Ketone body infusion abrogates growth hormone-induced lipolysis and insulin resistance
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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
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TY - JOUR
T1 - Ketone body infusion abrogates growth hormone-induced lipolysis and insulin resistance
AU - Høgild, Morten Lyng
AU - Hjelholt, Astrid Johannesson
AU - Hansen, Jakob
AU - Pedersen, Steen Bønløkke
AU - Møller, Niels
AU - Wojtaszewski, Jørgen
AU - Johannsen, Mogens
AU - Jessen, Niels
AU - Lunde Jørgensen, Jens Otto
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2023
Y1 - 2023
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.
KW - Faculty of Science
KW - Ketone bodies
KW - β-hydroxybutyrate
KW - Insulin sensitivity
KW - Glucose metabolism
KW - Growth hormone
KW - Free fatty acids
U2 - 10.1210/clinem/dgac595
DO - 10.1210/clinem/dgac595
M3 - Journal article
C2 - 36240323
VL - 108
SP - 653
EP - 664
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 3
ER -
ID: 322944118