Ketone body infusion abrogates growth hormone-induced lipolysis and insulin resistance

Morten Lyng Høgild, Astrid Johannesson Hjelholt*, Jakob Hansen, Steen Bønløkke Pedersen, Niels Møller, Jørgen Wojtaszewski, Mogens Johannsen, Niels Jessen, Jens Otto Lunde Jørgensen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Background: Exogenous ketone body administration lowers circulating glucose levels but the underlying mechanisms are uncertain. 

Objective: We tested the hypothesis that administration of the ketone body β-hydroxybutyrate (βOHB) acutely increases insulin sensitivity via feedback suppression of circulating free fatty acid (FFA) levels.

Methods: In a randomized, single-blinded crossover design, 8 healthy men were studied twice with a growth hormone (GH) infusion to induce lipolysis in combination with infusion of either βOHB or saline. Each study day comprised a basal period and a hyperinsulinemic-euglycemic clamp combined with a glucose tracer and adipose tissue and skeletal muscle biopsies.

Results: βOHB administration profoundly suppressed FFA levels concomitantly with a significant increase in glucose disposal and energy expenditure. This was accompanied by a many-fold increase in skeletal muscle content of both βOHB and its derivative acetoacetate.

Conclusion: Our data unravel an insulin-sensitizing effect of βOHB, which we suggest is mediated by concomitant suppression of lipolysis.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume108
Issue number3
Pages (from-to)653-664
Number of pages12
ISSN0021-972X
DOIs
Publication statusPublished - 2023

Bibliographical note

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Keywords

  • Faculty of Science
  • Ketone bodies
  • β-hydroxybutyrate
  • Insulin sensitivity
  • Glucose metabolism
  • Growth hormone
  • Free fatty acids

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