Loss of Hdac3 in osteoprogenitors increases bone expression of osteoprotegerin, improving systemic insulin sensitivity

Meghan Elizabeth McGee Lawrence, Jessica L. Pierce, Kanglun Yu, Natasha R. Culpepper, Elizabeth W. Bradley, Jennifer J. Westendorf

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Type 2 diabetes is an emerging global health epidemic. Foundations for new therapies are arising from understanding interactions between body systems. Bonederived factors that reduce RANKL (receptor activator of NF-kappa B ligand) signaling in the liver may prevent insulin resistance and the onset of type 2 diabetes. Here we demonstrate that deletion of the epigenetic regulator, Hdac3, in Osx1-expressing osteoprogenitors prevents insulin resistance induced by high fat diet by increasing serum and skeletal gene expression levels of osteoprotegerin (Opg), a natural inhibitor of RANKL signaling. Removal of one Opg allele in mice lacking Hdac3 in Osx1+ osteoprogenitors increases the insulin resistance of the Hdac3-deficient mice on a high fat diet. Thus, Hdac3-depletion in osteoblasts increases expression of Opg, subsequently preserving insulin sensitivity. The Hdac inhibitor vorinostat also increased Opg transcription and histone acetylation of the Opg locus. These results define a new mechanism by which bone regulates systemic insulin sensitivity.

Original languageEnglish (US)
Pages (from-to)2671-2680
Number of pages10
JournalJournal of Cellular Physiology
Volume233
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Osteoprotegerin
Insulin Resistance
Bone
Insulin
Receptor Activator of Nuclear Factor-kappa B
Bone and Bones
High Fat Diet
Nutrition
Medical problems
Type 2 Diabetes Mellitus
Fats
Ligands
Acetylation
Osteoblasts
Transcription
Epigenomics
Gene expression
Liver
Histones
Alleles

Keywords

  • Energy metabolism
  • Histone deacetylase 3
  • Insulin sensitivity
  • Mellitus
  • Osteoblast
  • Osteoprotegerin
  • Type 2 diabetes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Loss of Hdac3 in osteoprogenitors increases bone expression of osteoprotegerin, improving systemic insulin sensitivity. / McGee Lawrence, Meghan Elizabeth; Pierce, Jessica L.; Yu, Kanglun; Culpepper, Natasha R.; Bradley, Elizabeth W.; Westendorf, Jennifer J.

In: Journal of Cellular Physiology, Vol. 233, No. 4, 01.04.2018, p. 2671-2680.

Research output: Contribution to journalArticle

McGee Lawrence, Meghan Elizabeth ; Pierce, Jessica L. ; Yu, Kanglun ; Culpepper, Natasha R. ; Bradley, Elizabeth W. ; Westendorf, Jennifer J. / Loss of Hdac3 in osteoprogenitors increases bone expression of osteoprotegerin, improving systemic insulin sensitivity. In: Journal of Cellular Physiology. 2018 ; Vol. 233, No. 4. pp. 2671-2680.
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