The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study

Abstract Lipocalin-2 (LCN2) has three main variants; polyaminated (hLCN2) and non-polyaminated (C87A and R81E). The polyaminated form is proposed to positively influence energy control, whereas the non-polyaminated forms negatively impact energy control in mice. Glucocorticoids negatively affect glu...

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Main Authors: Carlie Bauer, Rhiannon K. Patten, Qiyang Sun, Haoyun Li, Daniels Konja, Mary Woessner, Xuzhu Lin, Andrew Garnham, David L. Hare, Peter R. Ebeling, Marc Sim, Joshua R. Lewis, Yu Wang, Lewan Parker, Itamar Levinger
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-88115-z
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author Carlie Bauer
Rhiannon K. Patten
Qiyang Sun
Haoyun Li
Daniels Konja
Mary Woessner
Xuzhu Lin
Andrew Garnham
David L. Hare
Peter R. Ebeling
Marc Sim
Joshua R. Lewis
Yu Wang
Lewan Parker
Itamar Levinger
author_facet Carlie Bauer
Rhiannon K. Patten
Qiyang Sun
Haoyun Li
Daniels Konja
Mary Woessner
Xuzhu Lin
Andrew Garnham
David L. Hare
Peter R. Ebeling
Marc Sim
Joshua R. Lewis
Yu Wang
Lewan Parker
Itamar Levinger
author_sort Carlie Bauer
collection DOAJ
description Abstract Lipocalin-2 (LCN2) has three main variants; polyaminated (hLCN2) and non-polyaminated (C87A and R81E). The polyaminated form is proposed to positively influence energy control, whereas the non-polyaminated forms negatively impact energy control in mice. Glucocorticoids negatively affect glucose regulation and exercise has a positive effect. We hypothesise that glucocorticoids will suppress, while exercise will increase hLCN2, and decrease C87A and R81E, which will be associated with improved insulin sensitivity. In a randomised crossover design, nine young healthy men (aged 27.8 ± 4.9 years; BMI 24.4 ± 2.4 kg/m2) completed 30 min of high-intensity aerobic exercise (90–95% heart rate reserve) after glucocorticoid or placebo ingestion. Blood was collected and analyzed for LCN2 and its variants levels at baseline, immediately, 60 min and 180 min post-exercise. Insulin sensitivity was assessed using hyperinsulinemic-euglycemic clamp. A main effect, increase in LCN2 was detected for prednisolone ingestion (overall treatment effect p = 0.001), but not LCN2 variants (all p > 0.05). Main effects for time were observed for exercise for LCN2 and all variants (overall time effect all p < 0.02). Regardless of treatment, LCN2, C87A, R81E, and hLCN2 increased immediately after exercise compared with baseline (all p < 0.04). C87A, but not LCN2 or its other variants, remained elevated at 180 min post-ex (p = 0.007). LCN2, but not its variants, was elevated in response to prednisolone ingestion. LCN2 and its variants are transiently increased by acute exercise, but this increase was not related to insulin sensitivity. The clinical implication of elevated LCN2 and its variants post-exercise on satiety and energy regulation, as well as the mechanisms involved warrant further investigation. Clinical trial registration: www.anzctr.org.au , ACTRN12615000755538.
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spelling doaj-art-87a3dd60e4114350827df7450ac04f742025-02-09T12:34:32ZengNature PortfolioScientific Reports2045-23222025-02-011511910.1038/s41598-025-88115-zThe effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover studyCarlie Bauer0Rhiannon K. Patten1Qiyang Sun2Haoyun Li3Daniels Konja4Mary Woessner5Xuzhu Lin6Andrew Garnham7David L. Hare8Peter R. Ebeling9Marc Sim10Joshua R. Lewis11Yu Wang12Lewan Parker13Itamar Levinger14Institute for Health and Sport (IHES), Victoria UniversityInstitute for Health and Sport (IHES), Victoria UniversityState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong KongState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong KongState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong KongInstitute for Health and Sport (IHES), Victoria UniversityCentre for Cancer Research, Hudson Institute of Medical ResearchInstitute for Health and Sport (IHES), Victoria UniversityDepartment of Cardiology, Austin Health, University of MelbourneDepartment of Medicine, School of Clinical Sciences, Monash UniversityNutrition & Health Innovation Research Institute, Edith Cowan UniversityNutrition & Health Innovation Research Institute, Edith Cowan UniversityState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong KongInstitute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin UniversityInstitute for Health and Sport (IHES), Victoria UniversityAbstract Lipocalin-2 (LCN2) has three main variants; polyaminated (hLCN2) and non-polyaminated (C87A and R81E). The polyaminated form is proposed to positively influence energy control, whereas the non-polyaminated forms negatively impact energy control in mice. Glucocorticoids negatively affect glucose regulation and exercise has a positive effect. We hypothesise that glucocorticoids will suppress, while exercise will increase hLCN2, and decrease C87A and R81E, which will be associated with improved insulin sensitivity. In a randomised crossover design, nine young healthy men (aged 27.8 ± 4.9 years; BMI 24.4 ± 2.4 kg/m2) completed 30 min of high-intensity aerobic exercise (90–95% heart rate reserve) after glucocorticoid or placebo ingestion. Blood was collected and analyzed for LCN2 and its variants levels at baseline, immediately, 60 min and 180 min post-exercise. Insulin sensitivity was assessed using hyperinsulinemic-euglycemic clamp. A main effect, increase in LCN2 was detected for prednisolone ingestion (overall treatment effect p = 0.001), but not LCN2 variants (all p > 0.05). Main effects for time were observed for exercise for LCN2 and all variants (overall time effect all p < 0.02). Regardless of treatment, LCN2, C87A, R81E, and hLCN2 increased immediately after exercise compared with baseline (all p < 0.04). C87A, but not LCN2 or its other variants, remained elevated at 180 min post-ex (p = 0.007). LCN2, but not its variants, was elevated in response to prednisolone ingestion. LCN2 and its variants are transiently increased by acute exercise, but this increase was not related to insulin sensitivity. The clinical implication of elevated LCN2 and its variants post-exercise on satiety and energy regulation, as well as the mechanisms involved warrant further investigation. Clinical trial registration: www.anzctr.org.au , ACTRN12615000755538.https://doi.org/10.1038/s41598-025-88115-z
spellingShingle Carlie Bauer
Rhiannon K. Patten
Qiyang Sun
Haoyun Li
Daniels Konja
Mary Woessner
Xuzhu Lin
Andrew Garnham
David L. Hare
Peter R. Ebeling
Marc Sim
Joshua R. Lewis
Yu Wang
Lewan Parker
Itamar Levinger
The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study
Scientific Reports
title The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study
title_full The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study
title_fullStr The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study
title_full_unstemmed The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study
title_short The effect of prednisolone ingestion and acute exercise on lipocalin-2 and its variants in young men: a pilot randomised crossover study
title_sort effect of prednisolone ingestion and acute exercise on lipocalin 2 and its variants in young men a pilot randomised crossover study
url https://doi.org/10.1038/s41598-025-88115-z
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