Effect of high-fat diet on rat myometrium during pregnancy—isolated myometrial mitochondria are not affected

  • Christiane Marie Bourgin Folke Gam
  • Ole Hartvig Mortensen
  • Klaus Qvortrup
  • Peter Damm
  • Bjørn Quistorff
Muscle physiology

Abstract

Laboring women with elevated body mass index (BMI) have an increased risk of inefficient uterine labor contractions, and despite the significance of mitochondria in the production of energy to drive uterine contractions, mitochondrial function in the myometrium with reference to the BMI has not been explored. The objective of this study was to determine whether obesity prior to and during gestation affects oxidative capacity and/or morphology of mitochondria in the myometrium at term in an animal model. Rat dams were fed for 47 days prior to impregnation and during gestation with either (1) a regular chow diet, (2) a low-fat high-carbohydrate diet, or (3) a high-fat low-carbohydrate diet (n = 10 in each group). On day 20 of gestation, corresponding to term pregnancy, total hysterectomy was performed with subsequent examination of the function and morphology of myometrial mitochondria. Body composition was regularly assessed by quantitative magnetic resonance imaging, and blood sampling was done prior to diet assignment, impregnation, and hysterectomy. Dams on the high-fat low-carbohydrate diet achieved higher fat percentage compared to rats on the regular chow diet (p < 0.05). Maximal oxygen consumption, phosphate/oxygen ratio, or the amount of mitochondria per gram of myometrium did not differ between the three feeding groups. Electron microscopic examinations did not reveal any morphological differences in mitochondria between groups; however, a previously undescribed subsarcolemmal localization of the mitochondria in the myocyte was identified. We did not find evidence of altered myometrial mitochondrial function or morphology in this animal model of obesity prior to and during pregnancy.

Keywords

Mitochondria Myometrium Obesity Pregnancy Rat 

Abbreviations

BMI

Body mass index

CS

Citrate syntase

CH

Chow

FFA

Free fatty acid

HC

High-carbohydrate low-fat

HF

High-fat low-carbohydrate

HOMA-IR

Homeostatic assessment of insulin resistance

mtDNA

Mitochondrial deoxyribonucleic acid

mtDNA/gDNA

Mitochondrial-to-genomic DNA ratio

References

  1. 1.
    Ainge H, Thompson C, Ozanne SE, Rooney KB (2011) A systematic review on animal models of maternal high fat feeding and offspring glycaemic control. Int J Obes (Lond) 35(3):325–335. doi:10.1038/ijo.2010.149 CrossRefGoogle Scholar
  2. 2.
    Akyol A, Langley-Evans SC, McMullen S (2009) Obesity induced by cafeteria feeding and pregnancy outcome in the rat. Br J Nutr 102(11):1601–1610. doi:10.1017/S0007114509990961 CrossRefPubMedGoogle Scholar
  3. 3.
    Armitage JA, Taylor PD, Poston L (2005) Experimental models of developmental programming: consequences of exposure to an energy rich diet during development. J Physiol 565(Pt 1):3–8. doi:10.1113/jphysiol.2004.079756 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Boudina S, Bugger H, Sena S, O’Neill BT, Zaha VG, Ilkun O, Wright JJ, Mazumder PK, Palfreyman E, Tidwell TJ, Theobald H, Khalimonchuk O, Wayment B, Sheng X, Rodnick KJ, Centini R, Chen D, Litwin SE, Weimer BE, Abel ED (2009) Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart. Circulation 119(9):1272–1283. doi:10.1161/CIRCULATIONAHA.108.792101 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bugger H, Abel ED (2008) Molecular mechanisms for myocardial mitochondrial dysfunction in the metabolic syndrome. Clin Sci (Lond) 114(3):195–210. doi:10.1042/CS20070166 CrossRefGoogle Scholar
  6. 6.
    Cedergren MI (2009) Non-elective caesarean delivery due to ineffective uterine contractility or due to obstructed labour in relation to maternal body mass index. Eur J Obstet Gynecol Reprod Biol 145(2):163–166. doi:10.1016/S0301-2115(09)00333-9 CrossRefPubMedGoogle Scholar
  7. 7.
    Clark JF, Kuznetsov AV, Khuchua Z, Veksler V, Ventura-Clapier R, Saks V (1994) Creatine kinase function in mitochondria isolated from gravid and non-gravid guinea-pig uteri. FEBS Lett 347(2–3):147–151CrossRefPubMedGoogle Scholar
  8. 8.
    Clark JF, Kuznetsov AV, Radda GK (1997) ADP-regenerating enzyme systems in mitochondria of guinea pig myometrium and heart. Am J Physiol 272(2 Pt 1):C399–C404PubMedGoogle Scholar
  9. 9.
    Consitt LA, Bell JA, Houmard JA (2009) Intramuscular lipid metabolism, insulin action, and obesity. IUBMB Life 61(1):47–55. doi:10.1002/iub.142 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Dumas JF, Simard G, Flamment M, Ducluzeau PH, Ritz P (2009) Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans? Diabetes Metab 35(3):159–167CrossRefPubMedGoogle Scholar
  11. 11.
    Fritzen AJ, Grunnet N, Quistorff B (2007) Flux control analysis of mitochondrial oxidative phosphorylation in rat skeletal muscle: pyruvate and palmitoyl-carnitine as substrates give different control patterns. Eur J Appl Physiol 101(6):679–689CrossRefPubMedGoogle Scholar
  12. 12.
    Galvao TF, Brown BH, Hecker PA, O’Connell KA, O’Shea KM, Sabbah HN, Rastogi S, Daneault C, Des Rosiers C, Stanley WC (2012) High intake of saturated fat, but not polyunsaturated fat, improves survival in heart failure despite persistent mitochondrial defects. Cardiovasc Res 93(1):24–32. doi:10.1093/cvr/cvr258 CrossRefPubMedGoogle Scholar
  13. 13.
    Garfield RE, Daniel EE (1976) Light and dark smooth muscle cells in estrogen-stimulated rat myometrium. Can J Physiol Pharmacol 54(6):822–833CrossRefPubMedGoogle Scholar
  14. 14.
    Geyer H, Muller U, Afting EG (1977) Enzyme activities in different cell compartments of the involuting rat myometrium. Eur J Biochem 79(2):483–490CrossRefPubMedGoogle Scholar
  15. 15.
    Geyer H, Riebschlager M (1974) Effect of pregnancy on cytoplasmic and mitochondrial enzymes in human and animal myometrium. Acta Endocrinol (Copenh) 77(2):368–379Google Scholar
  16. 16.
    Gimpl G, Fahrenholz F (2000) Human oxytocin receptors in cholesterol-rich vs. cholesterol-poor microdomains of the plasma membrane. Eur J Biochem 267(9):2483–2497CrossRefPubMedGoogle Scholar
  17. 17.
    Gostynski M, Gutzwiller F, Kuulasmaa K, Doring A, Ferrario M, Grafnetter D, Pajak A (2004) Analysis of the relationship between total cholesterol, age, body mass index among males and females in the WHO MONICA Project. Int J Obes Relat Metab Disord 28(8):1082–1090. doi:10.1038/sj.ijo.0802714 CrossRefPubMedGoogle Scholar
  18. 18.
    Gupte AA, Minze LJ, Reyes M, Ren Y, Wang X, Brunner G, Ghosn M, Cordero-Reyes AM, Ding K, Pratico D, Morrisett J, Shi ZZ, Hamilton DJ, Lyon CJ, Hsueh WA (2013) High-fat feeding-induced hyperinsulinemia increases cardiac glucose uptake and mitochondrial function despite peripheral insulin resistance. Endocrinology 154(8):2650–2662. doi:10.1210/en.2012-2272 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Hadden DR, McLaughlin C (2009) Normal and abnormal maternal metabolism during pregnancy. Semin Fetal Neonatal Med 14(2):66–71. doi:10.1016/S1744-165X(08)00115-7 CrossRefPubMedGoogle Scholar
  20. 20.
    Harrod JS, Rada CC, Pierce SL, England SK, Lamping KG (2011) Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice. Am J Physiol Endocrinol Metab 301(2):E362–E369. doi:10.1152/ajpendo.00696.2010 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Hayes EK, Lechowicz A, Petrik JJ, Storozhuk Y, Paez-Parent S, Dai Q, Samjoo IA, Mansell M, Gruslin A, Holloway AC, Raha S (2012) Adverse fetal and neonatal outcomes associated with a life-long high fat diet: role of altered development of the placental vasculature. PLoS One 7(3):e33370. doi:10.1371/journal.pone.0033370 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hehir MP, Glavey SV, Morrison JJ (2008) Uterorelaxant effect of ghrelin on human myometrial contractility. Am J Obstet Gynecol 198(3):323 e1–5. doi:10.1016/j.ajog.2007.09.040
  23. 23.
    Hehir MP, Morrison JJ (2012) The adipokine apelin and human uterine contractility. Am J Obstet Gynecol 206(4):359 e1–5. doi:10.1016/j.ajog.2012.01.032
  24. 24.
    Higgins CA, Martin W, Anderson L, Blanks AM, Norman JE, McConnachie A, Nelson SM (2010) Maternal obesity and its relationship with spontaneous and oxytocin-induced contractility of human myometrium in vitro. Reprod Sci 17(2):177–185. doi:10.1177/1933719109349780
  25. 25.
    Holloway GP, Bonen A, Spriet LL (2009) Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals. Am J Clin Nutr 89(1):455S–462SCrossRefPubMedGoogle Scholar
  26. 26.
    Kates M (1986) Techniques in lipidology. Elsevier, New YorkGoogle Scholar
  27. 27.
    Kluge MA, Fetterman JL, Vita JA (2013) Mitochondria and endothelial function. Circ Res 112(8):1171–1188. doi:10.1161/112/8/1171 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Lain KY, Catalano PM (2007) Metabolic changes in pregnancy. Clin Obstet Gynecol 50(4):938–948. doi:10.1097/GRF.0b013e31815a5494 CrossRefPubMedGoogle Scholar
  29. 29.
    Lowe NK, Corwin EJ (2011) Proposed biological linkages between obesity, stress, and inefficient uterine contractility during labor in humans. Med Hypotheses 76(5):755–760. doi:10.1016/S0306-9877(11)00069-7 CrossRefPubMedGoogle Scholar
  30. 30.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275PubMedGoogle Scholar
  31. 31.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419CrossRefPubMedGoogle Scholar
  32. 32.
    McInerny SC, Brown AL, Smith DW (2009) Region-specific changes in mitochondrial D-loop in aged rat CNS. Mech Ageing Dev 130(5):343–349. doi:10.1016/S0047-6374(09)00035-9 CrossRefPubMedGoogle Scholar
  33. 33.
    Moynihan AT, Hehir MP, Glavey SV, Smith TJ, Morrison JJ (2006) Inhibitory effect of leptin on human uterine contractility in vitro. Am J Obstet Gynecol 195(2):504–509. doi:10.1016/j.ajog.2006.01.106 CrossRefPubMedGoogle Scholar
  34. 34.
    Niemann B, Chen Y, Teschner M, Li L, Silber RE, Rohrbach S (2011) Obesity induces signs of premature cardiac aging in younger patients: the role of mitochondria. J Am Coll Cardiol 57(5):577–585. doi:10.1016/S0735-1097(10)04601-2 CrossRefPubMedGoogle Scholar
  35. 35.
    Nivoit P, Morens C, Van Assche FA, Jansen E, Poston L, Remacle C, Reusens B (2009) Established diet-induced obesity in female rats leads to offspring hyperphagia, adiposity and insulin resistance. Diabetologia 52(6):1133–1142. doi:10.1007/s00125-009-1316-9 CrossRefPubMedGoogle Scholar
  36. 36.
    Noble K, Zhang J, Wray S (2006) Lipid rafts, the sarcoplasmic reticulum and uterine calcium signalling: an integrated approach. J Physiol 570(Pt 1):29–35CrossRefPubMedGoogle Scholar
  37. 37.
    Pagel-Langenickel I, Bao J, Pang L, Sack MN (2010) The role of mitochondria in the pathophysiology of skeletal muscle insulin resistance. Endocr Rev 31(1):25–51CrossRefPubMedGoogle Scholar
  38. 38.
    Passonneau JV, Gatfield PD, Schulz DW, Lowry OH (1967) An enzymic method for measurement of glycogen. Anal Biochem 19(2):315–326CrossRefPubMedGoogle Scholar
  39. 39.
    Ramsay JE, Ferrell WR, Crawford L, Wallace AM, Greer IA, Sattar N (2002) Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocrinol Metab 87(9):4231–4237. doi:10.1210/jc.2002-020311 CrossRefPubMedGoogle Scholar
  40. 40.
    Scheibye-Knudsen M, Quistorff B (2009) Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle. Eur J Appl Physiol 105(2):279–287. doi:10.1007/s00421-008-0901-9 CrossRefPubMedGoogle Scholar
  41. 41.
    Shanklin DR, Sibai BM (1990) Ultrastructural aspects of preeclampsia. II. Mitochondrial changes. Am J Obstet Gynecol 163(3):943–953CrossRefPubMedGoogle Scholar
  42. 42.
    Shepherd D, Garland PB (1969) The kinetic properties of citrate synthase from rat liver mitochondria. Biochem J 114(3):597–610CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Smith RD, Babiychuk EB, Noble K, Draeger A, Wray S (2005) Increased cholesterol decreases uterine activity: functional effects of cholesterol alteration in pregnant rat myometrium. Am J Physiol Cell Physiol 288(5):C982–C988CrossRefPubMedGoogle Scholar
  44. 44.
    Sweeney EM, Crankshaw DJ, O’Brien Y, Dockery P, Morrison JJ (2013) Stereology of human myometrium in pregnancy: influence of maternal body mass index and age. Am J Obstet Gynecol 208(4):324 e1–6. doi:10.1016/S0002-9378(13)00055-0
  45. 45.
    Walsh J, Foley M, O’Herlihy C (2011) Dystocia correlates with body mass index in both spontaneous and induced nulliparous labors. J Matern Fetal Neonatal Med 24(6):817–821. doi:10.3109/14767058.2010.531313 CrossRefPubMedGoogle Scholar
  46. 46.
    Wieland O (1984) Methods of enzymatic analysis, vol VI. Verlag Chemie, Weinheim, pp 504–510Google Scholar
  47. 47.
    Wikstrom M, Ahonen P, Luukkainen T (1975) The role of mitochondria in uterine contractions. FEBS Lett 56(1):120–123CrossRefPubMedGoogle Scholar
  48. 48.
    Wray S (2007) Insights into the uterus. Exp Physiol 92(4):621–631. doi:10.1113/expphysiol.2007.038125 CrossRefPubMedGoogle Scholar
  49. 49.
    Yener T, Turkkani Tunc A, Aslan H, Aytan H, Cantug Caliskan A (2007) Determination of oestrous cycle of the rats by direct examination: how reliable? Anat Histol Embryol 36(1):75–77. doi:10.1111/j.1439-0264.2006.00743.x CrossRefPubMedGoogle Scholar
  50. 50.
    Zhang J, Bricker L, Wray S, Quenby S (2007) Poor uterine contractility in obese women. BJOG 114(3):343–348. doi:10.1111/j.1471-0528.2006.01233.x CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Christiane Marie Bourgin Folke Gam
    • 1
    • 3
  • Ole Hartvig Mortensen
    • 1
  • Klaus Qvortrup
    • 2
  • Peter Damm
    • 3
  • Bjørn Quistorff
    • 1
  1. 1.Cellular and Metabolic Research Section, Department of Biomedical Sciences, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  2. 2.Core Facility for Integrated Microscopy, Department of Biomedical Sciences, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
  3. 3.Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark

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