Transcriptional profiling of mouse liver tissue following control, choline and methonine/choline deficient diet intervention
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Marcus Lyall
PROVIDER: E-MTAB-3943 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here we demonstrate that the catabolism of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased FGF21, and an altered epigenetic methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display a decreased hepatic triglyceride likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver.
2022-11-30 | GSE217137 | GEO
Project description:Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here we demonstrate that the catabolism of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased FGF21, and an altered epigenetic methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display a decreased hepatic triglyceride likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver.
2022-11-30 | GSE217136 | GEO
Project description:Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here we demonstrate that the catabolism of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased FGF21, and an altered epigenetic methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display a decreased hepatic triglyceride likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver.
2022-11-30 | GSE217135 | GEO
Project description:Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here we demonstrate that the catabolism of membrane phosphatidylcholine (PC) into water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased FGF21, and an altered histone/DNA methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display a decreased hepatic triglyceride likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver.
2022-12-03 | GSE219003 | GEO
Project description:The feeding/fasting cycles controlled by our circadian clock impose great daily metabolic and physiological changes, and yet investigations into the consequences of metabolic deficiencies, either dietary or genetic, have often ignored the time of day or the circadian time of the animals or subjects. In addition, these deficiencies may themselves disrupt our circadian clock, causing secondary metabolic, physiological and behavioural disorders. Dietary methionine/choline deficiency in rodents is a common model for human non-alcoholic steatohepatitis, but methionine and choline are nutrients essential for many other processes beyond fatty acid synthesis in the liver, including biological methylations and 1-carbon metabolism, regulation of translation notably via the mTOR pathway, phospholipid synthesis, polyamine pathway and glutathione synthesis. We have previously shown that circadian rhythms in many organisms are highly sensitive to deficiency or excesses of 1-carbon metabolites. Using a methionine/choline deficient diet in mice, we illustrate the nutrigenomic crosstalk between circadian rhythms and 1-carbon metabolism. We show not only that circadian locomotor activity behaviour is profoundly, rapidly and reversibly affected by methionine/choline deficiency, but also that the effects of methionine/choline deficiency on gene expression and 1-carbon metabolites are dependent on circadian time, illustrating the importance of considering circadian rhythms in metabolic studies. This study also highlights the impact of what we eat, or don't, on our behaviour and biological rhythms.
2024-01-05 | GSE252364 | GEO
Project description:The objective of this study was to identify metabolic regulatory mechanisms affected by choline availability in rainbow trout (Oncorhynchus mykiss) broodstock diets associated with increased offspring growth performance. Three customized diets were formulated to have different levels of choline: (a) 0% choline supplementation (Low Choline: 2065 ppm choline), (b) 0.6% choline supplementation (Medium Choline: 5657 ppm choline), and (c) 1.2% choline supplementation (High Choline: 9248 ppm choline). Six all-female rainbow trout families were fed experimental diets beginning 18 months post-hatch until spawning; their offspring were fed a commercial diet. Experimental broodstock diet did not affect overall choline, fatty acid, or amino acid content in the oocytes (p > 0.05), apart from tyrosine (p ≤ 0.05). Offspring body weights from the High and Low Choline diets did not differ from those in the Medium Choline diet (p > 0.05); however, family-by-diet and sire-by-diet interactions on offspring growth were detected (p ≤ 0.05). The High Choline diet did not improve growth performance in the six broodstock families at final harvest (520-days post-hatch, or dph). Numerous genes associated with muscle development and lipid metabolism were identified, including myosin, troponin C, and fatty acid binding proteins, which were associated with key signaling pathways of lipid metabolism, muscle cell development, muscle cell proliferation, and muscle cell differentiation. These findings indicate that supplementing broodstock diets with choline does regulate expression of genes related to growth and nutrient partitioning but does not lead to growth benefits in rainbow trout families selected for disease resistance.
2024-02-09 | GSE243186 | GEO
Project description:C57BL/6 mice received methionine/choline deficient (MCD) diet to establish the model of non-alcoholic fatty liver disease (NAFLD) with or without Diethyldithiocarbamate (DDC) treatment. DDC improves hepatic steatosis, ballooning, inflammation and fibrosis in rodent models of NAFLD through modulating lipid metabolism and oxidative stress.
2018-12-26 | GSE113843 | GEO
Project description:Weanling rats fed a choline-deficient diet develop acute renal failure (ARF) after 6-7 days of receiving the experimental diet. Its pathogenesis is controversial. Menhaden oil has a protective effect in this experimental model. The aim of this study is to describe both the genetic profile and its changes when vegetable oils are replaced by menhaden oil. Wistar, weanling rats from the Animal Facility of the Centre of Experimental and Applied Pathology were divided into 4 groups and fed with the following diets: 1- Choline-deficient diet with vegetable oils as lipids (corn and hydrogenated oils); 2- Choline-supplemented diet with vegetable oils as lipids; 3- Choline-deficient diet with menhaden oil as lipid; and 4- Choline supplemented diet with menhaden oil as lipid. Animals were sacrificed after 6 days of receiving the experimental diets. The right kidney was cryopreserved. In this assay biological duplicated samples were used. In order to evaluate changes in gene expression WT Expression Kit (Ambion, USA) over the platform GeneChip® Gene 1.0 ST Rat Genome Array (Affymetrix Inc, USA) was used. Fluorescent distribution in the array was obtained using the language R (www-r-project.org), in house own algorithms and other formsbioconductor tools http://www.bioconductor.org/. We analyzed the differential gene expression, using as cut value p<0.01 with fdr control & |log FC|>1.5, in all groups. Rats fed with diets 2, 3 and 4 have similar genetic profiles. However, the comparison between rats fed with diets 2 and 4 showed 35 genes with diferential expression. As these rats did not have renal necrosis, we can hypothesize that the differential expression is due to the menhaden oil of the diet. In short, the massive analysis of genetic expression allowed to confirm that menhaden oil has a protective effect in this experimental model and to identify 35 genes that could be responsible of that protection. Twenty eight animals were sacrificed after 6 days of receiving the experimental diets. The right kidney was cryopreserved for microarray analysis. Cryopreserved kidney was pulverized under liquid-nitrogen conditions. Total RNA was purified from 30 mg of frozen rat kidney tissue. Each sample represents a pool of 3 animals (except CD+AM SN with 2 animals/pool), to reduce biological variation. In this assay biological duplicated samples were used.
2011-12-06 | E-GEOD-34139 | biostudies-arrayexpress
Project description:The objective of this paper was to determine whether shifts in the methylome in rainbow trout (Oncorhynchus mykiss) are correlated with transcriptomic changes during early development in response to maternal dietary choline intake. Three experimental diets were formulated to have different levels of choline: (a) 2065 ppm choline (Low Choline, 0% supplementation), (b) 5657 ppm choline (Medium Choline, 0.6% supplementation), and (c) 9248 ppm choline (High Choline, 1.2% choline supplementation). Six rainbow trout families were fed experimental diets beginning 18 months post-hatch until spawning; their offspring were fed a commercial diet. Reduced representational bisulfite sequencing (RRBS) was utilized to measure genome-wide methylation differences in offspring immediately after hatching. When comparing to the Medium Choline offspring, differential DNA methylation occurred more in the Low Choline offspring than High Choline, especially in genic features like promoters. The differentially methylated CpGs (q ≤ 0.01) were identified evenly between CpG islands and shores in the genome, mostly found in the introns of genes. Genes such as fabp2 and leap2B associated with protein binding, fatty acid binding, DNA binding, and response to bacteria were differentially methylated and detected as differentially regulated genes by previous RNA-seq analysis. Although these findings indicate that levels of dietary choline available in broodstock diets alters offspring DNA methylation; most differentially expressed genes were not associated with differential DNA methylation, suggesting additional mechanisms playing a role in regulating gene expression in response to maternal choline intake.
2024-11-21 | GSE269087 | GEO
Project description:Abstract: Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assess the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community to lack a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria show increased susceptibility to metabolic disease. Furthermore, bacterially-induced reduction of methyl-donor availability alters global DNA methylation patterns in both adult mice and their offspring in utero and engenders anxious behavior. Altogether, our results reveal an underappreciated aspect of bacterial choline metabolism (i.e., methyl-donor depletion) that is linked to alterations in metabolism, epigenetics, and behavior. More broadly, this work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal levels of nutrient intake.
2017-07-28 | GSE100983 | GEO