Changes in Skeletal Integrity and Marrow Adiposity during High-Fat Diet and after Weight Loss

Abstract

The prevalence of obesity has continued to rise over the past three decades leading to significant increases in obesity-related medical care costs from metabolic and non-metabolic sequelae. It is now clear that expansion of body fat leads to an increase in inflammation with systemic effects on metabolism. In mouse models of diet-induced obesity, there is also an expansion of bone marrow adipocytes. However, the persistence of these changes after weight loss has not been well described. The objective of this study was to investigate the impact of high-fat diet (HFD) and subsequent weight loss on skeletal parameters in C57Bl6/J mice. Male mice were given a normal chow diet (ND) or 60% HFD at 6 weeks of age for 12, 16, or 20 weeks. A third group of mice was put on HFD for 12 weeks and then on ND for 8 weeks to mimic weight loss. After these dietary challenges, the tibia and femur were removed and analyzed by micro computed-tomography for bone morphology. Decalcification followed by osmium staining was used to assess bone marrow adiposity, and mechanical testing was performed to assess bone strength. After 12, 16, or 20 weeks of HFD, mice had significant weight gain relative to controls. Body mass returned to normal after weight loss. Marrow adipose tissue (MAT) volume in the tibia increased after 16 weeks of HFD and persisted in the 20-week HFD group. Weight loss prevented HFD-induced MAT expansion. Trabecular bone volume fraction, mineral content, and number were decreased after 12, 16, or 20 weeks of HFD, relative to ND controls, with only partial recovery after weight loss. Mechanical testing demonstrated decreased fracture resistance after 20 weeks of HFD. Loss of mechanical integrity did not recover after weight loss. Our study demonstrates that HFD causes long-term, persistent changes in bone quality, despite prevention of marrow adipose tissue accumulation, as demonstrated through changes in bone morphology and mechanical strength in a mouse model of diet-induced obesity and weight loss.

Effects of High-Fat Diet and Body Mass on Bone Morphology and Mechanical Properties in 1100 Advanced Intercross Mice

“…In our study, we examined dietary effects during growth—from weaning to adulthood (18 to 26 weeks on diet). Within this time frame, both positive and negative effects of high‐fat diet on cortical bone have been reported in male C57BL/6J mice. The main difference between these two prior studies was the use of 45% high‐fat diet with diacylglycerol enrichment in the former versus 60% lard/soybean oil in the latter .…”

“…Within this time frame, both positive and negative effects of high‐fat diet on cortical bone have been reported in male C57BL/6J mice. The main difference between these two prior studies was the use of 45% high‐fat diet with diacylglycerol enrichment in the former versus 60% lard/soybean oil in the latter . The dietary composition we used (42% milk fat) was comparable to the first study and, like that report, we demonstrated positive absolute effects of high‐fat diet on cortical bone.…”

Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass

“…Ultimately, the physiologic underpinnings of weight loss in an obese person are likely to be distinct from those of weight loss in a normal or underweight person (as in anorexia). This distinction is suggested by the results of a recent study in mice, in which mice fed a high‐fat diet then switched to a normal diet experienced weight loss and a decrease in marrow fat at the tibia and femur …”

Development, regulation, metabolism and function of bone marrow adipose tissues

“…For example, mice with high fat diet-induced obesity show much higher osmium staining of proximal tibial marrow lipid than lean mice. Elevated lipid in proximal tibia is due to an increase in both BMA number and size 35, 37, 38 (Figure 2). In contrast, neither bone marrow lipid nor the size/number of BMAs is different in distal tibial cBMAT of lean and obese mice (Figure 2).…”