Researchers from Vanderbilt University characterized a complex cellular receptor type that, when activated, curbs hunger.
A research team led by Jens Meiler, professor of chemistry and pharmacology at Vanderbilt University discovered a complex cellular receptor that can potentially beat obesity at the cellular level. Neuropeptide Y receptors are responsible for processes such as appetite, circadian rhythm, and anxiety. These receptors belong to class seven-(pass)-transmembrane domain receptors and are activated by the peptide hormones that affect the endocrine system of animals, including humans. Neuropeptide Y, peptide YY and pancreatic polypeptide are the major examples of peptide hormones. Meiler along with Brian J. Bender, a Ph.D. student determined the first crystal structure for the neuropeptide Y receptor. They decoded the molecules and learnt the binding mechanism of oxygen, carbon and nitrogen in the receptor. The inherently low-quality data about the atoms was deciphered to build accurate computer models of both the inactive receptor and the active receptor. The computer models reveled the exact coordinates of the atoms sitting in the space and the locations of its bind molecules. This provided a keyhole for the researchers to build a small molecule to bind with the receptors. The report was published online in the journal Nature on April 18, 2018 along with the contributions from the Chinese Academy of Sciences in Shanghai and Leipzig University in Germany.
The molecular level research needs further advancements in target validation to prove that the receptor really does control hunger. Obesity was observed in prior experiments with mice, when the receptors were blocked from functioning. The peptide hormones neuropeptide Y activates the receptor after consuming food, which restricts the feeling of hunger anymore. The research aims to upgrade the receptor with a small molecule to control hunger and subsequently curb obesity in humans.