The Role of Skeletal Muscle Estrogen Receptors in Metabolic Homeostasis and Insulin Sensitivity

  • Andrea L. Hevener
  • Zhenqi Zhou
  • Brian G. Drew
  • Vicent Ribas
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1043)

Abstract

Women in the modern era are challenged with facing menopausal symptoms as well as heightened disease risk associated with increasing adiposity and metabolic dysfunction for up to three decades of life. Treatment strategies to combat metabolic dysfunction and associated pathologies have been hampered by our lack of understanding regarding the biological causes of these clinical conditions and our incomplete understanding regarding the effects of estrogens and the tissue-specific functions and molecular actions of its receptors. In this chapter we provide evidence supporting a critical and protective role for skeletal muscle estrogen receptor α in the maintenance of metabolic homeostasis and insulin sensitivity. Studies identifying the critical ER-regulated pathways essential for disease prevention will lay the important foundation for the rational design of novel therapeutic strategies to improve the health of women while limiting secondary complications that have plagued traditional hormone replacement interventions.

Keywords

Estrogen receptors Insulin resistance Metabolic dysfunction Obesity 

Notes

Acknowledgements

This work was supported by grants from National Institutes of Health DK89109 and DK063491, NIH Nuclear Receptor Signaling Atlas (NURSA NDSP), UCLA Department of Medicine, UCLA Iris-Cantor Women’s Health Foundation, and the UCLA Jonsson Comprehensive Cancer Center. We would like to acknowledge all of the terrific science performed on ERα by many of our esteemed colleagues; however due to page limits we are unable to cite a large number of studies. We would like to take this opportunity to thank Dr. Kenneth Korach for his generous support of our research and for providing us with the ERα floxed mouse as well as a variety of powerful molecular tools.

References

  1. Adams, J. M., 2nd, Pratipanawatr, T., Berria, R., Wang, E., DeFronzo, R. A., Sullards, M. C., & Mandarino, L. J. (2004). Ceramide content is increased in skeletal muscle from obese insulin-resistant humans. Diabetes, 53(1), 25–31.CrossRefPubMedGoogle Scholar
  2. Alberti, K. G., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., Fruchart, J. C., James, W. P., Loria, C. M., Smith, S. C., Jr., & International Diabetes Federation Task Force on E, Prevention, Hational Heart L, Blood I, American Heart A, World Heart F, International Atherosclerosis S, International Association for the Study of O. (2009). Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation, 120(16), 1640–1645.  https://doi.org/10.1161/CIRCULATIONAHA.109.192644.CrossRefPubMedGoogle Scholar
  3. Alonso, A., Ordonez, P., Fernandez, R., Moreno, M., Llaneza, P., Patterson, A. M., & Gonzalez, C. (2009). 17beta-estradiol treatment is unable to reproduce p85 alpha redistribution associated with gestational insulin resistance in rats. The Journal of Steroid Biochemistry and Molecular Biology, 116(3–5), 160–170. doi:S0960-0760(09)00164-2 [pii].  https://doi.org/10.1016/j.jsbmb.2009.05.010.CrossRefPubMedGoogle Scholar
  4. Alonso, A., Gonzalez-Pardo, H., Garrido, P., Conejo, N. M., Llaneza, P., Diaz, F., Del Rey, C. G., & Gonzalez, C. (2010). Acute effects of 17 beta-estradiol and genistein on insulin sensitivity and spatial memory in aged ovariectomized female rats. Age (Dordrecht, Netherlands), 32(4), 421–434.  https://doi.org/10.1007/s11357-010-9148-6.CrossRefGoogle Scholar
  5. Amati, F., Dube, J. J., Alvarez-Carnero, E., Edreira, M. M., Chomentowski, P., Coen, P. M., Switzer, G. E., Bickel, P. E., Stefanovic-Racic, M., Toledo, F. G., & Goodpaster, B. H. (2011). Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes? Diabetes, 60(10), 2588–2597. doi:db10-1221 [pii].  https://doi.org/10.2337/db10-1221.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Arnal, J. F., Fontaine, C., Abot, A., Valera, M. C., Laurell, H., Gourdy, P., & Lenfant, F. (2013). Lessons from the dissection of the activation functions (AF-1 and AF-2) of the estrogen receptor alpha in vivo. Steroids, 78(6), 576–582.  https://doi.org/10.1016/j.steroids.2012.11.011.CrossRefPubMedGoogle Scholar
  7. Baltgalvis, K. A., Greising, S. M., Warren, G. L., & Lowe, D. A. (2010). Estrogen regulates estrogen receptors and antioxidant gene expression in mouse skeletal muscle. PLoS One, 5(4), e10164.  https://doi.org/10.1371/journal.pone.0010164.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Banks, E. A., Brozinick, J. T., Jr., Yaspelkis, B. B., 3rd, Kang, H. Y., & Ivy, J. L. (1992). Muscle glucose transport, GLUT-4 content, and degree of exercise training in obese Zucker rats. The American Journal of Physiology, 263(5 Pt 1), E1010–E1015.PubMedGoogle Scholar
  9. Barros, R. P., & Gustafsson, J. A. (2011). Estrogen receptors and the metabolic network. Cell Metabolism, 14(3), 289–299. doi:S1550-4131(11)00312-3 [pii].  https://doi.org/10.1016/j.cmet.2011.08.005.CrossRefPubMedGoogle Scholar
  10. Barros, R. P. A., Machado, U. F., Warner, M., & Gustafsson, J.-Å. (2006). Muscle GLUT4 regulation by estrogen receptors ERβ and ERα. Proceedings of the National Academy of Sciences of the United States of America, 103(5), 1605–1608.  https://doi.org/10.1073/pnas.0510391103.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Barros, R. P., Morani, A., Moriscot, A., & Machado, U. F. (2008). Insulin resistance of pregnancy involves estrogen-induced repression of muscle GLUT4. Molecular and Cellular Endocrinology, 295(1–2), 24–31. doi:S0303-7207(08)00286-4 [pii].  https://doi.org/10.1016/j.mce.2008.07.008.CrossRefPubMedGoogle Scholar
  12. Befroy, D. E., Petersen, K. F., Dufour, S., Mason, G. F., de Graaf, R. A., Rothman, D. L., & Shulman, G. I. (2007). Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients. Diabetes, 56(5), 1376–1381.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Boland, R., Vasconsuelo, A., Milanesi, L., Ronda, A. C., & de Boland, A. R. (2008). 17beta-estradiol signaling in skeletal muscle cells and its relationship to apoptosis. Steroids, 73(9–10), 859–863. doi:S0039-128X(07)00258-9 [pii].  https://doi.org/10.1016/j.steroids.2007.12.027.CrossRefPubMedGoogle Scholar
  14. Bonds, D. E., Lasser, N., Qi, L., Brzyski, R., Caan, B., Heiss, G., Limacher, M. C., Liu, J. H., Mason, E., Oberman, A., O'Sullivan, M. J., Phillips, L. S., Prineas, R. J., & Tinker, L. (2006). The effect of conjugated equine oestrogen on diabetes incidence: The Women’s Health Initiative randomised trial. Diabetologia, 49(3), 459–468.CrossRefPubMedGoogle Scholar
  15. Borras, C., Sastre, J., Garcia-Sala, D., Lloret, A., Pallardo, F. V., & Vina, J. (2003). Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radical Biology & Medicine, 34(5), 546–552. doi:S0891584902013564 [pii].CrossRefGoogle Scholar
  16. Brozinick, J. T., Jr., Etgen, G. J., Jr., Yaspelkis, B. B., 3rd, Kang, H. Y., & Ivy, J. L. (1993). Effects of exercise training on muscle GLUT-4 protein content and translocation in obese Zucker rats. The American Journal of Physiology, 265(3 Pt 1), E419–E427.PubMedGoogle Scholar
  17. Brozinick, J. T., Jr., Etgen, G. J., Jr., Yaspelkis, B. B., 3rd, & Ivy, J. L. (1994). Glucose uptake and GLUT-4 protein distribution in skeletal muscle of the obese Zucker rat. The American Journal of Physiology, 267(1 Pt 2), R236–R243.PubMedGoogle Scholar
  18. Bryzgalova, G., Gao, H., Ahren, B., Zierath, J. R., Galuska, D., Steiler, T. L., Dahlman-Wright, K., Nilsson, S., Gustafsson, J. A., Efendic, S., & Khan, A. (2006). Evidence that oestrogen receptor-alpha plays an important role in the regulation of glucose homeostasis in mice: Insulin sensitivity in the liver. Diabetologia, 49(3), 588–597.  https://doi.org/10.1007/s00125-005-0105-3.CrossRefPubMedGoogle Scholar
  19. Campbell, S. E., & Febbraio, M. A. (2002). Effect of the ovarian hormones on GLUT4 expression and contraction-stimulated glucose uptake. American Journal of Physiology. Endocrinology and Metabolism, 282(5), E1139–E1146.CrossRefPubMedGoogle Scholar
  20. Campbell, S. E., Mehan, K. A., Tunstall, R. J., Febbraio, M. A., & Cameron-Smith, D. (2003). 17beta-estradiol upregulates the expression of peroxisome proliferator-activated receptor alpha and lipid oxidative genes in skeletal muscle. Journal of Molecular Endocrinology, 31(1), 37–45.CrossRefPubMedGoogle Scholar
  21. Casazza, K., Page, G. P., & Fernandez, J. R. (2010). The association between the rs2234693 and rs9340799 estrogen receptor alpha gene polymorphisms and risk factors for cardiovascular disease: A review. Biological Research for Nursing, 12(1), 84–97. doi:12/1/84 [pii].  https://doi.org/10.1177/1099800410371118.CrossRefPubMedGoogle Scholar
  22. Charn, T. H., Liu, E. T., Chang, E. C., Lee, Y. K., Katzenellenbogen, J. A., & Katzenellenbogen, B. S. (2010). Genome-wide dynamics of chromatin binding of estrogen receptors alpha and beta: Mutual restriction and competitive site selection. Molecular Endocrinology, 24(1), 47–59.  https://doi.org/10.1210/me.2009-0252.
  23. Chen, J. Q., Delannoy, M., Cooke, C., & Yager, J. D. (2004). Mitochondrial localization of ERalpha and ERbeta in human MCF7 cells. American Journal of Physiology Endocrinology and Metabolism, 286(6), E1011–E1022.CrossRefPubMedGoogle Scholar
  24. Chen, Z., Bassford, T., Green, S. B., Cauley, J. A., Jackson, R. D., LaCroix, A. Z., Leboff, M., Stefanick, M. L., & Margolis, K. L. (2005). Postmenopausal hormone therapy and body composition--a substudy of the estrogen plus progestin trial of the Women's Health Initiative. The American Journal of Clinical Nutrition, 82(3), 651–656. doi:82/3/651 [pii].CrossRefPubMedGoogle Scholar
  25. Choi, C. S., Fillmore, J. J., Kim, J. K., Liu, Z. X., Kim, S., Collier, E. F., Kulkarni, A., Distefano, A., Hwang, Y. J., Kahn, M., Chen, Y., Yu, C., Moore, I. K., Reznick, R. M., Higashimori, T., & Shulman, G. I. (2007). Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance. The Journal of Clinical Investigation, 117(7), 1995–2003.  https://doi.org/10.1172/JCI13579.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Chung, S. S., Kim, M., Youn, B. S., Lee, N. S., Park, J. W., Lee, I. K., Lee, Y. S., Kim, J. B., Cho, Y. M., Lee, H. K., & Park, K. S. (2009). Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells. Molecular and Cellular Biology, 29(1), 20–30. doi:MCB.00544-08 [pii].  https://doi.org/10.1128/MCB.00544-08.CrossRefPubMedGoogle Scholar
  27. Clemmensen, C., Muller, T. D., Finan, B., Tschop, M. H., & DiMarchi, R. (2016). Current and emerging treatment options in diabetes care. Handbook of Experimental Pharmacology, 233, 437–459.  https://doi.org/10.1007/164_2015_7.CrossRefPubMedGoogle Scholar
  28. Cooke, P. S., Heine, P. A., Taylor, J. A., & Lubahn, D. B. (2001). The role of estrogen and estrogen receptor-alpha in male adipose tissue. Molecular and Cellular Endocrinology, 178(1–2), 147–154.CrossRefPubMedGoogle Scholar
  29. Cornier, M. A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008). The metabolic syndrome. Endocrine Reviews, 29(7), 777–822.  https://doi.org/10.1210/er.2008-0024.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Cortright, R. N., & Koves, T. R. (2000). Sex differences in substrate metabolism and energy homeostasis. Canadian Journal of Applied Physiology, 25(4), 288–311.CrossRefPubMedGoogle Scholar
  31. Couse, J. F., & Korach, K. S. (1999). Estrogen receptor null mice: What have we learned and where will they lead us? Endocrine Reviews, 20(3), 358–417.  https://doi.org/10.1210/edrv.20.3.0370.CrossRefPubMedGoogle Scholar
  32. Couse, J. F., Curtis, S. W., Washburn, T. F., Eddy, E. M., Schomberg, D. W., & Korach, K. S. (1995). Disruption of the mouse oestrogen receptor gene: Resulting phenotypes and experimental findings. Biochemical Society Transactions, 23(4), 929–935.CrossRefPubMedGoogle Scholar
  33. DeFronzo, R. A., Bonadonna, R. C., & Ferrannini, E. (1992). Pathogenesis of NIDDM. A balanced overview. Diabetes Care, 15(3), 318–368.CrossRefPubMedGoogle Scholar
  34. Dela, F., Ploug, T., Handberg, A., Petersen, L. N., Larsen, J. J., Mikines, K. J., & Galbo, H. (1994). Physical training increases muscle GLUT4 protein and mRNA in patients with NIDDM. Diabetes, 43(7), 862–865.CrossRefPubMedGoogle Scholar
  35. Deng, H. W., Li, J., Li, J. L., Dowd, R., Davies, K. M., Johnson, M., Gong, G., Deng, H., & Recker, R. R. (2000). Association of estrogen receptor-alpha genotypes with body mass index in normal healthy postmenopausal Caucasian women. The Journal of Clinical Endocrinology and Metabolism, 85(8), 2748–2751.PubMedGoogle Scholar
  36. D'Eon, T. M., Rogers, N. H., Stancheva, Z. S., & Greenberg, A. S. (2008). Estradiol and the estradiol metabolite, 2-hydroxyestradiol, activate AMP-activated protein kinase in C2C12 myotubes. Obesity (Silver Spring), 16(6), 1284–1288. doi:oby200850 [pii].  https://doi.org/10.1038/oby.2008.50.CrossRefGoogle Scholar
  37. Dieli-Conwright, C. M., Spektor, T. M., Rice, J. C., Sattler, F. R., & Schroeder, E. T. (2009). Hormone therapy attenuates exercise-induced skeletal muscle damage in postmenopausal women. Journal of Applied Physiology, 107(3), 853–858. doi:00404.2009 [pii].  https://doi.org/10.1152/japplphysiol.00404.2009.
  38. Ding, E. L., Song, Y., Manson, J. E., Rifai, N., Buring, J. E., & Liu, S. (2007). Plasma sex steroid hormones and risk of developing type 2 diabetes in women: A prospective study. Diabetologia, 50(10), 2076–2084.  https://doi.org/10.1007/s00125-007-0785-y.CrossRefPubMedGoogle Scholar
  39. Donath, M. Y., & Shoelson, S. E. (2011). Type 2 diabetes as an inflammatory disease. Nature Reviews. Immunology, 11(2), 98–107. doi:nri2925 [pii].  https://doi.org/10.1038/nri2925.CrossRefPubMedGoogle Scholar
  40. Enns, D. L., & Tiidus, P. M. (2008). Estrogen influences satellite cell activation and proliferation following downhill running in rats. Journal of Applied Physiology, 104(2), 347–353. doi:00128.2007 [pii].  https://doi.org/10.1152/japplphysiol.00128.2007.CrossRefPubMedGoogle Scholar
  41. Enns, D. L., Iqbal, S., & Tiidus, P. M. (2008). Oestrogen receptors mediate oestrogen-induced increases in post-exercise rat skeletal muscle satellite cells. Acta Physiologica (Oxford, England), 194(1), 81–93. doi:APS1861 [pii].  https://doi.org/10.1111/j.1748-1716.2008.01861.x.CrossRefGoogle Scholar
  42. Foryst-Ludwig, A., Clemenz, M., Hohmann, S., Hartge, M., Sprang, C., Frost, N., Krikov, M., Bhanot, S., Barros, R., Morani, A., Gustafsson, J. A., Unger, T., & Kintscher, U. (2008). Metabolic actions of estrogen receptor beta (ERbeta) are mediated by a negative cross-talk with PPARgamma. PLoS Genetics, 4(6), e1000108.  https://doi.org/10.1371/journal.pgen.1000108.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Frias, J. P., Macaraeg, G. B., Ofrecio, J., Yu, J. G., Olefsky, J. M., & Kruszynska, Y. T. (2001). Decreased susceptibility to fatty acid-induced peripheral tissue insulin resistance in women. Diabetes, 50(6), 1344–1350.CrossRefPubMedGoogle Scholar
  44. Fu, M. H., Maher, A. C., Hamadeh, M. J., Ye, C., & Tarnopolsky, M. A. (2009). Exercise, sex, menstrual cycle phase, and 17beta-estradiol influence metabolism-related genes in human skeletal muscle. Physiological Genomics, 40(1), 34–47. doi:00115.2009 [pii].  https://doi.org/10.1152/physiolgenomics.00115.2009.CrossRefPubMedGoogle Scholar
  45. Furtado, L. M., Somwar, R., Sweeney, G., Niu, W., & Klip, A. (2002). Activation of the glucose transporter GLUT4 by insulin. Biochemistry and Cell Biology, 80(5), 569–578.CrossRefPubMedGoogle Scholar
  46. Galluzzo, P., Rastelli, C., Bulzomi, P., Acconcia, F., Pallottini, V., & Marino, M. (2009). 17beta-Estradiol regulates the first steps of skeletal muscle cell differentiation via ER-alpha-mediated signals. American Journal of Physiology Cell Physiology, 297(5), C1249–C1262. doi:00188.2009 [pii].  https://doi.org/10.1152/ajpcell.00188.2009.CrossRefPubMedGoogle Scholar
  47. Gan, Z., Burkart-Hartman, E. M., Han, D. H., Finck, B., Leone, T. C., Smith, E. Y., Ayala, J. E., Holloszy, J., & Kelly, D. P. (2011). The nuclear receptor PPARbeta/delta programs muscle glucose metabolism in cooperation with AMPK and MEF2. Genes & Development, 25(24), 2619–2630. doi:gad.178434.111 [pii].  https://doi.org/10.1101/gad.178434.111.CrossRefGoogle Scholar
  48. Garvey, W. T., Maianu, L., Hancock, J. A., Golichowski, A. M., & Baron, A. (1992). Gene expression of GLUT4 in skeletal muscle from insulin-resistant patients with obesity, IGT, GDM, and NIDDM. Diabetes, 41(4), 465–475.CrossRefPubMedGoogle Scholar
  49. Garvey, W. T., Maianu, L., Zhu, J. H., Brechtel-Hook, G., Wallace, P., & Baron, A. D. (1998). Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. The Journal of Clinical Investigation, 101(11), 2377–2386.  https://doi.org/10.1172/JCI1557.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Gomez-Perez, Y., Amengual-Cladera, E., Catala-Niell, A., Thomas-Moya, E., Gianotti, M., Proenza, A. M., & Llado, I. (2008). Gender dimorphism in high-fat-diet-induced insulin resistance in skeletal muscle of aged rats. Cellular Physiology and Biochemistry, 22(5–6), 539–548. doi:000185538 [pii].  https://doi.org/10.1159/000185538.CrossRefPubMedGoogle Scholar
  51. Gong, H., Xie, J., Zhang, N., Yao, L., & Zhang, Y. (2011). MEF2A binding to the Glut4 promoter occurs via an AMPKalpha2-dependent mechanism. Medicine and Science in Sports and Exercise, 43(8), 1441–1450.  https://doi.org/10.1249/MSS.0b013e31820f6093.CrossRefPubMedGoogle Scholar
  52. Gorres, B. K., Bomhoff, G. L., Morris, J. K., & Geiger, P. C. (2011). In vivo stimulation of oestrogen receptor alpha increases insulin-stimulated skeletal muscle glucose uptake. The Journal of Physiology, 589(Pt 8), 2041–2054.  https://doi.org/10.1113/jphysiol.2010.199018.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Green, S., Walter, P., Greene, G., Krust, A., Goffin, C., Jensen, E., Scrace, G., Waterfield, M., & Chambon, P. (1986). Cloning of the human oestrogen receptor cDNA. Journal of Steroid Biochemistry, 24(1), 77–83.CrossRefPubMedGoogle Scholar
  54. Guercio, G., Di Palma, M. I., Pepe, C., Saraco, N. I., Prieto, M., Saure, C., Mazza, C., Rivarola, M. A., & Belgorosky, A. (2009). Metformin, estrogen replacement therapy and gonadotropin inhibition fail to improve insulin sensitivity in a girl with aromatase deficiency. Hormone Research, 72(6), 370–376. doi:000249165 [pii].  https://doi.org/10.1159/000249165.CrossRefPubMedGoogle Scholar
  55. Hamadeh, M. J., Devries, M. C., & Tarnopolsky, M. A. (2005). Estrogen supplementation reduces whole body leucine and carbohydrate oxidation and increases lipid oxidation in men during endurance exercise. The Journal of Clinical Endocrinology and Metabolism, 90(6), 3592–3599. doi:jc.2004-1743 [pii].  https://doi.org/10.1210/jc.2004-1743.CrossRefPubMedGoogle Scholar
  56. Hamilton, D. J., Minze, L. J., Kumar, T., Cao, T. N., Lyon, C. J., Geiger, P. C., Hsueh, W. A., & Gupte, A. A. (2016). Estrogen receptor alpha activation enhances mitochondrial function and systemic metabolism in high-fat-fed ovariectomized mice. Physiological Reports, 4(17). https://doi.org/10.14814/phy2.12913.
  57. Hammes, S. R., & Levin, E. R. (2007). Extranuclear steroid receptors: Nature and actions. Endocrine Reviews, 28(7), 726–741.CrossRefPubMedGoogle Scholar
  58. Hansen, P. A., McCarthy, T. J., Pasia, E. N., Spina, R. J., & Gulve, E. A. (1996). Effects of ovariectomy and exercise training on muscle GLUT-4 content and glucose metabolism in rats. Journal of Applied Physiology, 80(5), 1605–1611.CrossRefPubMedGoogle Scholar
  59. Hardie, D. G. (2011). AMP-activated protein kinase: An energy sensor that regulates all aspects of cell function. Genes & Development, 25(18), 1895–1908. doi:25/18/1895 [pii].  https://doi.org/10.1101/gad.17420111.CrossRefGoogle Scholar
  60. Heine, P. A., Taylor, J. A., Iwamoto, G. A., Lubahn, D. B., & Cooke, P. S. (2000). Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proceedings of the National Academy of Sciences of the United States of America, 97(23), 12729–12734.CrossRefPubMedPubMedCentralGoogle Scholar
  61. Hevener, A. L., Reichart, D., & Olefsky, J. (2000). Exercise and thiazolidinedione therapy normalize insulin action in the obese Zucker fatty rat. Diabetes, 49(12), 2154–2159.CrossRefPubMedGoogle Scholar
  62. Hevener, A., Reichart, D., Janez, A., & Olefsky, J. (2002). Female rats do not exhibit free fatty acid-induced insulin resistance. Diabetes, 51(6), 1907–1912.CrossRefPubMedGoogle Scholar
  63. Hevener, A. L., Olefsky, J. M., Reichart, D., Nguyen, M. T., Bandyopadyhay, G., Leung, H. Y., Watt, M. J., Benner, C., Febbraio, M. A., Nguyen, A. K., Folian, B., Subramaniam, S., Gonzalez, F. J., Glass, C. K., & Ricote, M. (2007). Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. The Journal of Clinical Investigation, 117(6), 1658–1669.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Hoeg, L., Roepstorff, C., Thiele, M., Richter, E. A., Wojtaszewski, J. F., & Kiens, B. (2009). Higher intramuscular triacylglycerol in women does not impair insulin sensitivity and proximal insulin signaling. Journal of Applied Physiology, 107(3), 824–831. doi:91382.2008 [pii].  https://doi.org/10.1152/japplphysiol.91382.2008.CrossRefPubMedGoogle Scholar
  65. Hoeg, L. D., Sjoberg, K. A., Jeppesen, J., Jensen, T. E., Frosig, C., Birk, J. B., Bisiani, B., Hiscock, N., Pilegaard, H., Wojtaszewski, J. F., Richter, E. A., & Kiens, B. (2011). Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling. Diabetes, 60(1), 64–73. doi:db10-0698 [pii].  https://doi.org/10.2337/db10-0698.CrossRefPubMedGoogle Scholar
  66. Holland, W. L., Brozinick, J. T., Wang, L. P., Hawkins, E. D., Sargent, K. M., Liu, Y., Narra, K., Hoehn, K. L., Knotts, T. A., Siesky, A., Nelson, D. H., Karathanasis, S. K., Fontenot, G. K., Birnbaum, M. J., & Summers, S. A. (2007a). Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metabolism, 5(3), 167–179.CrossRefPubMedGoogle Scholar
  67. Holland, W. L., Knotts, T. A., Chavez, J. A., Wang, L. P., Hoehn, K. L., & Summers, S. A. (2007b). Lipid mediators of insulin resistance. Nutrition Reviews, 65(6 Pt 2), S39–S46.CrossRefPubMedGoogle Scholar
  68. Hotamisligil, G. S. (2008). Inflammation and endoplasmic reticulum stress in obesity and diabetes. International Journal of Obesity, 32(Suppl 7), S52–S54. doi:ijo2008238 [pii].  https://doi.org/10.1038/ijo.2008.238.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Itani, S. I., Ruderman, N. B., Schmieder, F., & Boden, G. (2002). Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes, 51(7), 2005–2011.CrossRefPubMedGoogle Scholar
  70. Jensen, E. V., Jacobson, H. I., Walf, A. A., & Frye, C. A. (2010). Estrogen action: A historic perspective on the implications of considering alternative approaches. Physiology & Behavior, 99(2), 151–162.  https://doi.org/10.1016/j.physbeh.2009.08.013.CrossRefGoogle Scholar
  71. Jia, M., Dahlman-Wright, K., & Gustafsson, J. A. (2015). Estrogen receptor alpha and beta in health and disease. Best Practice & Research Clinical Endocrinology & Metabolism, 29(4), 557–568.  https://doi.org/10.1016/j.beem.2015.04.008.CrossRefGoogle Scholar
  72. Jones, M. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., & Simpson, E. R. (2000). Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proceedings of the National Academy of Sciences of the United States of America, 97(23), 12735–12740.CrossRefPubMedPubMedCentralGoogle Scholar
  73. Jones, M. E., McInnes, K. J., Boon, W. C., & Simpson, E. R. (2007). Estrogen and adiposity–utilizing models of aromatase deficiency to explore the relationship. The Journal of Steroid Biochemistry and Molecular Biology, 106(1–5), 3–7. doi:S0960-0760(07)00106-9 [pii].  https://doi.org/10.1016/j.jsbmb.2007.05.029.CrossRefPubMedGoogle Scholar
  74. Kalyani, R. R., Franco, M., Dobs, A. S., Ouyang, P., Vaidya, D., Bertoni, A., Gapstur, S. M., & Golden, S. H. (2009). The association of endogenous sex hormones, adiposity, and insulin resistance with incident diabetes in postmenopausal women. The Journal of Clinical Endocrinology and Metabolism, 94(11), 4127–4135. doi:jc.2009-0910 [pii].  https://doi.org/10.1210/jc.2009-0910.CrossRefPubMedPubMedCentralGoogle Scholar
  75. Kamanga-Sollo, E., White, M. E., Hathaway, M. R., Weber, W. J., & Dayton, W. R. (2010). Effect of Estradiol-17beta on protein synthesis and degradation rates in fused bovine satellite cell cultures. Domestic Animal Endocrinology, 39(1), 54–62. doi:S0739-7240(10)00009-3 [pii].  https://doi.org/10.1016/j.domaniend.2010.02.002.CrossRefPubMedGoogle Scholar
  76. Kanaya, A. M., Herrington, D., Vittinghoff, E., Lin, F., Grady, D., Bittner, V., Cauley, J. A., & Barrett-Connor, E. (2003). Glycemic effects of postmenopausal hormone therapy: The heart and estrogen/progestin replacement study. A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine, 138(1), 1–9.CrossRefPubMedGoogle Scholar
  77. Kim, J. Y., Jo, K. J., Kim, O. S., Kim, B. J., Kang, D. W., Lee, K. H., Baik, H. W., Han, M. S., & Lee, S. K. (2010). Parenteral 17beta-estradiol decreases fasting blood glucose levels in non-obese mice with short-term ovariectomy. Life Sciences, 87(11–12), 358–366. doi:S0024-3205(10)00316-4 [pii].  https://doi.org/10.1016/j.lfs.2010.07.009.CrossRefPubMedGoogle Scholar
  78. Kuiper, G. G., Enmark, E., Pelto-Huikko, M., Nilsson, S., & Gustafsson, J. A. (1996). Cloning of a novel receptor expressed in rat prostate and ovary. Proceedings of the National Academy of Sciences of the United States of America, 93(12), 5925–5930.CrossRefPubMedPubMedCentralGoogle Scholar
  79. Kuiper, G. G., Carlsson, B., Grandien, K., Enmark, E., Haggblad, J., Nilsson, S., & Gustafsson, J. A. (1997). Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology, 138(3), 863–870.CrossRefPubMedGoogle Scholar
  80. Lee, Y. R., Park, J., Yu, H. N., Kim, J. S., Youn, H. J., & Jung, S. H. (2005). Up-regulation of PI3K/Akt signaling by 17beta-estradiol through activation of estrogen receptor-alpha, but not estrogen receptor-beta, and stimulates cell growth in breast cancer cells. Biochemical and Biophysical Research Communications, 336(4), 1221–1226. doi:S0006-291X(05)01972-8 [pii].  https://doi.org/10.1016/j.bbrc.2005.08.256.CrossRefPubMedGoogle Scholar
  81. Leger, B., Derave, W., De Bock, K., Hespel, P., & Russell, A. P. (2008). Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation. Rejuvenation Research, 11(1), 163–175B.  https://doi.org/10.1089/rej.2007.0588.CrossRefPubMedGoogle Scholar
  82. Lemoine, S., Granier, P., Tiffoche, C., Berthon, P. M., Rannou-Bekono, F., Thieulant, M. L., Carre, F., & Delamarche, P. (2002a). Effect of endurance training on oestrogen receptor alpha transcripts in rat skeletal muscle. Acta Physiologica Scandinavica, 174(3), 283–289. doi:943 [pii].CrossRefPubMedGoogle Scholar
  83. Lemoine, S., Granier, P., Tiffoche, C., Berthon, P. M., Thieulant, M. L., Carre, F., & Delamarche, P. (2002b). Effect of endurance training on oestrogen receptor alpha expression in different rat skeletal muscle type. Acta Physiologica Scandinavica, 175(3), 211–217. doi:992 [pii].CrossRefPubMedGoogle Scholar
  84. Levin, E. R. (2015). Extranuclear steroid receptors are essential for steroid hormone actions. Annual Review of Medicine, 66, 271–280.  https://doi.org/10.1146/annurev-med-050913-021703.CrossRefPubMedGoogle Scholar
  85. Lewis, S. C., Uchiyama, L. F., & Nunnari, J. (2016). ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells. Science, 353(6296), aaf5549.  https://doi.org/10.1126/science.aaf5549.CrossRefPubMedPubMedCentralGoogle Scholar
  86. Liao, S. (1975). Cellular receptors and mechanisms of action of steroid hormones. International Review of Cytology, 41, 87–172.CrossRefPubMedGoogle Scholar
  87. Lipovka, Y., Chen, H., Vagner, J., Price, T. J., Tsao, T. S., & Konhilas, J. P. (2015). Oestrogen receptors interact with the alpha-catalytic subunit of AMP-activated protein kinase. Bioscience Reports, 35(5).  https://doi.org/10.1042/BSR20150074.
  88. Liu, S., & Mauvais-Jarvis, F. (2010). Minireview: Estrogenic protection of beta-cell failure in metabolic diseases. Endocrinology, 151(3), 859–864.  https://doi.org/10.1210/en.2009-1107.CrossRefPubMedGoogle Scholar
  89. Maffei, L., Murata, Y., Rochira, V., Tubert, G., Aranda, C., Vazquez, M., Clyne, C. D., Davis, S., Simpson, E. R., & Carani, C. (2004). Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene: Effects of testosterone, alendronate, and estradiol treatment. The Journal of Clinical Endocrinology and Metabolism, 89(1), 61–70.CrossRefPubMedGoogle Scholar
  90. Maffei, L., Rochira, V., Zirilli, L., Antunez, P., Aranda, C., Fabre, B., Simone, M. L., Pignatti, E., Simpson, E. R., Houssami, S., Clyne, C. D., & Carani, C. (2007). A novel compound heterozygous mutation of the aromatase gene in an adult man: Reinforced evidence on the relationship between congenital oestrogen deficiency, adiposity and the metabolic syndrome. Clinical Endocrinology, 67(2), 218–224. doi:CEN2864 [pii].  https://doi.org/10.1111/j.1365-2265.2007.02864.x.CrossRefPubMedGoogle Scholar
  91. Maher, A. C., Akhtar, M., & Tarnopolsky, M. A. (2010a). Men supplemented with 17beta-estradiol have increased beta-oxidation capacity in skeletal muscle. Physiological Genomics, 42(3), 342–347. doi:physiolgenomics.00016.2010 [pii].  https://doi.org/10.1152/physiolgenomics.00016.2010.CrossRefPubMedGoogle Scholar
  92. Maher, A. C., Akhtar, M., Vockley, J., & Tarnopolsky, M. A. (2010b). Women have higher protein content of beta-oxidation enzymes in skeletal muscle than men. PLoS One, 5(8), e12025.  https://doi.org/10.1371/journal.pone.0012025.CrossRefPubMedPubMedCentralGoogle Scholar
  93. Mannella, P., & Brinton, R. D. (2006). Estrogen receptor protein interaction with phosphatidylinositol 3-kinase leads to activation of phosphorylated Akt and extracellular signal-regulated kinase 1/2 in the same population of cortical neurons: A unified mechanism of estrogen action. The Journal of Neuroscience, 26(37), 9439–9447. doi:26/37/9439 [pii].  https://doi.org/10.1523/JNEUROSCI.1443-06.2006.CrossRefPubMedGoogle Scholar
  94. Margolis, K. L., Bonds, D. E., Rodabough, R. J., Tinker, L., Phillips, L. S., Allen, C., Bassford, T., Burke, G., Torrens, J., & Howard, B. V. (2004). Effect of oestrogen plus progestin on the incidence of diabetes in postmenopausal women: Results from the women’s health initiative hormone trial. Diabetologia, 47(7), 1175–1187.CrossRefPubMedGoogle Scholar
  95. Mauvais-Jarvis, F., Manson, J. E., Stevenson, J. C., & Fonseca, V. A. (2017). Menopausal hormone therapy and type 2 diabetes prevention: Evidence, mechanisms, and clinical implications. Endocrine Reviews, 38(3), 173–188.  https://doi.org/10.1210/er.2016-1146.CrossRefPubMedGoogle Scholar
  96. McLoughlin, T. J., Smith, S. M., DeLong, A. D., Wang, H., Unterman, T. G., & Esser, K. A. (2009). FoxO1 induces apoptosis in skeletal myotubes in a DNA-binding-dependent manner. American Journal of Physiology. Cell Physiology, 297(3), C548–C555. doi:00502.2008 [pii].  https://doi.org/10.1152/ajpcell.00502.2008.CrossRefPubMedPubMedCentralGoogle Scholar
  97. Messier, V., Rabasa-Lhoret, R., Barbat-Artigas, S., Elisha, B., Karelis, A. D., & Aubertin-Leheudre, M. (2011). Menopause and sarcopenia: A potential role for sex hormones. Maturitas, 68(4), 331–336. doi:S0378-5122(11)00030-2 [pii].  https://doi.org/10.1016/j.maturitas.2011.01.014.CrossRefPubMedGoogle Scholar
  98. Mihaylova, M. M., & Shaw, R. J. (2011). The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nature Cell Biology, 13(9), 1016–1023. doi:ncb2329 [pii].  https://doi.org/10.1038/ncb2329.CrossRefPubMedPubMedCentralGoogle Scholar
  99. Miranda, P. J., DeFronzo, R. A., Califf, R. M., & Guyton, J. R. (2005). Metabolic syndrome: Definition, pathophysiology, and mechanisms. American Heart Journal, 149(1), 33–45. doi:S0002870304004491 [pii].  https://doi.org/10.1016/j.ahj.2004.07.013.CrossRefPubMedGoogle Scholar
  100. Mora, S., & Pessin, J. E. (2000). The MEF2A isoform is required for striated muscle-specific expression of the insulin-responsive GLUT4 glucose transporter. The Journal of Biological Chemistry, 275(21), 16323–16328.  https://doi.org/10.1074/jbc.M910259199. M910259199 [pii].CrossRefPubMedGoogle Scholar
  101. Moreno, H., Serrano, A. L., Santalucia, T., Guma, A., Canto, C., Brand, N. J., Palacin, M., Schiaffino, S., & Zorzano, A. (2003). Differential regulation of the muscle-specific GLUT4 enhancer in regenerating and adult skeletal muscle. The Journal of Biological Chemistry, 278(42), 40557–40564.  https://doi.org/10.1074/jbc.M306609200. M306609200 [pii].CrossRefPubMedGoogle Scholar
  102. Morino, K., Petersen, K. F., Dufour, S., Befroy, D., Frattini, J., Shatzkes, N., Neschen, S., White, M. F., Bilz, S., Sono, S., Pypaert, M., & Shulman, G. I. (2005). Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. The Journal of Clinical Investigation, 115(12), 3587–3593.  https://doi.org/10.1172/JCI25151.CrossRefPubMedPubMedCentralGoogle Scholar
  103. Morishima, A., Grumbach, M. M., Simpson, E. R., Fisher, C., & Qin, K. (1995). Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. The Journal of Clinical Endocrinology and Metabolism, 80(12), 3689–3698.PubMedGoogle Scholar
  104. Murgia, M., Jensen, T. E., Cusinato, M., Garcia, M., Richter, E. A., & Schiaffino, S. (2009). Multiple signalling pathways redundantly control glucose transporter GLUT4 gene transcription in skeletal muscle. The Journal of Physiology, 587(17), 4319–4327.  https://doi.org/10.1113/jphysiol.2009.174888.CrossRefPubMedPubMedCentralGoogle Scholar
  105. Naaz, A., Zakroczymski, M., Heine, P., Taylor, J., Saunders, P., Lubahn, D., & Cooke, P. S. (2002). Effect of ovariectomy on adipose tissue of mice in the absence of estrogen receptor alpha (ERalpha): A potential role for estrogen receptor beta (ERbeta). Hormone and Metabolic Research, 34(11–12), 758–763.CrossRefPubMedGoogle Scholar
  106. Nadal, A., Alonso-Magdalena, P., Soriano, S., Quesada, I., & Ropero, A. B. (2009). The pancreatic beta-cell as a target of estrogens and xenoestrogens: Implications for blood glucose homeostasis and diabetes. Molecular and Cellular Endocrinology, 304(1–2), 63–68.  https://doi.org/10.1016/j.mce.2009.02.016.CrossRefPubMedGoogle Scholar
  107. Nilsson, S., Makela, S., Treuter, E., Tujague, M., Thomsen, J., Andersson, G., Enmark, E., Pettersson, K., Warner, M., & Gustafsson, J. A. (2001). Mechanisms of estrogen action. Physiological Reviews, 81(4), 1535–1565.CrossRefPubMedGoogle Scholar
  108. Nilsson, M., Dahlman, I., Ryden, M., Nordstrom, E. A., Gustafsson, J. A., Arner, P., & Dahlman-Wright, K. (2007). Oestrogen receptor alpha gene expression levels are reduced in obese compared to normal weight females. International Journal of Obesity, 31(6), 900–907. doi:0803528 [pii].  https://doi.org/10.1038/sj.ijo.0803528.CrossRefPubMedGoogle Scholar
  109. Niu, W., Huang, C., Nawaz, Z., Levy, M., Somwar, R., Li, D., Bilan, P. J., & Klip, A. (2003). Maturation of the regulation of GLUT4 activity by p38 MAPK during L6 cell myogenesis. The Journal of Biological Chemistry, 278(20), 17953–17962.  https://doi.org/10.1074/jbc.M211136200. M211136200 [pii].CrossRefPubMedGoogle Scholar
  110. Noh, E. M., Lee, Y. R., Chay, K. O., Chung, E. Y., Jung, S. H., Kim, J. S., & Youn, H. J. (2011). Estrogen receptor alpha induces down-regulation of PTEN through PI3-kinase activation in breast cancer cells. Molecular Medicine Report, 4(2), 215–219.  https://doi.org/10.3892/mmr.2011.412.Google Scholar
  111. North American Menopause Society. (2012). The 2012 hormone therapy position statement of: The North American Menopause Society. Menopause, 19(3), 257–271.  https://doi.org/10.1097/gme.0b013e31824b970a.CrossRefGoogle Scholar
  112. O’Malley, B. W. (1971). Mechanisms of action of steroid hormones. The New England Journal of Medicine, 284(7), 370–377.  https://doi.org/10.1056/NEJM197102182840710.CrossRefPubMedGoogle Scholar
  113. Ohlsson, C., Hellberg, N., Parini, P., Vidal, O., Bohlooly, Y. M., Rudling, M., Lindberg, M. K., Warner, M., Angelin, B., & Gustafsson, J. A. (2000). Obesity and disturbed lipoprotein profile in estrogen receptor-alpha-deficient male mice. Biochemical and Biophysical Research Communications, 278(3), 640–645.  https://doi.org/10.1006/bbrc.2000.3827. S0006-291X(00)93827-0 [pii].CrossRefPubMedGoogle Scholar
  114. Okura, T., Koda, M., Ando, F., Niino, N., Ohta, S., & Shimokata, H. (2003a). Association of polymorphisms in the estrogen receptor alpha gene with body fat distribution. International Journal of Obesity and Related Metabolic Disorders, 27(9), 1020–1027.CrossRefPubMedGoogle Scholar
  115. Okura, T., Koda, M., Ando, F., Niino, N., & Shimokata, H. (2003b). Relationships of resting energy expenditure with body fat distribution and abdominal fatness in Japanese population. Journal of Physiological Anthropology and Applied Human Science, 22(1), 47–52.CrossRefPubMedGoogle Scholar
  116. Okura, T., Koda, M., Ando, F., Niino, N., Tanaka, M., & Shimokata, H. (2003c). Association of the mitochondrial DNA 15497G/A polymorphism with obesity in a middle-aged and elderly Japanese population. Human Genetics, 113(5), 432–436.CrossRefPubMedGoogle Scholar
  117. Ordonez, P., Moreno, M., Alonso, A., Llaneza, P., Diaz, F., & Gonzalez, C. (2008). 17beta-Estradiol and/or progesterone protect from insulin resistance in STZ-induced diabetic rats. The Journal of Steroid Biochemistry and Molecular Biology, 111(3–5), 287–294. doi:S0960-0760(08)00190-8 [pii].  https://doi.org/10.1016/j.jsbmb.2008.07.001.CrossRefPubMedGoogle Scholar
  118. Oshel, K. M., Knight, J. B., Cao, K. T., Thai, M. V., & Olson, A. L. (2000). Identification of a 30-base pair regulatory element and novel DNA binding protein that regulates the human GLUT4 promoter in transgenic mice. The Journal of Biological Chemistry, 275(31), 23666–23673.  https://doi.org/10.1074/jbc.M001452200. M001452200 [pii].CrossRefPubMedGoogle Scholar
  119. Park, Y. W., Zhu, S., Palaniappan, L., Heshka, S., Carnethon, M. R., & Heymsfield, S. B. (2003). The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988–1994. Archives of Internal Medicine, 163(4), 427–436.CrossRefPubMedPubMedCentralGoogle Scholar
  120. Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., Landaker, E. J., Goldfine, A. B., Mun, E., DeFronzo, R., Finlayson, J., Kahn, C. R., & Mandarino, L. J. (2003). Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proceedings of the National Academy of Sciences of the United States of America, 100(14), 8466–8471.CrossRefPubMedPubMedCentralGoogle Scholar
  121. Pedram, A., Razandi, M., Blumberg, B., & Levin, E. R. (2016). Membrane and nuclear estrogen receptor alpha collaborate to suppress adipogenesis but not triglyceride content. The FASEB Journal, 30(1), 230–240.  https://doi.org/10.1096/fj.15-274878.CrossRefPubMedGoogle Scholar
  122. Pentti, K., Tuppurainen, M. T., Honkanen, R., Sandini, L., Kroger, H., Alhava, E., & Saarikoski, S. (2009). Hormone therapy protects from diabetes: The Kuopio osteoporosis risk factor and prevention study. European Journal of Endocrinology, 160(6), 979–983.  https://doi.org/10.1530/EJE-09-0151.CrossRefPubMedGoogle Scholar
  123. Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004). Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. The New England Journal of Medicine, 350(7), 664–671.CrossRefPubMedPubMedCentralGoogle Scholar
  124. Riant, E., Waget, A., Cogo, H., Arnal, J. F., Burcelin, R., & Gourdy, P. (2009). Estrogens protect against high-fat diet-induced insulin resistance and glucose intolerance in mice. Endocrinology, 150(5), 2109–2117.CrossRefPubMedGoogle Scholar
  125. Ribas, V., Drew, B. G., Soleymani, T., Daraei, P., & Hevener, A. (2010a). Skeletal muscle specific ER alpha deletion is causal for the metabolic syndrome. Endocrine Reviews, 31(3), S5.Google Scholar
  126. Ribas, V., Nguyen, M. T., Henstridge, D. C., Nguyen, A. K., Beaven, S. W., Watt, M. J., & Hevener, A. L. (2010b). Impaired oxidative metabolism and inflammation are associated with insulin resistance in ERalpha-deficient mice. American Journal of Physiology. Endocrinology and Metabolism, 298(2), E304–E319.  https://doi.org/10.1152/ajpendo.00504.2009.CrossRefPubMedGoogle Scholar
  127. Ribas, V., Drew, B. G., Zhou, Z., Phun, J., Kalajian, N. Y., Soleymani, T., Daraei, P., Widjaja, K., Wanagat, J., de Aguiar Vallim, T. Q., Fluitt, A. H., Bensinger, S., Le, T., Radu, C., Whitelegge, J. P., Beaven, S. W., Tontonoz, P., Lusis, A. J., Parks, B. W., Vergnes, L., Reue, K., Singh, H., Bopassa, J. C., Toro, L., Stefani, E., Watt, M. J., Schenk, S., Akerstrom, T., Kelly, M., Pedersen, B. K., Hewitt, S. C., Korach, K. S., & Hevener, A. L. (2016). Skeletal muscle action of estrogen receptor alpha is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Science Translational Medicine, 8(334), 334ra354.  https://doi.org/10.1126/scitranslmed.aad3815.CrossRefGoogle Scholar
  128. Rochira, V., Madeo, B., Zirilli, L., Caffagni, G., Maffei, L., & Carani, C. (2007). Oestradiol replacement treatment and glucose homeostasis in two men with congenital aromatase deficiency: Evidence for a role of oestradiol and sex steroids imbalance on insulin sensitivity in men. Diabetic Medicine, 24(12), 1491–1495. doi:DME2304 [pii].  https://doi.org/10.1111/j.1464-5491.2007.02304.x.CrossRefPubMedGoogle Scholar
  129. Rodnick, K. J., Holloszy, J. O., Mondon, C. E., & James, D. E. (1990). Effects of exercise training on insulin-regulatable glucose-transporter protein levels in rat skeletal muscle. Diabetes, 39(11), 1425–1429.CrossRefPubMedGoogle Scholar
  130. Rogers, N. H., Witczak, C. A., Hirshman, M. F., Goodyear, L. J., & Greenberg, A. S. (2009). Estradiol stimulates Akt, AMP-activated protein kinase (AMPK) and TBC1D1/4, but not glucose uptake in rat soleus. Biochemical and Biophysical Research Communications, 382(4), 646–650. doi:S0006-291X(09)00441-0 [pii].  https://doi.org/10.1016/j.bbrc.2009.02.154.CrossRefPubMedPubMedCentralGoogle Scholar
  131. Ronda, A. C., & Boland, R. L. (2016). Intracellular distribution and involvement of GPR30 in the actions of E2 on C2C12 cells. Journal of Cellular Biochemistry, 117(3), 793–805.  https://doi.org/10.1002/jcb.25369.CrossRefPubMedGoogle Scholar
  132. Ronda, A. C., Buitrago, C., & Boland, R. (2010a). Role of estrogen receptors, PKC and Src in ERK2 and p38 MAPK signaling triggered by 17beta-estradiol in skeletal muscle cells. The Journal of Steroid Biochemistry and Molecular Biology, 122(4), 287–294. doi:S0960-0760(10)00234-7 [pii].  https://doi.org/10.1016/j.jsbmb.2010.05.002.CrossRefPubMedGoogle Scholar
  133. Ronda, A. C., Vasconsuelo, A., & Boland, R. (2010b). Extracellular-regulated kinase and p38 mitogen-activated protein kinases are involved in the antiapoptotic action of 17beta-estradiol in skeletal muscle cells. The Journal of Endocrinology, 206(2), 235–246. doi:JOE-09-0429 [pii].  https://doi.org/10.1677/JOE-09-0429.CrossRefPubMedGoogle Scholar
  134. Safe, S., & Kim, K. (2008). Non-classical genomic estrogen receptor (ER)/specificity protein and ER/activating protein-1 signaling pathways. Journal of Molecular Endocrinology, 41(5), 263–275.  https://doi.org/10.1677/JME-08-0103.CrossRefPubMedPubMedCentralGoogle Scholar
  135. Salehzadeh, F., Rune, A., Osler, M., & Al-Khalili, L. (2011). Testosterone or 17{beta}-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes. The Journal of Endocrinology, 210(2), 219–229. doi:JOE-10-0497 [pii].  https://doi.org/10.1530/JOE-10-0497.CrossRefPubMedGoogle Scholar
  136. Salpeter, S. R., Walsh, J. M., Ormiston, T. M., Greyber, E., Buckley, N. S., & Salpeter, E. E. (2006). Meta-analysis: Effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obesity & Metabolism, 8(5), 538–554.CrossRefGoogle Scholar
  137. Shang, Y., Hu, X., DiRenzo, J., Lazar, M. A., & Brown, M. (2000). Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell, 103(6), 843–852.CrossRefPubMedGoogle Scholar
  138. Simoncini, T., Hafezi-Moghadam, A., Brazil, D. P., Ley, K., Chin, W. W., & Liao, J. K. (2000). Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature, 407(6803), 538–541.CrossRefPubMedPubMedCentralGoogle Scholar
  139. Simoncini, T., Fornari, L., Mannella, P., Varone, G., Caruso, A., Liao, J. K., & Genazzani, A. R. (2002). Novel non-transcriptional mechanisms for estrogen receptor signaling in the cardiovascular system. Interaction of estrogen receptor alpha with phosphatidylinositol 3-OH kinase. Steroids, 67(12), 935–939. doi:S0039128X02000405 [pii].CrossRefPubMedGoogle Scholar
  140. Sipila, S., Taaffe, D. R., Cheng, S., Puolakka, J., Toivanen, J., & Suominen, H. (2001). Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: A randomized placebo-controlled study. Clinical Science (London, England), 101(2), 147–157.CrossRefGoogle Scholar
  141. Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S. (1994). Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. The New England Journal of Medicine, 331(16), 1056–1061.CrossRefPubMedGoogle Scholar
  142. Smith, J. A., Kohn, T. A., Chetty, A. K., & Ojuka, E. O. (2008). CaMK activation during exercise is required for histone hyperacetylation and MEF2A binding at the MEF2 site on the Glut4 gene. American Journal of Physiology. Endocrinology and Metabolism, 295(3), E698–E704. doi:00747.2007 [pii].  https://doi.org/10.1152/ajpendo.00747.2007.CrossRefPubMedGoogle Scholar
  143. Sorensen, M. B., Rosenfalck, A. M., Hojgaard, L., & Ottesen, B. (2001). Obesity and sarcopenia after menopause are reversed by sex hormone replacement therapy. Obesity Research, 9(10), 622–626.  https://doi.org/10.1038/oby.2001.81.CrossRefPubMedGoogle Scholar
  144. Sotiriadou, S., Kyparos, A., Albani, M., Arsos, G., Clarke, M. S., Sidiras, G., Angelopoulou, N., & Matziari, C. (2006). Soleus muscle force following downhill running in ovariectomized rats treated with estrogen. Applied Physiology, Nutrition, and Metabolism, 31(4), 449–459. doi:h06-008 [pii].  https://doi.org/10.1139/h06-008.CrossRefPubMedGoogle Scholar
  145. Stitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., Gonzalez, M., Yancopoulos, G. D., & Glass, D. J. (2004). The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Molecular Cell, 14(3), 395–403. doi:S1097276504002114 [pii].CrossRefPubMedGoogle Scholar
  146. Stubbins, R. E., Holcomb, V. B., Hong, J., & Nunez, N. P. (2011). Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance. European Journal of Nutrition.  https://doi.org/10.1007/s00394-011-0266-4.
  147. Summers, S. A. (2006). Ceramides in insulin resistance and lipotoxicity. Progress in Lipid Research, 45(1), 42–72. doi:S0163-7827(05)00050-0 [pii].  https://doi.org/10.1016/j.plipres.2005.11.002.CrossRefPubMedGoogle Scholar
  148. Sweeney, G., Somwar, R., Ramlal, T., Volchuk, A., Ueyama, A., & Klip, A. (1999). An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated glucose transport but not glucose transporter translocation in 3T3-L1 adipocytes and L6 myotubes. The Journal of Biological Chemistry, 274(15), 10071–10078.CrossRefPubMedGoogle Scholar
  149. Szmuilowicz, E. D., Stuenkel, C. A., & Seely, E. W. (2009). Influence of menopause on diabetes and diabetes risk. Nature Reviews Endocrinology, 5(10), 553–558.  https://doi.org/10.1038/nrendo.2009.166.CrossRefPubMedGoogle Scholar
  150. Takeda, K., Toda, K., Saibara, T., Nakagawa, M., Saika, K., Onishi, T., Sugiura, T., & Shizuta, Y. (2003). Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency. The Journal of Endocrinology, 176(2), 237–246.CrossRefPubMedGoogle Scholar
  151. Teixeira, P. J., Going, S. B., Houtkooper, L. B., Metcalfe, L. L., Blew, R. M., Flint-Wagner, H. G., Cussler, E. C., Sardinha, L. B., & Lohman, T. G. (2003). Resistance training in postmenopausal women with and without hormone therapy. Medicine and Science in Sports and Exercise, 35(4), 555–562.  https://doi.org/10.1249/01.MSS.0000058437.17262.11.CrossRefPubMedGoogle Scholar
  152. Thomas, A., Bunyan, K., & Tiidus, P. M. (2010). Oestrogen receptor-alpha activation augments post-exercise myoblast proliferation. Acta Physiologica (Oxford, England), 198(1), 81–89. doi:APS2033 [pii].  https://doi.org/10.1111/j.1748-1716.2009.02033.x.CrossRefGoogle Scholar
  153. Tiano, J. P., & Mauvais-Jarvis, F. (2012). Importance of oestrogen receptors to preserve functional beta-cell mass in diabetes. Nature Reviews Endocrinology.  https://doi.org/10.1038/nrendo.2011.242.
  154. Tiidus, P. M. (2000). Estrogen and gender effects on muscle damage, inflammation, and oxidative stress. Canadian Journal of Applied Physiology, 25(4), 274–287.CrossRefPubMedGoogle Scholar
  155. Turcotte, L. P., Richter, E. A., & Kiens, B. (1992). Increased plasma FFA uptake and oxidation during prolonged exercise in trained vs. untrained humans. The American Journal of Physiology, 262(6 Pt 1), E791–E799.PubMedGoogle Scholar
  156. Van Pelt, R. E., Gozansky, W. S., Schwartz, R. S., & Kohrt, W. M. (2003). Intravenous estrogens increase insulin clearance and action in postmenopausal women. American Journal of Physiology Endocrinology and Metabolism, 285(2), E311–E317.  https://doi.org/10.1152/ajpendo.00490.2002. 00490.2002 [pii].CrossRefPubMedPubMedCentralGoogle Scholar
  157. van Rooij, E., Fielitz, J., Sutherland, L. B., Thijssen, V. L., Crijns, H. J., Dimaio, M. J., Shelton, J., De Windt, L. J., Hill, J. A., & Olson, E. N. (2010). Myocyte enhancer factor 2 and class II histone deacetylases control a gender-specific pathway of cardioprotection mediated by the estrogen receptor. Circulation Research, 106(1), 155–165. doi:CIRCRESAHA.109.207084 [pii].  https://doi.org/10.1161/CIRCRESAHA.109.207084.CrossRefPubMedGoogle Scholar
  158. Vasconsuelo, A., Milanesi, L., & Boland, R. (2008). 17Beta-estradiol abrogates apoptosis in murine skeletal muscle cells through estrogen receptors: Role of the phosphatidylinositol 3-kinase/Akt pathway. The Journal of Endocrinology, 196(2), 385–397. doi:196/2/385 [pii].  https://doi.org/10.1677/JOE-07-0250.CrossRefPubMedGoogle Scholar
  159. Villablanca, A., Lubahn, D., Shelby, L., Lloyd, K., & Barthold, S. (2004). Susceptibility to early atherosclerosis in male mice is mediated by estrogen receptor alpha. Arteriosclerosis, Thrombosis, and Vascular Biology, 24(6), 1055–1061.  https://doi.org/10.1161/01.ATV.0000130467.65290.d4.CrossRefPubMedGoogle Scholar
  160. Vogel, H., Wolf, S., Rabasa, C., Rodriguez-Pacheco, F., Babaei, C. S., Stober, F., Goldschmidt, J., DiMarchi, R. D., Finan, B., Tschop, M. H., Dickson, S. L., Schurmann, A., & Skibicka, K. P. (2016). GLP-1 and estrogen conjugate acts in the supramammillary nucleus to reduce food-reward and body weight. Neuropharmacology, 110(Pt A), 396–406.  https://doi.org/10.1016/j.neuropharm.2016.07.039.CrossRefPubMedGoogle Scholar
  161. Wang, F., He, Q., Sun, Y., Dai, X., & Yang, X. P. (2010). Female adult mouse cardiomyocytes are protected against oxidative stress. Hypertension, 55(5), 1172–1178. doi:HYPERTENSIONAHA.110.150839 [pii].  https://doi.org/10.1161/HYPERTENSIONAHA.110.150839.CrossRefPubMedPubMedCentralGoogle Scholar
  162. Wellen, K. E., & Hotamisligil, G. S. (2005). Inflammation, stress, and diabetes. The Journal of Clinical Investigation, 115(5), 1111–1119.CrossRefPubMedPubMedCentralGoogle Scholar
  163. Wiik, A., Gustafsson, T., Esbjornsson, M., Johansson, O., Ekman, M., Sundberg, C. J., & Jansson, E. (2005). Expression of oestrogen receptor alpha and beta is higher in skeletal muscle of highly endurance-trained than of moderately active men. Acta Physiologica Scandinavica, 184(2), 105–112. doi:APS1433 [pii].  https://doi.org/10.1111/j.1365-201X.2005.01433.x.CrossRefPubMedGoogle Scholar
  164. Yamada, Y., Ando, F., Niino, N., Ohta, S., & Shimokata, H. (2002). Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density of the femoral neck in elderly Japanese women. Journal of Molecular Medicine, 80(7), 452–460.CrossRefPubMedGoogle Scholar
  165. Yang, G., Badeanlou, L., Bielawski, J., Roberts, A. J., Hannun, Y. A., & Samad, F. (2009a). Central role of ceramide biosynthesis in body weight regulation, energy metabolism, and the metabolic syndrome. American Journal of Physiology. Endocrinology and Metabolism, 297(1), E211–E224.  https://doi.org/10.1152/ajpendo.91014.2008.CrossRefPubMedPubMedCentralGoogle Scholar
  166. Yang, X., Deignan, J. L., Qi, H., Zhu, J., Qian, S., Zhong, J., Torosyan, G., Majid, S., Falkard, B., Kleinhanz, R. R., Karlsson, J., Castellani, L. W., Mumick, S., Wang, K., Xie, T., Coon, M., Zhang, C., Estrada-Smith, D., Farber, C. R., Wang, S. S., van Nas, A., Ghazalpour, A., Zhang, B., Macneil, D. J., Lamb, J. R., Dipple, K. M., Reitman, M. L., Mehrabian, M., Lum, P. Y., Schadt, E. E., Lusis, A. J., & Drake, T. A. (2009b). Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks. Nature Genetics, 41(4), 415–423. doi:ng.325 [pii].  https://doi.org/10.1038/ng.325.CrossRefPubMedPubMedCentralGoogle Scholar
  167. Yki-Jarvinen, H. (1984). Sex and insulin sensitivity. Metabolism, 33(11), 1011–1015.CrossRefPubMedGoogle Scholar
  168. Zorzano, A., Palacin, M., & Guma, A. (2005). Mechanisms regulating GLUT4 glucose transporter expression and glucose transport in skeletal muscle. Acta Physiologica Scandinavica, 183(1), 43–58. doi:APS1380 [pii]..  https://doi.org/10.1111/j.1365-201X.2004.01380.x.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Andrea L. Hevener
    • 1
  • Zhenqi Zhou
    • 1
  • Brian G. Drew
    • 1
  • Vicent Ribas
    • 1
  1. 1.Department of Medicine, Division of Endocrinology, Diabetes and HypertensionDavid Geffen School of Medicine, University of CaliforniaLos AngelesUSA

Personalised recommendations