The Effect Of The Tool-like Receptor 4 Signaling Pathway On Insulin Resistance In Small For Gestational Age Rats

Objective: To investigate the effect of the toll-like receptor 4(TLR-4) signaling pathway on insulin resistance in small for gestational age(SGA) rats after birth.Methods: Establishment of the SGA rat model was made by the starvation method in pregnant rats.Experiment group were divided into three groups:(1)Group S1: SGA with catch-up growth;(2)Group S2: SGA without catch-up growth;(3)Group AGA: Appropriate for gestational age(AGA). Blood, liver and omental adipose tissue were collected on the 4th and 12 th week after birth. The serum level of tumor necrosis factor-α( TNF-α) and interleukin-6(IL-6) were detected by ELISA method. The concentration of fasting blood-glucose, fasting insulin, free fatty acids, triglyceride, total cholesterol were analyzed. Homeostasis model assessment for insulin resistance index(HOMA-IR) was calculated.The m RNA expression of TLR-4, myeloid differentiation factor 88(My D88), nuclear factor ?B(NF-?B), TNF-α and IL-6 in liver and omental adipose tissue were evaluated by real-time quantitative RT-PCR.Results: Along with the growth, the serum level of fasting blood-glucose, fasting insulin, free fatty acids, triglyceride, total cholesterol, TNF-α and IL-6 in group S1 gradually became higher than that of in group AGA and group S2(P < 0.05).The m RNA expression level of TLR-4, My D88, NF-?B,TNF-α and IL-6 in liver and omental adipose tissue in group S1 were remarkably higher than that of in group AGA and group S2(P<0.05). In group S1, the TLR-4 signaling pathway was positively related to HOMA-IR. Higher degree of correlation was observed in omental adipose tissue than in liver(P<0.05).Conclusions: Abnormal glucose and lipid metabolism happened in SGA rats with catch-up growth with advancing age. Activation of TLR-4 signaling pathway in liver and adipose tissue induced the releasement of inflammatory cytokines such as TNF-α and IL-6, which resulted in chronic inflammatory reaction and promoted the development of insulin resistance. During the progression of the insulin resistance, the adipose tissue play more important role.