In a recent study, mice on a high-fat diet were given an injection of AP39, a compound that transports hydrogen sulfide directly to the mitochondria within cells. The findings revealed that this treatment notably decreased the pace of weight gain by an average of 32% over a span of 12 weeks. Additionally, researchers observed a reduction in fat accumulation in the liver, which can be a serious issue associated with obesity and may lead to harmful inflammation.
New research indicates that therapies aimed at delivering hydrogen sulfide to cells may eventually lead to innovative treatments for obesity and related disorders.
There is increasing evidence that hydrogen sulfide plays a vital role in liver health. Prior studies have indicated that small quantities of hydrogen sulfide in the body help regulate how the liver processes fats. However, until now, there was no precise method to achieve this regulation. This compound also influences the mitochondria’s performance, which are often referred to as the “powerhouses” of cells, responsible for energy production.
This study was conducted by Jagiellonian University Medical College in Poland and the University of Exeter, and the findings were published in Pharmacological Research. Mice on a high-fat diet were treated with AP39, which supplies hydrogen sulfide directly to the mitochondria. This treatment was found to considerably reduce weight gain rates and cut down fat buildup in the liver, a complication linked to obesity that can trigger inflammation.
AP39 was developed at the University of Exeter and is currently under the ownership of its spin-out firm, MitoRX Therapeutics. The study demonstrated that AP39 decreased the liver’s active processes that produce harmful fats, synthesize proteins that transport fat, and regulate dangerous signals for liver health. It also diminished the liver’s creation of new fats by inhibiting a crucial negative metabolic pathway (mTOR/SREBP1/NF-kB).
Matt Whiteman, a co-author of the study and Professor of Experimental Therapeutics at the University of Exeter Medical School, initiated his research on hydrogen sulfide’s role in the body back in 2004. He discovered that individuals with excess weight suffering from type 2 diabetes had lower levels of hydrogen sulfide in their bloodstream, correlating this reduction to higher body fat percentages which consequently resulted in poorer blood sugar control and elevated insulin resistance. This suggested that utilizing drug compounds to replace lost hydrogen sulfide could help prevent or reverse these negative effects.
Professor Whiteman expressed, “Our initial discoveries indicated that hydrogen sulfide might someday be beneficial in addressing diabetes, obesity, and complications arising from excess body fat. In today’s world, obesity poses a growing global health challenge, and there is a pressing need for improved treatment options. If our results regarding hydrogen sulfide-producing compounds that focus on mitochondria lead to similar outcomes in humans, we could open the door to promising new treatments. It’s rewarding to channel these insights into developing more effective drugs with MitoRx.”
Dr. Aneta Stachowicz from the Department of Pharmacology at Jagiellonian University Medical College, who is the lead author of the paper, commented: “Our findings show that AP39 effectively slows weight gain and significantly lowers several obesity indicators in mice. This is an exciting development, and we hope it signifies the dawn of a new era in the creation of innovative therapies for metabolic diseases through the use of hydrogen sulfide to regulate the body’s signaling mechanisms.”
Dr. Jon Rees, the Chief Executive Officer of MitoRx, stated: “This publication marks a significant milestone in MitoRx’s progress in developing mitochondrial-targeting therapies and highlights the enormous potential of AP39 in tapping into a new treatment pathway for obesity. Strong international research collaborations like this are essential for accelerating therapeutic progress to benefit patients.”
