title: 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.
authors: Division of Bone and Mineral Diseases, Department of Medicine, Washington University, St. Louis, MO, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors: Erica L
authors: EL
authors: Scheller
authors: Department of Orthopaedic Surgery, University of Michigan , Ann Arbor, MI , USA.
authors: Basma
authors: B
authors: Khoury
authors: Division of Bone and Mineral Diseases, Department of Medicine, Washington University , St. Louis, MO , USA.
authors: Kayla L
authors: KL
authors: Moller
authors: Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Darlinghurst , Sydney, NSW , Australia.
authors: Natalie K Y
authors: NK
authors: Wee
authors: Department of Molecular and Integrative Physiology, University of Michigan , Ann Arbor, MI , USA.
authors: Shaima
authors: S
authors: Khandaker
authors: Department of Orthopaedic Surgery, University of Michigan , Ann Arbor, MI , USA.
authors: Kenneth M
authors: KM
authors: Kozloff
authors: Division of Pediatric Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School , Ann Arbor, MI , USA.
authors: Simin H
authors: SH
authors: Abrishami
authors: Graduate Program in Immunology, University of Michigan , Ann Arbor, MI , USA.
authors: Brian F
authors: BF
authors: Zamarron
authors: Division of Pediatric Endocrinology, Department of Pediatrics and Communicable Diseases, University of Michigan Medical School , Ann Arbor, MI , USA.
authors: Kanakadurga
authors: K
authors: Singer
keywords: bone; fracture; high-fat diet; leptin; marrow adipose tissue; marrow fat; obesity; weight loss