Estrogen receptor alpha activation enhances mitochondrial function and systemic metabolism in high‐fat‐fed ovariectomized mice. Issue 17 (31st August 2016)

• Record Type: Journal Article
• Authors: Hamilton, Dale J.; Minze, Laurie J.; Kumar, Tanvi; Cao, Tram N.; Lyon, Christopher J.; Geiger, Paige C.; Hsueh, Willa A.; Gupte, Anisha A.
• Is Part Of: Physiological reports. Volume 4:Issue 17(2016)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2016-08-31
• Subjects: Energy balance -- ER α -- estrogen -- mitochondria; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.12913
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: Estrogen impacts insulin action and cardiac metabolism, and menopause dramatically increases cardiometabolic risk in women. However, the mechanism(s) of cardiometabolic protection by estrogen remain incompletely understood. Here, we tested the effects of selective activation of E2 receptor alpha (ER α ) on systemic metabolism, insulin action, and cardiac mitochondrial function in a mouse model of metabolic dysfunction (ovariectomy [OVX], insulin resistance, hyperlipidemia, and advanced age). Middle‐aged (12‐month‐old) female low‐density lipoprotein receptor ( Ldlr ) −/− mice were subjected to OVX or sham surgery and fed "western" high‐fat diet (WHFD) for 3 months. Selective ER α activation with 4, 4′, 4″‐(4‐Propyl‐[1H]‐pyrazole‐1, 3, 5‐triyl) (PPT), prevented weight gain, improved insulin action, and reduced visceral fat accumulation in WHFD‐fed OVX mice. PPT treatment also elevated systemic metabolism, increasing oxygen consumption and core body temperature, induced expression of several metabolic genes such as peroxisome proliferator‐activated receptor gamma, coactivator 1 alpha, and nuclear respiratory factor 1 in heart, liver, skeletal muscle, and adipose tissue, and increased cardiac mitochondrial function. Taken together, selective activation of ER α with PPT enhances metabolic effects including insulin resistance, whole body energy metabolism, and mitochondrial function in OVX mice with metabolic syndrome. Abstract : Loss of ovarian estrogen in hyperlipidemic middle‐aged female mice leads to dramatic down‐regulation of metabolism, greater weight gain, insulin resistance, and mitochondrial dysfunction when given a high‐fat diet. Specific activation of estrogen receptor alpha can enhance metabolism, prevent weight gain, increase insulin sensitivity, and increase mitochondrial function. Activation of estrogen receptor alpha enhances expression of genes in mitochondrial biogenesis and function, glucose metabolism, and fatty acid metabolism pathways.