AUTHOR=Kurgan Nigel , Baranowski Bradley , Stoikos Joshua , MacNeil Adam J. , Fajardo Val A. , MacPherson Rebecca E. K. , Klentrou Panagiota 

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

JOURNAL=Frontiers in Physiology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1061715

DOI=10.3389/fphys.2022.1061715

ISSN=1664-042X

ABSTRACT=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 (GSK3 and -catenin) within subcutaneous inguinal white adipose tissue (iWAT), and visceral epididymal WAT (eWAT) depots at rest and in response to acute aerobic exercise. 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 2h of endurance treadmill exercise at 15 m·min-1 with 5° incline (EX), creating 4 groups: LFD+SED (N=10), LFD+EX (N=10), HFD+SED (N=10), and HFD+EX (N=10). Serum and WAT depots were collected 2h post-exercise. 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 -catenin (+44%, p=0.03) and GSK3 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. -catenin and GSK3 were both unresponsive to diet and exercise within eWAT. 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.