image: Figure 1. The SAAR diet and BSO induce similar morphometric changes. Four groups of eighteen-week-old male C57BL/6NTac mice (n=7/group) were fed high-fat (60% Kcal from fat) diets with 0.86% w/w methionine (CD), 0.12% w/w methionine (SAAR), SAAR diet with 30 mM N-acetylcysteine in water (NAC), and CD diet with 30 mM DL-buthionine (S, R) sulfoximine (BSO). Compared to the CD, the SAAR diet caused weight loss (A–C) and increased food intake (D). Despite feeding on the SAAR diet, mice in the NAC group did not exhibit any changes (A–D). Except for the lack of increased food intake, changes in BSO mice were similar to those in the SAAR mice, despite feeding on a diet replete with sulfur amino acids (A–D). Note: One-way ANOVA followed by Tukey’s multiple comparison tests was used to find group-wise differences (*P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. Bars and error bars represent means and standard error of means). CD growth curves are invisible as NAC growth curves overlay them.
Credit: Copyright: © 2025 Ommi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“Data demonstrate that BSO recapitulates the SAAR-induced anti-obesity effects and that GSH plays a mechanistic role.”
BUFFALO, NY — May 13, 2025 — A new research paper was published in Aging (Aging-US) Volume 17, Issue 4, on April 7, 2025, titled “Pharmacological recapitulation of the lean phenotype induced by the lifespan-extending sulfur amino acid-restricted diet.”
In this study, the research team, led by first author Naidu B. Ommi and corresponding author Sailendra N. Nichenametla from the Orentreich Foundation for the Advancement of Science Inc., investigated whether the drug buthionine sulfoximine (BSO) could replicate the effects of sulfur amino acid restriction (SAAR), a challenging diet known to reduce obesity. The study found that BSO produced similar reductions in fat mass and weight gain. This drug-based approach may offer a simpler and safer treatment for obesity, especially for those unable to follow strict dietary plans.
Obesity and metabolic disorders raise the risk of chronic illnesses like heart disease, diabetes, and Alzheimer’s disease. While SAAR, a diet low in the amino-acids methionine and cysteine, has shown powerful health benefits in animal studies, its translation to humans has been limited by adherence challenges. This new study explored whether BSO, a compound that lowers glutathione (GSH) levels in the body, could mimic SAAR’s effects without dietary restriction.
Researchers tested four groups of obese mice on high-fat diets. One group received the SAAR diet, another was given a regular diet plus BSO, while two control groups received either no treatment or a supplement that increased GSH levels. The BSO-treated mice showed lower fat mass, reduced liver fat, and prevented weight gain, results comparable to those on the SAAR diet. These benefits occurred without reducing food intake or muscle mass, making BSO a particularly promising treatment option.
“BSO mice exhibited all SAAR-induced changes, with two notable differences, i.e., a smaller effect size than that of the SAAR diet and a higher predilection for molecular changes in kidneys than in the liver.”
Additional findings revealed that both the SAAR diet and BSO influenced metabolic activity by activating pathways related to fat storage, but they did so in different organs. The SAAR diet had stronger effects in the liver, while BSO acted more in the kidneys. Both interventions increased levels of the amino acid serine, which is associated with lower fat production.
Unlike many obesity treatments that suppress appetite or reduce muscle, BSO helped prevent fat accumulation while preserving lean mass and food consumption. No signs of liver or kidney toxicity were observed during the 13-week study, suggesting the drug’s safety at the tested dose.
Since BSO has previously been evaluated in human clinical trials for other conditions, repurposing it for metabolic diseases may be relatively straightforward. However, the researchers point out that there should be further studies in both animals and humans. If successful, this strategy could provide a practical alternative to difficult-to-maintain diets and help more people manage weight long-term.
Read the full paper: DOI: https://doi.org/10.18632/aging.206237
Corresponding author: Sailendra N. Nichenametla – snichenametla@orentreich.org
Keywords: aging, buthionine sulfoximine, thiols, serine, anti-obesity drugs
Click here to sign up for free Altmetric alerts about this article.
______
To learn more about the journal, please visit our website at www.Aging-US.com and connect with us on social media at:
- X
- YouTube
- Bluesky
- Spotify, and available wherever you listen to podcasts
Click here to subscribe to Aging publication updates.
For media inquiries, please contact media@impactjournals.com.
Journal
Aging-US
Article Title
Pharmacological recapitulation of the lean phenotype induced by the lifespan-extending sulfur amino acid-restricted diet
Article Publication Date
7-Apr-2025
COI Statement
The authors declare that they have no conflicts of interest.