"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
