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Metabolic reprogramming modulates cardiomyocyte hypertrophy via GLS1 in chronic kidney disease

ABSTRACT: Left ventricular hypertrophy (LVH) is critical in chronic kidney disease (CKD), but its mechanisms remain unclear. This study employed multi-omics approaches, including RNA-seq and integrated metabolomics, to characterize metabolic alterations in cardiomyocytes (CM) of CKD mice, revealing enhanced glutaminolysis and impaired oxidative phosphorylation. We identified that glutaminase 1 (GLS1), the rate-limiting enzyme of glutaminolysis, is significantly upregulated and enzymatically activated in CM under CKD conditions. A multi-center cohort study confirmed that serum-induced GLS1 activity was associated with LV hypertrophic remodeling. Cardiomyocyte-specific deletion or pharmacological inhibition of GLS1 attenuated CKD-induced cardiac hypertrophy. Proteomic analysis revealed that multiple circulating proteins in the serum of CKD patients are associated with GLS1 enzymatic activity. Furthermore, phosphate (Pi), a representative uremic toxin, functions as a critical modulator of GLS1 activity and expression, compromising mitochondrial bioenergetics by promoting ammonia production and reducing mitochondrially encoded respiratory chain proteins. These integrated metabolic effects underscore the pivotal role of GLS1 in orchestrating myocardial energy reprogramming, thereby contributing to CKD-induced LVH.

ORGANISM(S): Mus musculus

PROVIDER: GSE343701 | GEO | 2026/08/13

REPOSITORIES: GEO

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The role of GLS1 and MPC2 in germinal center B cell regulation

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Project description:Metabolic reprogramming modulates cardiomyocyte hypertrophy via GLS1 in chronic kidney disease

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2014-07-01 | E-GEOD-53512 | biostudies-arrayexpress

MicroRNAs in an Experimental Model of Physiologic Left Ventricular Hypertrophy: a Microarray-based Analysis

Project description:BACKGROUND - MicroRNAs (miRs) are a class of small non-coding RNAs that regulate gene expression. Transgenic models have proved that a single miR can induce pathological cardiac hypertrophy and failure. The roles of miRs in the genesis of physiologic left ventricular hypertrophy (LVH), however, are not well elucidated. OBJECTIVE - To evaluate miRs expression in an experimental model of exercise-induced LVH. METHODS - Male Balb/c mice were divided into sedentary (SED) and exercise (EXE) groups. Voluntary exercise was performed in odometer-monitored metal wheels during 35 days. Analyses were performed after 7 and 35 days of training, and consisted of transthoracic echocardiography, maximal exercise test, miRs microarray (miRBase v.16) and real-time qRT-PCR analysis. RESULTS - Left ventricular weight/body weight ratio increased by 7% in the EXE group at day 7 (p<0.01) and by 11% at 35 days of training (p<0.001) After 7 days of training, microarray identified 35 deregulated miRs: 20 had an increase in their expression and 15 were down-regulated (p=0.01). At day 35 of training, 25 miRs were deregulated: 15 were up-regulated and 10 had decreased their expression compared to the SED group (p<0.01). qRT-PCR confirmed an increase in miR-150 levels at both time points and a decrease in miR-26b, miR-27a and miR-143 after 7 days of voluntary exercise. CONCLUSIONS M-bM-^@M-^S We unraveled new miRs that can modulate physiological cardiac hypertrophy, particularly miR-26b, -150, 27a and -143. Our data also indicate that previously established regulatory gene pathways involved in pathological LVH are not deregulated in physiologic LVH. Experimental model of left ventricular hypertrophy induced by voluntary exercise Male Balb/c mice, 8-10 weeks old, 4 groups analyzed, each group consisted of a pool from 4 animals

2014-06-01 | E-GEOD-52278 | biostudies-arrayexpress

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