BoneKEy Reports | BoneKEy Watch
Fat metabolism is under the control of osteocytes
DOI:10.1038/bonekey.2013.239
Transgenic mice, in which the receptor for diphtheria toxin (DT) was under control of the dentin matrix protein-1 promoter, were injected with DT at 15 weeks to render them osteocyte-less (OL mice).
By the age of 18 weeks, OL mice showed a significantly lower leukocyte count in the peripheral blood compared to controls (wild-type mice injected with DT). As well as profound T- and B-cell lymphopenia, OL mice exhibited drastic atrophy of the thymus with a 90% reduction in thymocytes. All of these effects were reversed at 100 days when viable osteoblasts were introduced and the bone marrow was repopulated.
The reduction in B lymphopoiesis was due to the lack of stromal cells specific for B-lymphoid cells, while the reduction in T lymphocytes occurred because the microenvironment in the thymus was disrupted.
Notably, the OL mice lost weight after DT injection and showed a deficiency of white adipose tissue. Their mesenteric and subcutaneous fat was drastically reduced and the epididymal fat pad mass and retroperitoneal fatty tissue were not visible. Surprisingly, OL mice were not diabetic. Although the osteoclast number was slightly elevated in OL mice vs. controls, bone remodeling occurred at a similar rate in both.
Editor’s comment: This surprising report suggests that osteocytes regulate the microenvironment of the bone marrow and the thymus to control lymphopoiesis, and that osteocytes also control fat metabolism in cooperation with the hypothalamus. Whether this is mediated via a neuronal network remains to be determined.
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