Context: 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
JournalThe Journal of clinical endocrinology and metabolism
Pages (from-to)653-664
Number of pages12
Publication statusPublished - Mar 2023


  • free fatty acids
  • glucose metabolism
  • growth hormone
  • insulin sensitivity
  • ketone bodies
  • β-hydroxybutyrate
  • Growth Hormone
  • Humans
  • Male
  • Glucose
  • Lipolysis
  • Human Growth Hormone/pharmacology
  • 3-Hydroxybutyric Acid/pharmacology
  • Insulin/pharmacology
  • Fatty Acids, Nonesterified
  • Ketone Bodies
  • Insulin Resistance/physiology
  • Glucose Clamp Technique


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