b-Catenin directs long-Chain fatty acid catabolism in the osteoblasts of male mice

Julie L. Frey, Soohyun P. Kim, Zhu Li, Michael J Wolfgang, Ryan Riddle

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)272-284
Number of pages13
JournalEndocrinology
Volume159
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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ASJC Scopus subject areas

  • Endocrinology

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