In a new study titled “Hypothalamic Amylin Acts in Concert with Leptin to Regulate Food Intake,” researchers reported that the hormones leptin and amylin work together in the brain to regulate feeding behavior. The study was published in the journal Cell Metabolism.
Researchers at The Rockefeller University in New York investigated the role of a protein called amylin, previously identified in neurons within the region of the brain that controls appetite.
“How much a person eats is regulated by a complex circuit, and in order to understand it, we need to identify all the molecules involved,” Jeffrey Friedman, the Marilyn M. Simpson Professor, head of the Laboratory of Molecular Genetics at Rockefeller, and the study’s lead author said in a press release. “Amylin caught our attention when we were profiling a set of neurons in the hypothalamus, a part of the brain known to be involved in feeding behavior. Because it plays a role in sugar metabolism elsewhere in the body, we were interested in exploring its function in the brain.”
Researchers identified the precursor to amylin – called Iselt amyloid peptide (Iapp) – in the brain region hypothalamus, but in a mouse model for obesity the expression of Iapp was markedly decreased. In this model, where obesity is caused by lack of the leptin protein, when mice are administered with exogenous leptin, the levels of Iapp levels increased significantly. The results suggested that leptin regulates the expression of amylin.
Leptin, known as the “satiety hormone,” is produced by adipose cells and mediates long-term regulation of energy balance, suppressing food intake. Researchers then investigated the relationship between leptin and Iapp in regulating feeding.
“We also looked directly at how amylin and leptin affect feeding behavior,” said Zhiying Li, the study’s first author. “When we give leptin to mice, it significantly suppresses food intake. However, when we give leptin to mice in which amylin is rendered nonfunctional with an inhibitor, the effect of leptin is blunted. This means that leptin and amylin are working together in a way that reduces feeding.”
The team performed further studies and discovered that hypothalamic amylin is regulated by leptin, and that leptin and amylin act on the same neurons, working synergistically to control feeding.
“These findings confirm a functional role for amylin in the central nervous system, and provide a potential mechanism to treat obesity more effectively, through combination therapy. While this is a piece of the puzzle, we still need a better understanding of the cellular mechanisms involved in this system, which could provide new approaches that involve improved leptin signaling and sensitivity,” Friedman said.
