Wednesday – 7 Ramadan 1444 AH – March 29, 2023 AD
London: «Asharq Al-Awsat»
A new obesity treatment could provide dramatic weight loss without surgery or nausea. A new class of vehicle could do just that; These potential treatments significantly reduce weight and lower blood glucose.
The injectable compounds also avoid side effects common with current weight loss and diabetes medications such as nausea and vomiting. Scientists report that the new treatment not only reduces food intake, but also increases calorie burning.
The researchers will present their findings today at the ACS Spring 2023 meeting of the American Chemical Society. It is a mixed meeting that takes place from 26 to 30 March.
The new treatment could be a successful alternative to the “gastric bypass”, which is based on diverting the stomach.
To clarify further, Dr. Robert Doyle, one of the principal investigators on the project, who works at Syracuse University and Sunny Upstate Medical University with Dr. Christian Roth, who works at the Seattle Children’s Research Institute, said, “Obesity and diabetes were the epidemic before the Covid-19 pandemic. And it is expected to get worse.” According to the specialized medical website, “Medical Express”.
Gastric bypass and related procedures known as bariatric surgery offer one solution and often result in permanent weight loss and even remission of diabetes. But these operations carry risks, and are not suitable for everyone and are not accessible to the hundreds of millions of people worldwide who are obese or diabetic. Alternatively, according to Doyle, “they can treat their metabolic problems with a drug that replicates the long-term benefits of surgery.” These benefits are associated with a postoperative change in levels of intestinal secretion of certain hormones. including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY); Which indicate fullness, curb appetite and normalize blood sugar. Current drugs that aim to replicate this effect primarily activate cellular receptors for GLP-1 in the pancreas and brain. So this approach has shown great success in reducing weight and treating type 2 diabetes.”
“A lot of people can’t tolerate the side effects of medications,” Doyle adds. Within one year, 80 to 90 percent of people who start taking these medications will not return to them. To address this drawback, different researchers have designed other therapies that interact with more than one type of gut hormone receptor. For example, Doyle’s group created a peptide that activates two PYY receptors, in addition to the GLP-1 receptor. Dubbed GEP44, this compound caused obese mice to eat up to 80 percent less than they normally would. By the end of the 16-day study, she had lost an average of 12% of her body weight. This was more than three times the amount lost by mice treated with liraglutide, an injected drug that only activates the GLP-1 receptor and that has been approved by the US Food and Drug Administration to treat obesity.
In contrast to liraglutide, tests of GEP44 in rats and shrews (a mammal unlike mice that can vomit) revealed no sign of nausea or vomiting, possibly because activation of several receptors may suppress the intracellular signaling pathway that leads to these symptoms. , according to Doyle.
In their latest findings, Doyle’s team reports that weight loss caused by GEP44 can now be tracked not only to reduced eating, but also to increased energy burn, which can take the form of increased movement, heart rate or body temperature.
GEP44 has an in vivo half-life of only about one hour, but Doyle’s group has just engineered a peptide with a much longer half-life. This means that it can be injected once or twice a week instead of several times a day.
The researchers now say that mice treated with the next-generation compound maintain their new, thinner bodies even after the treatment ends. Which is not often the case with currently approved medications.
However, weight loss is not the only benefit of peptide therapies. Just as they reduce blood sugar by drawing glucose into muscle tissue, they can be used as fuel and turn certain cells in the pancreas into insulin-producing cells, helping to replace those damaged by diabetes.
Another benefit, according to Doyle and Heath Schmidt of the University of Pennsylvania, is that GEP44 reduces cravings for opioids such as fentanyl in mice. If this also works in humans, it could help addicts quit illegal drugs or avoid relapse.
The researchers filed patents for their compounds; They plan to test their peptides in primates. They will also study how the therapies alter gene expression and rewire the brain and what this might mean for these compounds, as well as for other types of drugs.
“For a long time, we didn’t think we could separate weight loss from nausea and vomiting because they’re connected to the same part of the brain,” Doyle concludes. But researchers have now separated these two pathways. This has implications for chemotherapy; which causes similar side effects.