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. 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.

DESIGN: In a randomized, single-blinded crossover design, eight healthy men were studied twice with a 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
Publication statusE-pub ahead of print - 14 Oct 2022

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