A therapy that delivers hydrogen sulfide into cells could one day form the basis of new treatments for obesity and related diseases, a new study concludes.
Increasing evidence suggests that hydrogen sulfide plays an important role in the liver. Previous research has shown that trace amounts of hydrogen sulfide in the body regulates how the liver processes fat, but until recently there was no specific way to do that. It also affects the function of mitochondria, known as the cell’s “power plants” that produce energy.
The new study was led by Poland’s Jagiellonian University School of Medicine and the University of Exeter and was published in the journal Pharmacological Research. In the study, mice were fed a high-fat diet and injected with AP39, a compound that delivers hydrogen sulfide directly to the mitochondria in cells. The study concluded that the treatment significantly slowed the rate of weight gain, with an average reduction of 32 percent. over a 12-week study period. The researchers also found that the treatment reduced the accumulation of fat in the liver, which is a complication of obesity and can cause harmful inflammation.
AP39 was invented at the University of Exeter and is now owned by its spin-out company, MitoRX Therapeutics. The study showed that treating mice with AP39 activated liver processes that produce certain harmful fats in the body, build fat-carrying proteins, and regulate important signals that can harm the liver. was found to have decreased. It also reduced new fat production in the liver by preventing activation of a key harmful metabolic pathway (mTOR/SREBP1/NF-kB).
Study co-author Matt Whiteman, professor of experimental therapeutics at the University of Exeter’s School of Medicine, first began researching the role of hydrogen sulphide in the body in 2004. He was the first to notice that overweight type 2 diabetics had low hydrogen levels. Their blood contains sulfide. This was determined by the amount of body fat they carried. Higher body fat content means lower blood sulfide levels, which in turn means less carbohydrate control and increased insulin resistance. This suggests that these deleterious changes could be prevented or reversed by drug molecules that replace the lost sulfide.
Professor Whiteman said: “These early findings suggest that hydrogen sulphide may one day play a role in treating diabetes, obesity and complications arising from too much fat in the body. Today “Obesity is a global health challenge, and new and better treatments are being developed.” If our findings that mitochondria-targeted hydrogen sulfide-generating molecules significantly slow weight gain can be translated to humans, it would be exciting to translate these observations into better clinically viable drugs. MitoRx.
“Our study shows that AP39 slows weight gain and significantly reduces multiple obesity markers in mice,” said Dr. Aneta Stahowicz, Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical School, Poland, and lead author of the pharmacology study. “We have demonstrated that it can be done.” This is very exciting and we hope it marks the beginning of a new era in the development of innovative treatments for metabolic diseases by using hydrogen sulfide to modulate the body’s signaling processes. ”
This publication is a major step in MitoRx advancing mitochondria-targeted therapies and demonstrates the great potential of AP39 to target new pathways for obesity treatment. Strong international research collaborations like this help accelerate progress in treatments for patients. ”
Dr. John Reese, CEO, MitoRx
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Reference magazines:
Stachowicz, A., et al. (2024). Mitochondria-targeted hydrogen sulfide donor reduces hepatic steatosis and obesity in mice fed a high-fat diet by inhibiting de novo adipogenesis and inflammation via mTOR/SREBP-1 and NF-κB signaling pathways I will. Pharmacological research. doi.org/10.1016/j.phrs.2024.107428.
