학술논문
Ketone Body Infusion Abrogates Growth Hormone--Induced Lipolysis and Insulin Resistance
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
Source
Journal of Clinical Endocrinology & Metabolism. March 2023, Vol. 108 Issue 3, p653, 12 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Ketone bodies are produced by the liver from [beta]-oxidation of fatty acids and serve as an alternative energy source in meta-bolically active tissues during stress and fasting (1). Interestingly, the [...]
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 [beta]-hydroxybutyrate ([beta]OHB) 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 [beta]OHB 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: [beta]OHB 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 [beta]OHB and its derivative acetoacetate. Conclusion: Our data unravel an insulin-sensitizing effect of [beta]OHB, which we suggest is mediated by concomitant suppression of lipolysis. Key Words: ketone bodies, [beta]-hydroxybutyrate, insulin sensitivity, glucose metabolism, growth hormone, free fatty acids
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 [beta]-hydroxybutyrate ([beta]OHB) 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 [beta]OHB 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: [beta]OHB 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 [beta]OHB and its derivative acetoacetate. Conclusion: Our data unravel an insulin-sensitizing effect of [beta]OHB, which we suggest is mediated by concomitant suppression of lipolysis. Key Words: ketone bodies, [beta]-hydroxybutyrate, insulin sensitivity, glucose metabolism, growth hormone, free fatty acids