Difference between revisions of "Ma 2018 MiPschool Tromso C1"
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== Affiliations == | == Affiliations == |
Latest revision as of 15:23, 18 October 2018
Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis. |
Link: MitoEAGLE
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, Joergensen ME, Linneberg A, Pedersen O, Kiebish MA, Qvortrup K, Han X, Pedersen BK, Jastroch M, Mandrup S, Kjaer A, Gygi SP, Hansen T, Gillum MP, Grarup N, Emanuelli B, Nielsen S, Scheele C, Tseng YH, Faergeman NJ, Gerhart-Hines Z (2018)
Event: MiPschool Tromso-Bergen 2018
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.
• Keywords: Cardiolipin, CRLS1, Phospholipidslipid, Metabolism, Mitochondria, Brown adipose, Beige adipose, Thermogenesis, Insulin resistance, CHOP-10 • Bioblast editor: Plangger M
Labels:
Organism: Human, Mouse
Tissue;cell: Fat
Event: C1, Oral
Affiliations
Sustarsic EG(1,2), Ma T(1,2), Lynes MD(3), Larsen M(2), Karavaeva I(1,2), Havelund JF(4), Nielsen CH(2,5), Jedrychowski MP(6), Moreno-Torres M(4), Lundh M(1), Plucinska K(1), Jespersen NZ(1,7), Grevengoed TJ(1), Kramar B(1), Peics J(1,2), Hansen JB(1,2), Shamsi F(3), Forss I(4), Neess D(4), Keipert S(8), Wang J(9), Stohlmann K(1), Brandslund I(10,11), Christensen C(10), Jørgensen ME(12,13), Linneberg A(14,15,16), Pedersen O(1), Kiebish MA(17), Qvortrup K(2), Han X(9), Pedersen BK(7), Jastroch M(8), Mandrup S(4), Kjær A(2,5), Gygi SP(6), Hansen T(1), Gillum MP(1), Grarup N(1), Emanuelli B(1), Nielsen S(7), Scheele C(1,7), Tseng YH(3), Færgeman NJ(4), Gerhart-Hines Z(1,2).
- Novo Nordisk Foundation Center Basic Metabolic Research
- Dept Biomedical Sciences; Univ Copenhagen, Denmark
- Section Integrative Physiology Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
- Dept Biochemistry Molecular Biol, Univ Southern Denmark, Odense, Denmark
- Dept Clinical Physiology, Nuclear Medicine PET Cluster Molecular Imaging, Rigshospitalet, Copenhagen, Denmark
- Dept Cell Biol, Harvard Medical School, Boston, MA, USA
- Centre Inflammation Metabolism and Centre Physical Activity Research, Rigshospitalet, Univ Hospital Copenhagen, Denmark
- Helmholtz Diabetes Center and German Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany
- Barshop Inst Longevity Aging Studies, Univ Texas Health Science Center San Antonio, TX, USA
- Lillebaelt Hospital, Vejle, Denmark
- Inst Regional Health Research, Univ Southern Denmark, Odense, Denmark
- Steno Diabetes Center, Gentofte, Denmark
- National Inst Public Health, Southern Denmark Univ, Copenhagen, Denmark
- Research Center Prevention Health, Glostrup, Denmark
- Center Clinical Research Prevention, Bispebjerg Frederiksberg Hospital, Copenhagen, Denmark
- Dept Clinical Medicine, Univ Copenhagen, Denmark
- BERG Health, Framingham, MA, USA