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.
| Study ID | ST003215 |
| Study Title | Protein restriction slows the development and progression of Alzheimer's disease in mice |
| Study Summary | Dietary 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 Name | Simcox |
| First Name | Judith |
| Address | 433 Babcock Dr, Madison, WI, 53706, USA |
| jsimcox@wisc.edu | |
| Phone | - |
| Submit Date | 2024-05-20 |
| Total Subjects | 40 |
| Num Males | 20 |
| Num Females | 20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzdata.xml |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-06-12 |
| Release Version | 1 |
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Sample Preparation:
| Sampleprep ID: | SP003341 |
| Sampleprep Summary: | Whole brain samples were pulverized and 20 mg were homogenized in 215 µL MeOH plus 10 µL of a 30 µM solution of each of the following internal standards: Cer d18:1(d7)_15:0 (Avanti #67492-15-3), Cer d18:1(d7)_16:0 (Avanti # 1840942-13-3), Cer d18:1(d7)_18:0 (Avanti #1840942-14-4), Cer d18:1(d7)_24:0 (Avanti #1840942-15-5), Cer d18:1(d7)_24:1 (Avanti # 1840942-16-6), and SM d18:1(d7)_18:1 (Avanti # 2342574-42-7). The samples were homogenized in bead tubes (1.4mm, Qiagen, #13113-50) in a Qiagen TissueLyzer II (catalog no.: 9244420) for 2 cycles in blocks chilled to 4°C. 250 µL H2O and 750 µL MTBE were then added, and the samples were inverted to mix and placed on ice. After 15 minutes, the samples were centrifuged at 4 °C at 16000 x g for 5 minutes, and 500 µL of the top organic phase was removed into a new tube and dried using a speedvac. Lipids were then resuspended in 150 µL IPA and stored at -20°C until analysis. An insoluble precipitate was also observed when the extracts were resuspended in IPA. |
