Dietary Oxysterol, 7-Ketocholesterol, Accelerates Hepatic Lipid Accumulation and Macrophage Infiltration in Obese Mice

概要

〔目的(Purpose)〕
　To test whether small amount of 7KC in diet might induce hepatic steatosis and inflammation in obese mice.

〔方法ならびに成績(Methods/Results)〕
　Ob/ob mice at age of six weeks were fed CD, CD+7KC, WD, or WD+7KC for four weeks. We found that addition of 0.01% 7KC either in CD or WD accelerated hepatic neutral lipid accumulation by Oil Red O staining. Importantly, by 1ipid extraction analysis, it has been recognized that triglyceride rather than cholesterol species was significantly accumulated in CD+7KC compared to CD as well as in WD+7KC compared to WD. 111111unostaining revealed that macrophages infiltration was increased in CD+7KC compared to CD, and also in WD+7KC compared to WD. These phenotypes were accompanied by inducing inflammatory response and downregulating fatty acid oxidation. Furthermore, RNA seauence analysis demonstrated that 7KC reduced expression of genes which related to autophagy process. Levels of LC3-II protein were decreased in WD+7KC compared to WD. Similarly, we have confirmed the effect of 7KC on acceleration of steatohepatitis in db/db mice model.

〔総括(Conclusion)〕
　Col 1 ec t i ve1y, our s tudy has demonstrated that sma 11 amount of dietary 7KC contributed to accelerate hepat ic steatosis and inf1 aromat ion in obese mice models.