title: High bone mass in adult mice with diet-induced obesity results from a combination of initial increase in bone mass followed by attenuation in bone formation; implications for high bone mass and decreased bone quality in obesity.
abstract: Obesity is generally recognized as a condition which positively influences bone mass and bone mineral density (BMD). Positive effect of high body mass index (BMI) on bone has been recognized as a result of increased mechanical loading exerted on the skeleton. However, epidemiologic studies indicate that obesity is associated with increased incidence of fractures. The results presented here offer a new perspective regarding the mechanisms which may be responsible for the increase of bone mass and concurrent decrease in bone quality. Two groups of 12 week old C57BL/6 males were fed either high fat diet (HFD) or regular diet (RD) for 11 weeks. Metabolic profile, bone parameters and gene expression were assessed in these groups at the end of the experiment. Additionally, bone status was evaluated in a third group of 12 week old animals corresponding to animals at the start of the feeding period. Administration of HFD resulted in development of a diet-induced obesity (DIO), glucose intolerance, alteration in energy metabolism, and impairment in WAT function, as compared to the age-matched control animals fed RD. The expression of adiponectin, FABP4/aP2, DIO2 and FoxC2 were decreased in WAT of DIO animals, as well as transcript levels for IGFBP2, the cytokine regulating both energy metabolism and bone mass. At the end of experiment, DIO mice had higher bone mass than both control groups on RD, however they had decreased bone formation, as assessed by calcein labeling, and increased marrow adipocyte content. This study suggests that the bone mass acquired in obesity is a result of a two-phase process. First phase would consist of either beneficial effect of fat expansion to increase bone mass by increased mechanical loading and/or increased production of bone anabolic adipokines and/or nutritional effect of fatty acids. This is followed by a second phase characterized by decreased bone formation and bone turnover resulting from development of metabolic impairment.
authors.affiliation: Department of Orthopaedic Surgery, University of Toledo Health Sciences Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA; Department of Physiology and Pharmacology, University of Toledo Health Sciences Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA; Center for Diabetes and Endocrine Research (CeDER), University of Toledo Health Sciences Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA. Electronic address: beata.leckaczernik@utoledo.edu.
authors.forename: B
authors.initials: B
authors.lastname: Lecka-Czernik
authors.affiliation: Department of Orthopaedic Surgery, University of Toledo Health Sciences Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA; Center for Diabetes and Endocrine Research (CeDER), University of Toledo Health Sciences Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Stechschulte
authors.affiliation: Department of Orthopaedic Surgery, University of Toledo Health Sciences Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Czernik
authors.affiliation: Department of Physiology and Pharmacology, University of Toledo Health Sciences Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Dowling
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D015519:Bone Density; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D018149:Glucose Intolerance / Q000139:chemically induced; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D010012:Osteogenesis
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Bone formation; Bone mass; Diet induced obesity; Energy metabolism; High fat diet; Obesity