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

Morten Lyng Høgild; Astrid Johannesson Hjelholt; Jakob Hansen; Steen Bønløkke Pedersen; Niels Møller; Jørgen Wojtaszewski; Mogens Johannsen; Niels Jessen; Jens Otto Lunde Jørgensen

doi:10.1210/clinem/dgac595

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

Morten Lyng Høgild, Astrid Johannesson Hjelholt^*, Jakob Hansen, Steen Bønløkke Pedersen, Niels Møller, Jørgen Wojtaszewski, Mogens Johannsen, Niels Jessen, Jens Otto Lunde Jørgensen

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

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 language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	108
Issue number	3
Pages (from-to)	653-664
Number of pages	12
ISSN	0021-972X
DOIs	https://doi.org/10.1210/clinem/dgac595
Publication status	Published - 2023

Bibliographical note

Keywords

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

Access to Document

10.1210/clinem/dgac595

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Ketone body infusion abrogates growth hormone-induced lipolysis and insulin resistance. / Høgild, Morten Lyng; Hjelholt, Astrid Johannesson; Hansen, Jakob; Pedersen, Steen Bønløkke; Møller, Niels; Wojtaszewski, Jørgen; Johannsen, Mogens; Jessen, Niels; Lunde Jørgensen, Jens Otto.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 108, No. 3, 2023, p. 653-664.

Research output: Contribution to journal › Journal article › Research › peer-review

Høgild, Morten Lyng ; Hjelholt, Astrid Johannesson ; Hansen, Jakob ; Pedersen, Steen Bønløkke ; Møller, Niels ; Wojtaszewski, Jørgen ; Johannsen, Mogens ; Jessen, Niels ; Lunde Jørgensen, Jens Otto. / Ketone body infusion abrogates growth hormone-induced lipolysis and insulin resistance. In: Journal of Clinical Endocrinology and Metabolism. 2023 ; Vol. 108, No. 3. pp. 653-664.

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abstract = "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.",

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AU - Høgild, Morten Lyng

AU - Hjelholt, Astrid Johannesson

AU - Hansen, Jakob

AU - Pedersen, Steen Bønløkke

AU - Møller, Niels

AU - Wojtaszewski, Jørgen

AU - Johannsen, Mogens

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AU - Lunde Jørgensen, Jens Otto

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N2 - 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.

AB - 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.

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