Summary of project PR002335
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002335. The data can be accessed directly via it's Project DOI: 10.21228/M8T25X This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002335 |
| Project DOI: | doi: 10.21228/M8T25X |
| Project Title: | Comprehensive Lipidomic Analysis Identifies Critical Lipid and Metabolic Pathway Shifts in Alport Syndrome |
| Project Summary: | Alport syndrome (AS) is a hereditary kidney disease caused by COL4A3-5 gene mutations, leading to glomerular basement membrane abnormalities. While the genetic and structural aspects of AS are well established, the mechanisms linking collagen IV defects to podocyte injury remain incompletely understood. Emerging evidence suggests that lipotoxicity and lipid dysregulation may play a pivotal role in mediating podocyte damage in AS, akin to its established role in diabetic kidney disease (DKD). We sought to identify plasma and urine lipid alterations in autosomal dominant (ADAS) and X-linked AS (XLAS) compared with DKD and healthy controls. Using liquid chromatography coupled to mass spectrometry (LC-MS), we annotated 580 and 203 lipid species in plasma and urine, respectively. Volcano plot and ROC analyses (AUC ≥ 0.80) identified key lipids, including urinary HexCer 18:0(3O)/24:0(2OH) and CAR 12:0. These analyses highlighted the most relevant lipotoxic pathways, which may warrant deeper investigation for drug development in AS. Compared to controls, AS exhibited unbalanced sphingolipid catabolism, ceramide overload, and impaired fatty acid β-oxidation, alongside phospholipid and cholesterol imbalances suggestive of compromised ABCA1-mediated lipid efflux and mitochondrial dysfunction. Comparisons with DKD indicated a shared lipotoxic environment with ceramide elevation and disrupted fatty acid metabolism. However, disease-specific adaptations emerged, with severe ABCA1 dysfunction and marked phospholipid/cholesterol derangements in DKD, whereas AS showed pronounced sphingomyelin depletion. These findings demonstrate that AS involves distinct lipidomic disruptions and underscore shared lipotoxic mechanisms. This improved understanding of disease-specific lipid imbalances provides new potential therapeutic targets to mitigate podocyte injury and slow progression of AS. |
| Institute: | Universidad CEU San Pablo |
| Department: | Centro de MEtabolómica y Bioanálisis (CEMBIO) |
| Last Name: | Gonzalez-Riano |
| First Name: | Carolina |
| Address: | Facultad de Farmacia, Universidad CEU San Pablo, Campus Monteprincipe, Boadilla del Monte, Boadilla del Monte, Madrid, 28668, Spain |
| Email: | car.gonzalez@ceindo.ceu.es |
| Phone: | 00 34 91 3724753 |
| Funding Source: | This work was supported by grants from the following entities: The Ministry of Science and Innovation of Spain (MICINN) and the European Regional Development Fund FEDER, grant number PID2021-122490NB-I00 (CGR, BF, SM and CB). Instituto de Salud Carlos III and the European Union’s European Regional Development Fund grants PI19/01624 and PI24/01711. European Union-Next generation EU, Mechanism for Recovery and Resilence (MRR) RICORS (RD21/0005/0030; RD24/0004/0014) (GFJ, ASF). Spanish Society of Nephrology (AS, TBB). |
Summary of all studies in project PR002335
| Study ID | Study Title | Species | Institute | Analysis (* : Contains Untargted data) |
Release Date | Version | Samples | Download (* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003751 | Comprehensive Lipidomic Analysis Identifies Critical Lipid and Metabolic Pathway Shifts in Alport Syndrome | Homo sapiens | Universidad CEU San Pablo | MS | 2025-03-17 | 1 | 241 | Uploaded data (31.9G)* |
