Exciting new research has determined that a variant of a drug used to treat pulmonary arterial hypertension induces weight-loss in obese mice. Among mice fed a high-fat diet, those who did not get the medication became obese while medicated mice did not.
The experimental drug used stimulates soluble guanylyl cyclase (sGC), and this drug is a member of the same class of novel drugs as the drug riociguat. The Food and Drug Administration approved riociguat in 2013 to treat high blood pressure in the lungs. Riocoguat is produced by Bayer HealthCare Pharmaceuticals, is marketed under the trade name Adempas.
In mice, the sCG stimulator stimulated a shift in fat tissue and turned stored white fat in the mice into brown fat, which burns up more energy and improves metabolic function. Beige or brown fat is a beneficial type of fat that is richly populated with mitochondria, which makes the tissue look brown under a microscope. White fat releases hormonal signals that prompt the storage of still more white fat, but brown fat burns up fat and protects against weight gain, even when caloric intake is high.
In this research, which was published in the journal Nature Communications, mice made obese by a high-fat, high-calorie diet were given the sCG stimulator. These mice not only experienced weight loss, but also showed improved glucose tolerance, reduced insulin levels and decreased the signs of fatty liver, which is a damaging consequence of established obesity. It also even shrunk white fat cells.
In plump mice on the sCG stimulator, circulating dietary fatty acids were increasingly drawn into the brown fat and burned up at high rates. Even muscle and white fat in those mice increased their use of the circulating fatty acids. These metabolic changes caused mice to burn more calories, and their abnormal metabolic function improved.
This new research was led by researchers at the University Hospital in Bonn, Germany, and it elucidated the biochemical pathway that generates brown fat. This brings potential targets into view that could shift white fat into brown fat.
The sCG stimulator used in this study, the authors concluded, “might be used to enhance weight loss induced by physical activity.”
If a drug related to riociguat is to enter broad use for obesity, however, it will need to be cheaper than its close chemical relative. At doses taken by those with pulmonary arterial hypertension, a typical month’s prescription of Adempas costs close to $2,800, or about $90,000 a year.
As a treatment for the nation’s more than 72 million obese adults, that cost could prove prohibitive, especially as obesity and its consequences are increasingly understood to be chronic conditions that will need long-term management.