Dataset Information

Vitamin C modulates the levels of several proteins of the mitochondrial complex III and its activity in the mouse liver

ABSTRACT: In the present study, we used the Gulo-/- female and male mice model which depends entirely on ascorbate derived from the diet. Importantly, the levels of ascorbate found in the serum of Gulo-/- mice reflect the amounts of ascorbate provided in drinking water. We tested different concentrations of ascorbate ranging from 0 to 0.4% (w/v) ascorbate, added into drinking water, until the age of four months. We performed label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) global quantitative proteomic profiling to identify and quantify proteins in microsomal enriched liver extracts (MEE) from our different ascorbate treated cohorts of Gulo-/- females and males. We found that the MS intensities of several proteins in the mitochondrial complex III of the electron transport chain correlated positively with liver ascorbate concentrations in both Gulo-/- females and males. Consequently, the mitochondrial complex III activity in Gulo-/- female and male mice treated with suboptimal hepatic concentrations of ascorbate was significantly lower than Gulo-/- mice treated with optimal ascorbate concentration. Finally, proteins involved in complement activation correlated negatively with liver ascorbate concentrations in both Gulo-/- males and females.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Michel Lebel

PROVIDER: MSV000089881 | MassIVE | Wed Jul 13 10:55:00 BST 2022

SECONDARY ACCESSION(S): PXD035312

REPOSITORIES: MassIVE

ACCESS DATA

Similar Datasets

Project description:Maternal high-fat diet consumption predisposes to metabolic and liver dysfunction in F1 male and female at young adulthood. Purpose: We used RNA-seq to determine the liver transcriptome of male and female F1 of MO and control fed mothers. Methods: Female Wistar rat mothers ate control (C) or obesogenic (MO) diet from the time they were weaned through breeding at postnatal day (PND) 120, delivery and lactation. After weaning all male and female F1 ate control diet. At PND 110 liver and fat were collected to analyze metabolites, histology and liver differentially expressed genes. To identify the functional F1 liver changes due to MO, we evaluated the differentially expressed genes (DEGs) between MO and C males and females with separate pairwise comparisons due to the marked differences between males and females. Genes were filtered based on ≥ 1.4 fold change (FC) and nominal P value <0.05 (Student´s t-test). Results: MOF1 males presented greater physiologic and histological NAFLD characteristics than MOF1 females. RNA-seq revealed 1,365 genes significantly changed in male MOF1 liver and only 70 genes in MOF1 female compared with controls. GO and KEGG analysis identified differentially expressed genes related to metabolic process. Male MOF1 liver showed the following altered pathways: insulin signaling (22 genes), phospholipase D signaling (14 genes), NAFLD (13 genes), and glycolysis/ gluconeogenesis (7 genes). In contrast, few genes were altered in these pathways in MOF1 females. Conclusions: These results improve understanding of the mechanism by which a maternal high fat diet affects their F1. In summary, MO programs sex-dependent F1 changes in insulin, glucose and lipid signaling pathways, leading to liver dysfunction and insulin resistance. Male adult MOF1 livers show global down-regulation of genes that are required for normal function of major liver metabolic pathways. This new knowledge is important for producing sex-specific interventions.

Dataset Information

Vitamin C modulates the levels of several proteins of the mitochondrial complex III and its activity in the mouse liver

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure