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Effect of Chromium Supplementation on Element Distribution in a Mouse Model of Polycystic Ovary Syndrome

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Abstract

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder and one of the most common causes of anovulatory infertility. In addition, insulin resistance is commonly associated with PCOS and contributed to pathophysiology connected to dietary minerals including chromium (Cr), copper (Cu), iron (Fe), and zinc (Zn). The aims of this study were to explore whether PCOS in mice alters levels of these elements and determine if Cr supplementation resolves changes. Twenty-four female BALB/c mice were divided into three groups of eight mice [normal control (NC), PCOS + placebo milk (PP), and PCOS + Cr-containing milk (PCr)]. Each group received a high-fat diet for 4 weeks. Our results show significantly higher levels of dehydroepiandrosterone (DHEA) (p < 0.001), fasting glucose (p < 0.05), and fasting insulin (p < 0.05) in the PP group compared with both NC and PCr group. However, Cr levels were significantly lower in muscle, bone, and serum in the PP group (p < 0.05) compared with NC and PCr groups. In liver, bone, and serum, Fe levels were significantly higher in the PP group compared with the NC group (p < 0.05). In addition, we found significant correlations between Cu/Zn ratio and fasting insulin in all mice (r = 0.61; p = 0.002). Given that significant research shows that Cr supplementation improves fasting glucose, fasting insulin, and metal metabolism disorders for PCOS mice, our data suggest that trace element levels can serve as biomarkers to prescribe therapeutic supplementation to maintain a healthy metabolic balance and treat disease conditions.

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Abbreviations

PCOS:

Polycystic ovary syndrome

Cr:

Chromium

Cu:

Copper

Fe:

Iron

Zn:

Zinc

NC:

Normal control

PP:

PCOS + placebo milk

PCr:

PCOS + Cr-containing milk

DHEA:

Dehydroepiandrosterone

HFD:

High-fat diet

DIO:

Diet-induced obese

SC:

Subcutaneous

IFG:

Impaired fasting glucose

IGT:

Impaired glucose tolerance

Cu-Zn SOD:

Cu-Zn superoxide dismutase

MCO:

Multi-copper oxidase

References

  1. Boyle J, Teede HJ (2012) Polycystic ovary syndrome-an update. Aust Fam Physician 41:752–756

    PubMed  Google Scholar 

  2. Hung JH, Hu LY, Tsai SJ et al (2014) Risk of psychiatric disorders following polycystic ovary syndrome: a nationwide population-based cohort study. PLoS One 9:e97041

    Article  PubMed Central  PubMed  Google Scholar 

  3. March WA, Moore VM, Willson KJ et al (2010) The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 25:544–551

    Article  PubMed  Google Scholar 

  4. Sirmans SM, Pate KA (2014) Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 6:1–13

    PubMed Central  Google Scholar 

  5. The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group (2014) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19:41–47

    Article  Google Scholar 

  6. Zawadzki JK, Dunaif A (1992) Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR (eds) Polycystic ovary syndrome. Blackwell Scientific, Boston, pp 377–384

    Google Scholar 

  7. Dunaif A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18:774–800

    CAS  PubMed  Google Scholar 

  8. Welt CK, Duran JM (2014) Genetics of polycystic ovary syndrome. Semin Reprod Med 32:177–182

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Chen WY, Chen CJ, Liu CH et al (2009) Chromium supplementation enhances insulin signalling in skeletal muscle of obese KK/HlJ diabetic mice. Diabetes Obes Metab 11:293–303

    Article  CAS  PubMed  Google Scholar 

  10. Chen WY, Chen CJ, Liao JW et al (2009) Chromium attenuates hepatic damage in a rat model of chronic cholestasis. Life Sci 84:606–614

    Article  CAS  Google Scholar 

  11. Amooee S, Parsanezhad ME, Ravanbod Shirazi M et al (2013) Metformin versus chromium picolinate in clomiphene citrate-resistant patients with PCOs: A double-blind randomized clinical trial. Iran J Reprod Med 11:611–618

    PubMed Central  CAS  PubMed  Google Scholar 

  12. Flores CR, Puga MP, Wrobel K et al (2011) Trace elements status in diabetes mellitus type 2: possible role of the interaction between molybdenum and copper in the progress of typical complications. Diabetes Res Clin Pract 91(3):333–341

    Article  CAS  PubMed  Google Scholar 

  13. Viktorínová A, Toserová E, Krizko M et al (2009) Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus. Metabolism 58(10):1477–1482

    Article  PubMed  Google Scholar 

  14. Xu J, Zhou Q, Liu G et al (2013) Analysis of serum and urinal copper and zinc in Chinese northeast population with the prediabetes or diabetes with and without complications. Oxid Med Cell Longev 2013:635214

    Article  PubMed Central  PubMed  Google Scholar 

  15. Celik C, Bastu E, Abali R et al (2013) The relationship between copper, homocysteine and early vascular disease in lean women with polycystic ovary syndrome. Gynecol Endocrinol 29(5):488–491

    Article  CAS  PubMed  Google Scholar 

  16. Chakraborty P, Ghosh S, Goswami SK et al (2013) Altered trace mineral milieu might play an aetiological role in the pathogenesis of polycystic ovary syndrome. Biol Trace Elem Res 152:9–15

    Article  CAS  PubMed  Google Scholar 

  17. Zheng G, Wang L, Guo Z et al. (2015) Association of serum heavy metals and trace element concentrations with reproductive hormone levels and polycystic ovary syndrome in a Chinese population. Biol Trace Elem Res (epub ahead of print)

  18. Kurdoglu Z, Kurdoglu M, Demir H et al (2012) Serum trace elements and heavy metals in polycystic ovary syndrome. Hum Exp Toxicol 31:452–456

    Article  CAS  PubMed  Google Scholar 

  19. Beletate V, El Dib R, Atallah ÁN (2007) Zinc supplementation for the prevention of type 2 diabetes mellitus. Cochrane Database Syst Rev 1:CD005525

    PubMed  Google Scholar 

  20. Foroozanfard F, Jamilian M, Jafari Z et al (2015) Effects of zinc supplementation on markers of insulin resistance and lipid profiles in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Exp Clin Endocrinol Diabetes 123(4):215–220

    Article  CAS  PubMed  Google Scholar 

  21. Pourteymour Fard Tabrizi F, Alipoor B, Sadagiani M et al (2010) Effect of zinc supplementation on cardiometabolic risk factors in women with polycystic ovary syndrome. J Cardiovasc Thorac Res 2:11–20

    Google Scholar 

  22. Guler I, Himmetoglu O, Turp A et al (2014) Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance. Biol Trace Elem Res 158(3):297–304

    Article  CAS  PubMed  Google Scholar 

  23. Noda Y, Ota K, Shirasawa T et al (2012) Copper/zinc superoxide dismutase insufficiency impairs progesterone secretion and fertility in female mice. Biol Reprod 86(1):1–8

    Article  PubMed  Google Scholar 

  24. Ho YS, Gargano M, Cao J et al (1998) Reduced fertility in female mice lacking copper-zinc superoxide dismutase. J Biol Chem 273(13):7765–7769

    Article  CAS  PubMed  Google Scholar 

  25. Escobar-Morreale HF (2012) Iron metabolism and the polycystic ovary syndrome. Trends Endocrinol Metab 23:509–515

    Article  CAS  PubMed  Google Scholar 

  26. Luque-Ramírez M, Alvarez-Blasco F, Botella-Carretero JI et al (2007) Increased body iron stores of obese women with polycystic ovary syndrome are a consequence of insulin resistance and hyperinsulinism and are not a result of reduced menstrual losses. Diabetes Care 30(9):2309–2313

    Article  PubMed  Google Scholar 

  27. Sam AH, Busbridge M, Amin A et al (2013) Hepcidin levels in diabetes mellitus and polycystic ovary syndrome. Diabet Med 30(12):1495–1499

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Luque-Ramírez M, Álvarez-Blasco F, Alpañés M et al (2011) Role of decreased circulating hepcidin concentrations in the iron excess of women with the polycystic ovary syndrome. J Clin Endocrinol Metab 96(3):846–852

    Article  PubMed  Google Scholar 

  29. Kim JW, Kang KM, Yoon TK et al (2014) Study of circulating hepcidin in association with iron excess, metabolic syndrome, and BMP-6 expression in granulosa cells in women with polycystic ovary syndrome. Fertil Steril 102(2):548–554

    Article  CAS  PubMed  Google Scholar 

  30. Turner-McGrievy G, Davidson CR, Billings DL (2015) Dietary intake, eating behaviors, and quality of life in women with polycystic ovary syndrome who are trying to conceive. Hum Fertil (Camb) 18(1):16–21

    Article  CAS  Google Scholar 

  31. Anderson RA (1997) Chromium as an essential nutrient for humans. Regul Toxicol Pharmacol 26(1 Pt 2):S35–S41

    Article  CAS  PubMed  Google Scholar 

  32. Mertz W (1993) Chromium in human nutrition: a review. J Nutr 123(4):626–633

    CAS  PubMed  Google Scholar 

  33. Di Bona KR, Love S, Rhodes NR et al (2011) Chromium is not an essential trace element for mammals: effects of a “low-chromium” diet. J Biol Inorg Chem 16(3):381–390

    Article  PubMed  Google Scholar 

  34. Vincent JB (2015) Is the pharmacological mode of action of chromium (III) as a second messenger? Biol Trace Elem Res (epub ahead of print)

  35. Yoshida M (2012) Is chromium an essential trace element in human nutrition? Nihon Eiseigaku Zasshi 67(4):485–491

    Article  CAS  PubMed  Google Scholar 

  36. Król E, Krejpcio Z, Michalak S et al (2012) Effects of combined dietary chromium(III) propionate complex and thiamine supplementation on insulin sensitivity, blood biochemical indices, and mineral levels in high-fructose-fed rats. Biol Trace Elem Res 150(1–3):350–359

    Article  PubMed Central  PubMed  Google Scholar 

  37. Vincent JB (2013) Chromium: is it essential, pharmacologically relevant, or toxic? Met Ions Life Sci 13:171–198

    Article  PubMed  Google Scholar 

  38. Pei D, Hsieh CH, Hung YJ et al (2006) The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism 55:923–927

    Article  CAS  PubMed  Google Scholar 

  39. Chen YL, Lin JD, Hsia TL et al (2014) The effect of chromium on inflammatory markers, 1st and 2nd phase insulin secretion in type 2 diabetes. Eur J Nutr 53:127–133

    Article  CAS  PubMed  Google Scholar 

  40. Staniek H, Rhodes NR, Di Bona KR et al (2013) Comparison of tissue metal concentrations in Zucker lean, Zucker obese, and Zucker diabetic fatty rats and the effects of chromium supplementation on tissue metal concentrations. Biol Trace Elem Res 151(3):373–383

    Article  CAS  PubMed  Google Scholar 

  41. Lucidi RS, Thyer AC, Easton CA et al (2005) Effect of chromium supplementation on insulin resistance and ovarian and menstrual cyclicity in women with polycystic ovary syndrome. Fertil Steril 84:1755–1757

    Article  CAS  PubMed  Google Scholar 

  42. Lydic ML, McNurlan M, Bembo S et al (2006) Chromium picolinate improves insulin sensitivity in obese subjects with polycystic ovary syndrome. Fertil Steril 86(1):243–246

    Article  CAS  PubMed  Google Scholar 

  43. Vincent JB (2013) The bioinorganic chemistry of chromium(III). Wiley, Chichester

    Google Scholar 

  44. Amr N, Abdel-Rahim HE (2015) The effect of chromium supplementation on polycystic ovary syndrome in adolescents. J Pediatr Adolesc Gynecol 28(2):114–118

    Article  PubMed  Google Scholar 

  45. Solano ME, Sander VA, Ho H et al (2011) Systemic inflammation, cellular influx and up-regulation of ovarian VCAM-1 expression in a mouse model of polycystic ovary syndrome (PCOS). J Reprod Immunol 92:33–44

    Article  CAS  PubMed  Google Scholar 

  46. Chen PW, Lin C, Chen CD et al (2013) Chromium levels in insulin-sensitive tissues and the thigh bone are modulated by prednisolone and high-fat diets in mice. Biometals 26:347–354

    Article  CAS  PubMed  Google Scholar 

  47. Lin C, Chen P, Chen W et al (2013) Glucagon and insulin have opposite effects on tissue chromium distribution in an obese mouse model. J Diabetes Investig 4:528–532

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Dowling AR, Nedorezov LB, Qiu X et al (2013) Genetic factors modulate the impact of pubertal androgen excess on insulin sensitivity and fertility. PLoS ONE 8:e79849

    Article  PubMed Central  PubMed  Google Scholar 

  49. van Houten EL, Visser JA (2014) Mouse models to study polycystic ovary syndrome: a possible link between metabolism and ovarian function? Reprod Biol 14:32–43

    Article  PubMed  Google Scholar 

  50. Sharifi F, Nasab NM, Zadeh HJ (2008) Elevated serum ferritin concentrations in prediabetic subjects. Diab Vasc Dis Res 5:15–18

    Article  PubMed  Google Scholar 

  51. Bennett R, Adams B, French A et al (2006) High-dose chromium(III) supplementation has no effects on body mass and composition while altering plasma hormone and triglycerides concentrations. Biol Trace Elem Res 113(1):53–66

    Article  CAS  PubMed  Google Scholar 

  52. Sohrabvand F, Shirazi M, Shariat M et al (2013) Serum zinc level in infertile women with and without polycystic ovary syndrome: a comparative study. Tehran Univ Med 71:157–163

    CAS  Google Scholar 

  53. Lim TH, Sargent T III, Kusubov N (1983) Kinetics of trace element chromium(III) in the human body. Am J Physiol 244:R445–R454

    CAS  PubMed  Google Scholar 

  54. Ibricevic D, Asimi ZV (2013) Frequency of prediabetes in women with polycystic ovary syndrome. Med Arch 67:282–285

    Article  PubMed  Google Scholar 

  55. Rafiei R, Habyby Z, Fouladi L et al (2014) Chromium level in prediction of diabetes in pre-diabetic patients. Adv Biomed Res 3:235

    Article  PubMed Central  PubMed  Google Scholar 

  56. Kottwitz K, Laschinsky N, Fischer R et al (2009) Absorption, excretion and retention of 51Cr from labelled Cr-(III)-picolinate in rats. Biometals 22(2):289–295

    Article  CAS  PubMed  Google Scholar 

  57. Vincent JB (2000) The biochemistry of chromium. J Nutr 130(4):715–718

    CAS  PubMed  Google Scholar 

  58. Campbell WW, Beard JL, Joseph LJ (1997) Chromium picolinate supplementation and resistive training by older men: effects on iron-status and hematologic indexes. Am J Clin Nutr 66:944–949

    CAS  PubMed  Google Scholar 

  59. Lukaski HC, Siders WA, Penland JG (2007) Chromium picolinate supplementation in women: effects on body weight, composition, and iron status. Nutrition 23:187–195

    Article  CAS  PubMed  Google Scholar 

  60. Tawfeeq FR, Abbas MR, Abdul Kareem Y (2008) Serum copper, zinc and Cu/Zn ratio in diabetics. Iraqi J Comm Med 21:64–68

    Google Scholar 

  61. Zheng Y, Li XK, Wang Y et al (2008) The role of zinc, copper and iron in the pathogenesis of diabetes and diabetic complications: therapeutic effects by chelators. Hemoglobin 32(1–2):135–145

    Article  CAS  PubMed  Google Scholar 

  62. González F, Rote NS, Minium J et al (2006) Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab 91(1):336–340

    Article  PubMed  Google Scholar 

  63. Kelly CC, Lyall H, Petrie JR et al (2001) Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 86(6):2453–2455

    Article  CAS  PubMed  Google Scholar 

  64. Gaier ED, Kleppinger A, Ralle M et al (2012) High serum Cu and Cu/Zn ratios correlate with impairments in bone density, physical performance and overall health in a population of elderly men with frailty characteristics. Exp Gerontol 47(7):491–496

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  65. Malavolta M, Giacconi R, Piacenza F et al (2010) Plasma copper/zinc ratio: an inflammatory /nutritional biomarker as predictor of all-cause mortality in elderly population. Biogerontology 11(3):309–319

    Article  CAS  PubMed  Google Scholar 

  66. Guo CH, Chen PC, Yeh MS et al (2011) Cu/Zn ratios are associated with nutritional status, oxidative stress, inflammation, and immune abnormalities in patients on peritoneal dialysis. Clin Biochem 44(4):275–280

    Article  CAS  PubMed  Google Scholar 

  67. Shrivastava R, Upreti RK, Seth PK et al (2002) Effects of chromium on the immune system. FEMS Immunol Med Microbiol 34(1):1–7

    Article  CAS  PubMed  Google Scholar 

  68. Walters KA, Allan CM, Handelsman DJ (2012) Rodent models for human polycystic ovary syndrome. Biol Reprod 86(149):11–12

    Google Scholar 

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Acknowledgment

This work was supported by the Ministry of Education (Taiwan) under the Aim for the Top University (ATU) plan.

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The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, 402, Taiwan

    Tsung-Sheng Chen, Yi-Ting Chen & Frank Chiahung Mao

  2. Department of Research and Development, Maxluck Biotechnology Corporation, Taichung, 402, Taiwan

    Chia-Hsin Liu & Chi-Ching Sun

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  1. Tsung-Sheng Chen
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Correspondence to Frank Chiahung Mao.

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Chen, TS., Chen, YT., Liu, CH. et al. Effect of Chromium Supplementation on Element Distribution in a Mouse Model of Polycystic Ovary Syndrome. Biol Trace Elem Res 168, 472–480 (2015). https://doi.org/10.1007/s12011-015-0384-6

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