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The mechanism of gluconeogenic enzyme Pck1 in ulcerative colitis through regulation of Pla2g6-mediated lipid metabolism II

ABSTRACT: The mechanism of gluconeogenic enzyme Pck1 in ulcerative colitis through regulation of Pla2g6-mediated lipid metabolism II

PROVIDER: PRJNA1259469 | ENA |

REPOSITORIES: ENA

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The mechanism of gluconeogenic enzyme Pck1 in ulcerative colitis through regulation of Pla2g6-mediated lipid metabolism

Project description:Metabolic dysregulation may serve as a pivotal driver of inflammatory bowel disease (IBD), with the crosstalk between metabolism and the immune system emerging as a critical research focus. Ulcerative colitis (UC) patients exhibit enhanced glycolysis but suppressed gluconeogenesis in the intestinal mucosa, yet the mechanistic links between these metabolic alterations and mucosal injury remain poorly defined. This study establishes phosphoenolpyruvate carboxykinase 1 (Pck1), a key rate-limiting enzyme in gluconeogenesis, as a central regulator of UC progression. We found Pck1 expression was significantly downregulated in colon tissues of UC patients and mice with DSS‑induced colitis. Utilizing an intestinal epithelial cell (IEC)-specific Pck1 knockout mouse model, we demonstrated for the first time that Pck1 deficiency exacerbates intestinal inflammation. Mechanistically, Pck1 depletion induces metabolic reprogramming that upregulates Pla2g6 expression, driving abnormal hydrolysis of phosphatidylcholine and phosphatidylethanolamine in IECs. Pharmacological inhibition of Pla2g6 ameliorated colitis in Pck1-deficient mice. These findings position Pck1 as a potential early diagnostic biomarker for UC and suggest that therapeutic targeting of the Pck1-Pla2g6 metabolic axis may yield novel strategies for UC management.

2025-05-05 | GSE295845 | GEO

The mechanism of gluconeogenic enzyme Pck1 in ulcerative colitis through regulation of Pla2g6-mediated lipid metabolism II

2025-05-07 | GSE296485 | GEO

The mechanism of gluconeogenic enzyme Pck1 in ulcerative colitis through regulation of Pla2g6-mediated lipid metabolism

Project description:The mechanism of gluconeogenic enzyme Pck1 in ulcerative colitis through regulation of Pla2g6-mediated lipid metabolism

| PRJNA1256478 | ENA

Transcriptomic analysis of liver mRNA from liver-specific Pck1-knockout mice fed with chow diet or NASH diet

Project description:To investigate the role of hepatic Pck1 in diet-induced nonalcoholic steatohepatitis (NASH), liver-specific Pck1-knockout mice were developed with Alb-Cre. Wild-type (WT) and Pck1-cKO mice were fed a Chow diet (Research Diets, D12450J: 10% Kcal fat, with tap water) or NASH-inducing diet (Research Diets, D12492: 60% Kcal fat, with drinking water containig 23.1 g/L fructose and 18.9 g/L glucose) for 24 weeks. RNA was extracted from the livers of mice from all treatment groups and used for RNA seqencing. RNA-seq data demonstrated that gluconeogenic enzyme PCK1 deficiency played an important role in the development of NASH.

2023-02-07 | GSE162211 | GEO

Spatial hepatocyte plasticity of gluconeogenic gene expression and gluconeogenic activity during the metabolic transitions between fed, fasted and starvation states [scRNA-Seq]

Project description:Single cell analyses of hepatocytes across the liver lobule demonstrated that gluconeogenic gene expression (Pck1 and G6pc) is relatively low in the fed state and gradually increase first in the periportal hepatocytes during the initial fasting period. As the time of fasting progresses, pericentral hepatocyte gluconeogenic gene expression increases and following entry into the starvation state the pericentral hepatocytes are not significantly different than the periportal hepatocytes. Similarly, pyruvate-dependent gluconeogenic activity is approximately 10-fold higher in the periportal hepatocytes during the initial fasting states but with only 1.5-fold different between the pericentral and periportal hepatocytes in the starvation state. In parallel, starvation induced a reduction of canonical beta-catenin signaling and redistribution of pericentral and periportal glutamine synthetase and glutaminase resulting in an enhanced pericentral glutamine-dependent gluconeogenesis. These data demonstrate that hepatocyte gluconeogenic gene expression and gluconeogenic activity are highly spatially and temporally plastic across the liver lobule and underscore the critical importance of using well-defined feeding and fasting times to define the basis of hepatic insulin resistance and glucose production.

2025-01-23 | GSE263418 | GEO

Spatial hepatocyte plasticity of gluconeogenic gene expression and gluconeogenic activity during the metabolic transitions between fed, fasted and starvation states [RNA-Seq]

2025-01-23 | GSE263415 | GEO

Spatial hepatocyte plasticity of gluconeogenic gene expression and gluconeogenic activity during the metabolic transitions between fed, fasted and starvation states [targeted scRNA-seq]

2025-01-23 | GSE263419 | GEO

Ulcerative Colitis subjects

Project description:Ulcerative Colitis subjects

| PRJNA420680 | ENA

Ulcerative colitis gene expressions file

Project description:Ulcerative colitis related gene expressions analysis in colonic biopsy samples from control and ulcerative colitis patients

2019-07-10 | GSE134025 | GEO

Methylation profiling in Ulcerative colitis

Project description:The series was designed to identify the different methylated single CpGs involved in the pathophysiology of ulcerative colitis. A cohort of n=20 monozygotic twins, discordant for ulcerative colitis was selected. Illumina and Nimblegen platforms were used.

2012-09-27 | E-GEOD-27899 | biostudies-arrayexpress

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