Skip to main content
SpringerLink
Log in

Role of Estrogens in the Regulation of Liver Lipid Metabolism

  • Chapter
  • First Online:
Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1043))

Abstract

Before menopause, women are protected from atherosclerotic heart disease associated with obesity relative to men. Sex hormones have been proposed as a mechanism that differentiates this risk. In this review, we discuss the literature around how the endogenous sex hormones and hormone treatment approaches after menopause regulate fatty acid, triglyceride, and cholesterol metabolism to influence cardiovascular risk.

The important regulatory functions of estrogen signaling pathways with regard to lipid metabolism have been in part obscured by clinical trials with hormone treatment of women after menopause, due to different formulations, routes of delivery, and pairings with progestins. Oral hormone treatment with several estrogen preparations increases VLDL triglyceride production. Progestins oppose this effect by stimulating VLDL clearance in both humans and animals. Transdermal estradiol preparations do not increase VLDL production or serum triglycerides.

Many aspects of sex differences in atherosclerotic heart disease risk are influenced by the distributed actions of estrogens in the muscle, adipose, and liver. In humans, 17β-estradiol (E2) is the predominant circulating estrogen and signals through estrogen receptor alpha (ERα), estrogen receptor beta (ERβ), and G-protein-coupled estrogen receptor (GPER). Over 1000 human liver genes display a sex bias in their expression, and the top biological pathways are in lipid metabolism and genes related to cardiovascular disease. Many of these genes display variation depending on estrus cycling in the mouse. Future directions will likely rely on targeting estrogens to specific tissues or specific aspects of the signaling pathways in order to recapitulate the protective physiology of premenopause therapeutically after menopause.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Aguilar-Salinas, C. A., Garcia-Garcia, E., Gomez Perez, F. J., & Rull, J. A. (2002). The healthy women bias and hormone replacement therapy in women with type 2 diabetes. Diabetes Care, 25(1), 246–247.

    Article  PubMed  Google Scholar 

  • Arai, T., Wang, N., Bezouevski, M., Welch, C., & Tall, A. R. (1999). Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene. The Journal of Biological Chemistry, 274(4), 2366–2371.

    Article  CAS  PubMed  Google Scholar 

  • Arii, K., Suehiro, T., Yamamoto, M., Ito, H., & Hashimoto, K. (1997). Suppression of plasma cholesteryl ester transfer protein activity in acute hyperinsulinemia and effect of plasma nonesterified fatty acid. Metabolism, 46(10), 1166–1170. doi:S0026-0495(97)90211-0 [pii].

    Article  CAS  PubMed  Google Scholar 

  • Badeau, R. M., Metso, J., Wahala, K., Tikkanen, M. J., & Jauhiainen, M. (2009). Human macrophage cholesterol efflux potential is enhanced by HDL-associated 17beta-estradiol fatty acyl esters. The Journal of Steroid Biochemistry and Molecular Biology, 116(1–2), 44–49. https://doi.org/10.1016/j.jsbmb.2009.04.008.

    Article  CAS  PubMed  Google Scholar 

  • Badeau, R. M., Metso, J., Kovanen, P. T., Lee-Rueckert, M., Tikkanen, M. J., & Jauhiainen, M. (2013). The impact of gender and serum estradiol levels on HDL-mediated reverse cholesterol transport. European Journal of Clinical Investigation, 43(4), 317–323. https://doi.org/10.1111/eci.12044.

    Article  CAS  PubMed  Google Scholar 

  • Baksu, B., Davas, I., Agar, E., Akyol, A., & Uluocak, A. (2007). Do different delivery systems of estrogen therapy influence serum lipids differently in surgically menopausal women? The Journal of Obstetrics and Gynaecology Research, 33(3), 346–352. https://doi.org/10.1111/j.1447-0756.2007.00534.x.

    Article  CAS  PubMed  Google Scholar 

  • Barrera, J., Chambliss, K. L., Ahmed, M., Tanigaki, K., Thompson, B., McDonald, J. G., Mineo, C., & Shaul, P. W. (2014). Bazedoxifene and conjugated estrogen prevent diet-induced obesity, hepatic steatosis, and type 2 diabetes in mice without impacting the reproductive tract. American Journal of Physiology Endocrinology and Metabolism, 307(3), E345–E354. https://doi.org/10.1152/ajpendo.00653.2013.

    Article  CAS  PubMed  Google Scholar 

  • Barrett-Connor, E., Slone, S., Greendale, G., Kritz-Silverstein, D., Espeland, M., Johnson, S. R., Waclawiw, M., & Fineberg, S. E. (1997). The postmenopausal estrogen/progestin interventions study: Primary outcomes in adherent women. Maturitas, 27(3), 261–274.

    Article  CAS  PubMed  Google Scholar 

  • Barrows, B. R., & Parks, E. J. (2006). Contributions of different fatty acid sources to very low-density lipoprotein-triacylglycerol in the fasted and fed states. The Journal of Clinical Endocrinology and Metabolism, 91(4), 1446–1452. https://doi.org/10.1210/jc.2005-1709.

    Article  CAS  PubMed  Google Scholar 

  • Barrows, B. R., Timlin, M. T., & Parks, E. J. (2005). Spillover of dietary fatty acids and use of serum nonesterified fatty acids for the synthesis of VLDL-triacylglycerol under two different feeding regimens. Diabetes, 54(9), 2668–2673.

    Article  CAS  PubMed  Google Scholar 

  • Bjornstrom, L., & Sjoberg, M. (2005). Mechanisms of estrogen receptor signaling: Convergence of genomic and nongenomic actions on target genes. Molecular Endocrinology, 19(4), 833–842. https://doi.org/10.1210/me.2004-0486.

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1007/s00125-005-0096-0.

    Article  CAS  PubMed  Google Scholar 

  • Bourassa, P. A., Milos, P. M., Gaynor, B. J., Breslow, J. L., & Aiello, R. J. (1996). Estrogen reduces atherosclerotic lesion development in apolipoprotein E-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 93(19), 10022–10027.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Bryzgalova, G., Lundholm, L., Portwood, N., Gustafsson, J. A., Khan, A., Efendic, S., & Dahlman-Wright, K. (2008). Mechanisms of antidiabetogenic and body weight-lowering effects of estrogen in high-fat diet-fed mice. American Journal of Physiology. Endocrinology and Metabolism, 295(4), E904–E912. https://doi.org/10.1152/ajpendo.90248.2008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Burch, J. C., Byrd, B. F., Jr., & Vaughn, W. K. (1974). The effects of long-term estrogen on hysterectomized women. American Journal of Obstetrics and Gynecology, 118(6), 778–782.

    Article  CAS  PubMed  Google Scholar 

  • Bush, T. L., Cowan, L. D., Barrett-Connor, E., Criqui, M. H., Karon, J. M., Wallace, R. B., Tyroler, H. A., & Rifkind, B. M. (1983). Estrogen use and all-cause mortality. Preliminary results from the lipid research clinics program follow-up study. JAMA, 249(7), 903–906.

    Article  CAS  PubMed  Google Scholar 

  • Camporez, J. P., Jornayvaz, F. R., Lee, H. Y., Kanda, S., Guigni, B. A., Kahn, M., Samuel, V. T., Carvalho, C. R., Petersen, K. F., Jurczak, M. J., & Shulman, G. I. (2013). Cellular mechanism by which estradiol protects female ovariectomized mice from high-fat diet-induced hepatic and muscle insulin resistance. Endocrinology, 154(3), 1021–1028. https://doi.org/10.1210/en.2012-1989.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Canoy, D., Boekholdt, S. M., Wareham, N., Luben, R., Welch, A., Bingham, S., Buchan, I., Day, N., & Khaw, K. T. (2007). Body fat distribution and risk of coronary heart disease in men and women in the European prospective investigation into cancer and nutrition in Norfolk cohort: A population-based prospective study. Circulation, 116(25), 2933–2943. https://doi.org/10.1161/CIRCULATIONAHA.106.673756.

    Article  PubMed  Google Scholar 

  • Chambliss, K. L., Wu, Q., Oltmann, S., Konaniah, E. S., Umetani, M., Korach, K. S., Thomas, G. D., Mineo, C., Yuhanna, I. S., Kim, S. H., Madak-Erdogan, Z., Maggi, A., Dineen, S. P., Roland, C. L., Hui, D. Y., Brekken, R. A., Katzenellenbogen, J. A., Katzenellenbogen, B. S., & Shaul, P. W. (2010). Non-nuclear estrogen receptor alpha signaling promotes cardiovascular protection but not uterine or breast cancer growth in mice. The Journal of Clinical Investigation, 120(7), 2319–2330. https://doi.org/10.1172/JCI38291.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chambliss, K. L., Barrera, J., Umetani, M., Umetani, J., Kim, S. H., Madak-Erdogan, Z., Huang, L., Katzenellenbogen, B. S., Katzenellenbogen, J. A., Mineo, C., & Shaul, P. W. (2016). Nonnuclear estrogen receptor activation improves hepatic steatosis in female mice. Endocrinology, 157(10), 3731–3741. https://doi.org/10.1210/en.2015-1629.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen, F. P., Lee, N., Soong, Y. K., & Huang, K. E. (2001). Comparison of transdermal and oral estrogen-progestin replacement therapy: Effects on cardiovascular risk factors. Menopause, 8(5), 347–352.

    Article  CAS  PubMed  Google Scholar 

  • Chow, J. D., Jones, M. E., Prelle, K., Simpson, E. R., & Boon, W. C. (2011). A selective estrogen receptor alpha agonist ameliorates hepatic steatosis in the male aromatase knockout mouse. The Journal of Endocrinology, 210(3), 323–334. https://doi.org/10.1530/JOE-10-0462.

    Article  CAS  PubMed  Google Scholar 

  • Ciana, P., Raviscioni, M., Mussi, P., Vegeto, E., Que, I., Parker, M. G., Lowik, C., & Maggi, A. (2003). In vivo imaging of transcriptionally active estrogen receptors. Nature Medicine, 9(1), 82–86. https://doi.org/10.1038/nm809.

    Article  CAS  PubMed  Google Scholar 

  • Clegg, D., Hevener, A. L., Moreau, K. L., Morselli, E., Criollo, A., Van Pelt, R. E., & Vieira-Potter, V. J. (2017). Sex hormones and cardiometabolic health: Role of estrogen and estrogen receptors. Endocrinology, 158(5), 1095–1105. https://doi.org/10.1210/en.2016-1677.

    Article  PubMed  Google Scholar 

  • Colditz, G. A., Willett, W. C., Stampfer, M. J., Rosner, B., Speizer, F. E., & Hennekens, C. H. (1987). Menopause and the risk of coronary heart disease in women. The New England Journal of Medicine, 316(18), 1105–1110. https://doi.org/10.1056/NEJM198704303161801.

    Article  CAS  PubMed  Google Scholar 

  • Cole, L. K., Jacobs, R. L., & Vance, D. E. (2010). Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology, 52(4), 1258–1265. https://doi.org/10.1002/hep.23813.

    Article  CAS  PubMed  Google Scholar 

  • Cooper, A. D., Nutik, R., & Chen, J. (1987). Characterization of the estrogen-induced lipoprotein receptor of rat liver. Journal of Lipid Research, 28(1), 59–68.

    CAS  PubMed  Google Scholar 

  • Cote, I., Yasari, S., Pighon, A., Barsalani, R., Rabasa-Lhoret, R., Prud'homme, D., & Lavoie, J. M. (2012). Liver fat accumulation may be dissociated from adiposity gain in ovariectomized rats. Climacteric, 15(6), 594–601. https://doi.org/10.3109/13697137.2011.637650.

    Article  CAS  PubMed  Google Scholar 

  • Criqui, M. H., Suarez, L., Barrett-Connor, E., McPhillips, J., Wingard, D. L., & Garland, C. (1988). Postmenopausal estrogen use and mortality. Results from a prospective study in a defined, homogeneous community. American Journal of Epidemiology, 128(3), 606–614.

    Article  CAS  PubMed  Google Scholar 

  • Croft, P., & Hannaford, P. (1989). Risk factors for acute myocardial infarction in women. BMJ, 298(6674), 674.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Davis, R. A. (1997). Evolution of processes and regulators of lipoprotein synthesis: From birds to mammals. The Journal of Nutrition, 127(5 Suppl), 795S–800S.

    Article  CAS  PubMed  Google Scholar 

  • de Koning, L., Merchant, A. T., Pogue, J., & Anand, S. S. (2007). Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: Meta-regression analysis of prospective studies. European Heart Journal, 28(7), 850–856. https://doi.org/10.1093/eurheartj/ehm026.

    Article  PubMed  Google Scholar 

  • De Marinis, E., Martini, C., Trentalance, A., & Pallottini, V. (2008). Sex differences in hepatic regulation of cholesterol homeostasis. The Journal of Endocrinology, 198(3), 635–643. https://doi.org/10.1677/JOE-08-0242.

    Article  CAS  PubMed  Google Scholar 

  • de Oliveira, M. C., Gilglioni, E. H., de Boer, B. A., Runge, J. H., de Waart, D. R., Salgueiro, C. L., Ishii-Iwamoto, E. L., Oude Elferink, R. P., & Gaemers, I. C. (2016). Bile acid receptor agonists INT747 and INT777 decrease oestrogen deficiency-related postmenopausal obesity and hepatic steatosis in mice. Biochimica et Biophysica Acta, 1862(11), 2054–2062. https://doi.org/10.1016/j.bbadis.2016.07.012.

    Article  CAS  PubMed  Google Scholar 

  • de Vries, R., Perton, F. G., Dallinga-Thie, G. M., van Roon, A. M., Wolffenbuttel, B. H., van Tol, A., & Dullaart, R. P. (2005). Plasma cholesteryl ester transfer is a determinant of intima-media thickness in type 2 diabetic and nondiabetic subjects: Role of CETP and triglycerides. Diabetes, 54(12), 3554–3559.

    Article  PubMed  Google Scholar 

  • Della Torre, S., Rando, G., Meda, C., Stell, A., Chambon, P., Krust, A., Ibarra, C., Magni, P., Ciana, P., & Maggi, A. (2011). Amino acid-dependent activation of liver estrogen receptor alpha integrates metabolic and reproductive functions via IGF-1. Cell Metabolism, 13(2), 205–214. https://doi.org/10.1016/j.cmet.2011.01.002.

    Article  CAS  PubMed  Google Scholar 

  • Della Torre, S., Mitro, N., Fontana, R., Gomaraschi, M., Favari, E., Recordati, C., Lolli, F., Quagliarini, F., Meda, C., Ohlsson, C., Crestani, M., Uhlenhaut, N. H., Calabresi, L., & Maggi, A. (2016). An essential role for liver ER alpha in coupling hepatic metabolism to the reproductive cycle. Cell Reports, 15(2), 360–371. https://doi.org/10.1016/j.celrep.2016.03.019.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Di Croce, L., Bruscalupi, G., & Trentalance, A. (1996). Independent behavior of rat liver LDL receptor and HMGCoA reductase under estrogen treatment. Biochemical and Biophysical Research Communications, 224(2), 345–350. https://doi.org/10.1006/bbrc.1996.1031.

    Article  PubMed  Google Scholar 

  • Di Croce, L., Vicent, G. P., Pecci, A., Bruscalupi, G., Trentalance, A., & Beato, M. (1999). The promoter of the rat 3-hydroxy-3-methylglutaryl coenzyme A reductase gene contains a tissue-specific estrogen-responsive region. Molecular Endocrinology, 13(8), 1225–1236. https://doi.org/10.1210/mend.13.8.0333.

    Article  PubMed  Google Scholar 

  • Distefano, E., Marino, M., Gillette, J. A., Hanstein, B., Pallottini, V., Bruning, J., Krone, W., & Trentalance, A. (2002). Role of tyrosine kinase signaling in estrogen-induced LDL receptor gene expression in HepG2 cells. Biochimica et Biophysica Acta, 1580(2–3), 145–149.

    Article  CAS  PubMed  Google Scholar 

  • El Khoudary, S. R., Hutchins, P. M., Matthews, K. A., Brooks, M. M., Orchard, T. J., Ronsein, G. E., & Heinecke, J. W. (2016). Cholesterol efflux capacity and subclasses of HDL particles in healthy women transitioning through menopause. The Journal of Clinical Endocrinology and Metabolism, 101(9), 3419–3428. https://doi.org/10.1210/jc.2016-2144.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Espeland, M. A., Hogan, P. E., Fineberg, S. E., Howard, G., Schrott, H., Waclawiw, M. A., & Bush, T. L. (1998). Effect of postmenopausal hormone therapy on glucose and insulin concentrations. PEPI Investigators. Postmenopausal Estrogen/Progestin Interventions. Diabetes Care, 21(10), 1589–1595.

    Article  CAS  PubMed  Google Scholar 

  • Fabbrini, E., Magkos, F., Mohammed, B. S., Pietka, T., Abumrad, N. A., Patterson, B. W., Okunade, A., & Klein, S. (2009). Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proceedings of the National Academy of Sciences of the United States of America, 106(36), 15430–15435. https://doi.org/10.1073/pnas.0904944106.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ferrara, A., Karter, A. J., Ackerson, L. M., Liu, J. Y., Selby, J. V., & Northern California Kaiser Permanente Diabetes R. (2001). Hormone replacement therapy is associated with better glycemic control in women with type 2 diabetes: The Northern California Kaiser Permanente Diabetes Registry. Diabetes Care, 24(7), 1144–1150.

    Article  CAS  PubMed  Google Scholar 

  • Finan, B., Yang, B., Ottaway, N., Stemmer, K., Muller, T. D., Yi, C. X., Habegger, K., Schriever, S. C., Garcia-Caceres, C., Kabra, D. G., Hembree, J., Holland, J., Raver, C., Seeley, R. J., Hans, W., Irmler, M., Beckers, J., de Angelis, M. H., Tiano, J. P., Mauvais-Jarvis, F., Perez-Tilve, D., Pfluger, P., Zhang, L., Gelfanov, V., DiMarchi, R. D., & Tschop, M. H. (2012). Targeted estrogen delivery reverses the metabolic syndrome. Nature Medicine, 18(12), 1847–1856. https://doi.org/10.1038/nm.3009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Finkelstein, J. S., Lee, H., Burnett-Bowie, S. A., Pallais, J. C., Yu, E. W., Borges, L. F., Jones, B. F., Barry, C. V., Wulczyn, K. E., Thomas, B. J., & Leder, B. Z. (2013). Gonadal steroids and body composition, strength, and sexual function in men. The New England Journal of Medicine, 369(11), 1011–1022. https://doi.org/10.1056/NEJMoa1206168.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Freedman, D. S., Otvos, J. D., Jeyarajah, E. J., Shalaurova, I., Cupples, L. A., Parise, H., D’Agostino, R. B., Wilson, P. W., & Schaefer, E. J. (2004). Sex and age differences in lipoprotein subclasses measured by nuclear magnetic resonance spectroscopy: The Framingham Study. Clinical Chemistry, 50(7), 1189–1200. https://doi.org/10.1373/clinchem.2004.032763.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Fukata, Y., Yu, X., Imachi, H., Nishiuchi, T., Lyu, J., Seo, K., Takeuchi, A., Iwama, H., Masugata, H., Hoshikawa, H., Hosomi, N., Iwasaki, Y., & Murao, K. (2014). 17beta-Estradiol regulates scavenger receptor class BI gene expression via protein kinase C in vascular endothelial cells. Endocrine, 46(3), 644–650. https://doi.org/10.1007/s12020-013-0134-5.

    Article  CAS  PubMed  Google Scholar 

  • Galien, R., & Garcia, T. (1997). Estrogen receptor impairs interleukin-6 expression by preventing protein binding on the NF-κB site. Nucleic Acids Research, 25(12), 2424–2429. https://doi.org/10.1093/nar/25.12.2424.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gao, H., Bryzgalova, G., Hedman, E., Khan, A., Efendic, S., Gustafsson, J. A., & Dahlman-Wright, K. (2006). Long-term administration of estradiol decreases expression of hepatic lipogenic genes and improves insulin sensitivity in ob/ob mice: A possible mechanism is through direct regulation of signal transducer and activator of transcription 3. Molecular Endocrinology, 20(6), 1287–1299. https://doi.org/10.1210/me.2006-0012.

    Article  CAS  PubMed  Google Scholar 

  • Gao, H., Falt, S., Sandelin, A., Gustafsson, J. A., & Dahlman-Wright, K. (2008). Genome-wide identification of estrogen receptor alpha-binding sites in mouse liver. Molecular Endocrinology, 22(1), 10–22. https://doi.org/10.1210/me.2007-0121.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Glueck, C. J., Fallat, R. W., & Scheel, D. (1975). Effects of estrogenic compounds on triglyceride kinetics. Metabolism, 24(4), 537–545. doi:0026-0495(75)90078-5 [pii].

    Article  CAS  PubMed  Google Scholar 

  • Grady, D., Rubin, S. M., Petitti, D. B., Fox, C. S., Black, D., Ettinger, B., Ernster, V. L., & Cummings, S. R. (1992). Hormone therapy to prevent disease and prolong life in postmenopausal women. Annals of Internal Medicine, 117(12), 1016–1037.

    Article  CAS  PubMed  Google Scholar 

  • Grady, D., Herrington, D., Bittner, V., Blumenthal, R., Davidson, M., Hlatky, M., Hsia, J., Hulley, S., Herd, A., Khan, S., Newby, L. K., Waters, D., Vittinghoff, E., Wenger, N., & Group HR. (2002). Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and estrogen/progestin replacement study follow-up (HERS II). JAMA : The Journal of the American Medical Association, 288(1), 49–57.

    Article  PubMed  Google Scholar 

  • Grodstein, F., & Stampfer, M. (1995). The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Progress in Cardiovascular Diseases, 38(3), 199–210.

    Article  CAS  PubMed  Google Scholar 

  • Hammond, C. B., Jelovsek, F. R., Lee, K. L., Creasman, W. T., & Parker, R. T. (1979). Effects of long-term estrogen replacement therapy. I. Metabolic effects. American Journal of Obstetrics and Gynecology, 133(5), 525–536.

    Article  CAS  PubMed  Google Scholar 

  • Henderson, B. E., Paganini-Hill, A., & Ross, R. K. (1991). Decreased mortality in users of estrogen replacement therapy. Archives of Internal Medicine, 151(1), 75–78.

    Article  CAS  PubMed  Google Scholar 

  • Hernandez Avila, M., Walker, A. M., & Jick, H. (1990). Use of replacement estrogens and the risk of myocardial infarction. Epidemiology, 1(2), 128–133.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Hodis, H. N., Mack, W. J., Lobo, R. A., Shoupe, D., Sevanian, A., Mahrer, P. R., Selzer, R. H., Liu Cr, C. R., Liu Ch, C. H., Azen, S. P., & Estrogen in the Prevention of Atherosclerosis Trial Research G. (2001). Estrogen in the prevention of atherosclerosis. A randomized, double-blind, placebo-controlled trial. Annals of Internal Medicine, 135(11), 939–953.

    Article  CAS  PubMed  Google Scholar 

  • Hodis, H. N., Mack, W. J., Azen, S. P., Lobo, R. A., Shoupe, D., Mahrer, P. R., Faxon, D. P., Cashin-Hemphill, L., Sanmarco, M. E., French, W. J., Shook, T. L., Gaarder, T. D., Mehra, A. O., Rabbani, R., Sevanian, A., Shil, A. B., Torres, M., Vogelbach, K. H., Selzer, R. H., & Women’s Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial Research G. (2003). Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. The New England Journal of Medicine, 349(6), 535–545. https://doi.org/10.1056/NEJMoa030830.

    Article  CAS  PubMed  Google Scholar 

  • Hodis, H. N., Mack, W. J., Henderson, V. W., Shoupe, D., Budoff, M. J., Hwang-Levine, J., Li, Y., Feng, M., Dustin, L., Kono, N., Stanczyk, F. Z., Selzer, R. H., Azen, S. P., & Group ER. (2016). Vascular effects of early versus late postmenopausal treatment with estradiol. The New England Journal of Medicine, 374(13), 1221–1231. https://doi.org/10.1056/NEJMoa1505241.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hsia, J., Langer, R. D., Manson, J. E., Kuller, L., Johnson, K. C., Hendrix, S. L., Pettinger, M., Heckbert, S. R., Greep, N., Crawford, S., Eaton, C. B., Kostis, J. B., Caralis, P., Prentice, R., & Investigato, W. H. I. (2006). Conjugated equine estrogens and coronary heart disease – The women’s health initiative. Archives of Internal Medicine, 166(3), 357–365. https://doi.org/10.1001/Archinte.166.3.357.

    Article  CAS  PubMed  Google Scholar 

  • Hu, F. B., Grodstein, F., Hennekens, C. H., Colditz, G. A., Johnson, M., Manson, J. E., Rosner, B., & Stampfer, M. J. (1999). Age at natural menopause and risk of cardiovascular disease. Archives of Internal Medicine, 159(10), 1061–1066.

    Article  CAS  PubMed  Google Scholar 

  • Hulley, S., Grady, D., Bush, T., Furberg, C., Herrington, D., Riggs, B., & Vittinghoff, E. (1998). Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and estrogen/progestin replacement study (HERS) research group. JAMA, 280(7), 605–613.

    Article  CAS  PubMed  Google Scholar 

  • Jensen, M. D., Martin, M. L., Cryer, P. E., & Roust, L. R. (1994). Effects of estrogen on free fatty acid metabolism in humans. The American Journal of Physiology, 266(6 Pt 1), E914–E920.

    CAS  PubMed  Google Scholar 

  • Jiang, X. C., Moulin, P., Quinet, E., Goldberg, I. J., Yacoub, L. K., Agellon, L. B., Compton, D., Schnitzer-Polokoff, R., & Tall, A. R. (1991). Mammalian adipose tissue and muscle are major sources of lipid transfer protein mRNA. The Journal of Biological Chemistry, 266(7), 4631–4639.

    CAS  PubMed  Google Scholar 

  • Johansson, L. E., Danielsson, A. P., Parikh, H., Klintenberg, M., Norstrom, F., Groop, L., & Ridderstrale, M. (2012). Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance. The American Journal of Clinical Nutrition, 96(1), 196–207. https://doi.org/10.3945/ajcn.111.020578.

    Article  CAS  PubMed  Google Scholar 

  • 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. https://doi.org/10.1073/pnas.97.23.12735.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jones, M. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Misso, M. L., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., & Simpson, E. R. (2001). Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. The Journal of Steroid Biochemistry and Molecular Biology, 79(1–5), 3–9.

    Article  CAS  PubMed  Google Scholar 

  • Jornayvaz, F. R., Birkenfeld, A. L., Jurczak, M. J., Kanda, S., Guigni, B. A., Jiang, D. C., Zhang, D., Lee, H. Y., Samuel, V. T., & Shulman, G. I. (2011). Hepatic insulin resistance in mice with hepatic overexpression of diacylglycerol acyltransferase 2. Proceedings of the National Academy of Sciences of the United States of America, 108(14), 5748–5752. https://doi.org/10.1073/pnas.1103451108.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kannel, W. B., Hjortland, M. C., McNamara, P. M., & Gordon, T. (1976). Menopause and risk of cardiovascular disease: The Framingham study. Annals of Internal Medicine, 85(4), 447–452.

    Article  CAS  PubMed  Google Scholar 

  • Kim, H. J., & Kalkhoff, R. K. (1975). Sex steroid influence on triglyceride metabolism. The Journal of Clinical Investigation, 56(4), 888–896. https://doi.org/10.1172/JCI108168.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim, J. H., Meyers, M. S., Khuder, S. S., Abdallah, S. L., Muturi, H. T., Russo, L., Tate, C. R., Hevener, A. L., Najjar, S. M., Leloup, C., & Mauvais-Jarvis, F. (2014). Tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice. Molecular Metabolism, 3(2), 177–190. https://doi.org/10.1016/j.molmet.2013.12.009.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kissebah, A. H., Harrigan, P., & Wynn, V. (1973). Mechanism of hypertriglyceridaemia associated with contraceptive steroids. Hormone and Metabolic Research, 5(3), 184–190. https://doi.org/10.1055/s-0028-1093969.

    Article  CAS  PubMed  Google Scholar 

  • Kushwaha, R. S., Hazzard, W. R., Gagne, C., Chait, A., & Albers, J. J. (1977). Type III hyperlipoproteinemia: Paradoxical hypolipidemic response to estrogen. Annals of Internal Medicine, 87(5), 517–525.

    Article  CAS  PubMed  Google Scholar 

  • Levin, E. R. (2009). Plasma membrane estrogen receptors. Trends in Endocrinology and Metabolism, 20(10), 477–482. https://doi.org/10.1016/j.tem.2009.06.009.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li, C., Briggs, M. R., Ahlborn, T. E., Kraemer, F. B., & Liu, J. (2001). Requirement of Sp1 and estrogen receptor alpha interaction in 17beta-estradiol-mediated transcriptional activation of the low density lipoprotein receptor gene expression. Endocrinology, 142(4), 1546–1553. https://doi.org/10.1210/endo.142.4.8096.

    Article  CAS  PubMed  Google Scholar 

  • Liao, C. C., Chiu, Y. S., Chiu, W. C., Tung, Y. T., Chuang, H. L., Wu, J. H., & Huang, C. C. (2015). Proteomics analysis to identify and characterize the molecular signatures of hepatic steatosis in ovariectomized rats as a model of postmenopausal status. Nutrients, 7(10), 8752–8766. https://doi.org/10.3390/nu7105434.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lindberg, M. K., Weihua, Z., Andersson, N., Moverare, S., Gao, H., Vidal, O., Erlandsson, M., Windahl, S., Andersson, G., Lubahn, D. B., Carlsten, H., Dahlman-Wright, K., Gustafsson, J. A., & Ohlsson, C. (2002). Estrogen receptor specificity for the effects of estrogen in ovariectomized mice. The Journal of Endocrinology, 174(2), 167–178.

    Article  CAS  PubMed  Google Scholar 

  • Lloyd-Jones, D., Adams, R., Carnethon, M., De Simone, G., Ferguson, T. B., Flegal, K., Ford, E., Furie, K., Go, A., Greenlund, K., Haase, N., Hailpern, S., Ho, M., Howard, V., Kissela, B., Kittner, S., Lackland, D., Lisabeth, L., Marelli, A., McDermott, M., Meigs, J., Mozaffarian, D., Nichol, G., O'Donnell, C., Roger, V., Rosamond, W., Sacco, R., Sorlie, P., Stafford, R., Steinberger, J., Thom, T., Wasserthiel-Smoller, S., Wong, N., Wylie-Rosett, J., Hong, Y., & American Heart Association Statistics C, Stroke Statistics S. (2009). Heart disease and stroke statistics – 2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 119(3), e21–181. https://doi.org/10.1161/CIRCULATIONAHA.108.191261.

    Article  PubMed  Google Scholar 

  • Lopez, D., & McLean, M. P. (2006). Estrogen regulation of the scavenger receptor class B gene: Anti-atherogenic or steroidogenic, is there a priority? Molecular and Cellular Endocrinology, 247(1–2), 22–33. https://doi.org/10.1016/j.mce.2005.10.005.

    Article  CAS  PubMed  Google Scholar 

  • Ma, P. T., Yamamoto, T., Goldstein, J. L., & Brown, M. S. (1986). Increased mRNA for low density lipoprotein receptor in livers of rabbits treated with 17 alpha-ethinyl estradiol. Proceedings of the National Academy of Sciences of the United States of America, 83(3), 792–796.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • 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. https://doi.org/10.1210/jc.2003-030313.

    Article  CAS  PubMed  Google Scholar 

  • Magkos, F., & Mittendorfer, B. (2009). Gender differences in lipid metabolism and the effect of obesity. Obstetrics and Gynecology Clinics of North America, 36(2), 245–265., vii. https://doi.org/10.1016/j.ogc.2009.03.001.

    Article  PubMed  Google Scholar 

  • Magkos, F., Patterson, B. W., & Mittendorfer, B. (2006). No effect of menstrual cycle phase on basal very-low-density lipoprotein triglyceride and apolipoprotein B-100 kinetics. American Journal of Physiology Endocrinology and Metabolism, 291(6), E1243–E1249. https://doi.org/10.1152/ajpendo.00246.2006.

    Article  CAS  PubMed  Google Scholar 

  • Magkos, F., Patterson, B. W., & Mittendorfer, B. (2007a). Reproducibility of stable isotope-labeled tracer measures of VLDL-triglyceride and VLDL-apolipoprotein B-100 kinetics. Journal of Lipid Research, 48(5), 1204–1211. https://doi.org/10.1194/jlr.D600048-JLR200.

    Article  CAS  PubMed  Google Scholar 

  • Magkos, F., Patterson, B. W., Mohammed, B. S., Klein, S., & Mittendorfer, B. (2007b). Women produce fewer but triglyceride-richer very low-density lipoproteins than men. The Journal of Clinical Endocrinology and Metabolism, 92(4), 1311–1318. https://doi.org/10.1210/jc.2006-2215.

    Article  CAS  PubMed  Google Scholar 

  • Manson, J. E., Hsia, J., Johnson, K. C., Rossouw, J. E., Assaf, A. R., Lasser, N. L., Trevisan, M., Black, H. R., Heckbert, S. R., Detrano, R., Strickland, O. L., Wong, N. D., Crouse, J. R., Stein, E., Cushman, M., & Women’s Health Initiative I. (2003). Estrogen plus progestin and the risk of coronary heart disease. The New England Journal of Medicine, 349(6), 523–534. https://doi.org/10.1056/NEJMoa030808.

    Article  CAS  PubMed  Google Scholar 

  • Manson, J. E., Allison, M. A., Rossouw, J. E., Carr, J. J., Langer, R. D., Hsia, J., Kuller, L. H., Cochrane, B. B., Hunt, J. R., Ludlam, S. E., Pettinger, M. B., Gass, M., Margolis, K. L., Nathan, L., Ockene, J. K., Prentice, R. L., Robbins, J., Stefanick, M. L., WHI, & Investigators W-C. (2007). Estrogen therapy and coronary-artery calcification. The New England Journal of Medicine, 356(25), 2591–2602. https://doi.org/10.1056/NEJMoa071513.

    Article  CAS  PubMed  Google Scholar 

  • Marino, M., Pallottini, V., & Trentalance, A. (1998). Estrogens cause rapid activation of IP3-PKC-alpha signal transduction pathway in HEPG2 cells. Biochemical and Biophysical Research Communications, 245(1), 254–258. https://doi.org/10.1006/bbrc.1998.8413.

    Article  CAS  PubMed  Google Scholar 

  • Marino, M., Distefano, E., Pallottini, V., Caporali, S., Bruscalupi, G., & Trentalance, A. (2001). Activation of IP(3)-protein kinase C-alpha signal transduction pathway precedes the changes of plasma cholesterol, hepatic lipid metabolism and induction of low-density lipoprotein receptor expression in 17-beta-oestradiol-treated rats. Experimental Physiology, 86(1), 39–45.

    Article  CAS  PubMed  Google Scholar 

  • Marino, M., Galluzzo, P., & Ascenzi, P. (2006). Estrogen signaling multiple pathways to impact gene transcription. Current Genomics, 7(8), 497–508.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marotti, K. R., Castle, C. K., Boyle, T. P., Lin, A. H., Murray, R. W., & Melchior, G. W. (1993). Severe atherosclerosis in transgenic mice expressing simian cholesteryl ester transfer protein. Nature, 364(6432), 73–75. https://doi.org/10.1038/364073a0.

    Article  CAS  PubMed  Google Scholar 

  • Marsh, M. M., Walker, V. R., Curtiss, L. K., & Banka, C. L. (1999). Protection against atherosclerosis by estrogen is independent of plasma cholesterol levels in LDL receptor-deficient mice. Journal of Lipid Research, 40(5), 893–900.

    CAS  PubMed  Google Scholar 

  • Matsuo, K., Gualtieri, M. R., Cahoon, S. S., Jung, C. E., Paulson, R. J., Shoupe, D., Muderspach, L. I., Wakatsuki, A., Wright, J. D., & Roman, L. D. (2016). Surgical menopause and increased risk of nonalcoholic fatty liver disease in endometrial cancer. Menopause, 23(2), 189–196. https://doi.org/10.1097/GME.0000000000000500.

    Article  PubMed  Google Scholar 

  • Matthan, N. R., Jalbert, S. M., Barrett, P. H., Dolnikowski, G. G., Schaefer, E. J., & Lichtenstein, A. H. (2008). Gender-specific differences in the kinetics of nonfasting TRL, IDL, and LDL apolipoprotein B-100 in men and premenopausal women. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(10), 1838–1843. https://doi.org/10.1161/ATVBAHA.108.163931.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • McKenzie, J., Fisher, B. M., Jaap, A. J., Stanley, A., Paterson, K., & Sattar, N. (2006). Effects of HRT on liver enzyme levels in women with type 2 diabetes: A randomized placebo-controlled trial. Clinical Endocrinology, 65(1), 40–44. https://doi.org/10.1111/j.1365-2265.2006.02543.x.

    Article  CAS  PubMed  Google Scholar 

  • Meyer, M. R., Fredette, N. C., Howard, T. A., Hu, C., Ramesh, C., Daniel, C., Amann, K., Arterburn, J. B., Barton, M., & Prossnitz, E. R. (2014). G Protein-coupled estrogen receptor protects from atherosclerosis. Scientific Reports, 4, 7564. https://doi.org/10.1038/srep07564. https://www.nature.com/articles/srep07564-supplementary-information.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mittendorfer, B., Patterson, B. W., & Klein, S. (2003). Effect of sex and obesity on basal VLDL-triacylglycerol kinetics. The American Journal of Clinical Nutrition, 77(3), 573–579.

    Article  CAS  PubMed  Google Scholar 

  • Murata, Y., Ogawa, Y., Saibara, T., Nishioka, A., Fujiwara, Y., Fukumoto, M., Inomata, T., Enzan, H., Onishi, S., & Yoshida, S. (2000). Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients. Oncology Reports, 7(6), 1299–1304.

    CAS  PubMed  Google Scholar 

  • Nilsson, B. O., Olde, B., & Leeb-Lundberg, L. M. (2011). G protein-coupled oestrogen receptor 1 (GPER1)/GPR30: A new player in cardiovascular and metabolic oestrogenic signalling. British Journal of Pharmacology, 163(6), 1131–1139. https://doi.org/10.1111/j.1476-5381.2011.01235.x.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nishino, M., Hayakawa, K., Nakamura, Y., Morimoto, T., & Mukaihara, S. (2003). Effects of tamoxifen on hepatic fat content and the development of hepatic steatosis in patients with breast cancer: High frequency of involvement and rapid reversal after completion of tamoxifen therapy. AJR American Journal of Roentgenology, 180(1), 129–134. https://doi.org/10.2214/ajr.180.1.1800129.

    Article  PubMed  Google Scholar 

  • O’Sullivan, A. J., Crampton, L. J., Freund, J., & Ho, K. K. (1998). The route of estrogen replacement therapy confers divergent effects on substrate oxidation and body composition in postmenopausal women. The Journal of Clinical Investigation, 102(5), 1035–1040. https://doi.org/10.1172/JCI2773.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Oien, K. A., Moffat, D., Curry, G. W., Dickson, J., Habeshaw, T., Mills, P. R., & MacSween, R. N. (1999). Cirrhosis with steatohepatitis after adjuvant tamoxifen. Lancet, 353(9146), 36–37. https://doi.org/10.1016/S0140-6736(05)74872-8.

    Article  CAS  PubMed  Google Scholar 

  • Osborne, C. K., & Schiff, R. (2005). Estrogen-receptor biology: Continuing progress and therapeutic implications. Journal of Clinical Oncology, 23(8), 1616–1622. https://doi.org/10.1200/JCO.2005.10.036.

    Article  CAS  PubMed  Google Scholar 

  • Otero, Y. F., Stafford, J. M., & McGuinness, O. P. (2014). Pathway-selective insulin resistance and metabolic disease: The importance of nutrient flux. The Journal of Biological Chemistry, 289(30), 20462–20469. https://doi.org/10.1074/jbc.R114.576355.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Owman, C., Blay, P., Nilsson, C., & Lolait, S. J. (1996). Cloning of human cDNA encoding a novel heptahelix receptor expressed in Burkitt’s lymphoma and widely distributed in brain and peripheral tissues. Biochemical and Biophysical Research Communications, 228(2), 285–292. https://doi.org/10.1006/bbrc.1996.1654.

  • Paech, K., Webb, P., Kuiper, G. G. J. M., Nilsson, S., Gustafsson, J.-Å., Kushner, P. J., & Scanlan, T. S. (1997). Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science, 277(5331), 1508.

    Article  CAS  PubMed  Google Scholar 

  • Palmisano, B. T., Le, T. D., Zhu, L., Lee, Y. K., & Stafford, J. M. (2016). Cholesteryl ester transfer protein alters liver and plasma triglyceride metabolism through two liver networks in female mice. Journal of Lipid Research, 57(8), 1541–1551. https://doi.org/10.1194/jlr.M069013.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Paquette, A., Shinoda, M., Rabasa Lhoret, R., Prud'homme, D., & Lavoie, J. M. (2007). Time course of liver lipid infiltration in ovariectomized rats: Impact of a high-fat diet. Maturitas, 58(2), 182–190. https://doi.org/10.1016/j.maturitas.2007.08.002.

    Article  CAS  PubMed  Google Scholar 

  • Park, C. J., Zhao, Z., Glidewell-Kenney, C., Lazic, M., Chambon, P., Krust, A., Weiss, J., Clegg, D. J., Dunaif, A., Jameson, J. L., & Levine, J. E. (2011). Genetic rescue of nonclassical ERalpha signaling normalizes energy balance in obese Eralpha-null mutant mice. The Journal of Clinical Investigation, 121(2), 604–612. https://doi.org/10.1172/JCI41702.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Parks, B. W., Sallam, T., Mehrabian, M., Psychogios, N., Hui, S. T., Norheim, F., Castellani, L. W., Rau, C. D., Pan, C., Phun, J., Zhou, Z., Yang, W. P., Neuhaus, I., Gargalovic, P. S., Kirchgessner, T. G., Graham, M., Lee, R., Tontonoz, P., Gerszten, R. E., Hevener, A. L., & Lusis, A. J. (2015). Genetic architecture of insulin resistance in the mouse. Cell Metabolism, 21(2), 334–346. https://doi.org/10.1016/j.cmet.2015.01.002.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pasqualini, J. R., Chetrite, G., Blacker, C., Feinstein, M. C., Delalonde, L., Talbi, M., & Maloche, C. (1996). Concentrations of estrone, estradiol, and estrone sulfate and evaluation of sulfatase and aromatase activities in pre- and postmenopausal breast cancer patients. The Journal of Clinical Endocrinology and Metabolism, 81(4), 1460–1464. https://doi.org/10.1210/jcem.81.4.8636351.

    CAS  PubMed  Google Scholar 

  • Pedram, A., Razandi, M., O’Mahony, F., Harvey, H., Harvey, B. J., & Levin, E. R. (2013). Estrogen reduces lipid content in the liver exclusively from membrane receptor signaling. Science Signaling, 6(276), ra36. https://doi.org/10.1126/scisignal.2004013.

    Article  CAS  PubMed  Google Scholar 

  • Petitti, D. B., Perlman, J. A., & Sidney, S. (1987). Noncontraceptive estrogens and mortality: Long-term follow-up of women in the Walnut Creek Study. Obstetrics and Gynecology, 70(3 Pt 1), 289–293.

    CAS  PubMed  Google Scholar 

  • Qian, Y. M., Sun, X. J., Tong, M. H., Li, X. P., Richa, J., & Song, W. C. (2001). Targeted disruption of the mouse estrogen sulfotransferase gene reveals a role of estrogen metabolism in intracrine and paracrine estrogen regulation. Endocrinology, 142(12), 5342–5350. https://doi.org/10.1210/endo.142.12.8540.

    Article  CAS  PubMed  Google Scholar 

  • Rader, D. J., & Tall, A. R. (2012). The not-so-simple HDL story: Is it time to revise the HDL cholesterol hypothesis? Nature Medicine, 18(9), 1344–1346. https://doi.org/10.1038/nm.2937.

    Article  CAS  PubMed  Google Scholar 

  • Rader, D. J., Alexander, E. T., Weibel, G. L., Billheimer, J., & Rothblat, G. H. (2009). The role of reverse cholesterol transport in animals and humans and relationship to atherosclerosis. Journal of Lipid Research, 50 Suppl, S189–194. https://doi.org/10.1194/jlr.R800088-JLR200.

  • Reaven, G. M., & Bernstein, R. M. (1978). Effect of obesity on the relationship between very low density lipoprotein production rate and plasma triglyceride concentration in normal and hypertriglyceridemic subjects. Metabolism, 27(9), 1047–1054.

    Article  CAS  PubMed  Google Scholar 

  • Ribas, V., Nguyen, M. T., Henstridge, D. C., Nguyen, A. K., Beaven, S. W., Watt, M. J., & Hevener, A. L. (2010). 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.

    Article  CAS  PubMed  Google Scholar 

  • 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 α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Science Translational Medicine, 8(334), 334ra354.

    Article  CAS  Google Scholar 

  • 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. https://doi.org/10.1111/j.1464-5491.2007.02304.x.

    Article  CAS  PubMed  Google Scholar 

  • Roe, A., Hillman, J., Butts, S., Smith, M., Rader, D., Playford, M., Mehta, N. N., & Dokras, A. (2014). Decreased cholesterol efflux capacity and atherogenic lipid profile in young women with PCOS. The Journal of Clinical Endocrinology and Metabolism, 99(5), E841–E847. https://doi.org/10.1210/jc.2013-3918.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Roger, V. L., Go, A. S., Lloyd-Jones, D. M., Adams, R. J., Berry, J. D., Brown, T. M., Carnethon, M. R., Dai, S., de Simone, G., Ford, E. S., Fox, C. S., Fullerton, H. J., Gillespie, C., Greenlund, K. J., Hailpern, S. M., Heit, J. A., Ho, P. M., Howard, V. J., Kissela, B. M., Kittner, S. J., Lackland, D. T., Lichtman, J. H., Lisabeth, L. D., Makuc, D. M., Marcus, G. M., Marelli, A., Matchar, D. B., McDermott, M. M., Meigs, J. B., Moy, C. S., Mozaffarian, D., Mussolino, M. E., Nichol, G., Paynter, N. P., Rosamond, W. D., Sorlie, P. D., Stafford, R. S., Turan, T. N., Turner, M. B., Wong, N. D., & Wylie-Rosett, J. (2011). Heart disease and stroke statistics–2011 update: A report from the American Heart Association. Circulation, 123(4), e18–e209. https://doi.org/10.1161/CIR.0b013e3182009701.

    Article  PubMed  Google Scholar 

  • Rogers, N. H., Perfield, J. W., 2nd, Strissel, K. J., Obin, M. S., & Greenberg, A. S. (2009). Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology, 150(5), 2161–2168. https://doi.org/10.1210/en.2008-1405.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Romero-Aleshire, M. J., Diamond-Stanic, M. K., Hasty, A. H., Hoyer, P. B., & Brooks, H. L. (2009). Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 297(3), R587–R592. https://doi.org/10.1152/ajpregu.90762.2008.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rosenson, R. S., Brewer, H. B., Jr., Davidson, W. S., Fayad, Z. A., Fuster, V., Goldstein, J., Hellerstein, M., Jiang, X. C., Phillips, M. C., Rader, D. J., Remaley, A. T., Rothblat, G. H., Tall, A. R., & Yvan-Charvet, L. (2012). Cholesterol efflux and atheroprotection: Advancing the concept of reverse cholesterol transport. Circulation, 125(15), 1905–1919. https://doi.org/10.1161/CIRCULATIONAHA.111.066589.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rossi, R., Origliani, G., & Modena, M. G. (2004). Transdermal 17-beta-estradiol and risk of developing type 2 diabetes in a population of healthy, nonobese postmenopausal women. Diabetes Care, 27(3), 645–649.

    Article  CAS  PubMed  Google Scholar 

  • Rudling, M., Norstedt, G., Olivecrona, H., Reihner, E., Gustafsson, J. A., & Angelin, B. (1992). Importance of growth hormone for the induction of hepatic low density lipoprotein receptors. Proceedings of the National Academy of Sciences of the United States of America, 89(15), 6983–6987.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ryu, S., Suh, B. S., Chang, Y., Kwon, M. J., Yun, K. E., Jung, H. S., Kim, C. W., Kim, B. K., Kim, Y. J., Choi, Y., Ahn, J., Cho, Y. K., Kim, K. H., Ahn, Y., Park, H. Y., Chung, E. C., Shin, H., & Cho, J. (2015). Menopausal stages and non-alcoholic fatty liver disease in middle-aged women. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 190, 65–70. https://doi.org/10.1016/j.ejogrb.2015.04.017.

    Article  PubMed  Google Scholar 

  • Sanada, M., Tsuda, M., Kodama, I., Sakashita, T., Nakagawa, H., & Ohama, K. (2004). Substitution of transdermal estradiol during oral estrogen-progestin therapy in postmenopausal women: Effects on hypertriglyceridemia. Menopause, 11(3), 331–336.

    Article  PubMed  Google Scholar 

  • Schaefer, E. J., Foster, D. M., Zech, L. A., Lindgren, F. T., Brewer, H. B., Jr., & Levy, R. I. (1983). The effects of estrogen administration on plasma lipoprotein metabolism in premenopausal females. The Journal of Clinical Endocrinology and Metabolism, 57(2), 262–267. https://doi.org/10.1210/jcem-57-2-262.

    Article  CAS  PubMed  Google Scholar 

  • Semenkovich, C. F., & Ostlund, R. E., Jr. (1987). Estrogens induce low-density lipoprotein receptor activity and decrease intracellular cholesterol in human hepatoma cell line Hep G2. Biochemistry, 26(16), 4987–4992.

    Article  CAS  PubMed  Google Scholar 

  • Sharma, G., Mauvais-Jarvis, F., & Prossnitz, E. R. (2017). Roles of G protein-coupled estrogen receptor GPER in metabolic regulation. The Journal of Steroid Biochemistry and Molecular Biology. https://doi.org/10.1016/j.jsbmb.2017.02.012.

  • 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. https://doi.org/10.1056/NEJM199410203311604.

    Article  CAS  PubMed  Google Scholar 

  • Smith, G. I., Reeds, D. N., Okunade, A. L., Patterson, B. W., & Mittendorfer, B. (2014). Systemic delivery of estradiol, but not testosterone or progesterone, alters very low density lipoprotein-triglyceride kinetics in postmenopausal women. The Journal of Clinical Endocrinology and Metabolism, 99(7), E1306–E1310. https://doi.org/10.1210/jc.2013-4470.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stampfer, M. J., Willett, W. C., Colditz, G. A., Rosner, B., Speizer, F. E., & Hennekens, C. H. (1985). A prospective study of postmenopausal estrogen therapy and coronary heart disease. The New England Journal of Medicine, 313(17), 1044–1049. https://doi.org/10.1056/NEJM198510243131703.

    Article  CAS  PubMed  Google Scholar 

  • Starr, A. E., Lemieux, V., Noad, J., Moore, J. I., Dewpura, T., Raymond, A., Chretien, M., Figeys, D., & Mayne, J. (2015). Beta-estradiol results in a proprotein convertase subtilisin/kexin type 9-dependent increase in low-density lipoprotein receptor levels in human hepatic HuH7 cells. The FEBS Journal, 282(14), 2682–2696. https://doi.org/10.1111/febs.13309.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Steinberg, M., Tolksdorf, S., & Gordon, A. S. (1967). Relation of the adrenal and pituitary to the hypocholesterolemic effect of estrogen in rats. Endocrinology, 81(2), 340–344. https://doi.org/10.1210/endo-81-2-340.

    Article  CAS  PubMed  Google Scholar 

  • Strandberg, T. E., Ylikorkala, O., & Tikkanen, M. J. (2003). Differing effects of oral and transdermal hormone replacement therapy on cardiovascular risk factors in healthy postmenopausal women. The American Journal of Cardiology, 92(2), 212–214.

    Article  CAS  PubMed  Google Scholar 

  • Sullivan, J. M., Vander Zwaag, R., Hughes, J. P., Maddock, V., Kroetz, F. W., Ramanathan, K. B., & Mirvis, D. M. (1990). Estrogen replacement and coronary artery disease. Effect on survival in postmenopausal women. Archives of Internal Medicine, 150(12), 2557–2562.

    Article  CAS  PubMed  Google Scholar 

  • Svendsen, O. L., Hassager, C., & Christiansen, C. (1995). Age- and menopause-associated variations in body composition and fat distribution in healthy women as measured by dual-energy X-ray absorptiometry. Metabolism, 44(3), 369–373.

    Article  CAS  PubMed  Google Scholar 

  • Tato, F., Vega, G. L., & Grundy, S. M. (1995). Bimodal distribution of cholesteryl ester transfer protein activities in normotriglyceridemic men with low HDL cholesterol concentrations. Arteriosclerosis, Thrombosis, and Vascular Biology, 15(4), 446–451. https://doi.org/10.1161/01.atv.15.4.446.

    Article  CAS  PubMed  Google Scholar 

  • Trial TWGftP. (1995). Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI Trial. JAMA, 273(3), 199–208.

    Article  Google Scholar 

  • Tuazon, M. A., McConnell, T. R., Wilson, G. J., Anthony, T. G., & Henderson, G. C. (2015). Intensity-dependent and sex-specific alterations in hepatic triglyceride metabolism in mice following acute exercise. Journal of Applied Physiology. (1985, 118(1), 61–70. https://doi.org/10.1152/japplphysiol.00440.2014.

    Article  CAS  PubMed  Google Scholar 

  • Ulloa, N., Arteaga, E., Bustos, P., Duran-Sandoval, D., Schulze, K., Castro, G., Jauhiainen, M., Fruchart, J. C., & Calvo, C. (2002). Sequential estrogen-progestin replacement therapy in healthy postmenopausal women: Effects on cholesterol efflux capacity and key proteins regulating high-density lipoprotein levels. Metabolism, 51(11), 1410–1417.

    Article  CAS  PubMed  Google Scholar 

  • Vague, J. (1947). La différenciation sexuelle; facteur déterminant des formes de l'obésité. Presse Médicale, 55(30), 339.

    CAS  PubMed  Google Scholar 

  • van der Schouw, Y. T., van der Graaf, Y., Steyerberg, E. W., Eijkemans, J. C., & Banga, J. D. (1996). Age at menopause as a risk factor for cardiovascular mortality. Lancet, 347(9003), 714–718.

    Article  PubMed  Google Scholar 

  • Villa, A., Della Torre, S., Stell, A., Cook, J., Brown, M., & Maggi, A. (2012). Tetradian oscillation of estrogen receptor alpha is necessary to prevent liver lipid deposition. Proceedings of the National Academy of Sciences of the United States of America, 109(29), 11806–11811. https://doi.org/10.1073/pnas.1205797109.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Walsh, B. W., Schiff, I., Rosner, B., Greenberg, L., Ravnikar, V., & Sacks, F. M. (1991). Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. The New England Journal of Medicine, 325(17), 1196–1204. https://doi.org/10.1056/NEJM199110243251702.

    Article  CAS  PubMed  Google Scholar 

  • Wang, H. H., Afdhal, N. H., & Wang, D. Q. (2004). Estrogen receptor alpha, but not beta, plays a major role in 17beta-estradiol-induced murine cholesterol gallstones. Gastroenterology, 127(1), 239–249.

    Article  CAS  PubMed  Google Scholar 

  • Wang, H. H., Afdhal, N. H., & Wang, D. Q. H. (2006). Overexpression of estrogen receptor a increases hepatic cholesterogenesis, leading to biliary hypersecretion in mice. Journal of Lipid Research, 47(4), 778–786. https://doi.org/10.1194/Jlr.M500454-Jlr200.

    Article  CAS  PubMed  Google Scholar 

  • Wang, X., Lu, Y., Wang, E., Zhang, Z., Xiong, X., Zhang, H., Lu, J., Zheng, S., Yang, J., Xia, X., Yang, S., & Li, X. (2015). Hepatic estrogen receptor alpha improves hepatosteatosis through upregulation of small heterodimer partner. Journal of Hepatology, 63(1), 183–190. https://doi.org/10.1016/j.jhep.2015.02.029.

    Article  CAS  PubMed  Google Scholar 

  • Wiegratz, I., Jung-Hoffmann, C., Gross, W., & Kuhl, H. (1998). Effect of two oral contraceptives containing ethinyl estradiol and gestodene or norgestimate on different lipid and lipoprotein parameters. Contraception, 58(2), 83–91. https://doi.org/10.1016/S0010-7824(98)00074-2.

    Article  CAS  PubMed  Google Scholar 

  • Wilmot, K. A., O’Flaherty, M., Capewell, S., Ford, E. S., & Vaccarino, V. (2015). <span hwp:id=&quot;article-title-1&quot; class=&quot;article-title&quot;>Coronary Heart Disease Mortality Declines in the United States From 1979 Through 2011</span><span hwp:id=&quot;article-title-50&quot; class=&quot;sub-article-title&quot;>CLINICAL PERSPECTIVE</span&gt. Circulation 132(11), 997.

    Google Scholar 

  • Wilson, P. W., Garrison, R. J., & Castelli, W. P. (1985). Postmenopausal estrogen use, cigarette smoking, and cardiovascular morbidity in women over 50. The Framingham Study. The New England Journal of Medicine, 313(17), 1038–1043. https://doi.org/10.1056/NEJM198510243131702.

    Article  CAS  PubMed  Google Scholar 

  • Windler, E. E., Kovanen, P. T., Chao, Y. S., Brown, M. S., Havel, R. J., & Goldstein, J. L. (1980). The estradiol-stimulated lipoprotein receptor of rat liver. A binding site that membrane mediates the uptake of rat lipoproteins containing apoproteins B and E. The Journal of Biological Chemistry, 255(21), 10464–10471.

    CAS  PubMed  Google Scholar 

  • Wolf, P. H., Madans, J. H., Finucane, F. F., Higgins, M., & Kleinman, J. C. (1991). Reduction of cardiovascular disease-related mortality among postmenopausal women who use hormones: Evidence from a national cohort. American Journal of Obstetrics and Gynecology, 164(2), 489–494.

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto, Y., Moore, R., Hess, H. A., Guo, G. L., Gonzalez, F. J., Korach, K. S., Maronpot, R. R., & Negishi, M. (2006). Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity. The Journal of Biological Chemistry, 281(24), 16625–16631. https://doi.org/10.1074/jbc.M602723200.

    Article  CAS  PubMed  Google Scholar 

  • Yang, J. D., Abdelmalek, M. F., Pang, H., Guy, C. D., Smith, A. D., Diehl, A. M., & Suzuki, A. (2014). Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis. Hepatology, 59(4), 1406–1414. https://doi.org/10.1002/hep.26761.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yusuf, S., Hawken, S., Ounpuu, S., Bautista, L., Franzosi, M. G., Commerford, P., Lang, C. C., Rumboldt, Z., Onen, C. L., Lisheng, L., Tanomsup, S., Wangai, P., Jr., Razak, F., Sharma, A. M., Anand, S. S., & Investigators IS. (2005). Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: A case-control study. Lancet, 366(9497), 1640–1649. https://doi.org/10.1016/S0140-6736(05)67663-5.

    Article  PubMed  Google Scholar 

  • Zegura, B., Guzic-Salobir, B., Sebestjen, M., & Keber, I. (2006). The effect of various menopausal hormone therapies on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins in healthy postmenopausal women. Menopause, 13(4), 643–650. https://doi.org/10.1097/01.gme.0000198485.70703.7a.

    Article  PubMed  Google Scholar 

  • Zhang, Y., Howard, B. V., Cowan, L. D., Yeh, J., Schaefer, C. F., Wild, R. A., Wang, W., & Lee, E. T. (2002). The effect of estrogen use on levels of glucose and insulin and the risk of type 2 diabetes in American Indian postmenopausal women: The strong heart study. Diabetes Care, 25(3), 500–504.

    Google Scholar 

  • Zhang, Y., Da Silva, J. R., Reilly, M., Billheimer, J. T., Rothblat, G. H., & Rader, D. J. (2005). Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo. The Journal of Clinical Investigation, 115(10), 2870–2874. https://doi.org/10.1172/JCI25327.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang, Y., Klein, K., Sugathan, A., Nassery, N., Dombkowski, A., Zanger, U. M., & Waxman, D. J. (2011). Transcriptional profiling of human liver identifies sex-biased genes associated with polygenic dyslipidemia and coronary artery disease. PLoS One, 6(8), e23506. https://doi.org/10.1371/journal.pone.0023506.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang, H., Liu, Y., Wang, L., Li, Z., Zhang, H., Wu, J., Rahman, N., Guo, Y., Li, D., Li, N., Huhtaniemi, I., Tsang, S. Y., Gao, G. F., & Li, X. (2013). Differential effects of estrogen/androgen on the prevention of nonalcoholic fatty liver disease in the male rat. Journal of Lipid Research, 54(2), 345–357. https://doi.org/10.1194/jlr.M028969.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang, Z. C., Liu, Y., Xiao, L. L., Li, S. F., Jiang, J. H., Zhao, Y., Qian, S. W., Tang, Q. Q., & Li, X. (2015). Upregulation of miR-125b by estrogen protects against non-alcoholic fatty liver in female mice. Journal of Hepatology, 63(6), 1466–1475. https://doi.org/10.1016/j.jhep.2015.07.037.

    Article  CAS  PubMed  Google Scholar 

  • Zhu, L., Brown, W. C., Cai, Q., Krust, A., Chambon, P., McGuinness, O. P., & Stafford, J. M. (2013). Estrogen treatment after ovariectomy protects against fatty liver and may improve pathway-selective insulin resistance. Diabetes, 62(2), 424–434. https://doi.org/10.2337/db11-1718.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu, L., Martinez, M. N., Emfinger, C. H., Palmisano, B. T., & Stafford, J. M. (2014). Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity. American Journal of Physiology. Endocrinology and Metabolism, 306(10), E1188–E1197. https://doi.org/10.1152/ajpendo.00579.2013.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Funding Sources

The Department of Veterans Affairs (BX002223) and NIH (R01DK109102) provided support to JMS. BP is supported by the Vanderbilt Medical Scientist Training Program (T32GM07347) and (F30DK104514).

Author information

Authors and Affiliations

  1. Tennessee Valley Healthcare System, Veterans Affairs, Nashville, TN, USA

    Brian T. Palmisano, Lin Zhu & John M. Stafford

  2. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA

    Brian T. Palmisano, Lin Zhu & John M. Stafford

  3. Division of Endocrinology, Diabetes and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA

    Brian T. Palmisano & John M. Stafford

Authors
  1. Brian T. Palmisano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John M. Stafford
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John M. Stafford .

Editor information

Editors and Affiliations

  1. Department of Medicine, Section of Endocrinology and Metabolism, Tulane University Health Sciences Center, School of Medicine, New Orleans, Louisiana, USA

    Franck Mauvais-Jarvis

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Palmisano, B.T., Zhu, L., Stafford, J.M. (2017). Role of Estrogens in the Regulation of Liver Lipid Metabolism. In: Mauvais-Jarvis, F. (eds) Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity. Advances in Experimental Medicine and Biology, vol 1043. Springer, Cham. https://doi.org/10.1007/978-3-319-70178-3_12

Download citation

Publish with us

Policies and ethics

Search

Navigation