Incorporating Refractory Period in Mechanical Stimulation Mitigates Obesity-Induced Adipose Tissue Dysfunction in Adult Mice

OBJECTIVE: To determine whether inclusion of a refractory period between bouts of low magnitude mechanical stimulation (LMMS) can curb obesity-induced adipose tissue dysfunction and sequelae in adult mice. METHODS: A diet-induced obesity model with 45kcal% fat diet was employed with intention-to-treat. C57BL/6J mice were weight-matched into four groups: low fat diet (LFD, n=8), high fat diet (HF, n=8), high fat diet with one bout of 30min LMMS (HFv, n=9), and high fat diet with two bouts of 15min LMMS with 5-hour separation (refractory period, RHFv, n=9). 2-week of diet was followed by 6-week of diet+LMMS. RESULTS: HF and HFv continued gaining body weight and visceral adiposity throughout the experiment, which was mitigated in RHFv. HF and HFv had increased adipocyte hypertrophy, immune cell infiltration (B-cells, T cells, and macrophages) into adipose tissue, adipose tissue inflammation (TNF-α gene expression), and decreased proportion of mesenchymal stem cells in adipose tissue, as compared to LFD, all of which was rescued in RHFv. Glucose intolerance, sequelae of adipose tissue dysfunction, were elevated in HF and HFv, but not in RHFv, as compared to LFD. CONCLUSION: Incorporating a 5-hour refractory period between bouts of LMMS attenuates obesity-induced adipose tissue dysfunction and mitigates glucose intolerance.