Scientists at Indiana University and international collaborators have found a way to link two hormones into a single molecule, producing a more effective therapy with fewer side effects for potential use as treatment for obesity and related medical conditions.
The studies were carried out in the laboratories of Richard DiMarchi, the Standiford H. Cox Distinguished Professor of Chemistry and the Linda & Jack Gill Chair in Biomolecular Sciences in the IU Bloomington College of Arts and Sciences, and of Matthias Tschöp, professor of medicine and director of the Institute of Diabetes and Obesity, Helmholtz Center Munich, Germany. Results were published online this week by the journal Nature Medicine.
Researchers combined a peptide hormone from the digestive system, GLP-1, with the hormone estrogen and administered it to obese laboratory mice. While both GLP-1 and estrogen have demonstrated efficacy as therapy for obesity and adult-onset diabetes, the combination was more effective in producing weight loss and other beneficial results than using either compound on its own. And it produced fewer adverse effects, such as excessive tissue growth linked to tumor formation.
"We find that combining the hormones as a single molecule dramatically enhanced their efficacy and their safety," DiMarchi said. "The combination improves the ability to lower body weight and the ability to manage glucose, and it does so without showing the hallmark toxicities associated with estrogen."
The researchers believe GLP-1 acts as a "medicinal chaperone," targeting estrogen to the hypothalamus and pancreas, which are involved with metabolic processes. The precise targeting reduces the likelihood that the estrogen will produce negative effects, such as cancer and stroke.
Brian Finan, a former doctoral student in DiMarchi's lab, is the lead author of the paper, "Targeted estrogen delivery reverses the metabolic syndrome."
Co-authors include Bin Yang and Vasily Gelfanov, research scientists in the IU Bloomington Department of Chemistry, and DiMarchi. Finan is now a post-doctoral researcher at the Helmholtz Zentrum München in Germany, directed by Tschöp, who is DiMarchi's longtime collaborator and a corresponding co-author. Affiliations of the other 20 co-authors include the University of Cincinnati where, also led by Tschöp, many of the in vivo pharmacology and molecular mechanism studies were conducted; Northwestern University; and research laboratories in Germany and China.
Associated with what health authorities are calling a global epidemic of obesity, the metabolic syndrome consists of obesity associated with other factors such as high blood pressure, high triglycerides, hyperglycemia and low HDL cholesterol. The International Diabetes Federation estimates that as much as 20 percent of the world's adult population has some form of the metabolic syndrome and that they are three times as likely to have a heart attack or stroke and five times as likely to develop adult-onset diabetes as people without the syndrome.
DiMarchi said investigation continues in the optimization of the peptide-based hormone conjugates with an emphasis on determining the specific mechanism of biological action and identification of an optimal drug candidate suitable for human study. The combination of other peptides and nuclear hormones for targeting other medical conditions holds considerable promise and opportunity for future research.
Indiana University: http://newsinfo.iu.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Researchers are trying to figure out how "jackass" penguins—nicknamed for their braying vocalizations—communicate
The rind of good cheese is a thriving microbial community. A single gram—a tiny crumb—contains 10 billion microbial cells, a mix of bacteria and fungi that contribute delicious and sometimes funky flavors.
The world's largest amphipod has been caught on film for the first time – and even if you love shrimp, this critter may give you nightmares
If someone were to create an award for "mother of the year" in the animal kingdom, a remarkably dedicated eight-limbed mom from the dark and frigid depths of the Pacific Ocean might be a strong contender.
Why the lionfish is here to stay
Juhan Sonin is donating his DNA to the hunt for medical breakthroughs. He explains why he decided to share his genome, and why you might want to do the same
The sperm of one nematode species harms the females of other species, perhaps explaining why the species remain distinct
Once-endangered gray seal population is rebounding; Cape Cod fishermen say there are now too many -- and they're taking all the fish
That strong, sturdy handshake your grandpa taught you isn't the cleanest way to greet someone, scientists say. So should doctors and nurses in hospitals start bumping fists?
The Natural Trap Cave in Wyoming may hold specimens of DNA from animals who roamed thousands of years ago. Julie Meachem, a paleontologist leading the expedition into the cave, speaks with Audie Cornish about the secrets she hopes to find.