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JCI Insight. 2017 Aug 17;2(16). pii: 92704. doi: 10.1172/jci.insight.92704. eCollection 2017 Aug 17.

Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner.

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Department of Orthopaedic Surgery.
Department of Biological Chemistry, and.
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Division of Nephrology, University of Kentucky, Lexington, Kentucky, USA.
Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Cancer Molecular and Functional Imaging Program, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA.


Postnatal bone formation is influenced by nutritional status and compromised by disturbances in metabolism. The oxidation of dietary lipids represents a critical source of ATP for many cells but has been poorly studied in the skeleton, where the prevailing view is that glucose is the primary energy source. Here, we examined fatty acid uptake by bone and probed the requirement for fatty acid catabolism during bone formation by specifically disrupting the expression of carnitine palmitoyltransferase 2 (Cpt2), an obligate enzyme in fatty acid oxidation, in osteoblasts and osteocytes. Radiotracer studies demonstrated that the skeleton accumulates a significant fraction of postprandial fatty acids, which was equal to or in excess of that acquired by skeletal muscle or adipose tissue. Female, but not male, Cpt2 mutant mice exhibited significant impairments in postnatal bone acquisition, potentially due to an inability of osteoblasts to modify fuel selection. Intriguingly, suppression of fatty acid utilization by osteoblasts and osteocytes also resulted in the development of dyslipidemia and diet-dependent modifications in body composition. Taken together, these studies demonstrate a requirement for fatty acid oxidation during bone accrual and suggest a role for the skeleton in lipid homeostasis.


Bone Biology

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