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| Status |
Public on Jun 18, 2016 |
| Title |
Malnutrition-associated hepatic steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction and rescued by fenofibrate |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. To investigate the underlying mechanisms of hepatic dysfunction we used a rat model of malnutrition by placing weanling rats on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Low protein diet-fed rats developed hypoalbuminemia and severe hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated impaired peroxisomal function. Loss of peroxisomes was followed by accumulation of dysfunctional mitochondria and decreased hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial fatty acid β-oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. These findings provide important insight into the metabolic
disturbances associated with malnutrition and have potentially profound clinical consequences with respect to the management of malnourished children worldwide.
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| Overall design |
24 rats in 4 groups of 6 animals per group where placed on a normal 20% or low protein 5% diet for a period of 4 weeks
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| Contributor(s) |
van Zutphen T, Ciapaite J, Allgayer de Moraes R, Reijngoud DJ, Jurdzinski A, Ackereley C, Wolters JC, Wanders RJ, Houten SM, Bloks VW, Bronte-Tinkew D, Groen AK, Jonker JW, Bakker BM, Kim PK, Bandsma RH, Zhang L, Gerding A, Shatseva T, Lewis GF, Bischoff R |
| Citation(s) |
27312946 |
| Submission date |
Nov 07, 2014 |
| Last update date |
Mar 14, 2017 |
| Contact name |
vincent bloks |
| Organization name |
UMCG
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| Department |
Pediatrics
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| Lab |
Pediatrics
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| Street address |
Hanzeplein1
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| City |
Groningen |
| ZIP/Postal code |
9713GZ |
| Country |
Netherlands |
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| Platforms (1) |
| GPL11534 |
[RaGene-1_1-st] Affymetrix Rat Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA266610 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63096_RAW.tar |
108.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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