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Omega‐3 fatty acid‐rich fish oil supplementation prevents rosiglitazone‐induced osteopenia in insulin resistant C57BL/6 mice
Author(s) -
Rahman Md Mizanur,
Halade Ganesh,
Williams Paul
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.692.3
Subject(s) - fish oil , medicine , endocrinology , bone mineral , rosiglitazone , docosahexaenoic acid , bone resorption , bone marrow , eicosapentaenoic acid , osteopenia , osteoporosis , chemistry , fatty acid , insulin , polyunsaturated fatty acid , biochemistry , biology , fishery , fish <actinopterygii>
Rosiglitazone (RSG) is a very effective insulin sensitizing and glucose‐lowering drug, however, associated with bone loss resulting in increased peripheral fractures. RSG‐induced bone loss occurs mainly due to increased bone resorption, and bone marrow adiposity. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)‐rich fish oil is known to attenuate both bone resorption and bone marrow adiposity. We hypothesize that co‐administration of EPA and DHA‐rich fish oil prevents RSG‐induced bone loss. In this report, we investigated the effect of co‐administration of fish oil on RSG‐induced bone loss in C57BL/6 mice and the mechanisms underlying this preventive effect. Twelve‐month‐old C57BL/6 female mice were fed iso‐caloric diet supplemented with corn oil (CO), fish oil (FO), RSG+CO and RSG+FO for 5 months. Bone mineral density (BMD) was analyzed by dual energy x‐ray absorptiometry (DXA). RSG treatment reduced BMD in both CO and FO groups. However, mice fed RSG+FO exhibited significantly higher levels of bone mineral density (BMD) in different bone regions as compared to CO alone or RSG+CO fed groups. Reduced activity of COX‐2, enhanced activity of alkaline phosphatase were observed in LPS treated bone marrow (BM) cells from RSG+FO treated mice as compared to RSG+CO group. LPS treated BM cells from RSG+FO treated mice also expressed lower levels of Cathepsin K and PPAR‐γ as compared to RSG+CO group. LPS‐stimulated BM and splenocytes from RSG+FO also produced significantly lower level of pro‐inflammatory cytokines, TNF‐alpha and IL‐6 and higher level of anti‐inflammatory cytokine, IL‐10 as compared to RSG+CO group. We further examined the effect of DHA and EPA with RSG on bone morphogenic protein‐2 (BMP‐2)‐induced osteogenesis and adipogenesis in C3H10T1/2 cells and RANKL‐induced osteoclastogenesis in RAW264.7 cells in‐vitro . DHA restored RSG‐induced reduction of osteoblast differentiation and RSG‐induced up‐regulation of adipocyte differentiation in C3H10T1/2 cells. DHA also inhibited RSG‐induced up‐regulation of osteoclast differentiation of RANKL treated RAW264.7 cells. In conclusion, we provide evidence that FO co‐administration with RSG may prevent RSG‐induced bone loss by inhibiting markers of inflammation, osteoclastogenesis and adipogenesis and by enhancing osteogenesis in bone microenvironment. Support or Funding Information This study was supported by NIH contract grant number AG034233 (M.R.)