Bone Abstracts

Objective: To comparing the role of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in fat and bone communication.

Methods: Male wild type (WT) mice, IL-6 knockout (IL-6^−/−) mice, and tumor necrosis factor alpha (TNF-α) were fed with either standard diet (SD) or high fat diet (HFD) for 12 weeks. Bone mass and bone microstructure were evaluated by micro-CT. Gene expression related to lipid and bone metabolisms was assayed with real-time qRT-PCR. All animal experiments were performed in accordance with the guidelines for the care and use of laboratory animals and were approved by the Institutional Animal Care and Use Committee at the West China Hospital, Sichuan University.

Results: On the SD, the levels of plasma total cholesterol (TC) and low density lipoprotein (LDL-C) in IL-6^−/− mice and TNF-α^−/− mice were higher than that in WT mice, and IL-6^−/− mice showed higher level of TC while TNF-α^−/− mice showed higher level of LDL-C. HFD increased the levels of TC and LDL-C in all three strain mice, and the change was more obvious in TNF-α^−/− mice. The changes of adipocyteogenesis were also different, HFD increased the expression of PPAR-r and leptin mRNA levels in only WT mice, but not in IL-6^−/− mice and TNF-α^−/− mice.

On the SD, IL-6^−/− mice exhibited significantly higher trabecular thickness (Tb.Th), but TNF-α^−/− mice exhibited significantly higher trabecular number (Tb.N) than WT mice. After HFD feeding, trabecular bone volume fraction (Tb.BV/TV), Tb.N and Tb.Th were down-regulated, and trabecular space (Tb.Sp) was up-regulated in WT mice. Changes of these parameters were in similar tendency in IL-6^−/− mice, but they were in opposite tendency in TNF-α^−/− mice.

Conclusion: Both of IL-6 and TNF-α played a critical role in the HFD-related trabecular bone loss; and their roles in regulate fat and bone metabolism significant differently.