Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Beta-hydroxybutyrate suppresses hepatic production of the ghrelin receptor antagonist, LEAP2

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Evidence for glucagon secretion and function within the human gut

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Using a Reporter Mouse to Map Known and Novel Sites of GLP-1 Receptor Expression in Peripheral Tissues of Male Mice

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Repeated Activation of Noradrenergic Receptors in the Ventromedial Hypothalamus Suppresses the Response to Hypoglycemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Hypophosphatemic Hypovitaminosis D induces Osteomalacia in the adult female rat

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Activin A determines steroid levels and composition in the fetal testis

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. THERAPY OF ENDOCRINE DISEASE: Amylin and calcitonin - physiology and pharmacology

    Research output: Contribution to journalReviewResearchpeer-review

  2. LEAP2 reduces postprandial glucose excursions and ad libitum food intake in healthy men

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Long-acting amylin analogues for the management of obesity

    Research output: Contribution to journalReviewResearchpeer-review

  4. Gastric Aspiration Improves Postprandial Glucose Tolerance Without Causing a Compensatory Increase in Appetite and Food Intake

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

INTRODUCTION: Liver-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.

METHODS: Hepatic 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.

RESULTS: We 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.

CONCLUSION: From 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.

Original languageEnglish
JournalEndocrinology
Volume163
Issue number6
Pages (from-to)bqac038
ISSN0013-7227
DOIs
Publication statusPublished - 1 Jun 2022

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

    Research areas

  • 3-Hydroxybutyric Acid/metabolism, Animals, Diet, Ketogenic, Ghrelin/metabolism, Liver/metabolism, Mice, Obesity/metabolism, Receptors, Ghrelin/metabolism

ID: 76296708