An Essential Role for Liver ER alpha in Coupling Hepatic Metabolism to the Reproductive Cycle

• Lipoprotein synthesis is controlled by estrogens, but the exact mechanisms underpinning this regulation and the role of the hepatic estrogen receptor alpha (ER alpha) in cholesterol physiology are unclear. Utilizing a mouse model involving selective ablation of ER alpha in the liver, we demonstrate that hepatic ER alpha couples lipid metabolism to the reproductive cycle. We show that this receptor regulates the synthesis of cholesterol transport proteins, enzymes for lipoprotein remodeling, and receptors for cholesterol uptake. Additionally, ER alpha is indispensable during proestrus for the generation of high-density lipoproteins efficient in eliciting cholesterol efflux from macrophages. We propose that a specific interaction with liver X receptor alpha (LXR alpha) mediates the broad effects of ER alpha on the hepatic lipid metabolism.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

cholesterol efflux capacity

estrogen-receptor

fatty liver

gene-expression

lipoprotein metabolism

postmenopausal women

binding-sites

mouse-liver

x-receptor

a-i

Cell Biology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)