Journal
BONE
Volume 116, Issue -, Pages 120-134Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2018.07.015
Keywords
High-fat diet; Exercise; Bone metabolism; Insulin signaling; Dickkopf-1
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Funding
- Deutsche Forschungsgemeinschaft, DFG [TRR67/B02]
- Danish Research Council [DFF-4004-00233]
- Novo Nordisk Foundation [NNF18OC0032082]
- MeDDrive grant program of the medical faculty of the TU Dresden, Young Investigator Award of the Dachverband Osteologie e.V
- Joachim Herz Stiftung
- DFG [BU 2562/2-1/3-1]
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Bone microarchitecture and strength are impaired by obesity and physical inactivity, but the underlying molecular regulation of bone metabolism in response to these factors is not well understood. Therefore, we analyzed bone and energy metabolism in male mice fed a high-fat or standard chow diet for 12 weeks with or without free access to running wheels. High-fat diet (HFD) mimicked the human condition of obesity and insulin resistance, including symptoms such as elevated serum glucose and insulin levels and reduced insulin-stimulated glucose uptake into muscle and adipose tissue. Interestingly, HFD also decreased (44%) glucose uptake into bone marrow. Bone mass was reduced (45%) by HFD due to a diminished (45%) bone remodeling rate. Bone matrix quality aspects, such as biomechanical stability, were additionally decreased. Concurrently, the bone marrow adiposity increased (+ 63%) in response to a HFD. Further, we detected elevated expression of the Wnt signaling inhibitor dickkopfI (Dkk-1, + 42%) in mice fed a HFD, but this was not reflected in serum samples obtained from obese humans. In mice, exercise attenuated the adverse effects of HFD by reversing the glucose uptake into bone marrow, improving the bone mass and bone matrix quality while decreasing the bone marrow adiposity. This data shows that exercise prevents some, but not all of the negative effects of HFD on bone health and suggests that insulin signaling in bone marrow and Dkk-1 signaling may be involved in the pathogenesis of bone loss induced by HFD.
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