A team of scientists from Indiana University and international collaborators combined a peptide hormone from the digestive system, known as GLP-1, with the hormone estrogen and gave it to several obese laboratory mice.
Both GLP-1 and estrogen have shown efficacy as treatment for obesity and adult-onset diabetes, the mix was more effective in causing weight loss and other advantageous outcomes than just using each hormone on its own. It also showed fewer harmful effects, like extra tissue growth associated with tumor formation.
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, said:
"We find that combining the hormones as a single molecule dramatically enhanced their efficacy and their safety. 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 peptide-based targeting strategy was seen to inhibit side effects of estrogen in both male and female mice, like reproductive endocrine toxicity and oncogenicity. As a whole, critical activation of estrogen receptors in GLP-1 targeted tissues results in surprising efficiency to boost the metabolic advantages of GLP-1 agonism.
A former student in DiMarchi's lab, Brian Finan, is lead author of the paper, "Targeted estrogen delivery reverses the metabolic syndrome." The "metabolic syndrome" is made up of obesity associated with other elements like high triglycerides, hyperglycemia, low HDL cholesterol, and high blood pressure. This syndrome is connected with the global epidemic of obesity.
Around 20 percent of the world's adult population has a form of the metabolic syndrome and are three times more likely to have a stroke or heart attack, as well as fives times more likely to develop diabetes compared with people who do not have the syndrome, according to the International Diabetes Federation.
The investigation will continue to identify the most effective way the peptide-based hormone conjugates, with special attention on determining the exact mechanism of biological action and choosing an ideal drug choice acceptable for human study.
The mixture of nuclear hormones and other peptides as therapeutic substances is a significant and promising opportunity for research in the near future.