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

Autor:	Veliova M; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Ferreira CM; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Benador IY; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA., Jones AE; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Mahdaviani K; Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA., Brownstein AJ; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Molecular Cellular Integrative Physiology, University of California, Los Angeles, CA, USA., Desousa BR; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Acín-Pérez R; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Petcherski A; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Assali EA; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Department of Clinical Biochemistry, School of Medicine, Ben Gurion University of The Negev, Beer-Sheva, Israel., Stiles L; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Divakaruni AS; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Prentki M; Department of Nutrition, , Université de Montréal, Montreal Diabetes Research Center and CRCHUM, Montréal, QC, Canada., Corkey BE; Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA., Liesa M; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA., Oliveira MF; Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil., Shirihai OS; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.; Nutrition and Metabolism, Graduate Medical Sciences, Boston University School of Medicine, Boston, MA, USA.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2020 Dec 03; Vol. 21 (12), pp. e49634. Date of Electronic Publication: 2020 Dec 04.
DOI:	10.15252/embr.201949634
Abstrakt:	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. (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)
Databáze:	MEDLINE
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