Adipose tissue browning and metabolic health

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Abstract

Accumulation of excess white adipose tissue (WAT) has deleterious consequences for metabolic health. The activation of brown adipose tissue (BAT), the primary organ for heat production, confers beneficial effects on adiposity, insulin resistance and hyperlipidaemia, at least in mice. As the amount of metabolically active BAT seems to be particularly low in patients with obesity or diabetes mellitus who require immediate therapy, new avenues are needed to increase the capacity for adaptive thermogenesis. In this light, we review the findings that BAT in human adults might consist of not only classic brown adipocytes but also inducible brown adipocytes (also called beige, brown-in-white, or brite adipocytes), which are phenotypically distinct from both white and brown adipocytes. Stimulating the development of beige adipocytes in WAT (so called 'browning') might reduce adverse effects of WAT and could help to improve metabolic health. This article focuses on the development and regulatory control of beige adipocytes at the transcriptional and hormonal levels. Emerging insights into the metabolic role of beige adipocytes are also discussed, along with the developments that can be expected from these promising targets for therapy of metabolic disease in the future.

Key Points

  • The term browning describes the emergence of beige adipocytes in white adipose tissue—a reversible process that represents adaptation to increased thermogenic demand and exercise

  • Human brown adipose tissue is diverse and consists of both brown and beige adipocytes, in proportions that differ according to the fat depot's anatomical location and the age of the person

  • Beige adipocytes are generated by both de novo recruitment from progenitor cells and transdifferentiation from white adipocytes—independent processes that might coexist

  • Cellular energy sensing, in addition to sympathetic tone, are the driving forces that regulate the transcriptional networks controlling browning

  • Cold exposure and other metabolic challenges elicit complex hormonal responses that facilitate communication between tissues and prepare the body for adaptive thermogenesis

  • Brown adipose tissue is a critical regulator of metabolic health in mice; yet, whether induction of browning will be a promising avenue to treat metabolic disorders in humans remains unclear

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Figure 1: Phenotypes of adipose tissue depots.
Figure 2: Browning of adipose tissue is an adaptive and reversible response to environmental challenges.
Figure 3: Anatomical sites of brown, white and beige adipocytes in mice and humans.
Figure 4: Hormonal control of browning.
Figure 5: Contributions of browning to systemic nutrient handling.

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Acknowledgements

The authors thank all members of the Heeren lab for continuous support and enjoyable atmosphere, and are grateful to Rudolph Reimer for providing pictures taken by electron microscopy. A. Bartelt is supported by a Deutsche Forschungsgemeinschaft Research Fellowship (BA 4925/1-1). J. Heeren is supported by a grant from the Fondation Leducq—Triglyceride Metabolism in Obesity and Cardiovascular Disease and by EU FP7 project RESOLVE (FP7-HEALTH-2012-305707).

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Both authors contributed equally to all aspects of this article.

Correspondence to Alexander Bartelt or Joerg Heeren.

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Bartelt, A., Heeren, J. Adipose tissue browning and metabolic health. Nat Rev Endocrinol 10, 24–36 (2014) doi:10.1038/nrendo.2013.204

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