Novel anti-obesity drug breaks the cycle of appetite and weight gain
A team of scientists in the US investigating the relationship between metabolic syndrome and a key hormone have demonstrated how a promising new drug could play an important preventative role in a variety of conditions. The experiments were carried out in mice but have the researchers optimistic about the drug's potential in humans, where it could suppress appetite and blood glucose, and help prevent ailments such as obesity and diabetes.
The research was carried out by scientists at Harrington Discovery Institute at University Hospitals in Cleveland and centers on a hormone called asprosin, which the team had previously found plays a regulatory role in appetite and, by extension, glucose and insulin levels in the blood. Earlier experiments showed that people with lower levels of asprosin experienced lower levels of hunger, and that, conversely, its levels were higher in those suffering from metabolic syndrome, a group of conditions including obesity, high blood pressure and insulin resistance that combine to increase risk of diabetes, stroke and heart disease.
“In 2016, we discovered a hormone called asprosin, which stimulates appetite and increases blood glucose levels by acting on the hypothalamus and the liver,” explains Atul Chopra, senior author on the study. “For reasons that are unclear, asprosin levels are elevated in patients with metabolic syndrome, leading to even higher appetite, body weight and blood glucose. We found that we can break that disease cycle by neutralizing asprosin with monoclonal antibodies.”
The scientists used three different mouse models of metabolic syndrome, and tested out monoclonal antibodies designed to inhibit asprosin, finding that the treated mice exhibited a reduced appetite, body weight and blood glucose levels.
“When mice were treated with monoclonal antibodies that neutralize asprosin, they ate less, lost weight, and their blood glucose levels normalized,” says Dr. Mishra. “Elevated appetite, body weight and blood glucose are three critical features of metabolic syndrome, and they were all corrected with these antibody treatments.”
Using animal models as part of pre-clinical research always carries the risk that the results won't translate to human subjects, but because asprosin is already known to play a key role in metabolic syndrome in people, the scientists are optimistic about the possibilities.
“We already know what happens to humans when asprosin is low,” says Chopra. “That’s a very privileged situation in biomedical science because of the confidence it creates for drug development. Many drugs succeed in mice but fail in humans. In this case, knowing that humans with low asprosin have reduced appetite, body weight and blood glucose and insulin is tremendously helpful at designing and developing drugs to mimic this beneficial effect in patients with metabolic syndrome.”
Adapting the drug for use in humans will involve exploring the ideal dosage as a way of limiting unwanted effects, as the scientists eye potential therapeutic use for the monoclonal antibodies further down the track.
“Progress towards clinical trials and making the drug ready for humans is the last piece of the puzzle,” says Chopra. “We want to keep the dose of the drug low and don’t want side effects. While we know this concept and this drug works, our next step in the process is to make it better and ready for humans.”
The research was published in the journal eLife.