Examination of voluntary wheel running on markers of adipose thermogenesis in intact and ovariectomized female mice

Abstract

Estrogen plays an important role in adipose tissue (AT) metabolism. Post-menopausal estrogen loss leads to increased abdominal fat and worsened metabolic outcomes. Exercise, known to enhance energy expenditure and promote AT browning, may offer therapeutic potential to mitigate these adverse effects, particularly through the modulation of brain-derived neurotrophic factor (BDNF) and uncoupling protein-1 (UCP1) in adipose tissue. This study aimed to investigate the effect of voluntary wheel running (VWR) in ovariectomized (OVX) mice on whole body energy expenditure and body composition, key protein markers of thermogenesis and adipose tissue browning, and fluctuations in circulating and AT BDNF and receptor content. It was hypothesized VWR would either prevent or mitigate increases in adiposity due to OVX, enhance thermogenesis and AT browning in WAT depots, and elevate BDNF levels in both circulation and AT. A total of forty C57BL/6J female mice (24 weeks of age) were utilized for this study, twenty of which were subjected to bilateral ovariectomy (OVX=20) while the remaining twenty underwent a sham surgery (SHAM=20). SHAM and OVX mice were further randomized into one of two experimental groups: 1) sedentary (SHAM SED=10, OVX SED=10) and 2) voluntary wheel running (SHAM VWR=10, OVX VWR=10) for the duration of the study period (8-weeks). OVX mice gained more weight over the course of the 8-week study when compared to SHAM mice (P=0.0008). Serum BDNF was higher in mice with VWR access (P=0.0004). Final week lean body mass of VWR groups was trending (P=0.0641), with higher lean mass compared to SED groups. Key tissue specific protein markers responded in a depot-specific manner; notably, TH which was consistently lower in all depots in response to OVX, yet only higher in response to VWR in gWAT (P=0.040). Additionally, VWR groups also had higher ERα (P=0.045) and ERβ (P=0.008) protein content in the gWAT and iWAT depot respectively. This study demonstrates that estrogen deficiency with ovariectomy disrupts adipose tissue function and overall metabolism, while voluntary wheel running can mitigate some of these effects, emphasizing the importance of exercise in maintaining adipose tissue functionality and health in post-menopausal women.