Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus

Glenn C. Rowe, Vincent Vialou, Kazusa Sato, Hiroaki Saito, Min Yin, Thomas A. Green, Sutada Lotinun, Marie Kveiborg, William C. Horne, Eric J. Nestler, Roland Baron

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The regulation of bone and fat homeostasis and its relationship to energy expenditure has recently been the focus of increased attention because of its potential relevance to osteoporosis, obesity, and diabetes. Although central effectors within the hypothalamus have been shown to contribute to the regulation of both energy balance and bone homeostasis, little is known of the underlying mechanisms, including the possible involvement of transcriptional factors within the hypothalamus. Transgenic mice overexpressing ΔFosB, a splice variant of the AP-1 transcription factor FosB with mixed agonist-antagonistic properties, have increased energy expenditure and bone mass. Because these mice express ΔFosB in bone, fat, and hypothalamus, we sought to determine 1) whether overexpression of ΔFosB within the hypothalamus was sufficient to regulate energy expenditure and whether it would also regulate bone mass, and 2) whether these effects were the result of antagonism to AP-1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ΔFosB to the ventral hypothalamus of wild-type mice induced a profound increase in both energy expenditure and bone formation and bone mass. This effect was phenocopied, at an even stronger level, by overexpression of a dominant-negative DNJunD, a pure AP-1 antagonist. Taken together, these results suggest that downregulation of AP-1 activity in the hypothalamus profoundly increases energy expenditure and bone formation, leading to both a decrease in adipose mass and an increase in bone mass. These findings may have physiological implications because ΔFosB is expressed and regulated in the hypothalamus.

Original languageEnglish (US)
Pages (from-to)1649-1658
Number of pages10
JournalJournal of Bone and Mineral Research
Volume27
Issue number8
DOIs
StatePublished - Aug 1 2012

Keywords

  • AP-1
  • BONE FORMATION
  • ENERGY EXPENDITURE
  • HYPOTHALAMUS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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    Rowe, G. C., Vialou, V., Sato, K., Saito, H., Yin, M., Green, T. A., Lotinun, S., Kveiborg, M., Horne, W. C., Nestler, E. J., & Baron, R. (2012). Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus. Journal of Bone and Mineral Research, 27(8), 1649-1658. https://doi.org/10.1002/jbmr.1618