The Hypothalamic Glucagon-Like Peptide 1 Receptor Is Sufficient but Not Necessary for the Regulation of Energy Balance and Glucose Homeostasis in Mice

Mice lacking hypothalamic glucagon-like peptide 1 receptor (GLP-1R) showed increased food intake and energy expenditure without a net change in body weight.

• Knocking down Glp1r expression in the hypothalamus led to increased food intake in chow-fed mice.
• High-fat diet feeding resulted in normal food intake but elevated energy expenditure in Glp1R-knockdown mice, reducing weight gain.
• Acute effects on appetite suppression and glucose tolerance from GLP-1 receptor agonists were maintained in all mouse lines tested.
• Chronic treatment with liraglutide decreased body weight in GLP-1R-knockdown mice on a chow diet but this effect was less pronounced on a high-fat diet.
• Hypothalamic regions are sufficient for the impacts of GLP-1 receptor agonists, but not individually necessary for nutrient regulation.

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