ABSTRACT
Postmenopausal women are prone to develop obesity and insulin resistance, which might be related to skeletal muscle mitochondrial dysfunction. In a rat model of ovariectomy (OVX), skeletal muscle mitochondrial function was examined at short- and long-term periods after castration. Mitochondrial parameters in the soleus and white gastrocnemius muscle fibers were analyzed. Three weeks after surgery, there were no differences in coupled mitochondrial respiration (ATP synthesis) with pyruvate, malate, and succinate; proton leak respiration; or mitochondrial reactive oxygen species production. However, after 3 wk of OVX, the soleus and white gastrocnemius muscles of the OVX animals showed a lower use of palmitoyl-carnitine and glycerol-phosphate substrates, respectively, and decreased peroxisome proliferator-activated receptor-γ coactivator-1α expression. Estrogen replacement reverted all of these phenotypes. Eight weeks after OVX, ATP synthesis was lower in the soleus and white gastrocnemius muscles of the OVX animals than in the sham-operated and estrogen-treated animals; however, when normalized by citrate synthase activity, these differences disappeared, indicating a lower muscle mitochondria content. No differences were observed in the proton leak parameter. Mitochondrial alterations did not impair the treadmill exercise capacity of the OVX animals. However, blood lactate levels in the OVX animals were higher after the physical test, indicating a compensatory extramitochondrial ATP synthesis system, but this phenotype was reverted by estrogen replacement. These results suggest early mitochondrial dysfunction related to lipid substrate use, which could be associated with the development of the overweight phenotype of ovariectomized animals.
Subject(s)
Energy Metabolism/drug effects , Estradiol/analogs & derivatives , Estrogen Replacement Therapy , Mitochondria, Muscle/drug effects , Muscle Fibers, Skeletal/drug effects , Ovariectomy , Adenosine Triphosphate/metabolism , Adiposity , Animals , Citrate (si)-Synthase/metabolism , Estradiol/administration & dosage , Estradiol/blood , Exercise Tolerance , Female , Lipid Metabolism/drug effects , Mitochondria, Muscle/metabolism , Mitochondrial Turnover/drug effects , Muscle Fibers, Skeletal/metabolism , Overweight/etiology , Overweight/metabolism , Oxygen Consumption , Phenotype , Rats , Rats, Wistar , Time Factors , Weight GainABSTRACT
Physical exercise increases serum glucocorticoids, which is believed to be involved in the fall of T3 after high intensity exercise. The objective was to evaluate whether a physical exercise session alters the thyroid economy and adrenal axis in humans, and the possible role of corticosteroids in thyroid function disturbance. Active but not athlete subjects were enrolled in an open field competition and cortisol, TSH, T3, and T4 were measured before and after the race. To give new insights into the mechanisms underlying the changes in thyroid economy after exercise, we used a rat model to evaluate the impact of blocking corticosterone synthesis during treadmill exercise by metyrapone administration. Cortisol levels increased 1.5-fold (from 28.2±3.8 to 42.2±2.2 µg/dl; p<0.05), while serum T3 decreased by 13% (from 115±5 to 99±5 µg/dl; p<0.05) 6 h after the race in humans. Also, in rats, glucocorticoid increased by 2-fold while T3 decreased 15% after exercise session (p<0.05). However, the complete blockage of corticosterone peak did not impair serum T3 decrease observed in rats submitted to exercise. Interestingly, the lack of corticosterone peak led not only to lower serum T3, but also to decreased serum T4, indicating that corticosterone might be fundamental for the maintenance of serum thyroid hormone levels after high intensity exercise. Although cortisol increases and T3 decreases after high intensity exercise in both humans and rats, it does not seem to be a cause-effect response since pharmacological blockage of corticosterone peak does not modulate T3 response.
