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Mitochondrial Capacity is Decreased in Skeletal Muscle with Estrogen Depletion
Author(s) -
Torres Maria,
Gilliam Laura,
Reese Lauren,
Buddo Katherine,
Smith Cheryl,
Neufer Darrell
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.824.18
Subject(s) - endocrinology , medicine , skeletal muscle , estrogen , basal (medicine) , insulin , citrate synthase , menopause , homeostasis , glucose homeostasis , biology , oxidative phosphorylation , chemistry , insulin resistance , biochemistry , enzyme
Menopause increases a woman's risk for developing cardiovascular disease and type‐2 diabetes. Menopause coincides with a decline in ovarian hormone production, particularly 17β‐estradiol (E2), a key regulator of energy and glucose homeostasis. Skeletal muscle is responsible for ~80% of insulin‐stimulated glucose uptake, and mitochondrial function in muscle has been linked to the control of insulin sensitivity. To examine the potential underlying mechanism(s) by which E2 regulates insulin sensitivity in skeletal muscle, young but sexually mature (12 week‐old) C57BL‐female mice were studied 2 weeks after ovariectomy (OVX). In permeabilized fibers from red gastrocnemius, basal complex I‐supported respiration was slightly reduced (p<0.1). Maximal ADP‐stimulated respiration was reduced (p<0.05) 17‐25% with complex I plus II‐, and complex IV‐ linked substrates in OVX compared with normally cycling females in proestrus (CTL). Expression of complex IV and V was as well as citrate synthase activity were reduced by 15‐25% and 33% respectively, providing evidence of a rapid decline in muscle mitochondrial content. The ratio of GSH/GSSG decreased with E2 depletion, indicative of a more oxidized redox environment. Although fasting blood glucose was elevated (43%), both oral glucose and insulin tolerance were similar in OVX and CTLs. These findings indicate reduced skeletal muscle mitochondrial OXPHOS capacity and a shift to a more oxidized redox state develop early during acute E2 depletion, providing a potential mechanism(s) by which menopause sets a pro‐diabetogenic state. NIH DK096907