Sclerostin Influences Exercise‐Induced Adaptations in Body Composition and White Adipose Tissue Morphology in Male Mice

• Published in: Journal of bone and mineral research Vol. 38; no. 4; pp. 541 - 555
• Main Authors: Kurgan, Nigel, Stoikos, Joshua, Baranowski, Bradley J., Yumol, Jenalyn, Dhaliwal, Roopan, Sweezey‐Munroe, Jake B., Fajardo, Val A., Gittings, William, Macpherson, Rebecca E.K., Klentrou, Panagiota
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.04.2023; Wiley Subscription Services, Inc
• Subjects: Adaptation; Adaptor Proteins, Signal Transducing - metabolism; Adipocytes; ADIPOSE TISSUE; Adipose Tissue - metabolism; Adipose Tissue, White - metabolism; Animals; Body Composition; Body fat; Body mass; Bone composition; Cell size; Energy expenditure; Energy metabolism; EXERCISE; Fitness training programs; Food intake; GSK3; LRP4; Male; Metabolism; Mice; Mice, Inbred C57BL; Mitochondria; Oxygen consumption; Physical Conditioning, Animal - physiology; Physical training; Receptor density; SCLEROSTIN; Signal transduction; SOST protein; Wnt protein; WNT SIGNALING; SCLEROSTIN; LRP4; GSK3; WNT SIGNALING; ADIPOSE TISSUE; EXERCISE
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1002/jbmr.4768

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).