Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast

Julie L. Frey, Zhu Li, Jessica M. Ellis, Qian Zhang, Charles R. Farber, Susan Aja, Michael J. Wolfgang, Thomas L. Clemens, Ryan C. Riddle

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Pages1979-1991
Number of pages13
JournalMolecular and Cellular Biology
Volume35
Issue number11
DOIs
StatePublished - 2015

Fingerprint

Osteoblasts
Fatty Acids
Bone and Bones
Osteocytes
Osteocalcin
beta Catenin
Nonesterified Fatty Acids
Skeleton
Energy Metabolism
Adipose Tissue
Triglycerides
Homeostasis
Alleles
Glucose
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast. / Frey, Julie L.; Li, Zhu; Ellis, Jessica M.; Zhang, Qian; Farber, Charles R.; Aja, Susan; Wolfgang, Michael J.; Clemens, Thomas L.; Riddle, Ryan C.

In: Molecular and Cellular Biology, Vol. 35, No. 11, 2015, p. 1979-1991.

Research output: Contribution to journalArticle

Frey JL, Li Z, Ellis JM, Zhang Q, Farber CR, Aja S et al. Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast. Molecular and Cellular Biology. 2015;35(11):1979-1991. Available from, DOI: 10.1128/MCB.01343-14
Frey, Julie L. ; Li, Zhu ; Ellis, Jessica M. ; Zhang, Qian ; Farber, Charles R. ; Aja, Susan ; Wolfgang, Michael J. ; Clemens, Thomas L. ; Riddle, Ryan C./ Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast. In: Molecular and Cellular Biology. 2015 ; Vol. 35, No. 11. pp. 1979-1991
@article{4bc2c098a1fb4d4d95afae3ce744dbae,
title = "Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast",
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.",
author = "Frey, {Julie L.} and Zhu Li and Ellis, {Jessica M.} and Qian Zhang and Farber, {Charles R.} and Susan Aja and Wolfgang, {Michael J.} and Clemens, {Thomas L.} and Riddle, {Ryan C.}",
year = "2015",
doi = "10.1128/MCB.01343-14",
language = "English (US)",
volume = "35",
pages = "1979--1991",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - Wnt-Lrp5 signaling regulates fatty acid metabolism in the osteoblast

AU - Frey,Julie L.

AU - Li,Zhu

AU - Ellis,Jessica M.

AU - Zhang,Qian

AU - Farber,Charles R.

AU - Aja,Susan

AU - Wolfgang,Michael J.

AU - Clemens,Thomas L.

AU - Riddle,Ryan C.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84929413373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929413373&partnerID=8YFLogxK

U2 - 10.1128/MCB.01343-14

DO - 10.1128/MCB.01343-14

M3 - Article

VL - 35

SP - 1979

EP - 1991

JO - Molecular and Cellular Biology

T2 - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 11

ER -