High-fat diet-induced obesity stimulates ketone body utilization in osteoclasts of the mouse bone.
High-fat diet-induced obesity stimulates ketone body utilization in osteoclasts of the mouse bone.
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DOI：
10.1016/j.bbrc.2016.03.115
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发表时间：
2016-04
影响因子：
3.1
通讯作者：
M. Yamasaki;S. Hasegawa;M. Imai;N. Takahashi;T. Fukui
中科院分区：
文献类型：
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作者：
M. Yamasaki;S. Hasegawa;M. Imai;N. Takahashi;T. Fukui
以往的研究表明，高脂饮食(HFD)诱导的肥胖增加了脂肪组织中乙酰乙酰-辅酶A合成酶(AACS)基因的表达。为了研究肥胖对其他组织中AACS基因的影响，我们检测了高脂饲料喂养的小鼠AACS基因水平的变化。原位杂交显示，AAC存在于胚胎的几个区域，包括脊柱区(尤其是体节)和成人股骨的骨骺。饲喂高脂饲料的小鼠成年股骨AACS基因的表达高于普通饲料喂养的小鼠，但在高蔗糖饮食(HSD)诱导的肥胖小鼠中没有观察到这种增加。此外，在3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)和白介素6(IL)-6基因中观察到HFD特异性的增加。此外，我们检测到在分化的破骨细胞(RAW 264)中有较高的AACS mRNA表达，并发现只有在破骨细胞中，IL-6显著上调了AACS mRNA的表达。这些结果提示了酮体在骨代谢中的新功能。由于IL-6对破骨细胞的异常激活导致骨吸收，我们的数据提示AAC和酮体是肥胖与骨质疏松关系中的重要因素。
Previous studies have shown that high-fat diet (HFD)-induced obesity increases the acetoacetyl-CoA synthetase (AACS) gene expression in lipogenic tissue. To investigate the effect of obesity on the AACS gene in other tissues, we examined the alteration of AACS mRNA levels in HFD-fed mice. In situ hybridization revealed that AACS was observed in several regions of the embryo, including the backbone region (especially in the somite), and in the epiphysis of the adult femur. AACS mRNA expression in the adult femur was higher in HFD-fed mice than in normal-diet fed mice, but this increase was not observed in high sucrose diet (HSD)-induced obese mice. In addition, HFD-specific increases were observed in the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) and interleukin (IL)-6 genes. Moreover, we detected higher AACS mRNA expression in the differentiated osteoclast cells (RAW 264), and found that AACS mRNA expression was significantly up-regulated by IL-6 treatment only in osteoclasts. These results indicate the novel function of the ketone body in bone metabolism. Because the abnormal activation of osteoclasts by IL-6 induces bone resorption, our data suggest that AACS and ketone bodies are important factors in the relationship between obesity and osteoporosis.