Brainstem GLP-1 neurons modulate physiological satiation and drive sustained weight loss in obese mice
Jiang, W.; Skoug, C.; Rodrigues, I.; Ciabatti, E.; Gribble, F. M.; Reimann, F.; Brierley, D. I.; Holt, M. K.; Trapp, S.
Show 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.
Matching journals
The top 2 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Relaxin/insulin-like family peptide receptor 4 (Rxfp4) expressing hypothalamic neurons modulate food intake and preference in mice 97%
- Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections 96%
- The Vagus Nerve Mediates the Physiological but not Pharmacological Effects of PYY3-36 on Food Intake 96%
Similar papers in this journal
Similar papers in this journal
- Nucleus accumbens D1- and D2-expressing neurons control the balance between feeding and activity-mediated energy expenditure 97%
- TrkB-expressing paraventricular hypothalamic neurons suppress appetite through multiple neurocircuits 96%
- Liver-innervating vagal sensory neurons play an indispensable role in the development of hepatic steatosis and anxiety-like behavior in mice fed a high-fat diet. 96%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.