GLP-1 Increases pre-ingestive satiation via hypothalamic circuits in mice and humans

GLP-1 receptor agonists (GLP-1RAs) are effective anti-obesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to obese patients and observed heightened sense of pre-ingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1R neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding pre-ingestive satiation. Optogenetic manipulation of DMHGLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding pre-ingestive satiation. GLP-1RA administration increased the activity of DMHGLP-1R neurons selectively during eating behavior. We further identified an intricate interplay between DMHGLP-1R neurons and arcuate NPY/AgRP neurons (ARCNPY/AgRP), to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control pre-ingestive satiation, offering novel neural targets for obesity and metabolic diseases., Analysis
Analysis was done using custom MATLAB code otherwise stated. 
Clinical trials
72 patients were assessed for eligibility, and 44 patients were screened, with 4 patients meeting the exclusion criteria. 40 obese individuals were enrolled, who were allocated randomly into two groups (Group A n=20, Group B n=20). The participants were prescribed liraglutide and received a weekly escalating dose of 0.6mg, 1.2mg, 1.8mg, 2.4mg daily over a four-weeks period. Patients were asked to write a diary to record the dose and date daily. Group A participants underwent control clinical tests prior to liraglutide injection, got 4 weeks of injection, and performed the same structured test scheme. Group B participants got 4 weeks of injection and underwent clinical tests, and after 2 weeks of washout period they performed the control clinical tests. A total of 28 patients were analyzed for study. (Withdrawn from trial: Group A n=0, Group B n=2. Excluded from analysis: Group A n=5, Group B n=5) Indi..., , # GLP-1 Increases Pre-ingestive Satiation via Hypothalamic Circuits in Mice and Humans

## Description of data

***Figure 1, Figure S1***

Path: Source Data and Codes\Figure 1, Figure S1

RAW_Control.xlsx : Raw data for Control test.

RAW_GLP1.xlsx : Raw data for GLP1 test.

Group: The group each person was designated, either A or B. Group number: The number each person was designated inside each group. Participant number: Number designated for those who participated in the test.

P1_1 to P4_29: Each participant’s answers to Questionnaires 1-29. Questionnaires were given to participants in Korean language, and may be provided upon request. P1_1 to P1_29: Baseline, P2_1 to P2_29: Pre-oral, P3_1 to P3_29: Oral, P4_1 to P4_29: Ingestion. N/A refers to not available data including the name and email of each participant, as well as missing data in the questionnaires performed. Missing data were omitted for analysis.

RAW_ingestion.xlsx

Sheet1: Total ingestion amount of food by each particip...