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Effects of Ovariectomy and Exercise Training on Mineral Status in a High-Fat Diet-Induced Obesity Rat Model

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Abstract

Osteoporosis is a growing public health issue for an aging society. Previous studies have found both beneficial and detrimental effects of obesity on bone health. The purpose of this study was to investigate the impact of estrogen deficiency and physical activity on bone and blood concentrations of macrominerals (Ca, P, and Mg) and microminerals (Zn, Se, Cu, and Fe) in a high-fat diet-induced obesity rat model. Forty-eight female Wistar rats were divided into six groups: sham-operated and ovariectomized rats that received a standard diet (SD), high-fat diet (HFD), or HFD accompanied by physical exercise. The effect of ovariectomy on bone minerals varied with diet. Ovariectomy significantly decreased femoral Ca and Mg in sedentary rats receiving a SD; femoral Se, Cu, Zn, and Fe in sedentary rats on HFD; and plasma Fe in both sedentary rats on SD and exercising rats on HFD. The interaction of ovariectomy and diet had the strongest impact on Mg and Se concentrations in femur. In ovariectomized rats, HFD showed to have a protective effect on bone mineralization (femoral Ca and Mg), and a negative one on antioxidant microminerals (femoral Se, Cu, and Zn). Physical activity reduced the decline of Se, Cu, Zn, and Fe in the femur of ovariectomized rats on HFD. In the current state of knowledge, it is difficult to suggest if decreased femoral levels of antioxidant microminerals may contribute to the pathophysiology of osteoporosis in obese individuals or just reflect the mineral status in the body.

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Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BMD:

bone mineral density

HFD:

high-fat diet

Ovx:

ovariectomized

R:

running

S:

sedentary

SD:

standard diet

Sham:

sham-operated

References

  1. Sozen T, Ozısık L, Basaran NC (2017) An overview and management of osteoporosis. Eur J Rheumatol 4(1):46–56. https://doi.org/10.5152/eurjrheum.2016.048

    Article  PubMed  Google Scholar 

  2. Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA (2008) The laboratory rat as an animal model for osteoporosis research. Comp Med 58(5):424–430

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Favus MJ, Bushinsky DA, Lemann J Jr (2006) Regulation of calcium, magnesium, and phosphate metabolism. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th edn. American Society for Bone and Mineral Research, Washington, DC, pp 76–117

    Google Scholar 

  4. Feng X, McDonald JM (2011) Disorders of bone remodeling. Annu Rev Pathol 6:121–145. https://doi.org/10.1146/annurev-pathol-011110-130203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. de Baaij JHF, Joost GJ, Hoenderop JGJ, Bindels RJM (2015) Magnesium in man: implications for health and disease. Physiol Rev 95(1):1–46. https://doi.org/10.1152/physrev.00012.2014

    Article  CAS  PubMed  Google Scholar 

  6. Odabasi E, Turan M, Aydin A, Akay C, Kutlu M (2008) Magnesium, zinc, copper, manganese, and selenium levels in postmenopausal women with osteoporosis. Can magnesium play a key role in osteoporosis? Ann Acad Med Singap 37(7):564–567

    PubMed  Google Scholar 

  7. Zeng H, Cao JJ, Combs GF Jr (2013) Selenium in bone health: roles in antioxidant protection and cell proliferation. Nutrients 5(1):97–110. https://doi.org/10.3390/nu5010097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Karita K, Yamanouchi Y, Takano T, Oku J, Kisaki T, Yano E (2008) Associations of blood selenium and serum lipid levels in Japanese premenopausal and postmenopausal women. Menopause 15(1):119–124. https://doi.org/10.1097/gme.0b013e31806bf32c

    Article  PubMed  Google Scholar 

  9. Hoeg A, Gogakos A, Murphy E, Mueller S, Kohrle J, Reid DM, Gluer CC, Felsenberg D, Roux C, Eastell R, Schomburg L, Williams GR (2012) Bone turnover and bone mineral density are independently related to selenium status in healthy euthyroid postmenopausal women. J Clin Endocrinol Metab 97:4061–4070. https://doi.org/10.1210/jc.2012-2121

    Article  CAS  PubMed  Google Scholar 

  10. Pepa GD, Brandi ML (2016) Microelements for bone boost: the last but not the least. Clin Cases Miner Bone Metab 13(3):181–185. https://doi.org/10.11138/ccmbm/2016.13.3.181

    Article  PubMed  Google Scholar 

  11. Qu X, He Z, Qiao H, Zhai Z, Mao Z, Yu Z, Dai K (2018) Serum copper levels are associated with bone mineral density and total fracture. J Orthop Translat 14:34–44. https://doi.org/10.1016/j.jot.2018.05.001

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yamaguchi M (2010) Role of nutritional zinc in the prevention of osteoporosis. Mol Cell Biochem 338(1-2):241–254. https://doi.org/10.1007/s11010-009-0358-0

    Article  CAS  PubMed  Google Scholar 

  13. Grochans E, Karakiewicz B, Kozielec T, Brodowska A, Brodowski J, Starczewski A, Laszczynska M, Nocen I, Grzywacz A, Samochowiec A, Chlubek D (2011) Serum Mg and Zn levels in postmenopausal women. Magnes Res 24(4):209–214. https://doi.org/10.1684/mrh.2011.0300

    Article  CAS  PubMed  Google Scholar 

  14. D’Amelio P, Cristofaro MA, Tamone C, Morra E, Di Bella S, Isaia G, Grimaldi A, Gennero L, Gariboldi A, Ponzetto A, Pescarmona GP, Isaia GC (2008) Role of iron metabolism and oxidative damage in postmenopausal bone loss. Bone 43(6):1010–1015. https://doi.org/10.1016/j.bone.2008.08.107

    Article  CAS  PubMed  Google Scholar 

  15. Reid IR (2010) Fat and bone. Arch Biochem Biophys 503(1):20–27. https://doi.org/10.1016/j.abb.2010.06.027

    Article  CAS  PubMed  Google Scholar 

  16. Greco EA, Lenzi A, Migliaccio S (2015) The obesity of bone. Ther Adv Endocrinol Metab 6(6):273–286. https://doi.org/10.1177/2042018815611004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fan Y, Zhang C, Bu J (2017) Relationship between selected serum metallic elements and obesity in children and adolescent in the U.S. Nutrients 9(2):104. https://doi.org/10.3390/nu9020104

    Article  CAS  PubMed Central  Google Scholar 

  18. Skalnaya MG, Skalny AV, Grabeklis AR, Serebryansky EP, Demidov VA, Tinkov AA (2018) Hair trace elements in overweight and obese adults in association with metabolic parameters. Biol Trace Elem Res 186(1):12–20. https://doi.org/10.1007/s12011-018-1282-5

    Article  CAS  PubMed  Google Scholar 

  19. Blazewicz A, Klatka M, Astel A, Korona-Glowniak I, Dolliver W, Szwerc W, Kocjan R (2015) Serum and urinary selenium levels in obese children: a cross-sectional study. J Trace Elem Med Biol 29:116–122. https://doi.org/10.1016/j.jtemb.2014.07.016

    Article  CAS  PubMed  Google Scholar 

  20. Celik N, Andiran N (2011) The relationship between serum phosphate levels with childhood obesity and insulin resistance. J Pediatr Endocrinol Metab 24(1-2):81–83. https://doi.org/10.1515/jpem.2011.116

    Article  CAS  PubMed  Google Scholar 

  21. Baltaci AK, Mogulkoc R, Baltaci SB (2019) The role of zinc in the endocrine system. Pak J Pharm Sci 32(1):231–239

    CAS  PubMed  Google Scholar 

  22. Aigner E, Feldman A, Datz C (2014) Obesity as an emerging risk factor for iron deficiency. Nutrients 6(9):3587–3600. https://doi.org/10.3390/nu6093587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ren XH, Yao YS, He LP, Jin YL, Chang WW, Li J, Chen Y, Song XL, Tang H, Ding LL, Guo DX, Li CP (2013) Overweight and obesity associated with increased total serum calcium level: comparison of cross-sectional data in the health screening for teaching faculty. Biol Trace Elem Res 156(1-3):74–78. https://doi.org/10.1007/s12011-013-9856-8

    Article  CAS  PubMed  Google Scholar 

  24. Kapetanovic A, Avdic D (2013) Physical activity and bone mineral density in postmenopausal women without estrogen deficiency in menstrual history. J Health Sci 2(3):205–209. https://doi.org/10.17532/jhsci.2013.108

    Article  Google Scholar 

  25. Alghadir AH, Gabr SA, Al-Eisa ES, Alghadir MH (2016) Correlation between bone mineral density and serum trace elements in response to supervised aerobic training in older adults. Clin Interv Aging 11:265–273. https://doi.org/10.2147/CIA.S100566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Skrypnik D, Bogdanski P, Skrypnik K, Madry E, Karolkiewicz J, Szulinska M, Suliburska J, Walkowiak J (2019) Influence of endurance and endurance-strength training on mineral status in women with abdominal obesity: a randomized trial. Medicine 98(12):e14909. https://doi.org/10.1097/MD.0000000000014909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Elkomy MM, Elsaid FG (2015) Anti-osteoporotic effect of medical herbs and calcium supplementation on ovariectomized rats. JOBAZ 72:81–88. https://doi.org/10.1016/j.jobaz.2015.04.007

    Article  CAS  Google Scholar 

  28. Mizoguchi T, Nagasawa S, Takahashi N, Yagasaki H, Ito M (2005) Dolomite supplementation improves bone metabolism through modulation of calcium-regulating hormone secretion in ovariectomized rats. J Bone Miner Metab 23(2):140–146. https://doi.org/10.1007/s00774-004-0552-9

    Article  CAS  PubMed  Google Scholar 

  29. Baltaci AK, Sunar F, Mogulkoc R, Acar M, Toy H (2014) The effect of zinc deficiency and zinc supplementation on element levels in the bone tissue of ovariectomized rats: histopathologic changes. Arch Physiol Biochem 120(2):80–85. https://doi.org/10.3109/13813455.2014.884141

    Article  CAS  PubMed  Google Scholar 

  30. Avila ME, Garcia SA, Salas MR, Antuna S, Lemini C (2009) Effect of the 17β-aminoestrogen pentolame on bone mineral levels in ovariectomized rats. Proc West Pharmacol Soc 52:43–46

    CAS  PubMed  Google Scholar 

  31. Noor Z, Kania N, Setiawan B (2014) Tibia bone properties at different time course of ovariectomized rats. J Diabetes Metab Disord 13:91. https://doi.org/10.1186/s40200-014-0091-4

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wang T, Zhu X, Dai F, Li C, Huang D, Fang Z, Zhang Q, Lu Y (2017) Effects of a standard high-fat diet with or without multiple deficiencies on bone parameters in ovariectomized mature rat. PLoS One 12(9):e0184983. https://doi.org/10.1371/journal.pone.0184983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhang Y, Lai WP, Leung PC, Wu CF, Wong MS (2007) Short- to mid-term effects of ovariectomy on bone turnover, bone mass and bone strength in rats. Biol Pharm Bull 30(5):898–903. https://doi.org/10.1248/bpb.30.898

    Article  CAS  PubMed  Google Scholar 

  34. Sonu Y, Avinash SS, Sreekantha, Arun Kumar K, Malathi M, Shivashankara AR (2016) Effect of oestrogen on altering the serum and urinary levels of calcium, phosphate and magnesium in hysterectomised women compared to natural menopausal South Indian women: a case control study. Indian J Clin Biochem 31(3):326–331. https://doi.org/10.1007/s12291-015-0532-y

    Article  CAS  PubMed  Google Scholar 

  35. Seelig MS (1993) Interrelationship of magnesium and estrogen in cardiovascular and bone disorders, eclampsia, migraine and premenstrual syndrome. J Am Coll Nutr 12(4):442–458. https://doi.org/10.1080/07315724.1993.10718335

    Article  CAS  PubMed  Google Scholar 

  36. Vorland CJ, Lachcik PJ, Swallow EA, Metzger CE, Allen MR, Chen NX, Moe SM, Hill Gallant KM (2019) Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats. Sci Rep 9(1):7936. https://doi.org/10.1038/s41598-019-44415-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rahnama M, Marciniak A (2002) Influence of estrogen deficiency on the level of magnesium in rat mandible and teeth. Bull Vet Inst Pulawy 46:267–271

    Google Scholar 

  38. Ulas M, Cay M (2011) Effects of 17β-estradiol and vitamin E treatments on blood trace element and antioxidant enzyme levels in ovariectomized rats. Biol Trace Elem Res 139(3):347–355. https://doi.org/10.1007/s12011-010-8669-2

    Article  CAS  PubMed  Google Scholar 

  39. Hariri N, Thibault L (2010) High-fat diet-induced obesity in animal models. Nutr Res Rev 23(2):270–299. https://doi.org/10.1017/S0954422410000168

    Article  CAS  PubMed  Google Scholar 

  40. Shapses SA, Sukumar D (2012) Bone metabolism in obesity and weight loss. Annu Rev Nutr 32:287–309. https://doi.org/10.1146/annurev.nutr.012809.104655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang Y, Dellatore P, Douard V, Qin L, Watford M, Ferraris RP, Lin T, Shapses SA (2016) High fat diet enriched with saturated, but not monounsaturated fatty acids adversely affects femur, and both diets increase calcium absorption in older female mice. Nutr Res 36(7):742–750. https://doi.org/10.1016/j.nutres.2016.03.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cifuentes M, Morano AB, Chowdhury HA, Shapses SA (2002) Energy restriction reduces fractional calcium absorption in mature obese and lean rats. J Nutr 132(9):2660–2666. https://doi.org/10.1093/jn/132.9.2660

    Article  CAS  PubMed  Google Scholar 

  43. Xiao Y, Cui J, Shi YH, Sun J, Wang ZP, Le GW (2010) Effects of duodenal redox status on calcium absorption and related genes expression in high-fat diet-fed mice. Nutrition 26(11-12):1188–1194. https://doi.org/10.1016/j.nut.2009.11.021

    Article  CAS  PubMed  Google Scholar 

  44. Savvidis C, Tournis S, Dede AD (2018) Obesity and bone metabolism. Hormones 17:205–217. https://doi.org/10.1007/s42000-018-0018-4

    Article  PubMed  Google Scholar 

  45. Cline-Smith A, Axelbaum A, Shashkova E, Chakraborty M, Sanford J, Panesar P, Peterson M, Cox L, Baldan A, Veis D, Aurora R (2020) ovariectomy activates chronic low-grade inflammation mediated by memory T cells, which promotes osteoporosis in mice. J Bone Miner Res 35(6):1174–1187. https://doi.org/10.1002/jbmr.3966

    Article  CAS  PubMed  Google Scholar 

  46. Galloway P, McMillan DC, Sattar N (2000) Effect of the inflammatory response on trace element and vitamin status. Ann Clin Biochem 37(3):289–297. https://doi.org/10.1258/0004563001899429

    Article  CAS  PubMed  Google Scholar 

  47. Olechnowicz J, Tinkov A, Skalny A, Suliburska J (2018) Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci 68(1):19–31. https://doi.org/10.1007/s12576-017-0571-7

    Article  CAS  PubMed  Google Scholar 

  48. Zofkova I, Davis M, Blahos J (2017) Trace elements have beneficial, as well as detrimental effects on bone homeostasis. Physiol Res 66(3):391–402

    Article  CAS  PubMed  Google Scholar 

  49. Zhou X, Smith AM, Failla ML, Hill KE, Yu Z (2012) Estrogen status alters tissue distribution and metabolism of selenium in female rats. J Nutr Biochem 23(6):532–538. https://doi.org/10.1016/j.jnutbio.2011.02.008

    Article  CAS  PubMed  Google Scholar 

  50. Duntas LH, Hubalewska-Dydejczyk A (2015) Selenium and inflammation - potential use and future perspectives. US Endocrinol 11(2):97–102. https://doi.org/10.17925/USE.2015.11.02.97

    Article  Google Scholar 

  51. Rahnama M (2002) Influence of estrogen deficiency on the copper level in rat teeth and mandible. Ann Univ Mariae Curie Sklodowska Med 57(1):352–356

    PubMed  Google Scholar 

  52. Tinkov AA, Gatiatulina ER, Popova EV, Polyakova VS, Skalnaya AA, Agletdinov EF, Nikonorov AA, Skalny AV (2017) Early high-fat feeding induces alteration of trace element content in tissues of juvenile male Wistar rats. Biol Trace Elem Res 175(2):367–374. https://doi.org/10.1007/s12011-016-0777-1

    Article  CAS  PubMed  Google Scholar 

  53. Doshi SB, Agarwal A (2013) The role of oxidative stress in menopause. J Midlife Health 4(3):140–146. https://doi.org/10.4103/0976-7800.118990

    Article  PubMed  PubMed Central  Google Scholar 

  54. Marseglia L, Manti S, D’Angelo G, Nicotera A, Parisi E, Di Rosa G, Gitto E, Arrigo T (2014) Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci 16(1):378–400. https://doi.org/10.3390/ijms16010378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Thomson CD (2004) Assessment of requirements for selenium and adequacy of selenium status: a review. Eur J Clin Nutr 58(3):391–402. https://doi.org/10.1038/sj.ejcn.1601800

    Article  CAS  PubMed  Google Scholar 

  56. Balogh E, Paragh G, Jeney V (2018) Influence of iron on bone homeostasis. Pharmaceuticals (Basel) 11(4):E107. https://doi.org/10.3390/ph11040107

    Article  CAS  Google Scholar 

  57. Raso MG, Irace C, Esposito E, Maffettone C, Iacono A, Di Pascale A, Santamaria R, Colonna A, Meli R (2009) Ovariectomy and estrogen treatment modulate iron metabolism in rat adipose tissue. Biochem Pharmacol 78(8):1001–1007. https://doi.org/10.1016/j.bcp.2009.05.034

    Article  CAS  Google Scholar 

  58. Lecube A, Carrera A, Losada E, Hernández C, Simo R, Mesa J (2006) Iron deficiency in obese postmenopausal women. Obesity (Silver Spring) 14(10):1724–1730. https://doi.org/10.1038/oby.2006.198

    Article  CAS  Google Scholar 

  59. Demerdash HM (2015) Obesity and trace elements. Obes Res Open J 2(3):98–100. https://doi.org/10.17140/OROJ-2-115

    Article  Google Scholar 

  60. Stotzer US, Rodrigues MF, Domingos MM, Silva GH, Duarte FO, Gatto CV, Duarte AC, Shiguemoto GE, Perez SE, Selistre-de-Araujo HS (2015) Resistance training suppresses intra-abdominal fatty acid synthesis in ovariectomized rats. Int J Sports Med 36(3):226–233. https://doi.org/10.1055/s-0034-1390494

    Article  CAS  PubMed  Google Scholar 

  61. Yoon JR, Ha GC, Ko KJ, Kang SJ (2018) Effects of exercise type on estrogen, tumor markers, immune function, antioxidant function, and physical fitness in postmenopausal obese women. J Exerc Rehabil 14(6):1032–1040. https://doi.org/10.12965/jer.1836446.223

    Article  PubMed  PubMed Central  Google Scholar 

  62. Al Dahamsheh Z, Al Rashdan K, Al Hadid A, Jaradat R, Al Bakheet M, Bataineh ZS (2019) The impact of aerobic exercise on female bone health indicators. Mediev Archaeol 73(1):35–38. https://doi.org/10.5455/medarh.2019.73.35-38

    Article  Google Scholar 

  63. Baltaci AK, Uzun A, Kilic M, Mogulkoc R (2009) Effects of acute swimming exercise on some elements in rats. Biol Trace Elem Res 127(2):148–153. https://doi.org/10.1007/s12011-008-8232-6

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors wish to thank Ms Natalia Hladikova for the linguistic corrections of this paper.

Funding

This article was created by the realization of the project “Center of excellence of environmental health”, ITMS No. 26240120033, based on the supporting Operational Research and Development Program financed from the European Regional Development Fund. The work was supported by the EEA and Norwegian Financial Mechanisms and the state budget of the Slovak Republic (Project SK0020).

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Authors and Affiliations

  1. Department of Metallomics, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia

    Vlasta Masanova, Monika Ursinyova & Iveta Uhnakova

  2. Department of Clinical and Experimental Pharmacotherapy, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia

    Zora Krivosikova, Patricia Kramarova & Martin Gajdos

  3. Department of Toxicology, Faculty of Public Health, Slovak Medical University, Bratislava, Slovakia

    Anton Kebis

  4. Institute of Biophysics, Informatics and Biostatistics, Faculty of Public Health, Slovak Medical University, Bratislava, Slovakia

    Ladislava Wsolova

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  1. Vlasta Masanova
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Correspondence to Vlasta Masanova.

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The experiment design was prepared in accordance with the current legislation on the use of experimental animals in Slovakia. The proposal was approved by the Ethical Committee for Animal Experiment of the Slovak Medical University and by the State Veterinary and Food Authority of the Slovak Republic (Ro-1651/11-221b). All experimental procedures were carried out in animal house in compliance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes.

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Masanova, V., Krivosikova, Z., Ursinyova, M. et al. Effects of Ovariectomy and Exercise Training on Mineral Status in a High-Fat Diet-Induced Obesity Rat Model. Biol Trace Elem Res 200, 624–634 (2022). https://doi.org/10.1007/s12011-021-02655-9

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