Molecules that produce hydrogen sulfide and specifically target mitochondria significantly reduced weight gain in mice.
According to new research, therapies that deliver hydrogen sulfide to cells may pave the way for future treatments for obesity and related diseases.
Growing evidence indicates that hydrogen sulfide plays a crucial role in liver function. Previous studies have demonstrated that small amounts of hydrogen sulfide help regulate fat metabolism in the liver, though targeting this process directly has been challenging until recently. Additionally, hydrogen sulfide affects the function of mitochondria, the “powerhouses” of cells responsible for energy production.
The new study is led by Jagiellonian University Medical College in Poland and the University of Exeter and published in Pharmacological Research. In the research, mice fed a high-fat diet were injected with the compound AP39, which delivers hydrogen sulfide directly to mitochondria in cells The research concluded that the treatment significantly slowed the rate of weight gain, reduced by 32 percent on average, over the 12 weeks of the study. The team also found that treatment reduced the accumulation of fat in the liver, which can be a complication of obesity and can lead to harmful inflammation.
AP39’s Mechanism of Action
AP39 was invented at the University of Exeter and is now owned by its spin-out company MitoRX Therapeutics. The study found that in the mice, treatment with AP39 reduced the activity of processes in the liver that help create certain detrimental fats in the body, build proteins that carry fat, and regulate important signals that can be harmful to the liver. It also lowered the liver’s production of new fats by preventing the activation of a key adverse metabolic pathway (mTOR/SREBP1/NF-kB).
Study co-author Matt Whiteman, Professor of Experimental Therapeutics at the University of Exeter Medical School, first began researching the role of hydrogen sulfide in the body in 2004. He first noticed that people with type 2 diabetes who were overweight had lower levels of hydrogen sulfide in their blood. This was determined by the amount of body fat they were carrying. Higher body fat content meant lower blood sulfide levels, which in turn meant poorer sugar control and greater insulin resistance. That suggested that these adverse changes could be prevented or reversed by drug molecules that replace the lost sulfide.
Potential Implications for Human Treatment
Professor Whiteman said: “These early findings suggested that hydrogen sulfide could one day play a role in treating diabetes, obesity, and complications arising from having too much fat in the body. Today, obesity is a growing global health challenge, and new and better treatments are desperately needed. If our findings that hydrogen sulfide-generating molecules that target mitochondria significantly slow weight gain translate to humans, we could be looking at an exciting new option for treatment. It is gratifying to translate these observations toward clinically viable and better drugs with MitoRx.
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 signaling processes.”
Dr Jon Rees, Chief Executive Officer of MitoRx, said: “This publication is a major step in MitoRx advancing our therapies which target mitochondria, and shows the huge potential for AP39 targeting a new pathway for treating obesity. Powerful international research collaborations like this help speed therapeutic advances to patients.”
Reference: “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” by Aneta Stachowicz, Klaudia Czepiel, Anna Wiśniewska, Kamila Stachyra, Magdalena Ulatowska-Białas, Beata Kuśnierz-Cabala, Marcin Surmiak, Grzegorz Majka, Katarzyna Kuś, Mark E. Wood, Roberta Torregrossa, Matthew Whiteman and Rafał Olszanecki, 18 September 2024, Pharmacological Research.
DOI: 10.1016/j.phrs.2024.107428
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3 Comments
There’s no tech-fix for unhealthy lifestyle.
“It is gratifying to translate these observations toward clinically viable and better drugs with MitoRx.”
From the study: “Declaration of Competing Interest – The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Mark E. Wood, Roberta Torregrossa, Matthew Whiteman has patent pending to slow-release sulfide-generating molecules and their therapeutic use. Matthew Whiteman is CSO of MitoRx Therapeutics, Oxford, U.K, developing organelle-targeted molecules for clinical use. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.”
I love the last sentence. “IF there are other authors, they declare they have no known competing financial interests…” That’s interesting. They don’t know if there are any other authors, but if there are, then they have no competing interests. You can’t make this up.
Bottom line: Another mouse study with no known relevance to humans, but a sales pitch for another method for targeting drugs, demonstrated in mice.
The real breakthrough will come when people realise the pharmaceutical industry is poisoning them with toxic chemicals, and that the best the way to lose weight is eat a balanced diet and do plenty of exercise.
I speak as someone who grew up during the war years, when we couldn’t over-eat, one walked or cycled most places and you hardly ever saw an obese adult, let alone a fat child. I’m 86, don’t eat junk food and still weigh the same as in my late teens.