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The emerging roles of lactate as a redox substrate and signaling molecule in adipose tissues

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Abstract

Thermogenic (brown and beige) adipose tissues improve glucose and lipid homeostasis and therefore represent putative targets to cure obesity and related metabolic diseases including type II diabetes. Beside decades of research and the very well-described role of noradrenergic signaling, mechanisms underlying adipocytes plasticity and activation of thermogenic adipose tissues remain incompletely understood. Recent studies show that metabolites such as lactate control the oxidative capacity of thermogenic adipose tissues. Long time viewed as a metabolic waste product, lactate is now considered as an important metabolic substrate largely feeding the oxidative metabolism of many tissues, acting as a signaling molecule and as an inter-cellular and inter-tissular redox carrier. In this review, we provide an overview of the recent findings highlighting the importance of lactate in adipose tissues, from its production to its role as a browning inducer and its metabolic links with brown adipose tissue. We also discuss additional function(s) than thermogenesis ensured by brown and beige adipose tissues, i.e., their ability to dissipate high redox pressure and oxidative stress thanks to the activity of the uncoupling protein-1, helping to maintain tissue and whole organism redox homeostasis and integrity.

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Acknowledgments

The Casteilla laboratory is supported by the Université Paul Sabatier-Université de Toulouse, the Centre National de la Recherche Scientifique (CNRS), the Etablissement Français du Sang (EFS), the Ecole Nationale Vétérinaire de Toulouse (ENVT), and the Institut pour la Recherche Médicale (Inserm). D.L. is fellow from the Ministère de l’Enseignement supérieur, de la Recherche et de lʼInnovation. We also thank Michel Rigoulet, Luc Pénicaud and Cédric Moro for helpful discussions as well as the members of STROMALab.

Funding

We thank our financial supports (Société Française de Nutrition and the European Union FP7 project DIABAT (HEALTH-F2-2011-278373)). Jean-Charles Portais is supported by a grant from the INSERM.

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Authors and Affiliations

  1. STROMALab, Université de Toulouse, CNRS ERL5311, EFS, ENVT, Inserm U1031, UPS, Toulouse, France

    Audrey Carrière, Damien Lagarde, Yannick Jeanson, Jean-Charles Portais, Anne Galinier, Isabelle Ader & Louis Casteilla

  2. MetaToul-MetaboHUB, National infrastructure of metabolomics and fluxomics, Toulouse Biotechnology Institute, TBI, Université de Toulouse, CNRS, INRAE, INSA, Toulouse, France

    Jean-Charles Portais

  3. Toulouse Biotechnology Institute, TBI-INSA de Toulouse INSA/CNRS 5504-UMR INSA/INRA 792, Toulouse, France

    Jean-Charles Portais

  4. Institut Fédératif de Biologie, CHU Purpan, Toulouse, France

    Anne Galinier

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  1. Audrey Carrière
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  2. Damien Lagarde
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  3. Yannick Jeanson
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  5. Anne Galinier
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  6. Isabelle Ader
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  7. Louis Casteilla
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Correspondence to Audrey Carrière.

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Key points

Lactate as a major contributor of oxidative metabolism

Lactate as a redox carrier driving brown/beige fat activity and development

Browning remodeling of white adipocytes as a way to cope with redox stress

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Carrière, A., Lagarde, D., Jeanson, Y. et al. The emerging roles of lactate as a redox substrate and signaling molecule in adipose tissues. J Physiol Biochem 76, 241–250 (2020). https://doi.org/10.1007/s13105-019-00723-2

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  • DOI: https://doi.org/10.1007/s13105-019-00723-2

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