1. 17β-Estradiol Directly Lowers Mitochondrial Membrane Microviscosity and Improves Bioenergetic Function in Skeletal Muscle.
- Author
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Torres MJ, Kew KA, Ryan TE, Pennington ER, Lin CT, Buddo KA, Fix AM, Smith CA, Gilliam LA, Karvinen S, Lowe DA, Spangenburg EE, Zeczycki TN, Shaikh SR, and Neufer PD
- Subjects
- Adiposity drug effects, Animals, Cell Respiration drug effects, Cellular Microenvironment drug effects, Diabetes Mellitus, Experimental complications, Electron Transport drug effects, Electron Transport Complex I metabolism, Female, Glucose metabolism, Homeostasis drug effects, Mice, Inbred C57BL, Mitochondria drug effects, Mitochondria metabolism, Mitochondrial Membranes drug effects, Muscle, Skeletal drug effects, Obesity etiology, Obesity metabolism, Obesity pathology, Ovary drug effects, Ovary metabolism, Oxidation-Reduction, Viscosity, Energy Metabolism drug effects, Estradiol pharmacology, Mitochondrial Membranes metabolism, Muscle, Skeletal metabolism
- Abstract
Menopause results in a progressive decline in 17β-estradiol (E2) levels, increased adiposity, decreased insulin sensitivity, and a higher risk for type 2 diabetes. Estrogen therapies can help reverse these effects, but the mechanism(s) by which E2 modulates susceptibility to metabolic disease is not well understood. In young C57BL/6N mice, short-term ovariectomy decreased-whereas E2 therapy restored-mitochondrial respiratory function, cellular redox state (GSH/GSSG), and insulin sensitivity in skeletal muscle. E2 was detected by liquid chromatography-mass spectrometry in mitochondrial membranes and varied according to whole-body E2 status independently of ERα. Loss of E2 increased mitochondrial membrane microviscosity and H
2 O2 emitting potential, whereas E2 administration in vivo and in vitro restored membrane E2 content, microviscosity, complex I and I + III activities, H2 O2 emitting potential, and submaximal OXPHOS responsiveness. These findings demonstrate that E2 directly modulates membrane biophysical properties and bioenergetic function in mitochondria, offering a direct mechanism by which E2 status broadly influences energy homeostasis., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2018
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