Toxic lipids stored by Kupffer cells correlates with their pro-inflammatory phenotype at an early stage of steatohepatitis

摘要: Background & Aims Non-alcoholic steatohepatitis (NASH) is characterized by steatosis associated with liver inflammation. Steatosis causes recruitment of lymphocytes into the and this worsened lipopolysaccharides (LPS). As macrophages may be involved in lymphocyte homing, we studied role lipids determining phenotype Kupffer cells (KCs) at stage steatosis. Methods was induced mice a high fat diet. The turnover KCs were analyzed vivo flow cytometry. assessed optical electron microscopy, cell culture vitro chemotaxis. Lipidomic analysis carried out mass-spectrometry gene expression TaqMan low density array. Results Although number not modified steatotic livers compared to normal livers, their phenotypes different. Electron microscopy demonstrated that from fatty enlarged loaded lipid droplets. Lipid synthesis trafficking dysregulated fat-laden toxic accumulated. Fat-laden recruited more CD4+ T B response LPS stimulation than did control produced levels pro-inflammatory cytokines/chemokines, which could reversed inhibition lipogenesis. Conclusions accumulation due dysregulation metabolism trafficking. are "primed" recruit exhibit phenotype, reversible