Author
CHEN, JIN-RAN - Arkansas Children'S Nutrition Research Center (ACNC) | |
LAZARENKO, OXANA - Arkansas Children'S Nutrition Research Center (ACNC) | |
BLACKBURN, MICHAEL - Arkansas Children'S Nutrition Research Center (ACNC) | |
CARVALHO, EUGENIA - Arkansas Children'S Nutrition Research Center (ACNC) | |
SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC) | |
BORSHEIM, ELIZABET - Arkansas Children'S Nutrition Research Center (ACNC) |
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only Publication Acceptance Date: 2/15/2017 Publication Date: 4/1/2017 Citation: Chen, J., Lazarenko, O.P., Blackburn, M.L., Carvalho, E., Shankar, K., Borsheim, E. 2017. Increased physical activity ameliorates high fat diet-induced bone resorption in mice. Journal of Federation of American Societies for Experimental Biology. 31(1):799.2. Interpretive Summary: Technical Abstract: It has been recognized that mechanical stresses associated with physical activity (PA) have beneficial effects on increasing bone mineral density (BMD) and improving bone quality. On the other hand, high fat diet (HFD) and obesity increase bone marrow adiposity leading to increased excretion of pro-inflammatory cytokines to activate RANKL-induced bone resorption. In the current study, we investigated whether increased PA via access to voluntary wheel running protects against HFD-induced bone resorption. One-month-old male C57BL6/J mice were provided ad libitum access to either control (17% fat) or HFD [20% protein (casein), 35% carbohydrate (dextrose and maltodextrin), and 45% fat (corn oil)] for 8 wk. Mice in each diet group were further divided into subgroups with or without PA by providing access to voluntary running wheels for 8 wk (8 to 9 km running per day). Using peripheral quantitative CT scan (pQCT) on tibias ex vivo, we found that bone mass especially trabecular BMD was significantly increased with PA in control diet animals compared to sedentary animals without access to wheels (102.8+/-3.5 vs. 91.5+/4.2 mg/cm3, n=6, p<0.05). PA ameliorated HFD-induced trabecular bone loss (PA+HFD, 93.6+/5.2 vs. HFD, 81.3+/4.7 mg/cm3, n=6, p<0.05). Femur bone marrow cells were aspirated and cultured, and non-adherent hematopoietic cells collected the following day were used for RANKL-induced osteoclastogenesis assay. We found that PA significantly blunted increases of HFD-induced osteoclastogenesis. In accordance with these data, signal transduction real-time PCR analysis showed that PA significantly inhibited HFD-induced Ezh2 and NFATc1 gene expression, but IRF8 expression was decreased in non-adherent hematopoietic cells from HFD mice. In conclusion, increased PA is capable of altering the HFD-induced bone marrow hematopoietic cell differentiation program to protect against increased bone resorption. |