Sclerostin Influences Exercise-Induced Adaptations in Body Composition and White Adipose Tissue Morphology in Male Mice
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Abstract
ABSTRACT Sclerostin is an inhibitor of the osteogenic Wnt/β-catenin signaling pathway that also has an endocrine role in regulating adipocyte differentiation and metabolism. Additionally, subcutaneous white adipose tissue (scWAT) sclerostin content decreases following exercise training (EXT). Therefore, we hypothesized that EXT-induced reductions in adipose tissue sclerostin may play a role in regulating adaptations in body composition and whole-body metabolism. To test this hypothesis, 10-week-old male C57BL/6J mice were either sedentary (SED) or performing 1 hour of treadmill running at ~65% to 70% maximum oxygen consumption (VO2max) 5 day/week (EXT) for 4 weeks and had subcutaneous injections of either saline (C) or recombinant sclerostin (S) (0.1 mg/kg body mass) 5 day/week; thus, making four groups (SED-C, EXT-C, SED-S, and EXT-S; n = 12/group). No differences in body mass were observed between experimental groups, whereas food intake was higher in EXT (p = 0.03) and S (p = 0.08) groups. There was a higher resting energy expenditure in all groups compared to SED-C. EXT-C had increased lean mass and decreased fat mass percentage compared to SED-C and SED-S. No differences in body composition were observed in either the SED-S or EXT-S groups. Lower scWAT (inguinal), epididymal white adipose tissue (eWAT) (visceral epididymal) mass, and scWAT adipocyte cell size and increased percentage of multilocular cells in scWAT were observed in the EXT-C group compared to SED-C, whereas lower eWAT was only observed in the EXT-S group. EXT mice had increased scWAT low-density lipoprotein receptor-related protein 4 (Lrp4) and mitochondrial content and sclerostin treatment only inhibited increased Lrp4 content with EXT. Together, these results provide evidence that reductions in resting sclerostin with exercise training may influence associated alterations in energy metabolism and body composition, particularly in scWAT. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Osteokines are novel exercise-inducible soluble factors secreted by osteocytes, osteoblasts, and osteoclasts that play an important role in the body's response to exercise, mainly including RANKL, sclerostin, osteocalcin, FGF23, Wnt3a, TGF-β, IGF-1, and PGE2.
“Osteokines, novel exercise-inducible soluble factors secreted by osteocytes, osteo blasts, and osteoclasts, play an important role in the body’s response to exercise, mainly including RANKL [127], sclerostin [128], osteocalcin [129], fibroblast growth factor 23 (FGF23) [95], Wnt3a [130], TGF-β [131], IGF-1 [132], and prostaglandin E2 (PGE2) [133] (Figure 3).”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [128]
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- Authors
- Kurgan, N., Stoikos, J., Baranowski, B. J., Yumol, J., Dhaliwal, R., Sweezey-Munroe, J. B., Fajardo, V. A., Gittings, W., Macpherson, R. E. K., & Klentrou, P.
- Affiliations
- Brock University (CA)
- Centre for Neuroscience Brock University St. Catharines ON Canada
- Corresponding author
- Klentrou, Panagiota
- ORCID
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-12-01
- Volume
- 38
- Issue
- 4
- Pages
- 541-555
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W4313646184
- Cited by
- 12
- References
- 66
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 1 · 2023: 3
- FWCI
- 0.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Bone and Mineral Research (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada (2020-00014, 2020‐00014)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- sclerostin, exercise training, white adipose tissue, body composition, subcutaneous adipose tissue, visceral adipose tissue, Wnt/β-catenin signaling, LRP4, mitochondrial content, energy expenditure, adipocyte size, adipocyte morphology, adipogenesis, dietary intake, male mice
- MeSH terms
- Adipose Tissue, Animals, Body Composition, Male, Mice, Inbred C57BL, Physical Conditioning, Animal, Adaptor Proteins, Signal Transducing, Mice, Adipose Tissue, White
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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