Monocarboxylate transporters facilitate succinate uptake into brown adipocytes

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Monocarboxylate transporters facilitate succinate uptake into brown adipocytes. / Reddy, Anita; Winther, Sally; Tran, Nhien; Xiao, Haopeng; Jakob, Josefine; Garrity, Ryan; Smith, Arianne; Ordonez, Martha; Laznik-Bogoslavski, Dina; Rothstein, Jeffrey D.; Mills, Evanna L.; Chouchani, Edward T.

In: Nature Metabolism, Vol. 6, No. 3, 2024, p. 567–577.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Reddy, A, Winther, S, Tran, N, Xiao, H, Jakob, J, Garrity, R, Smith, A, Ordonez, M, Laznik-Bogoslavski, D, Rothstein, JD, Mills, EL & Chouchani, ET 2024, 'Monocarboxylate transporters facilitate succinate uptake into brown adipocytes', Nature Metabolism, vol. 6, no. 3, pp. 567–577. https://doi.org/10.1038/s42255-024-00981-5

APA

Reddy, A., Winther, S., Tran, N., Xiao, H., Jakob, J., Garrity, R., Smith, A., Ordonez, M., Laznik-Bogoslavski, D., Rothstein, J. D., Mills, E. L., & Chouchani, E. T. (2024). Monocarboxylate transporters facilitate succinate uptake into brown adipocytes. Nature Metabolism, 6(3), 567–577. https://doi.org/10.1038/s42255-024-00981-5

Vancouver

Reddy A, Winther S, Tran N, Xiao H, Jakob J, Garrity R et al. Monocarboxylate transporters facilitate succinate uptake into brown adipocytes. Nature Metabolism. 2024;6(3):567–577. https://doi.org/10.1038/s42255-024-00981-5

Author

Reddy, Anita ; Winther, Sally ; Tran, Nhien ; Xiao, Haopeng ; Jakob, Josefine ; Garrity, Ryan ; Smith, Arianne ; Ordonez, Martha ; Laznik-Bogoslavski, Dina ; Rothstein, Jeffrey D. ; Mills, Evanna L. ; Chouchani, Edward T. / Monocarboxylate transporters facilitate succinate uptake into brown adipocytes. In: Nature Metabolism. 2024 ; Vol. 6, No. 3. pp. 567–577.

Bibtex

@article{f442a969600d4106ba4cde1c3e1b064b,
title = "Monocarboxylate transporters facilitate succinate uptake into brown adipocytes",
abstract = "Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole-body energy expenditure, counteracts obesity and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs). We show that succinate transport is strongly dependent on the proportion that is present in the monocarboxylate form. MCTs facilitate monocarboxylate succinate uptake, which is promoted by alkalinization of the cytosol driven by adrenoreceptor stimulation. In brown adipocytes, we show that MCT1 primarily facilitates succinate import. In male mice, we show that both acute pharmacological inhibition of MCT1 and congenital depletion of MCT1 decrease succinate uptake into BAT and consequent catabolism. In sum, we define a mechanism of succinate uptake in BAT that underlies its protective activity in mouse models of metabolic disease.",
author = "Anita Reddy and Sally Winther and Nhien Tran and Haopeng Xiao and Josefine Jakob and Ryan Garrity and Arianne Smith and Martha Ordonez and Dina Laznik-Bogoslavski and Rothstein, {Jeffrey D.} and Mills, {Evanna L.} and Chouchani, {Edward T.}",
note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2024.",
year = "2024",
doi = "10.1038/s42255-024-00981-5",
language = "English",
volume = "6",
pages = "567–577",
journal = "Nature Metabolism",
issn = "2522-5812",
publisher = "Springer",
number = "3",

}

RIS

TY - JOUR

T1 - Monocarboxylate transporters facilitate succinate uptake into brown adipocytes

AU - Reddy, Anita

AU - Winther, Sally

AU - Tran, Nhien

AU - Xiao, Haopeng

AU - Jakob, Josefine

AU - Garrity, Ryan

AU - Smith, Arianne

AU - Ordonez, Martha

AU - Laznik-Bogoslavski, Dina

AU - Rothstein, Jeffrey D.

AU - Mills, Evanna L.

AU - Chouchani, Edward T.

N1 - Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature Limited 2024.

PY - 2024

Y1 - 2024

N2 - Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole-body energy expenditure, counteracts obesity and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs). We show that succinate transport is strongly dependent on the proportion that is present in the monocarboxylate form. MCTs facilitate monocarboxylate succinate uptake, which is promoted by alkalinization of the cytosol driven by adrenoreceptor stimulation. In brown adipocytes, we show that MCT1 primarily facilitates succinate import. In male mice, we show that both acute pharmacological inhibition of MCT1 and congenital depletion of MCT1 decrease succinate uptake into BAT and consequent catabolism. In sum, we define a mechanism of succinate uptake in BAT that underlies its protective activity in mouse models of metabolic disease.

AB - Uptake of circulating succinate by brown adipose tissue (BAT) and beige fat elevates whole-body energy expenditure, counteracts obesity and antagonizes systemic tissue inflammation in mice. The plasma membrane transporters that facilitate succinate uptake in these adipocytes remain undefined. Here we elucidate a mechanism underlying succinate import into BAT via monocarboxylate transporters (MCTs). We show that succinate transport is strongly dependent on the proportion that is present in the monocarboxylate form. MCTs facilitate monocarboxylate succinate uptake, which is promoted by alkalinization of the cytosol driven by adrenoreceptor stimulation. In brown adipocytes, we show that MCT1 primarily facilitates succinate import. In male mice, we show that both acute pharmacological inhibition of MCT1 and congenital depletion of MCT1 decrease succinate uptake into BAT and consequent catabolism. In sum, we define a mechanism of succinate uptake in BAT that underlies its protective activity in mouse models of metabolic disease.

U2 - 10.1038/s42255-024-00981-5

DO - 10.1038/s42255-024-00981-5

M3 - Journal article

C2 - 38378996

AN - SCOPUS:85185303247

VL - 6

SP - 567

EP - 577

JO - Nature Metabolism

JF - Nature Metabolism

SN - 2522-5812

IS - 3

ER -

ID: 386366345