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| Status |
Public on May 18, 2015 |
| Title |
The ER-Associated Degradation Adapter Protein Sel1L Regulates Triglyceride Metabolism via Lipoprotein Lipase |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Sel1L is an adaptor protein for the E3 ligase Hrd1 in the endoplasmic reticulum-associated degradation (ERAD), but its physiological role in a cell-type-specific manner remains unclear. Here we show that mice with adipocyte-specific Sel1L deficiency are resistant to diet-induced obesity and exhibit postprandial hypertriglyceridemia. Mechanistically, our data demonstrate a critical requirement of Sel1L for the secretion of lipoprotein lipase (LPL), independently of its role in Hrd1-mediated ERAD and ER homeostasis. Further biochemical analyses revealed that Sel1L physically interacts and stabilizes the LPL maturation complex consisted of LPL and lipase-maturation factor 1 (LMF1). In the absence of Sel1L, LPL is retained in the ER and prone to the formation of protein aggregates, which are degraded by autophagy-mediated degradation. The Sel1L-mediated control of LPL secretion is seen in other LPL-expressing cell types as well such as cardiac muscle and macrophages. Thus, our study reports a novel role of Sel1L in LPL secretion and systemic lipid metabolism.
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| Overall design |
Sel1Lflox/flox mice were crossed with adiponectin promoter driven Cre mice to create adipose tissue-specific Sel1L-/- mice. Male wildtype C57Bl/6 mice and adipose tissue-specific Sel1l-/- mice were fed a high fat diet (Research Diets D12492) for 5 weeks. Adipose tissue was excised and used for microarray analysis.
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| Contributor(s) |
Sha H, Francisco A, Sun S, Ehrhardt N, Xue Z, Liu L, Lawrence P, Mattijssen F, Gruber R, Panhwar MS, Brenna JT, Shi H, Xue B, Kersten S, Bensadoun A, Péterfy M, Long Q, Qi L |
| Citation(s) |
25066055 |
| Submission date |
Apr 18, 2014 |
| Last update date |
Apr 18, 2017 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA244933 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE56918_RAW.tar |
37.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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