Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice

Yuwei Wu, Qisheng Tu, Paloma Valverde, Jin Zhang, Dana Murray, Lily Q. Dong, Jessica Cheng, Hua Jiang, Maribel Rios, Elise Morgan, Zhihui Tang, Jake Chen

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Adiponectin (APN), the most abundant adipocyte-secreted adipokine, regulates energy homeostasis and exerts well-characterized insulinsensitizing properties. The peripheral or central effects of APN regulating bone metabolism are beginning to be explored but are still not clearly understood. In the present study, we found that APN-knockout (APN-KO) mice fed a normal diet exhibited decreased trabecular structure and mineralization and increased bone marrow adiposity compared with wild-type (WT) mice. APN intracerebroventricular infusions decreased uncoupling protein 1 (UCP1) expression in brown adipose tissue, epinephrine and norepinephrine serum levels, and osteoclast numbers, whereas osteoblast osteogenic marker expression and trabecular bone mass increased in APN-KO and WT mice. In addition, centrally administered APN increased hypothalamic tryptophan hydroxylase 2 (TPH2), cocaine- and amphetamine-regulated transcript (CART), and 5-hydroxytryptamine (serotonin) receptor 2C (Htr2C) expressions but decreased hypothalamic cannabinoid receptor- 1 expression. Treatment of immortalized mouse neurons with APN demonstrated that APN-mediated effects on TPH2, CART, and Htr2C expression levels were abolished by downregulating adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif (APPL)-1 expression. Pharmacological increase in sympathetic activity stimulated adipogenic differentiation of bone marrow stromal cells (BMSC) and reversed APN-induced expression of the lysine-specific demethylases involved in regulating their commitment to the osteoblastic lineage. In conclusion, we found that APN regulates bone metabolism via central and peripheral mechanisms to decrease sympathetic tone, inhibit osteoclastic differentiation, and promote osteoblastic commitment of BMSC.

Original languageEnglish (US)
Pages (from-to)E1418-E1430
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume306
Issue number12
DOIs
StatePublished - Jun 15 2014

Keywords

  • Adaptor protein containing pleckstrin homology domain, Phosphotyrosine domain, and leucine zipper motif 1
  • Adiponectin
  • Bone marrow stromal cells
  • Hypothalamus
  • Tryptophan hydroxylase 2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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  • Cite this

    Wu, Y., Tu, Q., Valverde, P., Zhang, J., Murray, D., Dong, L. Q., Cheng, J., Jiang, H., Rios, M., Morgan, E., Tang, Z., & Chen, J. (2014). Central adiponectin administration reveals new regulatory mechanisms of bone metabolism in mice. American Journal of Physiology - Endocrinology and Metabolism, 306(12), E1418-E1430. https://doi.org/10.1152/ajpendo.00048.2014