Summary of Study ST003215

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 PR002005. The data can be accessed directly via it's Project DOI: 10.21228/M8FJ9V This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003215
Study TitleProtein restriction slows the development and progression of Alzheimer's disease in mice
Study SummaryDietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and many independent groups of researchers have shown that dietary protein restriction (PR) extends the lifespan and healthspan of mice. Here, we examined the effect of PR on metabolic health and the development and progression of Alzheimer’s disease (AD) in the 3xTg mouse model of AD. We found that PR has metabolic benefits for 3xTg mice and non-transgenic controls of both sexes, promoting leanness and glycemic control in 3xTg mice and rescuing the glucose intolerance of 3xTg females. We found that PR induces sex-specific alterations in circulating metabolites and in the brain lipidome, downregulating sphingolipid subclasses including ceramides, glucosylceramides, and sphingomyelins in 3xTg females. Consumption of a PR diet starting at 6 months of age reduced AD pathology in conjunction with reduced mTORC1 activity, increased autophagy, and had cognitive benefits for 3xTg mice. Finally, PR improved the survival of 3xTg mice. Our results demonstrate that PR slows the progression of AD at molecular and pathological levels, preserves cognition in this mouse model of AD, and suggests that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
Institute
University of Wisconsin-Madison
Last NameSimcox
First NameJudith
Address433 Babcock Dr, Madison, WI, 53706, USA
Emailjsimcox@wisc.edu
Phone-
Submit Date2024-05-20
Total Subjects40
Num Males20
Num Females20
Raw Data AvailableYes
Raw Data File Type(s)mzdata.xml
Analysis Type DetailLC-MS
Release Date2024-06-12
Release Version1
Judith Simcox Judith Simcox
https://dx.doi.org/10.21228/M8FJ9V
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN005272
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1290 Infinity II
Column Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Agilent 6495 QQQ
Ion Mode POSITIVE
Units ng lipid/mg brain
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