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

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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: journals.permissions@oup.com.

    Research areas

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

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