Mice CMECs TMT-based quantitative proteomic
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Lingyun Zu
PROVIDER: PXD027916 | iProX | Thu Aug 12 00:00:00 BST 2021
REPOSITORIES: iProX
Similar Datasets
Project description:ETX treatment promoted cardiomyocyte proliferation. To investigate the molecular mechanism, we performed microarray analysis to explore the molecular mechanism underlying the effect of ETX on cardiomyocyte proliferation. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. In neonatal mice, blockade of glycolysis by inhibiting glucokinase reduced cardiomyocyte proliferation, while blockade of fatty acid oxidation by inhibiting carnitine palmitoyltransferase 1 (CPT1) delayed the cell cycle arrest in cardiomyocytes. ETX (Etomoxir) is an effective inhibitor of CPT1 which is the key enzyme of fatty acid oxidation,ETX induced cardiomyocyte proliferation and improved cardiac function post-MI in adult mice.
2019-10-26 | GSE139381 | GEO
Project description:Pancreatic beta-cell dysfunction contributes to onset and progression of type 2 diabetes. In this state beta-cells become metabolically inflexible, losing the ability to select between carbohydrates and lipids as substrates for mitochondrial oxidation. These changes lead to beta-cell dedifferentiation. We have proposed that FoxO proteins are activated through deacetylation-dependent nuclear translocation to forestall the progression of these abnormalities. However, how deacetylated FoxO exert their actions remains unclear. To address this question, we analyzed islet function in mice homozygous for knock-in alleles encoding deacetylated FoxO1 (6KR). Islets expressing 6KR mutant FoxO1 have enhanced insulin secretion in vivo and ex vivo, and decreased fatty acid oxidation ex vivo. Remarkably, the gene expression signature associated with FoxO1 deacetylation differs from wild-type by only ~2% of the > 4,000 genes regulated in response to re-feeding. But this narrow swath includes key genes required for beta-cell identity, lipid metabolism, and mitochondrial fatty acid and solute transport. The data support the notion that deacetylated FoxO1 protects beta-cell function by limiting mitochondrial lipid utilization, and raise the possibility that inhibition of fatty acid oxidation in β-cells is beneficial to diabetes treatment.
2016-05-10 | GSE77652 | GEO
Project description:Mitochondrial fatty acid oxidation (FAO) is an important energy provider for cardiac work and changes in cardiac substrate preference are associated with different heart diseases. Carnitine palmitoyltransferase 1B (CPT1B) is thought to perform the rate limiting enzyme step in FAO and is inhibited by malonyl-CoA. The role of CPT1B in cardiac metabolism has been addressed by inhibiting or decreasing CPT1B protein or after modulation of tissue malonyl-CoA metabolism. We assessed the role of CPT1B malonyl-CoA sensitivity in cardiac metabolism.
2021-04-26 | GSE173256 | GEO
Project description:Metabolic reprogramming of glucose and amino acids has been documented to affect early development. Here, we show that peroxisome-mediated β-oxidation is involved in lipids reprogramming to achieve H3K4me3 erasure and then zygotic genome activation (ZGA) in early embryo development. The metabolic patterns of fatty acids (FAs), triglyceride (TG) and phospholipid (PL) are reprogrammed during the oocyte-to-embryo transition. Very long-chain fatty acids (VLCFAs), arachidonic acid (ARA), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (Lyso-PE), lysophosphatidylcholine (Lyso-PC), and methyl donors are stored in oocytes, and after fertilization, they are converted into phosphatidylcholine (PC) at the 2-cell stage. Mitochondrial β-oxidation prevails in oocytes, while peroxisomal β-oxidation plays a critical role in shortening the VLCFA to form TG and synthesize PC and balancing the ratio of saturated and unsaturated FAs, which consumes the methyl donors as conducive to H3K4me3 erasure at the 2-cell stage. Inhibiting the peroxisome-mediated β-oxidation disrupts lipids metabolism remodellingH3K4me3 erasure and subsequent ZGA, leading to embryo arrest at the 2-cell stage. Oocytes from obese mice show I a relatively low level of VLCFAs, defective peroxisomal β-oxidation, and incomplete H3K4me3 erasure and ZGA. Microinjection of two saturated fatty acids, palmitic and myristic acids, rescues 2-cell arrest caused by peroxisome-mediated β-oxidation inhibition and obesity, and overexpressing Pemt to consume the methyl donors has the same rescue effect. These results elucidate a novel link among the peroxisomal-β-oxidation-mediated lipid metabolism reprogramming, H3K4me3 modification and ZGA during oocyte-embryo transition, and may provide a unique approach to improve reproduction in obese women.
2023-09-07 | GSE242263 | GEO
Project description:Metabolic reprogramming of glucose and amino acids has been documented to affect early development. Here, we show that peroxisome-mediated β-oxidation is involved in lipids reprogramming to achieve H3K4me3 erasure and then zygotic genome activation (ZGA) in early embryo development. The metabolic patterns of fatty acids (FAs), triglyceride (TG) and phospholipid (PL) are reprogrammed during the oocyte-to-embryo transition. Very long-chain fatty acids (VLCFAs), arachidonic acid (ARA), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (Lyso-PE), lysophosphatidylcholine (Lyso-PC), and methyl donors are stored in oocytes, and after fertilization, they are converted into phosphatidylcholine (PC) at the 2-cell stage. Mitochondrial β-oxidation prevails in oocytes, while peroxisomal β-oxidation plays a critical role in shortening the VLCFA to form TG and synthesize PC and balancing the ratio of saturated and unsaturated FAs, which consumes the methyl donors as conducive to H3K4me3 erasure at the 2-cell stage. Inhibiting the peroxisome-mediated β-oxidation disrupts lipids metabolism remodellingH3K4me3 erasure and subsequent ZGA, leading to embryo arrest at the 2-cell stage. Oocytes from obese mice show I a relatively low level of VLCFAs, defective peroxisomal β-oxidation, and incomplete H3K4me3 erasure and ZGA. Microinjection of two saturated fatty acids, palmitic and myristic acids, rescues 2-cell arrest caused by peroxisome-mediated β-oxidation inhibition and obesity, and overexpressing Pemt to consume the methyl donors has the same rescue effect. These results elucidate a novel link among the peroxisomal-β-oxidation-mediated lipid metabolism reprogramming, H3K4me3 modification and ZGA during oocyte-embryo transition, and may provide a unique approach to improve reproduction in obese women.
2023-09-25 | GSE243450 | GEO
Project description:Glucagon supports glucose homeostasis by stimulating hepatic gluconeogenesis, in part by promoting the uptake and conversion of amino acids into gluconeogenic precursors. Genetic disruption or pharmacologic inhibition of glucagon signaling results in elevated plasma amino acids, and compensatory glucagon hypersecretion involving expansion of pancreatic α-cell mass. Regulation of pancreatic α- and β-cell growth has drawn a lot of attention because of potential therapeutic implications. Recent findings indicate that hyperaminoacidemia triggers pancreatic α-cell proliferation via an mTOR-dependent pathway. We confirm and extend these findings by demonstrating that glucagon pathway blockade selectively increases expression of the sodium-coupled neutral amino acid transporter Slc38a5 in a subset of highly proliferative α-cells, and that Slc38a5 is critical for the pancreatic response to glucagon pathway blockade; most notably, mice deficient in Slc38a5 exhibit markedly decreased α-cell hyperplasia to glucagon pathway blockade-induced hyperaminoacidemia. These results show that Slc38a5 is a key component of the feedback circuit between glucagon receptor signaling in the liver and amino acid-dependent regulation of pancreatic α-cell mass in mice.
2017-05-01 | GSE89636 | GEO
Project description:Metabolic remodeling is one of the earliest events that occur during the early differentiation of embryonic stem cells (ESCs), but how these metabolic changes are regulated and participate in the cell differentiation is still largely undissected. Here, we define the fatty acid metabolism as a key player in definitive endoderm (DE) differentiation from human ESCs. During DE differentiation, lipogenesis is decreased while fatty acid β oxidation is enhanced. This dynamic is due to the phosphorylation of lipogenic enzyme acetyl-CoA carboxylase (ACC), which is mediated by AMP-activated protein kinase (AMPK) and inhibits the de novo fatty acid synthesis. More importantly, inhibition of fatty acid synthesis by either its inhibitors or AMPK agonist, significantly promotes the human endoderm differentiation, while blockade of the fatty acid oxidation by genetic manipulation or chemical antagonists impairs the differentiation. The de novo fatty acid synthesis inhibition and fatty acid β oxidation maintaining contribute to the accumulation of cellular acetyl-CoA, which is the essential substrate for protein acetylation. Further study reveals that SMAD3 acetylation and the subsequent subcellular localization exhibit significant change upon interfering fatty acid metabolism. Mechanistically, the accumulation of cellular acetyl-CoA guarantees the acetylation of key transcription factor SMAD3, which further causes the nuclear localization and activation of SMAD signaling pathway to promote DE differentiation. Thus, our current study reveals a fatty acid synthesis/oxidation shift during early differentiation and presents an instructive role of fatty acid metabolism in regulating human early endoderm differentiation.
2023-07-02 | GSE218319 | GEO
Project description:Metabolic remodeling is one of the earliest events that occur during the early differentiation of embryonic stem cells (ESCs), but how these metabolic changes are regulated and participate in the cell differentiation is still largely undissected. Here, we define the fatty acid metabolism as a key player in definitive endoderm (DE) differentiation from human ESCs. During DE differentiation, lipogenesis is decreased while fatty acid β oxidation is enhanced. This dynamic is due to the phosphorylation of lipogenic enzyme acetyl-CoA carboxylase (ACC), which is mediated by AMP-activated protein kinase (AMPK) and inhibits the de novo fatty acid synthesis. More importantly, inhibition of fatty acid synthesis by either its inhibitors or AMPK agonist, significantly promotes the human endoderm differentiation, while blockade of the fatty acid oxidation by genetic manipulation or chemical antagonists impairs the differentiation. The de novo fatty acid synthesis inhibition and fatty acid β oxidation maintaining contribute to the accumulation of cellular acetyl-CoA, which is the essential substrate for protein acetylation. Further study reveals that SMAD3 acetylation and the subsequent subcellular localization exhibit significant change upon interfering fatty acid metabolism. Mechanistically, the accumulation of cellular acetyl-CoA guarantees the acetylation of key transcription factor SMAD3, which further causes the nuclear localization and activation of SMAD signaling pathway to promote DE differentiation. Thus, our current study reveals a fatty acid synthesis/oxidation shift during early differentiation and presents an instructive role of fatty acid metabolism in regulating human early endoderm differentiation.
2023-07-02 | GSE217992 | GEO
Project description:Quiescent endothelial cells upregulate fatty acid β-oxidation for vasculoprotection via redox homeostasis
| PRJEB25688 | ENA
Project description:vanEunen2013 - Network dynamics of fatty acid β-oxidation (time-course model)
Lipid metabolism plays an important role in the development of metabolic syndrome, a major risk factor for cardiovascular disease and diabetes. This model gives insights into the response of lipid oxidation to dietart and medical interventions. The model predicts the rate of lipid oxidation and the time course of most acyl carnitines. There are two models described in the paper, (i) steady-state model [ BIOMD0000000505
], (ii) time-course model [ BIOMD0000000506
]. This model corresponds to the time-course model.
This model is described in the article:
Biochemical competition makes fatty-acid β-oxidation vulnerable to substrate overload.
van Eunen K, Simons SM, Gerding A, Bleeker A, den Besten G, Touw CM, Houten SM, Groen BK, Krab K, Reijngoud DJ, Bakker BM.
PLoS Comput Biol. 2013;9(8):e1003186.
Abstract:
Fatty-acid metabolism plays a key role in acquired and inborn metabolic diseases. To obtain insight into the network dynamics of fatty-acid β-oxidation, we constructed a detailed computational model of the pathway and subjected it to a fat overload condition. The model contains reversible and saturable enzyme-kinetic equations and experimentally determined parameters for rat-liver enzymes. It was validated by adding palmitoyl CoA or palmitoyl carnitine to isolated rat-liver mitochondria: without refitting of measured parameters, the model correctly predicted the β-oxidation flux as well as the time profiles of most acyl-carnitine concentrations. Subsequently, we simulated the condition of obesity by increasing the palmitoyl-CoA concentration. At a high concentration of palmitoyl CoA the β-oxidation became overloaded: the flux dropped and metabolites accumulated. This behavior originated from the competition between acyl CoAs of different chain lengths for a set of acyl-CoA dehydrogenases with overlapping substrate specificity. This effectively induced competitive feedforward inhibition and thereby led to accumulation of CoA-ester intermediates and depletion of free CoA (CoASH). The mitochondrial [NAD⁺]/[NADH] ratio modulated the sensitivity to substrate overload, revealing a tight interplay between regulation of β-oxidation and mitochondrial respiration.
This model is hosted on BioModels Database
and identified
by: BIOMD0000000506
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
2024-09-02 | BIOMD0000000506 | BioModels