Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice

Abstract

Exposure of humans and rodents to cold activates thermogenic activity in brown adipose tissue (BAT). This protocol describes a mouse model to study the activation of BAT and angiogenesis in adipose tissues by cold acclimation. After a 1-week exposure to 4 °C, adult C57BL/6 mice show an obvious transition from subcutaneous white adipose tissue (WAT) into brown-like adipose tissue (BRITE). The BRITE phenotype persists after continuous cold exposure, and by the end of week 5 BRITE contains a high number of uncoupling protein-1–positive mitochondria, a characteristic feature of BAT. During the transition from WAT into BRITE, the vascular density is markedly increased owing to the activation of angiogenesis. In BAT, cold exposure stimulates thermogenesis by increasing the mitochondrial content and metabolic rate. BAT and the increased metabolic rate result in a lean phenotype. This protocol provides an outstanding opportunity to study the molecular mechanisms that control adipose mass.

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Figure 1: Postmortem dissection of iWAT and iBAT depots and low temperature–induced activation in BAT.
Figure 2: Increase of prohibitin-positive mitochondria in adipocytes by cold exposure.
Figure 3: Increase of vascular density and nonshivering thermogenesis in response to cold exposure.

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Acknowledgements

We thank B. Cannon and J. Nedergaard at the Stockholm University for providing the animal facility for our research. The author's laboratory was supported by research grants from the Swedish Research Council, the Swedish Cancer Foundation, the Karolinska Institute Foundation, the Karolinska Institute distinguished professor award, the Torsten Soderbergs Foundation, the European Union Integrated Project of Metoxia (project no. 222741) and the European Research Council advanced grant ANGIOFAT (project no. 250021).

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Y.C. designed the study. S.L., J.H., Y.X. and T.S. performed the experiments. S.L., J.H., Y.X., T.S. and Y.C. analyzed the data. S.L., J.H. and Y.C. wrote the paper. Z.C., P.A., X.Y. and K.H. participated in developing these protocols.

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Correspondence to Yihai Cao.

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The authors declare no competing financial interests.

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Lim, S., Honek, J., Xue, Y. et al. Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice. Nat Protoc 7, 606–615 (2012). https://doi.org/10.1038/nprot.2012.013

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