Role of Kupffer Cells in High Fat Diet Induced Hepatic Insulin Resistance / 天津医药

ABSTRACT

Objective To explore the role of Kupffer cells in high fat diet induced hepatic insulin resistance. Meth-ods Eighty-four C57BL/6J mice were divided into two groups normal chow (NC) group (7 subgroups) and high fat diet (HFD) group (7 subgroups). Glucose tolerance tests were performed at feeding time of 1,2,4,8,12 and 16 weeks in one NC group and one HFD group. The mice livers at the same feeding time were obtained in other 6 NC groups and 6 HFD groups respectively. The expression levels of IRS1-ser307, Akt-ser473, S6K1-thr389 and p-JNK were detected by Western blot as-say. The values of MCP-1,TNF-α,IL-1βand IL-10 mRNA 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 (4-16 weeks ) and p-JNK(2-16 weeks ) 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 (all P＜0.05). The hepatic pro-inflammatory factor MCP-1,TNF-αand IL-1βmRNA expressions were higher in HFD group than those in NC group during 2-16 weeks (all P ＜ 0.01). The anti-inflammatory factor IL-10 mRNA was significantly lower in HFD group than that in NC group during 4-16 weeks (all P＜0.01). Conclusion High fat diet maybe play a role in the hepatic insulin resistance by stimulating M1 Kupffer cells to secrete pro-inflammatory factor and inhibiting M2 Kupffer cells to se-crete anti-inflammatory factor.