Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast.

摘要: The Wnt coreceptors Lrp5 and Lrp6 are essential for normal postnatal bone accrual osteoblast function. In this study, we identify a previously unrecognized skeletal function unique to that enables osteoblasts oxidize fatty acids. Mice lacking the coreceptor specifically in osteocytes exhibit expected reductions mass but also an increase body fat with corresponding energy expenditure. Conversely, mice expressing high mutant allele leaner reduced plasma triglyceride free acid levels. context, Wnt-initiated signals downstream of Lrp5, not closely related coreceptor, regulate activation β-catenin thereby induce expression key enzymes required β-oxidation. These results suggest Wnt-Lrp5 signaling regulates basic cellular activities beyond those associated fate specification differentiation skeleton influences global homeostasis via mechanisms independent osteocalcin glucose metabolism.