Estrogens and the Regulation of Lipid Metabolism

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When it comes to heart disease associated with obesity, women (prior to the onset of menopause) are protected to a far greater extent than men. Sex hormones have been proposed as the factor that differentiates the risk. The authors of this study 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 (ER&#945, estrogen receptor beta (ER&#946, and G-protein-coupled estrogen receptor (GPER). Over 1000 human liver genes diEsplay a sex bias in their expression, and the top biological pathways are in lipid metabolism and genes related to cardiovascular disease.
• 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 pre-menopause therapeutically after menopause.

"Role of Estrogens in the Regulation of Liver Lipid Metabolism," Advances in Experimental Medicine and Biology, 2017;1043:227-256, https://www.ncbi.nlm.nih.gov/pubmed/29224098/