J Fertil Steril 2015; 9: 197-204
  • 12 Chen H, Li D, Chen J, Roberts GJ, Saldeen T, Mehta JL. EPA and DHA attenuate ox-LDL-induced expression of adhesion molecules in human coronary artery endothelial cells via protein kinase B pathway. J Mol Cell Cardiol 2003; 35: 769-775
  • 13 Coyne GS, Kenny DA, Childs S, Sreenan JM, Waters SM. Dietary n-3 polyunsaturated fatty acids alter the expression of genes involved in prostaglandin biosynthesis in the bovine uterus. Theriogenology 2008; 70: 772-782
  • 14 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004; 81: 19-25
  • 15 Huang A, Brennan K, Azziz R. Prevalence of hyperandrogenemia in the polycystic ovary syndrome diagnosed by the National Institutes of Health 1990 criteria. Fertil Steril 2010; 93: 1938-1941
  • 16 Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, O’Brien WL, Bassett Jr DR, Schmitz KH, Emplaincourt PO, Jacobs Jr DR, Leon AS. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000; 32: S498-S504
  • 17 Otomo K, Amengual O, Fujieda Y, Nakagawa H, Kato M, Oku K, Horita T, Yasuda S, Matsumoto M, Nakayama KI, Hatakeyama S, Koike T, Atsumi T. Role of apolipoprotein B100 and oxidized low-density lipoprotein in the monocyte tissue factor induction mediated by anti-beta2 glycoprotein I antibodies. Lupus 2016; 25: 1288-1298
  • 18 Hatch R, Rosenfield RL, Kim MH, Tredway D. Hirsutism: implications, etiology, and management. Am J Obstet Gynecol 1981; 140: 815-830
  • 19 Kolodziejczyk B, Duleba AJ, Spaczynski RZ, Pawelczyk L. Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome. Fertil Steril 2000; 73: 1149-1154
  • 20 Olsen EA, Hordinsky MK, Price VH, Roberts JL, Shapiro J, Canfield D, Duvic M, King Jr LE, McMichael AJ, Randall VA, Turner ML, Sperling L, Whiting DA, Norris D. Alopecia areata investigational assessment guidelines–Part II. National Alopecia Areata Foundation. J Am Acad Dermatol 2004; 51: 440-447
  • 21 Dunkley PR, Jarvie PE, Robinson PJ. A rapid Percoll gradient procedure for preparation of synaptosomes. Nat Protoc 2008; 3: 1718-1728
  • 22 Kozera B, Rapacz M. Reference genes in real-time PCR. J Appl Genet 2013; 54: 391-406
  • 23 Barber RD, Harmer DW, Coleman RA, Clark BJ. GAPDH as a housekeeping gene: analysis of GAPDH mRNA expression in a panel of 72 human tissues. Physiol Genomics 2005; 21: 389-395
  • 24 Mozdziak PE, Dibner JJ, McCoy DW. Glyceraldehyde-3-phosphate dehydrogenase expression varies with age and nutrition status. Nutrition 2003; 19: 438-440
  • 25 Asemi Z, Esmaillzadeh A. DASH diet, insulin resistance, and serum hs-CRP in polycystic ovary syndrome: a randomized controlled clinical trial. Horm Metab Res 2015; 47: 232-238
  • 26 Jamilian M, Razavi M, Fakhrie Kashan Z, Ghandi Y, Bagherian T, Asemi Z. Metabolic response to selenium supplementation in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Clin Endocrinol (Oxf) 2015; 82: 885-891
  • 27 Anderson EJ, Thayne KA, Harris M, Shaikh SR, Darden TM, Lark DS, Williams JM, Chitwood WR, Kypson AP, Rodriguez E. Do fish oil omega-3 fatty acids enhance antioxidant capacity and mitochondrial fatty acid oxidation in human atrial myocardium via PPARgamma activation?. Antioxid Redox Signal 2014; 21: 1156-1163
  • 28 Yang L, Yuan J, Liu L, Shi C, Wang L, Tian F, Liu F, Wang H, Shao C, Zhang Q, Chen Z, Qin W, Wen W. alpha-linolenic acid inhibits human renal cell carcinoma cell proliferation through PPAR-gamma activation and COX-2 inhibition. Oncol Lett 2013; 6: 197-202
  • 29 Mansoori A, Sotoudeh G, Djalali M, Eshraghian MR, Keramatipour M, Nasli-Esfahani E, Shidfar F, Alvandi E, Toupchian O, Koohdani F. Effect of DHA-rich fish oil on PPARgamma target genes related to lipid metabolism in type 2 diabetes: A randomized, double-blind, placebo-controlled clinical trial. J Clin Lipidol 2015; 9: 770-777
  • 30 Grindflek E, Sundvold H, Lien S, Rothschild MF. Rapid communication: physical and genetic mapping of the Peroxisome Proliferator Activated Receptor gamma (PPAR-gamma) gene to porcine chromosome 13. J Anim Sci 2000; 78: 1391-1392
  • 31 Strakova N, Ehrmann J, Bartos J, Malikova J, Dolezel J, Kolar Z. Peroxisome proliferator-activated receptors (PPAR) agonists affect cell viability, apoptosis and expression of cell cycle related proteins in cell lines of glial brain tumors. Neoplasma 2005; 52: 126-136
  • 32 Itoh T, Fairall L, Amin K, Inaba Y, Szanto A, Balint BL, Nagy L, Yamamoto K, Schwabe JW. Structural basis for the activation of PPARgamma by oxidized fatty acids. Nat Struct Mol Biol 2008; 15: 924-931
  • 33 Gani OA. Are fish oil omega-3 long-chain fatty acids and their derivatives peroxisome proliferator-activated receptor agonists?. Cardiovasc Diabetol 2008; 7: 6
  • 34 Nenseter MS, Drevon CA. Dietary polyunsaturates and peroxidation of low density lipoprotein. Curr Opin Lipidol 1996; 7: 8-13
  • 35 Gajos G, Zalewski J, Mostowik M, Konduracka E, Nessler J, Undas A. Polyunsaturated omega-3 fatty acids reduce lipoprotein-associated phospholipase A(2) in patients with stable angina. Nutr Metab Cardiovasc Dis 2014; 24: 434-439
  • 36 Nomura S, Kanazawa S, Fukuhara S. Effects of eicosapentaenoic acid on platelet activation markers and cell adhesion molecules in hyperlipidemic patients with Type 2 diabetes mellitus. J Diabetes Complications 2003; 17: 153-159
  • 37 Nestel PJ, Pomeroy SE, Sasahara T, Yamashita T, Liang YL, Dart AM, Jennings GL, Abbey M, Cameron JD. Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arterioscler Thromb Vasc Biol 1997; 17: 1163-1170
  • 38 Yamagata K, Suzuki S, Tagami M. Docosahexaenoic acid prevented tumor necrosis factor alpha-induced endothelial dysfunction and senescence. Prostaglandins Leukot Essent Fatty Acids 2016; 104: 11-18
  • 39 Yamagata K, Tusruta C, Ohtuski A, Tagami M. Docosahexaenoic acid decreases TNF-alpha-induced lectin-like oxidized low-density lipoprotein receptor-1 expression in THP-1 cells. Prostaglandins Leukot Essent Fatty Acids 2014; 90: 125-132
  • 40 Faghihi T, Jahed A, Mahmoudi-Gharaei J, Sharifi V, Akhondzadeh S, Ghaeli P. Role of Omega-3 fatty acids in preventing metabolic disturbances in patients on olanzapine plus either sodium valproate or lithium: a randomized double-blind placebo-controlled trial. Daru 2012; 20: 43
  • 41 Colussi GL, Baroselli S, Sechi L. Omega-3 polyunsaturated fatty acids decrease plasma lipoprotein(a) levels in hypertensive subjects. Clin Nutr 2004; 23: 1246-1247
  • 42 Herrmann W, Biermann J, Kostner GM. Comparison of effects of N-3 to N-6 fatty acids on serum level of lipoprotein(a) in patients with coronary artery disease. Am J Cardiol 1995; 76: 459-462
  • 43 Ishigaki Y, Oka Y, Katagiri H. Circulating oxidized LDL: a biomarker and a pathogenic factor. Curr Opin Lipidol 2009; 20: 363-369
  • 44 Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, Ginsberg H, Amarenco P, Catapano A, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 2010; 31: 2844-2853
  • 45 Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Lipoprotein(a) and risk of myocardial infarction–genetic epidemiologic evidence of causality. Scand J Clin Lab Invest 2011; 71: 87-93
  • 46 Steinberg D, Witztum JL. Oxidized low-density lipoprotein and atherosclerosis. Arterioscler Thromb Vasc Biol 2010; 30: 2311-2316
  • 47 Huang ZG, Liang C, Han SF, Wu ZG. Vitamin E ameliorates ox-LDL-induced foam cells formation through modulating the activities of oxidative stress-induced NF-kappaB pathway. Mol Cell Biochem 2012; 363: 11-19
  • 48 Oner G, Muderris II. Efficacy of omega-3 in the treatment of polycystic ovary syndrome. J Obstet Gynaecol 2013; 33: 289-291
  • 49 Nadjarzadeh A, Dehghani-Firouzabadi R, Daneshbodi H, Lotfi MH, Vaziri N, Mozaffari-Khosravi H. Effect of Omega-3 Supplementation on Visfatin, Adiponectin, and Anthropometric Indices in Women with Polycystic Ovarian Syndrome. J Reprod Infertil 2015; 16: 212-220