ArticleEndocrinology2022
Beta-Hydroxybutyrate Suppresses Hepatic Production of the Ghrelin Receptor Antagonist LEAP2.
Article in Endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Plasma LEAP-2 Following a Low-Calorie Diet with or without Interval Exercise in Women with Obesity.Nutrients · 2023Trial
- The Ghrelin-LEAP2 System in Obesity and Diabetes: Pathophysiological Roles and Therapeutic Potential.Current obesity reports · 2026Review
- LEAP2 as a therapeutic target in obesity and cardiometabolic disorders.Reviews in endocrine & metabolic disorders · 2026Review
- The value of targeting ketone body metabolism in inflammatory and autoimmune diseases.Journal of translational medicine · 2026Review
- Article
- Human milk cortisol is inversely associated with infant BMI and mediates the association between maternal plasma and infant salivary cortisol concentrations.International journal of obesity (2005) · 2025Observational
- Plasma LEAP2 concentration is associated with energy intake and postprandial insulin increase depending on meal size but not weight status in men.Diabetes, obesity & metabolism · 2025Article
- Advancing Obesity Management: the Very Low-Energy Ketogenic therapy (VLEKT) as an Evolution of the "Traditional" Ketogenic Diet.Current obesity reports · 2025Review
- Ghrelin-LEAP2 interactions along the stomach-liver axis.Endocrine journal · 2025Review
- Regulation of LEAP2 by insulin and glucagon in mice and humans.Cell reports. Medicine · 2025Article
- LEAP2 in Physiology-A Narrative Review.International journal of molecular sciences · 2025Review
- Elevated blood levels of liver-expressed antimicrobial peptide 2 in patients with insulinoma and its expression in insulinomas.Frontiers in endocrinology · 2025Article
- Brain-acting hepatokines: its impact on energy balance and metabolism.Frontiers in neuroscience · 2025Review
- [Correlation between serum ghrelin and liver-expressed antimicrobial peptide-2 with idiopathic short stature in children].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2024Article
- Satiety Hormone LEAP2 After Low-Calorie Diet With/Without Endobarrier Insertion in Obesity and Type 2 Diabetes Mellitus.Journal of the Endocrine Society · 2024Article
- Pre-prandial plasma liver-expressed antimicrobial peptide 2 (LEAP2) concentration in humans is inversely associated with hunger sensation in a ghrelin independent manner.European journal of nutrition · 2024Article
- To eat or not to eat: A role for ghrelin and LEAP2 in eating disorders?Neuroscience applied · 2024Review
- High-Fat Diet Induces Resistance to Ghrelin and LEAP2 Peptide Analogs in Mice.Physiological research · 2023Article
- Postprandial Increases in Liver-Gut Hormone LEAP2 Correlate with Attenuated Eating Behavior in Adults Without Obesity.Journal of the Endocrine Society · 2023Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionLiver-expressed antimicrobial peptide-2 (LEAP2) is an endogenous ghrelin receptor antagonist, which is upregulated in the fed state and downregulated during fasting. We hypothesized that the ketone body beta-hydroxybutyrate (BHB) is involved in the downregulation of LEAP2 during conditions with high circulating levels of BHB.
methodsHepatic and intestinal Leap2 expression were determined in 3 groups of mice with increasing circulating levels of BHB: prolonged fasting, prolonged ketogenic diet, and oral BHB treatment. LEAP2 levels were measured in lean and obese individuals, in human individuals following endurance exercise, and in mice after BHB treatment. Lastly, we investigated Leap2 expression in isolated murine hepatocytes challenged with BHB.
resultsWe confirmed increased circulating LEAP2 levels in individuals with obesity compared to lean individuals. The recovery period after endurance exercise was associated with increased plasma levels of BHB levels and decreased LEAP2 levels in humans. Leap2 expression was selectively decreased in the liver after fasting and after exposure to a ketogenic diet for 3 weeks. Importantly, we found that oral administration of BHB increased circulating levels of BHB in mice and decreased Leap2 expression levels and circulating LEAP2 plasma levels, as did Leap2 expression after direct exposure to BHB in isolated murine hepatocytes.
conclusionFrom our data, we suggest that LEAP2 is downregulated during different states of energy deprivation in both humans and rodents. Furthermore, we here provide evidence that the ketone body, BHB, which is highly upregulated during fasting metabolism, directly downregulates LEAP2 levels. This may be relevant in ghrelin receptor-induced hunger signaling during energy deprivation.
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Registered trials
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.