ISSN 2052-1219 (online)

Bone Abstracts (2016) 5 P267 | DOI: 10.1530/boneabs.5.P267

Altered bone metabolism after high fat diet and exercise: role of Wnt signaling and insulin resistance

Ann-Kristin Picke1, Lykke Sylow2, Lisbeth L V Møller2, Rasmus Kjøbsted2, Erik Richter2, Martina Rauner1, Christine Hofbauer3 & Lorenz C Hofbauer1,4

1Division of Endocrinology, Diabetes, and Metabolic Bone Diseases, Department of Medicine III, Technische Universität Dresden, Dresden, Germany; 2Molecular Physiology Group, Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark; 3University of Center of Orthopeadics and Traumatology, University Medicine Carl Gustav Carus Dresden, Dresden, Germany; 4Center for Regenerative Therapies Dresden, Dresden, Germany.

High fat diet (HFD), obesity, and physical inactivity characterize the modern lifestyle. This can lead to coronary heart diseases and type 2 diabetes mellitus. Recent studies have shown that these conditions frequently are associated with poor bone quality. However, the molecular mechanisms are poorly understood. To analyze the effect of HFD and exercise (EX) on bone homeostasis, we fed 6 week-old C57BL/6 mice a high fat (60% fat) or standard chow diet for 10 weeks (10-20 mice per group). Half of each group had free access to running wheels. Ten minutes before sacrifice, 3H-2-Deoxy-D-glucose (2-DG) was injected into the retro-orbital vein to investigate 2-DG uptake in tissue. Afterwards, blood, muscle and bone samples were collected. Bone mass was analyzed using micro-computed tomography, serum parameters by ELISA, and 2-DG-uptake by liquid scintillation counting.

HFD increased body weight (+14%) in sedentary mice. This increase was prevented in mice that exercised (8 km/d). Blood glucose and plasma insulin levels were increased in both HFD groups (up to +59% and +111%, respectively), but were not changed by EX. HFD decreased the uptake of 2-DG in the muscle (−55%) and in the tibial bone marrow (−44%), whereas EX increased the uptake back to control levels. The femoral trabecular and cortical bone volume per total volume (BV/TV) was reduced after HFD (−49%) while EX did not affect the BV/TV in control or HFD mice. While EX had no influence on bone turnover in control mice, it increased bone turnover in mice on a HFD (CTX: +29%, P1NP: +23%, osteocalcin: carboxylated +51%, undercarboxylated +20%). The Wnt inhibitor Dickkopf-1 was also elevated in both HFD groups and was not affected by EX.

These data suggest that Wnt signaling and insulin resistance may play key roles in the altered bone metabolism induced by HFD and a sedentary lifestyle.

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