Abstract
Glucagon-like peptide-1 receptor (GLP-1R) activation in the brain strongly reduces appetite, but most brain GLP-1Rs are not accessible for systemically administered GLP-1R agonists. Acute activation of nucleus tractus solitarius (NTS) GLP-1 neurons, targeting brain GLP-1Rs, strongly suppresses food intake separate from GLP-1R agonists. However, it is unknown if their chronic stimulation is a viable strategy for appetite suppression, or if obesity disrupts their function. Here we demonstrate that GLP-1 neurons, distributed through NTS and IRT, determine meal size and their number is inversely correlated with bodyweight gain. GLP-1 neurons in IRT and NTS differ in their inputs but generate outputs in largely overlapping areas. Higher body weight and fat mass predicts a higher percentage of active GLP-1 neurons. Their chemogenetic activation is an efficient means of reducing food intake, and in obese mice chronic activation elicits sustained weight loss. In conclusion, GLP-1 neurons are a feasible target for obesity treatment.
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Abstract
Glucagon-like peptide-1 receptor (GLP-1R) activation in the brain strongly reduces appetite, but most brain GLP-1Rs are not accessible for systemically administered GLP-1R agonists. Acute activation of nucleus tractus solitarius (NTS) GLP-1 neurons, targeting brain GLP-1Rs, strongly suppresses food intake separate from GLP-1R agonists. However, it is unknown if their chronic stimulation is a viable strategy for appetite suppression, or if obesity disrupts their function. Here we demonstrate that GLP-1 neurons, distributed through NTS and IRT, determine meal size and their number is inversely correlated with bodyweight gain. GLP-1 neurons in IRT and NTS differ in their inputs but generate outputs in largely overlapping areas. Higher body weight and fat mass predicts a higher percentage of active GLP-1 neurons. Their chemogenetic activation is an efficient means of reducing food intake, and in obese mice chronic activation elicits sustained weight loss. In conclusion, GLP-1 neurons are a feasible target for obesity treatment.
Competing Interest Statement
The authors have declared no competing interest.
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