Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
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.
I: Cell Metabolism, Bind 28, Nr. 1, 2018, s. 159-174.e11.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
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