Proteomics

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Human APOE3 expressing mice are more prone to develop fatty liver disease on a high fat and sugar diet compared to APOE4 mice


ABSTRACT: Recent findings suggest that the human APOE epsilon 4 allele protects against non-alcoholic fatty liver disease, while APOE epsilon 3 promotes hepatic steatosis and steatohepatitis. We performed an untargeted proteome analysis of the liver and identified a great number of proteins differently expressed in obese APOE3 and APOE4 mice. The majority of the proteins up-regulated in APOE3 can be grouped to inflammation and damage-associated response, cytoskeleton and lipid storage. In contrast, those proteins that are up-regulated in APOE4 can be related to intermediate filament modifications, biotransformation and amino acid metabolism. Results of the targeted quantitative RT-PCR and Western blot experiments contribute to the overall finding that APOE3 promotes hepatic steatosis, inflammatory- and damage-associated response signaling and fibrosis in the liver of obese mice. One of the proteins that were up-regulated in obese as well as lean APOE4 compared to APOE3 mice is parvulin 14 (Pin4). Up-regulation of parvulin 14 may be involved in the protection against fatty liver disease evident in the presence of APOE4.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Andreas Tholey  

LAB HEAD: Andreas Tholey

PROVIDER: PXD033973 | Pride | 2024-05-21

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20210707ApoE3AL-4AL_F2R3.raw Raw
20210707ApoE3AL-4AL__F3R1.raw Raw
20210707_ApoE3AL-4AL_F1R1.raw Raw
20210707_ApoE3AL-4AL_F1R2.raw Raw
20210707_ApoE3AL-4AL_F1R3.raw Raw
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Publications

Human APOE4 Protects High-Fat and High-Sucrose Diet Fed Targeted Replacement Mice against Fatty Liver Disease Compared to APOE3.

Huebbe Patricia P   Bilke Stephanie S   Rueter Johanna J   Schloesser Anke A   Campbel Graeme G   Glüer Claus-C CC   Lucius Ralph R   Röcken Christoph C   Tholey Andreas A   Rimbach Gerald G  

Aging and disease 20240201 1


Recent genome- and exome-wide association studies suggest that the human APOE ε4 allele protects against non-alcoholic fatty liver disease (NAFLD), while ε3 promotes hepatic steatosis and steatohepatitis. The present study aimed at examining the APOE genotype-dependent development of fatty liver disease and its underlying mechanisms in a targeted replacement mouse model. Male mice expressing the human APOE3 or APOE4 protein isoforms on a C57BL/6J background and unmodified C57BL/6J mice were chro  ...[more]

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