1. Inducible brown adipose tissue, or beige fat, is anabolic for the skeleton.
- Author
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Rahman S, Lu Y, Czernik PJ, Rosen CJ, Enerback S, and Lecka-Czernik B
- Subjects
- Adaptor Proteins, Signal Transducing, Adipocytes metabolism, Anabolic Agents metabolism, Animals, Bone and Bones cytology, Culture Media, Conditioned pharmacology, Forkhead Transcription Factors genetics, Forkhead Transcription Factors metabolism, Gene Expression, Glycoproteins genetics, Glycoproteins metabolism, Immunohistochemistry, Insulin-Like Growth Factor Binding Protein 2 genetics, Insulin-Like Growth Factor Binding Protein 2 metabolism, Intercellular Signaling Peptides and Proteins, Mice, Mice, Transgenic, Osteoblasts drug effects, Osteocytes drug effects, Phosphorylation, RANK Ligand genetics, RANK Ligand metabolism, Reverse Transcriptase Polymerase Chain Reaction, Wnt Proteins genetics, Wnt Proteins metabolism, beta Catenin genetics, beta Catenin metabolism, Adipose Tissue, Brown metabolism, Bone and Bones metabolism, Osteoblasts metabolism, Osteocytes metabolism
- 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 FoxC2(AD)(+/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. FoxC2(AD)(+/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.
- Published
- 2013
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