Abstract
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 language | English |
|---|---|
| Journal | The Journal of clinical endocrinology and metabolism |
| Volume | 108 |
| Issue | 3 |
| Pages (from-to) | 653-664 |
| Number of pages | 12 |
| ISSN | 0021-972X |
| DOIs | |
| Publication status | Published - Mar 2023 |
Keywords
- 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