title: High-fat diet causes bone loss in young mice by promoting osteoclastogenesis through alteration of the bone marrow environment.
abstract: Obesity is a severe health problem in children, afflicting several organ systems including bone. However, the role of obesity on bone homeostasis and bone cell function in children has not been studied in detail. Here we used young mice fed a high-fat diet (HFD) to model childhood obesity and investigate the effect of HFD on the phenotype of cells within the bone marrow environment. Five-week-old male mice were fed a HFD for 3, 6, and 12 weeks. Decreased bone volume was detected after 3 weeks of HFD treatment. After 6 and 12 weeks, HFD-exposed mice had less bone mass and increased osteoclast numbers. Bone marrow cells, but not spleen cells, from HFD-fed mice had increased osteoclast precursor frequency, elevated osteoclast formation, and bone resorption activity, as well as increased expression of osteoclastogenic regulators including RANKL, TNF, and PPAR-gamma. Bone formation rate and osteoblast and adipocyte numbers were also increased in HFD-fed mice. Isolated bone marrow cells also had a corresponding elevation in the expression of positive regulators of osteoblast and adipocyte differentiation. Our findings indicate that in juvenile mice, HFD-induced bone loss is mainly due to increased osteoclast bone resorption by affecting the bone marrow microenvironment. Thus, targeting osteoclast formation may present a new therapeutic approach for bone complications in obese children.
authors: Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 626, Rochester, NY, 14642, USA.
authors: Lei
authors: L
authors: Shu
authors: Eric
authors: E
authors: Beier
authors: Tzong
authors: T
authors: Sheu
authors: Hengwei
authors: H
authors: Zhang
authors: Michael J
authors: MJ
authors: Zuscik
authors: Edward J
authors: EJ
authors: Puzas
authors: Brendan F
authors: BF
authors: Boyce
authors: Robert A
authors: RA
authors: Mooney
authors: Lianping
authors: L
authors: Xing
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D015519:Bone Density; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D001862:Bone Resorption / Q000503:physiopathology*; D001842:Bone and Bones / Q000473:pathology; D002454:Cell Differentiation; D002469:Cell Separation; D059305:Diet, High-Fat / Q000009:adverse effects*; D005434:Flow Cytometry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D047495:PPAR gamma; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D017493:Leukocyte Common Antigens