In the liver of female mice, the transcriptional activity of estrogen receptor (ER) α oscillates in phase with the 4-d-long estrous cycle. Here systemic, genome-wide analysis demonstrates that ER tetradian oscillation is necessary to generate pulses of expression in genes for fatty acid and cholesterol synthesis. This ER-dependent metabolic programming changes with pregnancy and after cessation of ovarian function due to age or surgical menopause, suggesting that ER signaling is optimized to coordinate liver functions with the energetic requirements of each reproductive stage. Alterations of amplitude and frequency of the tetradian cycle, as observed after surgical menopause, age, or specific ablation of the hepatic Igf-1 gene, are associated with liver fat deposition. Appropriate hormone replacement therapy reinstating the oscillatory activity of liver ER prevents the effect of surgical menopause on fat deposition in liver.

Tetradian oscillation of estrogen receptor α is necessary to prevent liver lipid deposition / A. Villa, S. Della Torre, A. Stell, J. Cook, M. Brown, A. Maggi. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 109:29(2012 Jul 17), pp. 11806-11811. [10.1073/pnas.1205797109]

Tetradian oscillation of estrogen receptor α is necessary to prevent liver lipid deposition

A. Villa
Primo
;
S. Della Torre
Secondo
;
A. Stell;A. Maggi
Ultimo
2012-07-17

Abstract

In the liver of female mice, the transcriptional activity of estrogen receptor (ER) α oscillates in phase with the 4-d-long estrous cycle. Here systemic, genome-wide analysis demonstrates that ER tetradian oscillation is necessary to generate pulses of expression in genes for fatty acid and cholesterol synthesis. This ER-dependent metabolic programming changes with pregnancy and after cessation of ovarian function due to age or surgical menopause, suggesting that ER signaling is optimized to coordinate liver functions with the energetic requirements of each reproductive stage. Alterations of amplitude and frequency of the tetradian cycle, as observed after surgical menopause, age, or specific ablation of the hepatic Igf-1 gene, are associated with liver fat deposition. Appropriate hormone replacement therapy reinstating the oscillatory activity of liver ER prevents the effect of surgical menopause on fat deposition in liver.
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/203105
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