Conditional deletion of Hdac3 in osteoprogenitor cells attenuates diet-induced systemic metabolic dysfunction

Meghan Elizabeth McGee Lawrence, Thomas A. White, Nathan K. LeBrasseur, Jennifer J. Westendorf

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

Obesity is a major health epidemic in the United States and a leading cause of preventable diseases including type 2 diabetes. A growing body of evidence indicates that the skeleton influences whole body metabolism and suggests a new avenue for developing novel therapeutic agents, but the underlying mechanisms are not well understood. Here, it is demonstrated that conditional deletion of an epigenetic regulator, Hdac3, in osteoblast progenitor cells abrogates high fat diet-induced insulin resistance and hepatic steatosis. These Hdac3-deficient mice have reduced bone formation and lower circulating levels of total and undercarboxylated osteocalcin, coupled with decreased bone resorption activity. They also maintain lower body fat and fasting glucose levels on normal and high fat chow diets. The mechanisms by which Hdac3 controls systemic energy homeostasis from within osteoblasts have not yet been fully realized, but the current study suggests that it does not involve elevated levels of circulating osteocalcin. Thus, Hdac3 is a new player in the emerging paradigm that the skeleton influences systemic energy metabolism.

Original languageEnglish (US)
Pages (from-to)42-51
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume410
DOIs
StatePublished - Jul 5 2015

Fingerprint

Osteocalcin
High Fat Diet
Nutrition
Osteoblasts
Skeleton
Fats
Diet
Bone
Bone Resorption
Osteogenesis
Epigenomics
Type 2 Diabetes Mellitus
Energy Metabolism
Insulin Resistance
Adipose Tissue
Fasting
Homeostasis
Stem Cells
Obesity
Medical problems

Keywords

  • Bglap
  • Hdac3
  • Hepatic steatosis
  • High fat diet
  • Insulin resistance

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

Conditional deletion of Hdac3 in osteoprogenitor cells attenuates diet-induced systemic metabolic dysfunction. / McGee Lawrence, Meghan Elizabeth; White, Thomas A.; LeBrasseur, Nathan K.; Westendorf, Jennifer J.

In: Molecular and Cellular Endocrinology, Vol. 410, 05.07.2015, p. 42-51.

Research output: Contribution to journalReview article

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AU - White, Thomas A.

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AU - Westendorf, Jennifer J.

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N2 - Obesity is a major health epidemic in the United States and a leading cause of preventable diseases including type 2 diabetes. A growing body of evidence indicates that the skeleton influences whole body metabolism and suggests a new avenue for developing novel therapeutic agents, but the underlying mechanisms are not well understood. Here, it is demonstrated that conditional deletion of an epigenetic regulator, Hdac3, in osteoblast progenitor cells abrogates high fat diet-induced insulin resistance and hepatic steatosis. These Hdac3-deficient mice have reduced bone formation and lower circulating levels of total and undercarboxylated osteocalcin, coupled with decreased bone resorption activity. They also maintain lower body fat and fasting glucose levels on normal and high fat chow diets. The mechanisms by which Hdac3 controls systemic energy homeostasis from within osteoblasts have not yet been fully realized, but the current study suggests that it does not involve elevated levels of circulating osteocalcin. Thus, Hdac3 is a new player in the emerging paradigm that the skeleton influences systemic energy metabolism.

AB - Obesity is a major health epidemic in the United States and a leading cause of preventable diseases including type 2 diabetes. A growing body of evidence indicates that the skeleton influences whole body metabolism and suggests a new avenue for developing novel therapeutic agents, but the underlying mechanisms are not well understood. Here, it is demonstrated that conditional deletion of an epigenetic regulator, Hdac3, in osteoblast progenitor cells abrogates high fat diet-induced insulin resistance and hepatic steatosis. These Hdac3-deficient mice have reduced bone formation and lower circulating levels of total and undercarboxylated osteocalcin, coupled with decreased bone resorption activity. They also maintain lower body fat and fasting glucose levels on normal and high fat chow diets. The mechanisms by which Hdac3 controls systemic energy homeostasis from within osteoblasts have not yet been fully realized, but the current study suggests that it does not involve elevated levels of circulating osteocalcin. Thus, Hdac3 is a new player in the emerging paradigm that the skeleton influences systemic energy metabolism.

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