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  • Review Article
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The evolving view of thermogenic adipocytes — ontogeny, niche and function

Nature Reviews Endocrinology volume 17, pages 726–744 (2021)Cite this article

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Abstract

The worldwide incidence of obesity and its sequelae, such as type 2 diabetes mellitus, have reached pandemic levels. Central to the development of these metabolic disorders is adipose tissue. White adipose tissue stores excess energy, whereas brown adipose tissue (BAT) and beige (also known as brite) adipose tissue dissipate energy to generate heat in a process known as thermogenesis. Strategies that activate and expand BAT and beige adipose tissue increase energy expenditure in animal models and offer therapeutic promise to treat obesity. A better understanding of the molecular mechanisms underlying the development of BAT and beige adipose tissue and the activation of thermogenic function is the key to creating practical therapeutic interventions for obesity and metabolic disorders. In this Review, we discuss the regulation of the tissue microenvironment (the adipose niche) and inter-organ communication between BAT and other tissues. We also cover the activation of BAT and beige adipose tissue in response to physiological cues (such as cold exposure, exercise and diet). We highlight advances in harnessing the therapeutic potential of BAT and beige adipose tissue by genetic, pharmacological and cell-based approaches in obesity and metabolic disorders.

Key points

  • Brown adipocytes and white adipocytes in different depots originate from distinct progenitor pools in the embryonic mesoderm.

  • Beige adipocytes are formed in white adipose tissue in response to cold acclimation, exercise training or pharmacological activation of β-adrenergic receptors through reprogramming of white adipocytes or de novo differentiation from adipocyte progenitors.

  • Adipose tissue plasticity enables the rapid adaptation of the organism to fluctuations in nutritional load and metabolic demand and is a hallmark of metabolic health.

  • Adipose-resident cell types establish an extensive network of cellular crosstalk to coordinate depot-specific functions and remodelling.

  • Communication between thermogenic adipose tissue and distant organs enables the regulation of systemic metabolism beyond thermogenesis.

  • Targeting thermogenic adipose tissue offers a potential therapeutic strategy to combat obesity and metabolic disorders, such as type 2 diabetes mellitus and cardiovascular diseases.

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Fig. 1: Cellular crosstalk between neurons and other adipose-resident cells.
Fig. 2: Cellular crosstalk between vasculature and other adipose-resident cells.
Fig. 3: Cellular crosstalk between immune cells and other adipose-resident cells.
Fig. 4: Autocrine and paracrine factors regulating brown and beige adipocytes.
Fig. 5: Inter-organ communication of thermogenic adipose tissue and other tissues.
Fig. 6: Cell-based, gene-based and pharmacological therapies for activation and conversion of thermogenic adipose tissue.

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Acknowledgements

The authors acknowledge the support of NIH grants R01DK077097, R01DK102898 and R01DK122808 (to Y.-H.T.), and P30DK036836 (to Joslin Diabetes Center’s Diabetes Research Center, DRC) from the National Institute of Diabetes and Digestive and Kidney Diseases, and of US Army Medical Research grant W81XWH-17-1-0428 (to Y.-H.T.). F.S. acknowledges the support of an American Diabetes Association Postdoctoral Fellowship #1-18-PDF-169 and NIH K01DK125608. C.-H.W. acknowledges the support of a Postdoctoral Research Abroad Program (106-2917-I-564-069) and a grant (MOST 110-2320-B-039-063-MY3) from the Ministry of Science and Technology, Taiwan.

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  1. These authors contributed equally: Farnaz Shamsi, Chih-Hao Wang.

Authors and Affiliations

  1. Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA

    Farnaz Shamsi, Chih-Hao Wang & Yu-Hua Tseng

  2. Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY, USA

    Farnaz Shamsi

  3. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

    Chih-Hao Wang

  4. Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA

    Yu-Hua Tseng

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F.S. and C.-H.W. researched data for the article. All authors contributed substantially to discussion of the content, wrote the article, and reviewed/edited the manuscript before submission.

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Correspondence to Yu-Hua Tseng.

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Competing interests

Y.-H.T. is an inventor on US Patent 7,576,052 related to BMP7 and US patent applications related to 12,13-diHOME and FGF6/9. The other authors declare no competing interests.

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Nature Reviews Endocrinology thanks M. Giralt, M. López, C. Scheele and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Somites

Segmental axial structures located on either side of the neural tube in the developing vertebrate embryo that contain the precursor populations of cells, which give rise to vertebral column, ribs, skeletal and smooth muscles, dermis, tendons, ligaments, cartilage and adipose tissue.

WAT browning

The formation of thermogenic beige adipocytes within the white adipose tissue depots.

M1 macrophages

Macrophages that secrete pro-inflammatory cytokines and chemokines and mediate host defence against pathogens.

Type 2 immune response

An immune response characterized by infiltration of alternatively activated (or M2) macrophages, eosinophils and innate lymphoid type 2 cells.

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Shamsi, F., Wang, CH. & Tseng, YH. The evolving view of thermogenic adipocytes — ontogeny, niche and function. Nat Rev Endocrinol 17, 726–744 (2021). https://doi.org/10.1038/s41574-021-00562-6

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