Sclerostin influences exercise-induced adaptations in body composition and white adipose tissue morphology in male mice

Abstract

Sclerostin is an inhibitor of the osteogenic Wnt/β-catenin signalling pathway that 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 1h of treadmill running at ~65-70% VO2max 5 d/week (EXT) for 4 weeks and had subcutaneous (s.c) injections of either saline (C) or recombinant sclerostin (S) (0.1 mg/kg body mass) 5 d/week; thus, making 4 groups (SED-C, EXT-C, SED-S, and EXT-S; n=12/group). No differences in body mass were observed between experimental groups, while 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 a higher lean mass and lower 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), vWAT (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, while lower vWAT was only observed in the EXT-S group. EXT mice had increased iWAT 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.