Hydrogen Sulfide: A New Treatment for Obesity

New research suggests that therapies that deliver hydrogen sulfide to cells could one day be used to develop new treatments for obesity and related disorders.

Increasing data suggests that hydrogen sulfide plays a crucial role in the liver. Previous study has shown that a trace amount of hydrogen sulfide in the body regulates how the liver consumes fat, but until recently, there was no method to do so directly. It also affects the function of mitochondria, the “powerhouse” of cells that generate energy.

The latest study, conducted by Jagiellonian University Medical College in Poland and the University of Exeter, was published in Pharmacological Research. In the study, mice were fed a high-fat diet and injected with the chemical AP39, which delivers hydrogen sulfide directly to mitochondria in cells. The study concluded that the medication considerably decreased the rate of weight gain, with an average reduction of 32% over the course of 12 weeks. The researchers also discovered that the medication reduced fat deposition in the liver, which is a consequence of obesity and can cause severe inflammation.

AP39 was developed at the University of Exeter and is now held by its spin-off business MitoRX Therapeutics. The study discovered that AP39 treatment in mice lowered the activity of liver enzymes that help manufacture certain toxic lipids in the body, build proteins that transport fat, and regulate critical signals that can be harmful to the liver. It also reduced the liver’s generation of new lipids by inhibiting the activation of an important unfavorable metabolic pathway (mTOR/SREBP1/NF-kB).

Matt Whiteman, Professor of Experimental Therapeutics at the University of Exeter Medical School, initially investigated the role of hydrogen sulfide in the body in 2004. He discovered that persons with type 2 diabetes who were overweight had lower levels of hydrogen sulfide in their blood. This was governed by how much body fat they carried. Higher body fat composition resulted with lower blood sulfide levels, poorer sugar management, and increased insulin resistance. This showed that pharmacological compounds that restore missing sulfide could prevent or reverse these negative effects.

Professor Whiteman stated, “These preliminary findings suggested that hydrogen sulfide could one day have a role in treating diabetes, obesity, and issues caused by having too much fat in the body. Obesity is now a major global health issue, and new and improved treatments are sorely needed. If our findings, which show that hydrogen sulfide-generating compounds that target mitochondria greatly reduce weight gain, apply to humans, we may have an interesting new therapeutic option. It is gratifying to see MitoRx integrate these discoveries into clinically viable and superior medications.

Dr. Aneta Stachowicz, Department of Pharmacology at the Faculty of Medicine, Jagellonian University Medical College, Poland, and lead author of the Pharmacological Research paper, said: “Our research demonstrates that AP39 slows weight gain and significantly reduces multiple markers of obesity in mice. This is very exciting, and we hope it marks the beginning of a new era in the development of an innovative therapeutic approach for metabolic diseases, by using hydrogen sulfide to modulate the body’s signalling processes.”

For more information: Mitochondria-targeted hydrogen sulfide donor reduces fatty liver and obesity in mice fed a high fat diet by inhibiting de novo lipogenesis and inflammation via mTOR/SREBP-1 and NF-κB signaling pathways, Pharmacological Research, https://doi.org/10.1016/j.phrs.2024.107428