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| Status |
Public on Jul 19, 2018 |
| Title |
Cardiolipin Synthesis Governs Systemic Energy Homeostasis through Thermogenic Fat Mitochondria |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Here we show that synthesis of the mitochondrial phospholipid cardiolipin is an indispensable driver of thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response by overexpressing cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency diminishes mitochondrial uncoupling in brown and beige adipocytes and elicits a nuclear transcriptional response through ER stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake and renders animals strikingly 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 is a powerful regulator of organismal energy homeostasis through thermogenic fat bioenergetics.
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| |
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| Overall design |
Genome-wide profiling of mRNA from brown adipose tissue (BAT) of five different mice of either wild-type (WT) or with knockout of CRLS1 (KO)
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| |
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| Contributor(s) |
Sustarsic EG, Forss I, Mandrup S, Gerhart-Hines Z |
| Citation(s) |
29861389 |
| |
| Submission date |
Feb 07, 2018 |
| Last update date |
Sep 12, 2018 |
| Contact name |
Susanne Mandrup |
| E-mail(s) |
s.mandrup@bmb.sdu.dk
|
| Phone |
+45 6550 2340
|
| Organization name |
University of Southern Denmark
|
| Department |
Biochemistry and Molecular Biology
|
| Street address |
Campusvej 55
|
| City |
Odense M |
| ZIP/Postal code |
5230 |
| Country |
Denmark |
| |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA433399 |
| SRA |
SRP132399 |
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