Cousin of Viagra Reduces Obesity by Stimulating Cells to Burn Fat, Hopkins Study Shows in Mouse Models

After being placed on high-fat diets, mice were either selected to take the PDE9 inhibiting oral drug or a placebo. The PDE9 inhibitor reduced total body and liver fat in mice without altering diet or physical activity. However, mice taking the placebo continued to gain body and liver fat throughout the 6-8-week drug trial. (Credit: Images courtesy of David Kass).
Researchers at Johns Hopkins Medicine have found that a drug first developed to treat Alzheimer’s disease, schizophrenia, and sickle cell disease reduces obesity and fatty liver in mice and improves their heart function--without changes in food intake or daily activity. These findings, published online October 7, 2021 in the Journal of Clinical Investigation, reveal that a chemical inhibitor of the enzyme PDE9 stimulates cells to burn more fat. This occurred in male mice and in female mice whose sex hormones were reduced by removing their ovaries, thus mimicking menopause. Postmenopausal women are well known to be at increased risk for obesity around their waist, as well as at risk for cardiovascular and metabolic disease. Inhibiting PDE9 did not cause these changes in female mice that had their ovaries, so female sex hormone status was important in the study. The JCI article is titled “Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice." “Currently, there isn’t a pill that has been proven effective for treating severe obesity, yet such obesity is a global health problem that increases the risk of many other diseases,” says senior investigator David Kass, M.D., Abraham and Virginia Weiss Professor of Cardiology at the Johns Hopkins University School of Medicine. “What makes our findings exciting is that we found an oral medication that activates fat-burning in mice to reduce obesity and fat buildup in organs like the liver and heart that contribute to disease; this is new.”
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