Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis

Research output: Contribution to journalJournal articlepeer-review

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Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis. / Sustarsic, Elahu G; Ma, Tao; Lynes, Matthew D; Larsen, Michael; Karavaeva, Iuliia; Havelund, Jesper F; Nielsen, Carsten H; Jedrychowski, Mark P; Moreno-Torres, Marta; Lundh, Morten; Plucinska, Kaja; Jespersen, Naja Z; Grevengoed, Trisha J; Kramar, Barbara; Peics, Julia; Hansen, Jakob B; Shamsi, Farnaz; Forss, Isabel; Neess, Ditte; Keipert, Susanne; Wang, Jianing; Stohlmann, Katharina; Brandslund, Ivan; Christensen, Cramer; Jørgensen, Marit E; Linneberg, Allan; Pedersen, Oluf; Kiebish, Michael A; Qvortrup, Klaus; Han, Xianlin; Pedersen, Bente Klarlund; Jastroch, Martin; Mandrup, Susanne; Kjær, Andreas; Gygi, Steven P; Hansen, Torben; Gillum, Matthew P; Grarup, Niels; Emanuelli, Brice; Nielsen, Søren; Scheele, Camilla; Tseng, Yu-Hua; Færgeman, Nils J; Gerhart-Hines, Zachary.

In: Cell Metabolism, Vol. 28, No. 1, 2018, p. 159-174.e11.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Sustarsic, EG, Ma, T, Lynes, MD, Larsen, M, Karavaeva, I, Havelund, JF, Nielsen, CH, Jedrychowski, MP, Moreno-Torres, M, Lundh, M, Plucinska, K, Jespersen, NZ, Grevengoed, TJ, Kramar, B, Peics, J, Hansen, JB, Shamsi, F, Forss, I, Neess, D, Keipert, S, Wang, J, Stohlmann, K, Brandslund, I, Christensen, C, Jørgensen, ME, Linneberg, A, Pedersen, O, Kiebish, MA, Qvortrup, K, Han, X, Pedersen, BK, Jastroch, M, Mandrup, S, Kjær, A, Gygi, SP, Hansen, T, Gillum, MP, Grarup, N, Emanuelli, B, Nielsen, S, Scheele, C, Tseng, Y-H, Færgeman, NJ & Gerhart-Hines, Z 2018, 'Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis', Cell Metabolism, vol. 28, no. 1, pp. 159-174.e11. https://doi.org/10.1016/j.cmet.2018.05.003

APA

Sustarsic, E. G., Ma, T., Lynes, M. D., Larsen, M., Karavaeva, I., Havelund, J. F., Nielsen, C. H., Jedrychowski, M. P., Moreno-Torres, M., Lundh, M., Plucinska, K., Jespersen, N. Z., Grevengoed, T. J., Kramar, B., Peics, J., Hansen, J. B., Shamsi, F., Forss, I., Neess, D., ... Gerhart-Hines, Z. (2018). Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis. Cell Metabolism, 28(1), 159-174.e11. https://doi.org/10.1016/j.cmet.2018.05.003

Vancouver

Sustarsic EG, Ma T, Lynes MD, Larsen M, Karavaeva I, Havelund JF et al. Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis. Cell Metabolism. 2018;28(1):159-174.e11. https://doi.org/10.1016/j.cmet.2018.05.003

Author

Sustarsic, Elahu G ; Ma, Tao ; Lynes, Matthew D ; Larsen, Michael ; Karavaeva, Iuliia ; Havelund, Jesper F ; Nielsen, Carsten H ; Jedrychowski, Mark P ; Moreno-Torres, Marta ; Lundh, Morten ; Plucinska, Kaja ; Jespersen, Naja Z ; Grevengoed, Trisha J ; Kramar, Barbara ; Peics, Julia ; Hansen, Jakob B ; Shamsi, Farnaz ; Forss, Isabel ; Neess, Ditte ; Keipert, Susanne ; Wang, Jianing ; Stohlmann, Katharina ; Brandslund, Ivan ; Christensen, Cramer ; Jørgensen, Marit E ; Linneberg, Allan ; Pedersen, Oluf ; Kiebish, Michael A ; Qvortrup, Klaus ; Han, Xianlin ; Pedersen, Bente Klarlund ; Jastroch, Martin ; Mandrup, Susanne ; Kjær, Andreas ; Gygi, Steven P ; Hansen, Torben ; Gillum, Matthew P ; Grarup, Niels ; Emanuelli, Brice ; Nielsen, Søren ; Scheele, Camilla ; Tseng, Yu-Hua ; Færgeman, Nils J ; Gerhart-Hines, Zachary. / Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis. In: Cell Metabolism. 2018 ; Vol. 28, No. 1. pp. 159-174.e11.

Bibtex

@article{8028fe7f422a440bb5d5c67606aa09aa,
title = "Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis",
abstract = "Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics.",
author = "Sustarsic, {Elahu G} and Tao Ma and Lynes, {Matthew D} and Michael Larsen and Iuliia Karavaeva and Havelund, {Jesper F} and Nielsen, {Carsten H} and Jedrychowski, {Mark P} and Marta Moreno-Torres and Morten Lundh and Kaja Plucinska and Jespersen, {Naja Z} and Grevengoed, {Trisha J} and Barbara Kramar and Julia Peics and Hansen, {Jakob B} and Farnaz Shamsi and Isabel Forss and Ditte Neess and Susanne Keipert and Jianing Wang and Katharina Stohlmann and Ivan Brandslund and Cramer Christensen and J{\o}rgensen, {Marit E} and Allan Linneberg and Oluf Pedersen and Kiebish, {Michael A} and Klaus Qvortrup and Xianlin Han and Pedersen, {Bente Klarlund} and Martin Jastroch and Susanne Mandrup and Andreas Kj{\ae}r and Gygi, {Steven P} and Torben Hansen and Gillum, {Matthew P} and Niels Grarup and Brice Emanuelli and S{\o}ren Nielsen and Camilla Scheele and Yu-Hua Tseng and F{\ae}rgeman, {Nils J} and Zachary Gerhart-Hines",
note = "Copyright {\textcopyright} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
doi = "10.1016/j.cmet.2018.05.003",
language = "English",
volume = "28",
pages = "159--174.e11",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis

AU - Sustarsic, Elahu G

AU - Ma, Tao

AU - Lynes, Matthew D

AU - Larsen, Michael

AU - Karavaeva, Iuliia

AU - Havelund, Jesper F

AU - Nielsen, Carsten H

AU - Jedrychowski, Mark P

AU - Moreno-Torres, Marta

AU - Lundh, Morten

AU - Plucinska, Kaja

AU - Jespersen, Naja Z

AU - Grevengoed, Trisha J

AU - Kramar, Barbara

AU - Peics, Julia

AU - Hansen, Jakob B

AU - Shamsi, Farnaz

AU - Forss, Isabel

AU - Neess, Ditte

AU - Keipert, Susanne

AU - Wang, Jianing

AU - Stohlmann, Katharina

AU - Brandslund, Ivan

AU - Christensen, Cramer

AU - Jørgensen, Marit E

AU - Linneberg, Allan

AU - Pedersen, Oluf

AU - Kiebish, Michael A

AU - Qvortrup, Klaus

AU - Han, Xianlin

AU - Pedersen, Bente Klarlund

AU - Jastroch, Martin

AU - Mandrup, Susanne

AU - Kjær, Andreas

AU - Gygi, Steven P

AU - Hansen, Torben

AU - Gillum, Matthew P

AU - Grarup, Niels

AU - Emanuelli, Brice

AU - Nielsen, Søren

AU - Scheele, Camilla

AU - Tseng, Yu-Hua

AU - Færgeman, Nils J

AU - Gerhart-Hines, Zachary

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics.

AB - Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics.

U2 - 10.1016/j.cmet.2018.05.003

DO - 10.1016/j.cmet.2018.05.003

M3 - Journal article

C2 - 29861389

VL - 28

SP - 159-174.e11

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 1

ER -

ID: 199067513