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Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice

Introduction: It is well established that sclerostin antagonizes the anabolic Wnt signalling pathway in bone, however, its physiological role in other tissues remains less clear. This study examined the effect of a high-fat diet (HFD) on sclerostin content and downstream markers of the Wnt signaling...

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Autores principales: Kurgan, Nigel, Baranowski, Bradley, Stoikos, Joshua, MacNeil, Adam J., Fajardo, Val A., MacPherson, Rebecca E. K., Klentrou, Panagiota
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846496/
https://www.ncbi.nlm.nih.gov/pubmed/36685192
http://dx.doi.org/10.3389/fphys.2022.1061715
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author Kurgan, Nigel
Baranowski, Bradley
Stoikos, Joshua
MacNeil, Adam J.
Fajardo, Val A.
MacPherson, Rebecca E. K.
Klentrou, Panagiota
author_facet Kurgan, Nigel
Baranowski, Bradley
Stoikos, Joshua
MacNeil, Adam J.
Fajardo, Val A.
MacPherson, Rebecca E. K.
Klentrou, Panagiota
author_sort Kurgan, Nigel
collection PubMed
description Introduction: It is well established that sclerostin antagonizes the anabolic Wnt signalling pathway in bone, however, its physiological role in other tissues remains less clear. This study examined the effect of a high-fat diet (HFD) on sclerostin content and downstream markers of the Wnt signaling pathway (GSK3β and β-catenin) within subcutaneous inguinal white adipose tissue (iWAT), and visceral epididymal WAT (eWAT) depots at rest and in response to acute aerobic exercise. Methods: Male C57BL/6 mice (n = 40, 18 weeks of age) underwent 10 weeks of either a low-fat diet (LFD) or HFD. Within each diet group, mice were assigned to either remain sedentary (SED) or perform 2 h of endurance treadmill exercise at 15 m min(−1) with 5° incline (EX), creating four groups: LFD + SED (N = 10), LFD + EX (N = 10), HFD + SED (N = 10), and HFD + EX (N = 10). Serum and WAT depots were collected 2 h post-exercise. Results: Serum sclerostin showed a diet-by-exercise interaction, reflecting HFD + EX mice having higher concentration than HFD + SED (+31%, p = 0.03), and LFD mice being unresponsive to exercise. iWAT sclerostin content decreased post-exercise in both 28 kDa (−31%, p = 0.04) and 30 kDa bands (−36%, main effect for exercise, p = 0.02). iWAT β-catenin (+44%, p = 0.03) and GSK3β content were higher in HFD mice compared to LFD (+128%, main effect for diet, p = 0.005). Monomeric sclerostin content was abolished in eWAT of HFD mice (−96%, main effect for diet, p < 0.0001), was only detectable as a 30 kDa band in LFD mice and was unresponsive to exercise. β-catenin and GSK3β were both unresponsive to diet and exercise within eWAT. Conclusion: These results characterized sclerostin’s content to WAT depots in response to acute exercise, which appears to be specific to a reduction in iWAT and identified a differential regulation of sclerostin’s form/post-translational modifications depending on diet and WAT depot.
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spelling pubmed-98464962023-01-19 Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice Kurgan, Nigel Baranowski, Bradley Stoikos, Joshua MacNeil, Adam J. Fajardo, Val A. MacPherson, Rebecca E. K. Klentrou, Panagiota Front Physiol Physiology Introduction: It is well established that sclerostin antagonizes the anabolic Wnt signalling pathway in bone, however, its physiological role in other tissues remains less clear. This study examined the effect of a high-fat diet (HFD) on sclerostin content and downstream markers of the Wnt signaling pathway (GSK3β and β-catenin) within subcutaneous inguinal white adipose tissue (iWAT), and visceral epididymal WAT (eWAT) depots at rest and in response to acute aerobic exercise. Methods: Male C57BL/6 mice (n = 40, 18 weeks of age) underwent 10 weeks of either a low-fat diet (LFD) or HFD. Within each diet group, mice were assigned to either remain sedentary (SED) or perform 2 h of endurance treadmill exercise at 15 m min(−1) with 5° incline (EX), creating four groups: LFD + SED (N = 10), LFD + EX (N = 10), HFD + SED (N = 10), and HFD + EX (N = 10). Serum and WAT depots were collected 2 h post-exercise. Results: Serum sclerostin showed a diet-by-exercise interaction, reflecting HFD + EX mice having higher concentration than HFD + SED (+31%, p = 0.03), and LFD mice being unresponsive to exercise. iWAT sclerostin content decreased post-exercise in both 28 kDa (−31%, p = 0.04) and 30 kDa bands (−36%, main effect for exercise, p = 0.02). iWAT β-catenin (+44%, p = 0.03) and GSK3β content were higher in HFD mice compared to LFD (+128%, main effect for diet, p = 0.005). Monomeric sclerostin content was abolished in eWAT of HFD mice (−96%, main effect for diet, p < 0.0001), was only detectable as a 30 kDa band in LFD mice and was unresponsive to exercise. β-catenin and GSK3β were both unresponsive to diet and exercise within eWAT. Conclusion: These results characterized sclerostin’s content to WAT depots in response to acute exercise, which appears to be specific to a reduction in iWAT and identified a differential regulation of sclerostin’s form/post-translational modifications depending on diet and WAT depot. Frontiers Media S.A. 2023-01-04 /pmc/articles/PMC9846496/ /pubmed/36685192 http://dx.doi.org/10.3389/fphys.2022.1061715 Text en Copyright © 2023 Kurgan, Baranowski, Stoikos, MacNeil, Fajardo, MacPherson and Klentrou. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Kurgan, Nigel
Baranowski, Bradley
Stoikos, Joshua
MacNeil, Adam J.
Fajardo, Val A.
MacPherson, Rebecca E. K.
Klentrou, Panagiota
Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice
title Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice
title_full Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice
title_fullStr Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice
title_full_unstemmed Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice
title_short Characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice
title_sort characterization of sclerostin’s response within white adipose tissue to an obesogenic diet at rest and in response to acute exercise in male mice
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846496/
https://www.ncbi.nlm.nih.gov/pubmed/36685192
http://dx.doi.org/10.3389/fphys.2022.1061715
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