title: Immature mice are more susceptible to the detrimental effects of high fat diet on cancellous bone in the distal femur.
abstract: With the increasing prevalence of obesity among children and adolescents, it is imperative to understand the implications of early diet-induced obesity on bone health. We hypothesized that cancellous bone of skeletally immature mice is more susceptible to the detrimental effects of a high fat diet (HFD) than mature mice, and that removing excess dietary fat will reverse these adverse effects. Skeletally immature (5weeks old) and mature (20weeks old) male C57BL/6J mice were fed either a HFD (60% kcal fat) or low fat diet (LFD; 10% kcal fat) for 12weeks, at which point, the trabecular bone structure in the distal femoral metaphysis and third lumbar vertebrae were evaluated by micro-computed tomography. The compressive strength of the vertebrae was also measured. In general, the HFD led to deteriorations in cancellous bone structure and compressive biomechanical properties in both age groups. The HFD-fed immature mice had a greater decrease in trabecular bone volume fraction (BVF) in the femoral metaphysis, compared to mature mice (p=0.017 by 2-way ANOVA). In the vertebrae, however, the HFD led to similar reductions in BVF and compressive strength in the two age groups. When mice on the HFD were switched to a LFD (HFD:LFD) for an additional 12weeks, the femoral metaphyseal BVF in immature mice showed no improvements, whereas the mature mice recovered their femoral metaphyseal BVF to that of age-matched lean controls. The vertebral BVF and compressive strength of HFD:LFD mouse bones, following diet correction, were equivalent to those of LFD:LFD mice in both age groups. These data suggest that femoral cancellous metaphyseal bone is more susceptible to the detrimental effects of HFD before skeletal maturity and is less able to recover after correcting the diet. Negative effects of HFD on vertebrae are less severe and can renormalize with LFD:LFD mice after diet correction, in both skeletally immature and mature animals.
authors: Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA; Department of Biomedical Engineering, University of Rochester, 207 Robert B. Goergen Hall, Rochester, NY 14642, USA. Electronic address: jason_inzana@urmc.rochester.edu.
authors: Jason A
authors: JA
authors: Inzana
authors: Ming
authors: M
authors: Kung
authors: Lei
authors: L
authors: Shu
authors: Daisuke
authors: D
authors: Hamada
authors: Lian Ping
authors: LP
authors: Xing
authors: Michael J
authors: MJ
authors: Zuscik
authors: Hani A
authors: HA
authors: Awad
authors: Robert A
authors: RA
authors: Mooney
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D005215:Fasting / Q000097:blood; D005269:Femur / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055114:X-Ray Microtomography
chemical_list: D001786:Blood Glucose; D020738:Leptin
keywords: Age dependence; Diet correction; High fat diet; Obesity; Trabecular bone
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