Dataset Information

Palm oil-rich diet affects murine liver proteome and S-palmitoylome

ABSTRACT: Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in lipid synthesis and β-oxidation, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein palmitoylation in the context of metabolic processes remains largely unknown. In this study we performed high-throughput proteomic analyses of the liver membrane fraction in the mouse to examine the influence of a palm oil-rich diet on the level and S-palmitoylation of proteins. For this purpose, mice were fed for 4 or 12 weeks a diet containing 19.1% of palm oil in addition to 4% soybean oil (45% kcal from fat) while 4% soybean oil (10% kcal from fat) was the only fat source in the control diet. Liver functioning and pro-inflammatory responses of the liver and peritoneal macrophages as well as the input of protein S-palmitoylation to these aspects were assessed in parallel. We found that the diet rich in palm oil induced transient accumulation of C16:0 and C18:1 fatty acids in murine liver leading to changes of the level and S-palmitoylation of numerous proteins involved in liver metabolism and selected innate immune responses. The relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, including dynamic protein S-palmitoylation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Agata Malinowska

LAB HEAD: Michal Dadlez

PROVIDER: PXD025935 | Pride | 2021-12-14

REPOSITORIES: Pride

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Palm Oil-Rich Diet Affects Murine Liver Proteome and S-Palmitoylome.

Ziemlińska Ewelina E Sobocińska Justyna J Świątkowska Anna A Hromada-Judycka Aneta A Traczyk Gabriela G Malinowska Agata A Świderska Bianka B Mietelska-Porowska Anna A Ciesielska Anna A Kwiatkowska Katarzyna K

International journal of molecular sciences 20211203 23

Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in synthesis and β-oxidation of other lipids, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein S-palmitoylation remains largely unknown. In this study we performed high-throughput proteomic analyses of a membrane-enriched fraction of murine liver to examine the influence of a palm oil-rich diet (HPD) on S-palmitoylation of pro ...[more]

PMID: 34884899

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Project description:Mutations in Ppt1, which is a depalmitoylation enzyme result in early onset neurodegeneration, therefore, we hypothesized that the protein content of brain membranes from mutant newborn mice will differ from those derived from wild-type. This unbiased analysis revealed that the majority of the differentially identified proteins are palmitoylated and their upstream pathway analysis point to neurodegenerative diseases. One of the differentially expressed proteins was Rab3IP, which is a direct downstream effector of Rab11 and affects the guanine nucleotide-exchange activity of Rab3IP toward Rab8. Rab3IP, Rab11 and Rab8 are known to be involved in ciliogenesis. Rab3IP distribution in cilia differed between the wild type and the mutant cells. Our analysis showed that these three proteins are palmitoylated. Site-directed mutagenesis of the palmitoylation sites of Rab11 affects its intracellular localization. Most importantly, in MEFs, neuroblasts, neurons and brain preparations, longer cilia were detected in Ppt1-/-. Collectively, our studies suggest that cilia abnormalities need to be considered as part of the pathophysiology of CLN1. Mutations in Ppt1, which is a depalmitoylation enzyme result in early onset neurodegeneration, therefore, we hypothesized that the protein content of brain membranes from mutant newborn mice will differ from those derived from wild-type. This unbiased analysis revealed that the majority of the differentially identified proteins are palmitoylated and their upstream pathway analysis point to neurodegenerative diseases. One of the differentially expressed proteins was Rab3IP, which is a direct downstream effector of Rab11 and affects the guanine nucleotide-exchange activity of Rab3IP toward Rab8. Rab3IP, Rab11 and Rab8 are known to be involved in ciliogenesis. Rab3IP distribution in cilia differed between the wild type and the mutant cells. Our analysis showed that these three proteins are palmitoylated. Site-directed mutagenesis of the palmitoylation sites of Rab11 affects its intracellular localization. Most importantly, in MEFs, neuroblasts, neurons and brain preparations, longer cilia were detected in Ppt1-/-. Collectively, our studies suggest that cilia abnormalities need to be considered as part of the pathophysiology of CLN1. Mutations in Ppt1 result in early onset neurodegeneration, therefore, we hypothesized that the levels of proteins extracted from purified brain membranes of newborn mice will differ. One of the main effects of palmitoylation is changing the hydrophobic index of proteins and thus affecting these proteins interactions with different membranal domains. Assuming that PPT1 substrates are over palmitoylated in Ppt1-/- brains it is possible that its localization to specific membranal domain is different than in the wild-type brains. We isolated Triton X-100 soluble membranes from three wild-type and three Ppt1-/- brains and identified the proteins by PalmPISC. Many of the identified proteins were found to be palmitoylated. A second feature, which was noted is that many of the differential proteins (62 out of 88, 70%) can be detected in the cilia proteome (http://v3.ciliaproteome.org/cgi-bin/index.php). This observation led to test whether ciliary proteins differ between wild-type and Ppt1-/-. Cilia were prepared from newborn dissociated brain cell cultures and analyzed by MS

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Dataset Information

Palm oil-rich diet affects murine liver proteome and S-palmitoylome

Dataset's files

Publications

Palm Oil-Rich Diet Affects Murine Liver Proteome and <i>S</i>-Palmitoylome.

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