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

Soohyun P. Kim, Zhu Li, Meredith L. Zoch, Julie L. Frey, Caitlyn E. Bowman, Priyanka Kushwaha, Kathleen A. Ryan, Brian C. Goh, Susanna Scafidi, Julie E. Pickett, Marie Claude Faugere, Erin E. Kershaw, Daniel L.J. Thorek, Thomas L. Clemens, Michael J. Wolfgang, Ryan C. Riddle

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


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.

Original languageEnglish
Article numbere92704
JournalJCI insight
Issue number16
StatePublished - Aug 17 2017

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© 2017 American Society for Clinical Investigation. All rights reserved.

ASJC Scopus subject areas

  • General Medicine


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