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The endocrine role of brown adipose tissue: An update on actors and actions

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Abstract

In recent years, brown adipose tissue (BAT) has been recognized not only as a main site of non-shivering thermogenesis in mammals, but also as an endocrine organ. BAT secretes a myriad of regulatory factors. These so-called batokines exert local autocrine and paracrine effects, as well as endocrine actions targeting tissues and organs at a distance. The endocrine batokines include peptide factors, such as fibroblast growth factor-21 (FGF21), neuregulin-4 (NRG4), phospholipid transfer protein (PLTP), interleukin-6, adiponectin and myostatin, and also lipids (lipokines; e.g., 12,13-dihydroxy-9Z-octadecenoic acid [12,13-diHOME]) and miRNAs (e.g., miR-99b). The liver, heart, and skeletal muscle are the most commonly reported targets of batokines. In response to BAT thermogenic activation, batokines such as NRG4 and PLTP are released and act to reduce hepatic steatosis and improve insulin sensitivity. Stress-induced interleukin-6-mediated signaling from BAT to liver favors hepatic glucose production through enhanced gluconeogenesis. Batokines may act on liver to induce the secretion of regulatory hepatokines (e.g. FGF21 and bile acids in response to miR-99b and PLTP, respectively), thereby resulting in a systemic expansion of BAT-originating signals. Batokines also target extrahepatic tissues: FGF21 and 12,13-diHOME are cardioprotective, whereas BAT-secreted myostatin and 12,13-diHOME influence skeletal muscle development and performance. Further research is needed to ascertain in humans the role of batokines, which have been identified mostly in experimental models. The endocrine role of BAT may explain the association between active BAT and a healthy metabolism in the human system, which is characterized by small amounts of BAT and a likely moderate BAT-mediated energy expenditure

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Funding

Supported by Ministerio de Ciencia, Innovación y Universidades, and Agencia Estatal de Investigación (Spain); and Fondo Europeo de Desarollo Regional, EU (grant SAF2017-85722-R) and Instituto de Salud Carlos III (grants PI17-00420 and PI20-00,106).

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Authors and Affiliations

  1. Departament de Bioquimica I Biomedicina Molecular, and Institut de Biomedicina de La Universitat de Barcelona, Barcelona, Catalonia, Spain

    Aleix Gavaldà-Navarro, Joan Villarroya, Rubén Cereijo, Marta Giralt & Francesc Villarroya

  2. Institut de Recerca Sant Joan de Déu, Esplugues, Catalonia, Spain

    Aleix Gavaldà-Navarro, Joan Villarroya, Marta Giralt & Francesc Villarroya

  3. CIBER Fisiopatología de La Obesidad Y Nutrición, Madrid, Spain

    Aleix Gavaldà-Navarro, Joan Villarroya, Rubén Cereijo, Marta Giralt & Francesc Villarroya

  4. Institut de Recerca Hospital de La Santa Creu I Sant Pau, Barcelona, Spain

    Rubén Cereijo

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  1. Aleix Gavaldà-Navarro
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  2. Joan Villarroya
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  5. Francesc Villarroya
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Correspondence to Francesc Villarroya.

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Gavaldà-Navarro, A., Villarroya, J., Cereijo, R. et al. The endocrine role of brown adipose tissue: An update on actors and actions. Rev Endocr Metab Disord 23, 31–41 (2022). https://doi.org/10.1007/s11154-021-09640-6

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