Possible mechanisms of metabolic dysfunction in ovariectomized rats: impact of intrinsic aerobic fitness
Metadata[+] Show full item record
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Ovariectomized (OVX) rodents are used as a model of human menopause as frequently both experience weight gain, decreased insulin sensitivity and decreased physical activity, which may manifest into metabolic syndrome. Intrinsic aerobic capacity may influence OVX-induced metabolic dysfunction. Female rats selectively bred for high (HCR) and low (LCR) aerobic capacity were used to elucidate the underlying mechanisms by which intrinsic aerobic fitness impacts OVX-associated metabolic dysfunction. We demonstrated that HCR were not fully protected against an OVX-induced decline in insulin sensitivity partially due to a ~30% attenuation of insulin-stimulated skeletal muscle glucose uptake. HCROVX were protective against HFD-associated insulin resistance through a unique mechanism of behavioral change (i.e. compensatory increase in spontaneous physical activity), while LCROVX exacerbated insulin resistance following HFD. HCR were not protected from OVX-induced reduction in voluntary wheel running; yet HCRhad greater DA activation, compared to LCR, which was associated with their enhanced running distance. Collectively, these data suggest that high aerobic fitness may play a critical role in attenuating metabolic dysfunction associated with OVX and external stress due to their intrinsically enhanced insulin sensitivity. However, high aerobic fitness is not fully protective to OVX-induced impairments in metabolic function and physical activity levels, indicative of a strong physiological effect of ovarian hormone loss.