Summary of project PR002163

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 PR002163. The data can be accessed directly via it's Project DOI: 10.21228/M81J94 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR002163
Project DOI:doi: 10.21228/M81J94
Project Title:Wheat-based protein slows cyst growth in Pkd1 knockout mice
Project Type:Untargeted Metabolomics
Project Summary:Abstract: Dietary load and composition are known contributors that accelerate cyst growth in polycystic kidney disease (PKD). High protein intake, which increases amino acid burden in the kidneys, is one such factor. Despite identical protein load, a plant-based wheat-gluten (WG) diet was recently reported to blunt the inflammatory response of animal-based casein diet in a hypertensive model. Considering the importance of pro-inflammatory signals on cystogenesis in PKD, we therefore sought to determine whether a WG compared to casein diet would decelerate cyst progression. Tamoxifen-inducible, global Pkd1 knockout (Pkd1KO) mice were fed either a low casein (6%), high casein (60%), or high wheat-gluten (60%) protein diet for 6 weeks. In a separate cohort, mice were gavaged daily with vehicle, lysine, or glutamine for 4 weeks while maintained on a normal protein (18%) diet. Tissues were used for histology, flow cytometry, mitochondrial function, metabolomics, and various biochemical assays. WG-fed mice had reduced kidney macrophage percentages, proinflammatory cytokine expression, and cyst growth compared to casein-fed mice. Protein source did not alter kidney mitochondria function. Supplementation with lysine, the highest amino acid in casein versus WG diet, increased kidney cyst growth, acid production, and metabolic disarray. This did not occur with glutamine supplementation, the highest amino acid in WG versus casein diet. Neither supplementation mounted an inflammatory response. A plant-based, low-lysine diet slows disease burden in a murine model of PKD. This easily modifiable diet may be a beneficial intervention for PKD patients.
Institute:University of Alabama at Birmingham
Department:Division of Nephrology, Department of Medicine
Last Name:Saigusa
First Name:Takamitsu
Address:McCallum Basic Health Science Building, Room 533, 1918 University Blvd. Birmingham, AL 35233
Email:tsaigusa@uabmc.edu
Phone:2059343462
Funding Source:NIDDK
Contributors:Randee Sedaka, Jifeng Huang, Shinobu Yamaguchi, Emily Hallit, Aida Moran-Reyna, Jung-Shan Hsu, Caleb Lovelady, Ayaka Fujihashi, Mohammad Sako, Malgorzata Kasztan, Gloria Benavides , Landon Wilson, Victor Darley-Usmar, Stephen Barnes

Summary of all studies in project PR002163

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ST003518 Wheat-based protein slows cyst growth in Pkd1 knockout mice Mus musculus University of Alabama, Birmingham MS 2026-01-12 1 60 Uploaded data (57.4G)*
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