Summary of project PR002200
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 PR002200. The data can be accessed directly via it's Project DOI: 10.21228/M87Z47 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002200 |
| Project DOI: | doi: 10.21228/M87Z47 |
| Project Title: | Unraveling cysteine deficiency-associated rapid weight loss |
| Project Summary: | Forty percent of the US population and 1 in 6 individuals worldwide are obese, with the incidence surging globally. Various dietary interventions, including carbohydrate, fat and more recently amino acid restriction, have been explored to combat this epidemic. We investigated the impact of removing individual amino acids on the weight profiles of mice. Here, we show that conditional cysteine restriction resulted in the most dramatic weight loss when compared to essential amino acid restriction, amounting to 30% within one week, which was readily reversed. We found that cysteine deficiency activated the integrated stress response and oxidative stress response, which amplify each other, leading to the induction of GDF15 and FGF21, which partly explained the phenotype. Surprisingly, we observed lower tissue coenzyme A (CoA), which has been considered to be extremely stable10, resulting in reduced mitochondrial functionality and metabolic rewiring. This results in energetically inefficient anaerobic glycolysis and defective TCA cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds, and amino acids In summary, our investigation reveals that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and stress signaling compared to other amino acid restrictions. These findings suggest novel strategies for addressing a range of metabolic diseases and the growing obesity crisis. |
| Institute: | NYU Grossman School of Medicine |
| Last Name: | Varghese |
| First Name: | Alan |
| Address: | 550 First Avenue, NY, NY 10016 |
| Email: | Alan.Varghese@nyulangone.org |
| Phone: | 212-263-7520 |
Summary of all studies in project PR002200
| Study ID | Study Title | Species | Institute | Analysis (* : Contains Untargted data) |
Release Date | Version | Samples | Download (* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003566 | Unraveling cysteine deficiency-associated rapid weight loss | Mus musculus | NYU Grossman School of Medicine | MS | 2025-03-05 | 1 | 102 | Uploaded data (41.7G)* |
