Animals and diet

The HCR/LCR rat model was used to assess the effect of voluntary wheel running (i.e., physical activity) on WAT and BAT inflammation and metabolic dysfunction associated with loss of ovarian hormones. Characterizations of the HCR/LCR rodents have been previously described [11,29–34]. This study is an extension of our previous findings that female LCR rats respond more adversely to OVX than HCR rats in terms of total fat gain, reduced energy expenditure and IR [11], which is exacerbated by an HFD [10]. Randomly cycling female rats aged 25–35 weeks (generation 31–33) were singularly housed under standard temperature (∼22°C) and humidity on a 12h-12h light/dark cycle. Rats were tested for running capacity at the University of Michigan at 11 weeks of age and shipped to the University of Missouri at 16–20 weeks of age. Animals were initially provided with standard rodent chow (Laboratory Diets 5001) and water ad libitum. Sham (SHM) sedentary (SED) rats (i.e., ovary-intact) remained on standard chow until study completion (N = 7–12 animals/group) [11]. Following OVX, animals were given an HFD (45% kcal fat, D12451, Research Diets) and half were randomly selected to either access running wheels (i.e., voluntary wheel running, VWR) (11cm wide with an inner diameter of 35 cm; bar running surface) or remain SED (N = 7–8 animals/group) for 11 weeks [23]. National Institutes of Health guidelines were strictly followed and all procedures were approved by the Institutional Animal Care and Use Committee at the University of Missouri prior to study initiation.