TY - JOUR
T1 - b-Catenin directs long-Chain fatty acid catabolism in the osteoblasts of male mice
AU - Frey, Julie L.
AU - Kim, Soohyun P.
AU - Li, Zhu
AU - Wolfgang, Michael J.
AU - Riddle, Ryan C.
N1 - Funding Information:
Financial Support: This work was supported by National Institutes of Health Grants DK099134 (to R.C.R.) and NS072241 (to M.J.W.), and the John Hopkins University–University of Maryland Diabetes Research Center (Grant DK079637).
Funding Information:
This work was supported by National Institutes of Health Grants DK099134 (to R.C.R.) and NS072241 (to M.J.W.), and the John Hopkins University–University of Maryland Diabetes Research Center (Grant DK079637).
Publisher Copyright:
Copyright © 2018 Endocrine Society.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Wnt-initiated signaling through a frizzled receptor and the low-density lipoprotein–related receptor-5 coreceptor instructs key anabolic events during skeletal development, homeostasis, and repair. Recent studies indicate that Wnt signaling also regulates the intermediary metabolism of osteoblastic cells, inducing glucose consumption in osteoprogenitors and fatty acid utilization in mature osteoblasts. In this study, we examined the role of the canonical Wnt-signaling target, b-catenin, in the control of osteoblast metabolism. In vitro, Wnt ligands and agonists that stimulated b-catenin activation in osteoblasts enhanced fatty acid catabolism, whereas genetic ablation of b-catenin dramatically reduced oleate oxidation concomitant with reduced osteoblast maturation and increased glycolytic metabolism. Temporal ablation of b-catenin expression in osteoblasts in vivo produced the expected low-bone-mass phenotype and also led to an increase in white adipose tissue mass, dyslipidemia, and impaired insulin sensitivity. Because the expression levels of enzymatic mediators of fatty acid b-oxidation are reduced in the skeleton of b-catenin mutants, these results further confirm the role of the osteoblast in lipid metabolism and indicate that the influence of Wnt signaling on fatty acid utilization proceeds via its canonical signaling pathway.
AB - Wnt-initiated signaling through a frizzled receptor and the low-density lipoprotein–related receptor-5 coreceptor instructs key anabolic events during skeletal development, homeostasis, and repair. Recent studies indicate that Wnt signaling also regulates the intermediary metabolism of osteoblastic cells, inducing glucose consumption in osteoprogenitors and fatty acid utilization in mature osteoblasts. In this study, we examined the role of the canonical Wnt-signaling target, b-catenin, in the control of osteoblast metabolism. In vitro, Wnt ligands and agonists that stimulated b-catenin activation in osteoblasts enhanced fatty acid catabolism, whereas genetic ablation of b-catenin dramatically reduced oleate oxidation concomitant with reduced osteoblast maturation and increased glycolytic metabolism. Temporal ablation of b-catenin expression in osteoblasts in vivo produced the expected low-bone-mass phenotype and also led to an increase in white adipose tissue mass, dyslipidemia, and impaired insulin sensitivity. Because the expression levels of enzymatic mediators of fatty acid b-oxidation are reduced in the skeleton of b-catenin mutants, these results further confirm the role of the osteoblast in lipid metabolism and indicate that the influence of Wnt signaling on fatty acid utilization proceeds via its canonical signaling pathway.
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U2 - 10.1210/en.2017-00850
DO - 10.1210/en.2017-00850
M3 - Article
C2 - 29077850
AN - SCOPUS:85040719477
SN - 0013-7227
VL - 159
SP - 272
EP - 284
JO - Endocrinology
JF - Endocrinology
IS - 1
ER -