Effects of Diet-Induced Obesity and Voluntary Wheel Running on Bone Properties in Young Male C57BL/6J Mice

Abstract

Both physical activity and body mass affect bone properties. In this study we examined how diet-induced obesity combined with voluntary physical activity affects bone properties. Forty 7-week-old male C57BL/6J mice were assigned to four groups evenly: control diet (C), control diet + running (CR), high-fat diet (HF, 60% energy from fat), and high-fat diet + running (HFR). After 21-week intervention, all mice were killed and the left femur was dissected for pQCT and mechanical measurements. Body mass increased 80% in HF and 62% in HFR, with increased epididymal fat pad weight and impaired insulin sensitivity. Except for total and trabecular volumetric bone mineral density (BMD), bone traits correlated positively with body mass, fat pad, leptin, and osteoprotegerin. Obesity induced by a high-fat diet resulted in increased femoral bone cross-sectional area, mineral content (BMC), polar moment of inertia, and mechanical parameters. Of the mice accessing the running wheel, those fed the control diet had thinner cortex and less total metaphyseal BMC and BMD, with enlarged metaphyseal marrow cavity, whereas mice fed the high-fat diet had significantly higher trabecular BMD and smaller marrow cavity. However, the runners had a weaker femoral neck as indicated by decreased maximum flexure load. These results suggest that voluntary running exercise affects bone properties in a site-specific manner and that there is a complex interaction between physical activity and obesity. Thus, both diet and exercise should be considered when optimizing the effects on body composition and bone, even though the underlying mechanisms remain partly unknown.

Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse

“…The changes in the various blood parameters, such as levels of triglycerides, cholesterol, and insulin, were similar between the HFD and PEG-SMLA treatments, although glucose levels were higher in HFD (8,39,40,58). A comparison of two inflammatory cytokines showed a similar pattern.…”

“…We limited our comparison to C57BL/6J mice, a strain that is known to be susceptible to diabetes on HFDs and is the genetic background for the ob/ob model; the results are compiled in Supplemental Table S2. The absolute weight gain in both HFD and PEG-SMLA treatments was similar, but the latter was achieved in 2-3 wk, in contrast to the much longer period required with a HFD (8,13,14,34,37,39,40,55,58,64,69), and the outcome could be rapidly reversed (27). However, the feeding behavior was different.…”

“…However, the feeding behavior was different. Under a HFD, energy intake parallels the controls for the first 4 wk and then gradually increases to about 15 to 20% above controls (54,55,58). In contrast, PEG-SMLAtreated mice eat regular chow but increase their food intake by 75-80% from the first days for 2 or 3 wk.…”

Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change

“…A repeated general linear model was used with weight gain, feeding efficiency and weekly running distance as parameters. Twoway ANOVA was used to determine the effect of diet (with 2 levels: low-fat diet and high-fat diet), exercise (with 2 levels: with and without voluntary running), and their interaction with the measured variables, as previously described [39]. Differences between the means of the intervention groups were evaluated, and the significance of differences was determined by Bonferroni post hoc testing.…”

“…After one week of adaptation to new environment, the mice were matched for body-weight (20.8 ± 1.4 g) and divided into four groups. The mice received for 19 weeks ad libitum either a lard-based purified high-fat diet (61% of energy from fat, 19% protein, 20% carbohydrates 5.16 kcal/g; D12492-Euro) to induce obesity and insulin resistance, or a low-fat diet as a control diet (10% of energy from fat, 19% protein, 71% carbohydrates, 3.78kcal/g; D12450-Euro, Purina Mills TestDiet Mice were housed individually in cages and the physically active mice had access to a running wheel, as previously described [39]. The amount of running was monitored via a computerized system across the study period.…”