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Fatty acid oxidation by the osteoblast is required for normal bone acquisition in a sex- and diet-dependent manner
Soohyun P. Kim, … , Michael J. Wolfgang, Ryan C. Riddle
Soohyun P. Kim, … , Michael J. Wolfgang, Ryan C. Riddle
Published August 17, 2017
Citation Information: JCI Insight. 2017;2(16):e92704. https://doi.org/10.1172/jci.insight.92704.
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Research Article Bone biology

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

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Abstract

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.

Authors

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

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Figure 1

Bone takes up a substantial fraction of postprandial lipid.

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Bone takes up a substantial fraction of postprandial lipid.
(A and C) Bi...
(A and C) Biodistribution of [3H]-bromopalmitate (A) and [14C]-oleate (C) in 12-week-old C57Bl/6 mice (n = 5–6 mice). Uptake (cpm) is normalized for tissue weight. Skeleton represents the combined uptake by femur, tibia, and calvaria. (B and D) Levels of [3H]-bromopalmitate (B) and [14C]-oleate (D) uptake in the skeleton relative to the indicated tissue. (E) Autoradiographic analysis of 125I-BMIPP uptake in the tibia, with whole mount tissue section on right (Representative of n = 4 mice). (F) Comparison of [3H]-acetate incorporation into tissue lipids in gonadal white adipose and the femur (n = 6-7 mice). All data are represented by mean ± SEM. *P < 0.05 by unpaired, two-tailed Student’s t test.

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