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Bi-directional interconversion of brite and white adipocytes

Nature Cell Biology volume 15, pages 659–667 (2013)Cite this article

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Abstract

Brown adipose tissue helps to maintain body temperature in hibernators, rodents and neonatal mammals by converting lipids and glucose into heat, thereby increasing energy expenditure. In addition to classical brown adipocytes, adult rodents—like adult humans—harbour brown-like adipocytes in the predominantly white adipose tissue. The formation of these brite (brown-in-white) adipocytes is a physiological response to chronic cold and their cellular origin is under debate. We show here that cold-induced formation of brite adipocytes in mice is reversed within 5 weeks of warm adaptation, but the brite adipocytes formed by cold stimulation are not eliminated. Genetic tracing and transcriptional characterization of isolated adipocytes demonstrates that they are converted into cells with the morphology and gene expression pattern of white adipocytes. Moreover, these white-typical adipocytes can convert into brite adipocytes on additional cold stimulation. Shifting the balance of this interconversion from the white towards the brite phenotype might provide a new means of counteracting obesity by increasing energy expenditure.

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Figure 1: Britening of inguinal adipose tissue during a 1-week cold stimulation at 8 °C is reversible within 5 weeks at 23 °C.
Figure 2: Transgenic mouse lines for transient and permanent labelling of brite and classical brown adipocytes proved that former brite adipocytes retain an adipocyte phenotype during whitening.
Figure 3: Brite adipocyte gene expression switches to a typical white gene expression during whitening.
Figure 4: White-adipocyte-typical transcripts were selected from a microarray study and confirmed by qPCR.
Figure 5: Former brite adipocytes but not classical brown adipocytes switch to a white-adipocyte-typical gene expression profile during whitening.
Figure 6: Brite adipocytes can form from white adipocytes.

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Acknowledgements

M.R. was supported by a Boehringer Ingelheim Fonds PhD Fellowship. This study received financial support from the Austrian Genome Research Programme GEN-AU II and III (T.R.), the ERC, the SNF and FP7 DIABAT (C.W.).

We thank Cornelius Fischer (Flow Cytometry Facility, UNIZH) for providing FACS sortings, E. Weber for cryosectioning and M. Stoffel, M. Kopf and N. Beaton for reviewing the manuscript.

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  1. Institute of Food, Nutrition and Health, ETH Zurich, Schorenstraße 16, CH-8603 Schwerzenbach, Switzerland

    Matthias Rosenwald, Aliki Perdikari & Christian Wolfrum

  2. Institute of Laboratory Animal Science, Vetmeduni Vienna, Veterinärplatz 1, A-1210 Vienna, Austria

    Thomas Rülicke

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  1. Matthias Rosenwald
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M.R. and C.W. designed the study and wrote the paper, M.R. performed most of the experiments, A.P. established and performed adipocyte sortings, and T.R. provided oocyte injections for transgenic animals.

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Correspondence to Christian Wolfrum.

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Rosenwald, M., Perdikari, A., Rülicke, T. et al. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol 15, 659–667 (2013). https://doi.org/10.1038/ncb2740

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