Abstract: Objective To investigate the effect of inhibiting the expression of TLR4 in the hypothalamus on obesity-related metabolic state. Methods After 1-week adaptive feeding, 40 four week-old male C57BL / 6 mice (SPF grade) were randomly divided into two groups, in which the mice were fed with normal diet (in NCD group) or high-fat diet (in HFD group) for 4 weeks respectively. The body weight of mice were measured once a week. The mice in each of the above groups were then randomly selected and divided into two group for the injection of TLR4 shRNA lentiviral particles or control viral particles respectively. Mice were sacrificed when reached 13-week old for further experiments. The expression of TLR4 in the hypothalamus was detected by fluorescence quantitative RT-PCR. The fasting blood glucose of the mice was detected by a blood glucose meter. The levels of serum TNF-α and IL-6 were detected by ELISA. The levels of serum low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, triglyceride and total cholesterol were detected by automatic biochemical analyzer. HE staining were performed in adipose tissues. Results After TLR4-shRNA lentivirus intervention, the expression level of TLR4 in the hypothalamus was significantly decreased (P< 0. 05), and the weight gain and energy intake of high-fat fed C57BL / 6 mice were significantly decreased (P < 0. 05), the levels of inflammatory factors, triglycerides, and fasting blood glucose were significantly decreased in high-fat fed C57BL / 6 mice (P < 0. 05). The hypertrophy of adipocyte was also alleviated after TLR4-shRNA lentivirus intervention. Conclusion Down-regulation of TLR4 expression in the hypothalamus can effectively improve obesity-related inflammatory response, and metabolic disorders on glucose and blood lipids.

Key words: TLR4, obesity, inflammatory response, metabolism