A receptor for the gut hormone Glucose-dependent insulinotropic polypeptide (GIP) has been shown to be present in several cell types in the adult hypothalamus and has been identified as a potential target for drugs aimed at weight control.
Researchers from the group of Frank Reimann and Fiona Gribble at the Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories in Cambridge developed a new mouse model with the aim to identify target sites for GIP signalling activity. They were able to characterise previously unrecognized populations of cells that express the receptor (Gipr) in key feeding centres of the brains of mice and humans, and to demonstrate that stimulating them potently suppresses food intake in mice.
Researchers found a number of hypothalamic cells in mouse and human that expressed both Gipr and Glp1r—the receptor for glucagon-like peptide-1 (GLP-1), a well-characterised appetite-reducing hormone. This suggests that GIP and GLP-1 may be acting in concert in certain cell populations. As GIP/GLP-1 dual agonists have recently reported significant and sustained body weight loss in clinical trials, their data may provide insight into how the drugs are mediating these effects.
The research identifies the central hypothalamic GIP signalling axis as an additional contributor to the control of energy homeostasis.
Adriaenssens et al., Glucose-Dependent Insulinotropic Polypeptide Receptor-Expressing Cells in the Hypothalamus Regulate Food Intake, Cell Metabolism (2019), https://doi.org/10.1016/j.cmet.2019.07.013