Abstract:

[Abstract]   Objective  To explore the role of Kupffer cells in high fat diet induced hepatic insulin resistance.      Methods   Eighty-four C57BL/6J mice were divided into two groups: normal chow (NC) group (7subgroups) and high fat diet(HFD) group (7subgroups). Glucose tolerance tests were performed at feeding time of1，2，4，8 ,  12and16weeks in one NC group and one HFD group. The mice livers at the same feeding time were obtained in other 6NC groups and 6HFD groups respectively. The expression levels of IRS1-ser307, Akt-ser473, S6K1-thr389and p-JNK were detected by Western blot as-say. The values of MCP-1，TNF-α，IL-1βand IL-10mRNA were examined by qRT-PCR.  Results  Compared with NC group, the impaired glucose tolerance was found from the first week in HFD group (P<0.05). The hepatic expressions of IRS1-ser307, S6K1-thr389(4-16weeks ) and p-JNK(2-16weeks ) increased and Akt-ser473（8-16 weeks）decreased in HFD group than those of NC group. The same results were gained by analysis of protein relative expression (allP<0.05). The hepatic pro-inflammatory factor MCP-1,TNF-αand IL-1βmRNA expressions were higher in HFD group than those in NC group during2-16weeks (allP<0.01). The anti- inflammatory factor IL-10mRNA was significantly lower in HFD group than that in NC group during4-16weeks (allP<0.01).   Conclusion   High fat diet maybe play a role in the hepatic insulin resistance by stimulating M1Kupffer cells to secrete pro-inflammatory factor and inhibiting M2Kupffer cells to secrete anti-inflammatory factor.

Key words: Kupffer cells, liver, tumor necrosis factor-alpha, interleukin-1beta, interleukin-10, insulin resistance, monocyte chemoattractantprotein 1, 高脂饮食