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, 64, 39-46

Bone Marrow Fat Accumulation Accelerated by High Fat Diet Is Suppressed by Exercise

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Bone Marrow Fat Accumulation Accelerated by High Fat Diet Is Suppressed by Exercise

Maya Styner et al. Bone.

Abstract

Marrow adipose tissue (MAT), associated with skeletal fragility and hematologic insufficiency, remains poorly understood and difficult to quantify. We tested the response of MAT to high fat diet (HFD) and exercise using a novel volumetric analysis, and compared it to measures of bone quantity. We hypothesized that HFD would increase MAT and diminish bone quantity, while exercise would slow MAT acquisition and promote bone formation. Eight week-old female C57BL/6 mice were fed a regular (RD) or HFD, and exercise groups were provided voluntary access to running wheels (RD-E, HFD-E). Femoral MAT was assessed by μCT (lipid binder osmium) using a semi-automated approach employing rigid co-alignment, regional bone masks and was normalized for total femoral volume (TV) of the bone compartment. MAT was 2.6-fold higher in HFD relative to RD mice. Exercise suppressed MAT in RD-E mice by more than half compared with RD. Running similarly inhibited MAT acquisition in HFD mice. Exercise significantly increased bone quantity in both diet groups. Thus, HFD caused significant accumulation of MAT; importantly running exercise limited MAT acquisition while promoting bone formation during both diets. That MAT is exquisitely responsive to diet and exercise, and its regulation by exercise appears to be inversely proportional to effects on exercise induced bone formation, is relevant for an aging and sedentary population.

Keywords: Bone micro architecture; Exercise; Lipid; Marrow adipose tissue; Micro-CT; Quantitative image analysis.

Figures

Figure 1
Figure 1. Overview of method for visualization and quantification of marrow adipose tissue (MAT)
Osmium-stained femorae were visualized via μCT. Femorae (A) were rigidly aligned (B). Bone masks (C) were averaged (D). Osmium within the bone mask was quantified as volumetric (mm3) measurements of low (red), mid (green) and high (blue) osmium containing regions in the femur and (E) overlaid on μCT images for viewing. 3D rendering of osmium regions (F) with same coloring as 3E, colors slightly offset due to transparent bone mask. In (G) we subdivided the femur into three anatomical regions of interest. (H) This is a pictorial representation of a data spreadsheet containing regional osmium measurements as osmium volume normalized to total femoral volume (in %).
Figure 2
Figure 2. White adipose tissue and weight are increased by HFD diet
C57BL/6 Mice had access to running wheels starting at the same time as the change in diet, age 8 wk. (A) Food intake. (B) Kcal consumed. (C) Body weight (D) Perigonadal fat pad weight normalized to body weight. Results expressed as means ± SEM.
Figure 3
Figure 3. Exercise suppresses marrow adiposity despite HFD diet
8 wk old C57BL/6 mice were fed a RD or HFD diet for 6 weeks and given access to voluntary running wheels. Visualization of osmium stain by μCT is demonstrated in the sagittal (A) coronal (B), and axial (D) planes. (C) Osmium heat map and pictorial representation of the anatomic planes demonstrated in A, B, D. Each image represents overlaid average of n=5 mice. (E) Quantification of osmium in metaphysis as a measure of MAT. (F) Triglyceride content of the femur (n=5 per group). Results expressed as means ± SEM.
Figure 4
Figure 4. Running increases bone quantity
Bone quantity was measured in the proximal tibial metaphysis and diaphysis to assess effects of 6 weeks of HFD and exercise via μCT.
Figure 5
Figure 5. Exercise reduces MAT in skeletally mature mice
Eight week-old and 10 week-old C57 BL/6 mice were fed a RD and provided access to running wheels (A) Visualization of osmium stain by μCT is demonstrated in the sagittal and coronal planes. (C) Quantification of osmium in the metaphysis as a measure of MAT. Results expressed as means ± SEM.

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