ArticleFrontiers in endocrinology2022
Involvement of POMC neurons in LEAP2 regulation of food intake and body weight.
Article in Frontiers in endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- LEAP2 Reduces Ad Libitum Food Intake and Attenuates Postprandial Glucose Excursions in Men With Obesity.Diabetes · 2026Trial
- Plasma LEAP-2 Following a Low-Calorie Diet with or without Interval Exercise in Women with Obesity.Nutrients · 2023Trial
- Hypothalamus-Peripheral Organ Crosstalk in Energy Metabolism: A Bidirectional Regulatory Network.Endocrinology and metabolism (Seoul, Korea) · 2026Review
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- The Ghrelin-LEAP2 System in Obesity and Diabetes: Pathophysiological Roles and Therapeutic Potential.Current obesity reports · 2026Review
- The role of LEAP2 on cognitive impulsivity after refeeding: evidence from a preclinical study in female mice and from patients with anorexia nervosa.Translational psychiatry · 2026Article
- Ghrelin and LEAP2: Their Interaction Effect on Appetite Regulation and the Alterations in Their Levels Following Bariatric Surgery.Medicina (Kaunas, Lithuania) · 2025Review
- LEAP2 in Physiology-A Narrative Review.International journal of molecular sciences · 2025Review
- Brain-acting hepatokines: its impact on energy balance and metabolism.Frontiers in neuroscience · 2025Review
- LEAP2, a ghrelin receptor inverse agonist, and its effect on alcohol-related responses in rodents.Translational psychiatry · 2024Article
- The LEAP2 Response to Cancer-Related Anorexia-Cachexia Syndrome in Male Mice and Patients.Endocrinology · 2024Article
- Article
- Postprandial Increases in Liver-Gut Hormone LEAP2 Correlate with Attenuated Eating Behavior in Adults Without Obesity.Journal of the Endocrine Society · 2023Article
- Liver-expressed antimicrobial peptide 2 elevation contributes to age-associated cognitive decline.JCI insight · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver-expressed antimicrobial peptide 2 (LEAP2) is a newly discovered antagonist of the growth hormone secretagogue receptor (GHSR) and is considered the first endogenous peptide that can antagonize the metabolic actions of ghrelin. The effects of ghrelin administration on feeding behavior, body weight, and energy metabolism involve the activation of orexigenic neurons in the arcuate nucleus (ARC) of the hypothalamus. It is unclear, however, if LEAP2 applied directly to the ARC of the hypothalamus affects these metabolic processes. Here, we show that overexpression of LEAP2 in the ARC through adeno-associated virus (AAV) reduced food intake and body weight in wild-type (WT) mice fed chow and a high-fat diet (HFD) and improved metabolic disorders. LEAP2 overexpression in the ARC overrides both central and peripheral ghrelin action on a chow diet. Interestingly, this AAV-LEAP2 treatment increased proopiomelanocortin (POMC) expression while agouti-related peptide (AGRP)/neuropeptide Y (NPY) and GHSR levels remained unchanged in the hypothalamus. Additionally, intracerebroventricular (i.c.v.) administration of LEAP2 decreased food intake, increased POMC neuronal activity, and repeated LEAP2 administration to mice induced body weight loss. Using chemogenetic manipulations, we found that inhibition of POMC neurons abolished the anorexigenic effect of LEAP2. These results demonstrate that central delivery of LEAP2 leads to appetite-suppressing and body weight reduction, which might require activation of POMC neurons in the ARC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.