1. Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast.
- Author
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Frey JL, Li Z, Ellis JM, Zhang Q, Farber CR, Aja S, Wolfgang MJ, Clemens TL, and Riddle RC
- Subjects
- Animals, Bone and Bones metabolism, Bone and Bones physiology, Cell Differentiation physiology, Low Density Lipoprotein Receptor-Related Protein-6 metabolism, Mice, Mice, Inbred C57BL, Osteogenesis physiology, beta Catenin metabolism, Fatty Acids metabolism, Low Density Lipoprotein Receptor-Related Protein-5 metabolism, Osteoblasts metabolism, Signal Transduction physiology, Wnt Proteins metabolism
- Abstract
The Wnt coreceptors Lrp5 and Lrp6 are essential for normal postnatal bone accrual and osteoblast function. In this study, we identify a previously unrecognized skeletal function unique to Lrp5 that enables osteoblasts to oxidize fatty acids. Mice lacking the Lrp5 coreceptor specifically in osteoblasts and osteocytes exhibit the expected reductions in postnatal bone mass but also exhibit an increase in body fat with corresponding reductions in energy expenditure. Conversely, mice expressing a high bone mass mutant Lrp5 allele are leaner with reduced plasma triglyceride and free fatty acid levels. In this context, Wnt-initiated signals downstream of Lrp5, but not the closely related Lrp6 coreceptor, regulate the activation of β-catenin and thereby induce the expression of key enzymes required for fatty acid β-oxidation. These results suggest that Wnt-Lrp5 signaling regulates basic cellular activities beyond those associated with fate specification and differentiation in bone and that the skeleton influences global energy homeostasis via mechanisms independent of osteocalcin and glucose metabolism., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
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