Journal article
Skeletal muscle action of estrogen receptor a is critical for the maintenance of mitochondrial function and metabolic homeostasis in females
V Ribas, BG Drew, Z Zhou, J Phun, NY Kalajian, T Soleymani, P Daraei, K Widjaja, J Wanagat, TQDA Vallim, AH Fluitt, S Bensinger, T Le, C Radu, JP Whitelegge, SW Beaven, P Tontonoz, AJ Lusis, BW Parks, L Vergnes Show all
Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2016
Abstract
Impaired estrogen receptor a (ERa) action promotes obesity and metabolic dysfunction in humans and mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal and oxidative metabolism, we established that reduced ERa expression in muscle is associated with glucose intolerance and adiposity in women and female mice. To test this relationship, we generated muscle-specific ERa knockout (MERKO) mice. Impaired glucose homeostasis and increased adiposity were paralleled by diminished muscle oxidative metabolism and bioactive lipid accumulation in MERKO mice. Aberrant mitochondrial morphology, overpr..
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Awarded by National Institutes of Health
Funding Acknowledgements
These studies were supported in part by research grants from the NIH [DK060484, DK073227, and Nuclear Receptor Signaling Atlas (NURSA) Data Source Project grant DK097748], UCLA Department of Medicine, and UCLA Iris Cantor Women's Health Center-UCLA Clinical and Translational Science Institute (UL1TR000124) to A.L.H. and Z.Z. V.R. was supported by the Spanish Ministry of Health, and B.G.D. was supported by the Australian National Health and Medical Research Council and the UCLA Jonsson Comprehensive Cancer Center. During the study period, the Centre of Inflammation and Metabolism was supported by a grant from the Danish National Research Foundation (DNRF55) to B.K.P. A.J.L. is supported by NIH (grants HL28481 and HL30568), and B.W.P. is supported by NIH R00 grant HL123021. The Centre for Physical Activity Research is supported by a grant from TrygFonden. A.J.L. is supported by NIH grants HL28481 and HL30568, and L.V. and K.R. are supported in part by NIH grant HL28481. The Seahorse XF24 instrument was acquired by a shared instrument grant from the NIH National Center for Research Resources (S10RR026744). P.T. is an investigator of the Howard Hughes Medical Institute and is supported by NIH (DK063491).