Differential effects of high-fat diet and exercise training on bone and energy metabolism

Bone. 2018 Nov;116:120-134. doi: 10.1016/j.bone.2018.07.015. Epub 2018 Jul 20.


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 dickkopf-1 (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.

Keywords: Bone metabolism; Dickkopf-1; Exercise; High-fat diet; Insulin signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity
  • Adult
  • Animals
  • Bone Marrow / metabolism
  • Bone Matrix / pathology
  • Bone and Bones / metabolism*
  • Bone and Bones / pathology
  • Cell Count
  • Diet, High-Fat / adverse effects*
  • Energy Metabolism*
  • Female
  • Glucose / metabolism
  • Humans
  • Hyperinsulinism / pathology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Obesity / pathology
  • Organ Size
  • Osteoclasts / pathology
  • Osteogenesis
  • Physical Conditioning, Animal*
  • Wnt Signaling Pathway


  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Glucose