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| Status |
Public on Apr 27, 2017 |
| Title |
Feeding Angptl4-/- mice trans fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
ANGPTL4 regulates plasma triglyceride levels by inhibiting lipoprotein lipase. Inactivation of ANGPTL4 decreases plasma triglycerides and reduces risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in mesenteric lymph nodes. In mice these pathological events exclusively unfold upon feeding a high saturated fatty acid diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites. Here we show that Angptl4-/- mice fed a diet rich in trans fatty acids develop numerous lipid-filled giant cells in their mesenteric lymph nodes, yet do not have elevated serum amyloid and haptoglobin, do not exhibit ascites, and survive, unlike Angptl4-/- mice fed a saturated fatty acid-rich diet. In RAW264.7 macrophages the saturated fatty acid palmitate markedly increases markers of inflammation and the unfolded protein response, whereas the trans-unsaturated elaidate and the cis-unsaturated oleate have the opposite effect. In conclusion, trans and saturated fatty acids have very distinct biological effects. Furthermore, lipid accumulation in mesenteric lymph nodes is uncoupled from activation of an acute-phase response and chylous ascites, suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia.
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| Overall design |
RAW264.7 macrophages were incubated with oleate, elaidate and palmitate for 6 hours and subjected to expression profiling.
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| Contributor(s) |
Oteng AB, Bhattacharya A, Brodesser S, Qi L, Tan NS, Kersten S |
| Citation(s) |
28412693 |
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| Submission date |
Apr 27, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
[email protected]
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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 (3) |
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| Relations |
| BioProject |
PRJNA384630 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE98303_RAW.tar |
12.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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