Abstract
Risk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We observed that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in female C57BL6/J mice. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with Vh or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed a low- or high- fat diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high-fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat diet and accompanied by a significant decrease in serum bone formation markers. Our novel observations will provide new information on basic bone biology, potential therapeutic targets and toxicological pathways.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Declarations
Funding: This work was supported by the National Institute of Environmental Health Sciences grant R21 ES021136 to J.J.S.
Conflicts of Interests/Competing Interests: The authors have none to declare.
Availability of Data and Material: The authors will provide data upon request.
Code Availability: Not applicable.
Ethics Approval: All animal studies were approved by the Institutional Animal Care and Use Committee at Boston University and performed in an American Association for the Accreditation of Laboratory Animal Care accredited facility (Animal Welfare Assurance Number: A3316-01).