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Endocrinology
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Endocrinology
Article . 2013 . Peer-reviewed
Data sources: Crossref
Endocrinology
Article . 2013
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Inducible Brown Adipose Tissue, or Beige Fat, Is Anabolic for the Skeleton

Authors: Sima, Rahman; Yalin, Lu; Piotr J, Czernik; Clifford J, Rosen; Sven, Enerback; Beata, Lecka-Czernik;

Inducible Brown Adipose Tissue, or Beige Fat, Is Anabolic for the Skeleton

Abstract

Abstract It is known that insulin resistance and type 2 diabetes mellitus are associated with increased fractures and that brown adipose tissue (BAT) counteracts many if not all of the symptoms associated with type 2 diabetes. By the use of FoxC2AD+/Tg mice, a well-established model for induction of BAT, or beige fat, we present data extending the beneficial action of beige fat to also include a positive effect on bone. FoxC2AD+/Tg mice are lean and insulin-sensitive and have high bone mass due to increased bone formation associated with high bone turnover. Inducible BAT is linked to activation of endosteal osteoblasts whereas osteocytes have decreased expression of the Sost transcript encoding sclerostin and elevated expression of Rankl. Conditioned media (CM) collected from forkhead box c2 (FOXC2)-induced beige adipocytes activated the osteoblast phenotype and increased levels of phospho-AKT and β-catenin in recipient cells. In osteocytes, the same media decreased Sost expression. Immunodepletion of CM with antibodies against wingless related MMTV integration site 10b (WNT10b) and insulin-like growth factor binding protein 2 (IGFBP2) resulted in the loss of pro-osteoblastic activity, and the loss of increase in the levels of phospho-AKT and β-catenin. Conversely, CM derived from cells overexpressing IGFBP2 or WNT10b restored osteoblastic activity in recipient cells. In conclusion, beige fat secretes endocrine/paracrine activity that is beneficial for the skeleton.

Keywords

Osteoblasts, Reverse Transcriptase Polymerase Chain Reaction, RANK Ligand, Gene Expression, Forkhead Transcription Factors, Mice, Transgenic, Immunohistochemistry, Osteocytes, Bone and Bones, Insulin-Like Growth Factor Binding Protein 2, Mice, Anabolic Agents, Adipose Tissue, Brown, Culture Media, Conditioned, Adipocytes, Animals, Intercellular Signaling Peptides and Proteins, Phosphorylation, Adaptor Proteins, Signal Transducing, Glycoproteins

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
116
Top 10%
Top 10%
Top 1%
bronze