Blocking mitochondrial pyruvate import in brown adipocytes induces energy wasting via lipid cycling

Abstract: Combined fatty acid esterification and lipolysis, termed lipid cycling, is an ATP‐consuming process that contributes to energy expenditure. Therefore, interventions that stimulate energy expenditure through lipid cycling are of great interest. Here we find that pharmacological and genetic inhibition of the mitochondrial pyruvate carrier (MPC) in brown adipocytes activates lipid cycling and energy expenditure, even in the absence of adrenergic stimulation. We show that the resulting increase in ATP demand elevates mitochondrial respiration coupled to ATP synthesis and fueled by lipid oxidation. We identify that glutamine consumption and the Malate‐Aspartate Shuttle are required for the increase in Energy Expenditure induced by MPC inhibition in Brown Adipocytes (MAShEEBA). We thus demonstrate that energy expenditure through enhanced lipid cycling can be activated in brown adipocytes by decreasing mitochondrial pyruvate availability. We present a new mechanism to increase energy expenditure and fat oxidation in brown adipocytes, which does not require adrenergic stimulation of mitochondrial uncoupling.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Blocking mitochondrial pyruvate import in brown adipocytes induces energy wasting via lipid cycling ; volume:21 ; number:12 ; year:2020 ; extent:17
EMBO reports / European Molecular Biology Organization ; 21, Heft 12 (2020) (gesamt 17)

Urheber
Veliova, Michaela
Ferreira, Caroline M.
Benador, Ilan Y.
Jones, Anthony E.
Mahdaviani, Kiana
Brownstein, Alexandra J.
Desousa, Brandon R.
Acín‐Pérez, Rebeca
Petcherski, Anton
Assali, Essam A.
Stiles, Linsey
Divakaruni, Ajit S.
Prentki, Marc
Corkey, Barbara E.
Liesa, Marc
Oliveira, Marcus F.
Shirihai, Orian S.

DOI
10.15252/embr.201949634
URN
urn:nbn:de:101:1-2022070407293756300420
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:28 MESZ

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Beteiligte

  • Veliova, Michaela
  • Ferreira, Caroline M.
  • Benador, Ilan Y.
  • Jones, Anthony E.
  • Mahdaviani, Kiana
  • Brownstein, Alexandra J.
  • Desousa, Brandon R.
  • Acín‐Pérez, Rebeca
  • Petcherski, Anton
  • Assali, Essam A.
  • Stiles, Linsey
  • Divakaruni, Ajit S.
  • Prentki, Marc
  • Corkey, Barbara E.
  • Liesa, Marc
  • Oliveira, Marcus F.
  • Shirihai, Orian S.

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