LEAP2: A new hormone with big implications for metabolism?
Often called the hunger hormone, ghrelin tells your brain you are hungry and increases your appetite. Another recently discovered hormone, LEAP2, prevents ghrelin from sending these signals, thereby lowering appetite. Scientists think it could hold promise for new approaches to weight management and treating cardiometabolic disease. However, much of the basic physiology of LEAP2 remains poorly understood.
In an article published today in Cell Reports Medicine by Cell Press, scientists in Christoffer Clemmensen’s Group explain how the hormones insulin and glucagon play a crucial role in regulating LEAP2 levels. Specifically, glucagon lowers LEAP2, while insulin is needed for LEAP2 to rise after a meal – findings that were observed in both healthy individuals and those with obesity and type 2 diabetes.
This research underscores the complex interplay of hormones in regulating energy balance.
“Following up on our findings in humans and animals, our analyses at the cellular level revealed that liver cells called hepatocytes are the primary source of LEAP2 production. We also identified that insulin and glucagon-regulated proteins bind to the DNA near the LEAP2 gene, suggesting a direct mechanism of control,” says Research Assistant Valdemar Brimnes Ingemann Johansen, first author of the study.
New knowledge on the role of understudied hormones, such as LEAP2, is especially relevant now, as it could lead to new therapeutic strategies for treating cardiometabolic disease.
“This fundamental characterization and understanding of how LEAP2 is regulated by classical hormones like glucagon and insulin is important. By manipulating the balance between LEAP2 and ghrelin, we may be able to create therapies that reduce hunger, improve blood sugar control, and promote better cardiometabolic health,” says Associate Professor Christoffer Clemmensen, corresponding author.
Read the article, 'Regulation of LEAP2 by insulin and glucagon in mice and humans', here.
The research was carried out in collaboration with researchers from Steno Diabetes Center Copenhagen Center, Gentofte Hospital and Novo Nordisk.
Additional authors: Anna Katrina Jógvansdóttir Gradel, Stephanie Holm, Joyceline Cuenco, Christoffer M., Natalia Petersen, Damien Demozay, Bharath Kumar Mani, Malte Palm Suppli, Magnus F. Gluud Grøndahl, Asger Bach Lund, Filip K. Knop, Cesar A. Prada-Medina, Wouter Hogendorf, Jens Lykkesfeldt, Myrte Merkestein, Kei Sakamoto & Birgitte Holst
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