To ensure the delivery of sufficient energy for homeostasis and new bone growth, the skeletal system produces hormones that act on distant tissues. Serum levels of such hormones reflect normal and dysregulated processes outside the skeleton, suggesting that bone cells influence whole-body metabolism.
Researchers investigated a possible endocrine function for sclerostin, an osteocyte-derived product of the SOST gene, the primary function of which is to inhibit local bone acquisition. Focusing on body composition, glucose homeostasis, and fatty acid metabolism, the authors report findings from two models: SOST knockout mice and mice that overproduce sclerostin via the liver.
The authors found that in addition to large gains in bone volume, SOST knockout mice accumulate less adipose tissue with increased insulin sensitivity, compared with wild-type mice.
By contrast, sclerostin overproduction stimulates adipocyte hypertrophy. Further, the authors demonstrated that a sclerostin-neutralizing antibody, which is similar to antibodies currently in clinical trials for osteoporosis treatment, confers resistance to obesity and metabolic disturbances associated with consumption of high fat diets in mice.
The findings suggest that sclerostin represents a currently unexplored link between skeletal and adipose tissue, according to the authors.
Bone-derived hormone influences adipose tissue in mice
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