Exploration on the mechanism of Yimai Granules regulating white fat browning in the intervention of learning and memory impairment in high-fat mice based on JAK2/STAT3 signaling pathway
Objective:To explore the mechanism of Yimai Granules in regulating white adipose browning and intervening in learning and memory disorders in high-fat mice through the JAK kinase 2(JAK2)/signal transduction and transcriptional activation protein 3(STAT3)signaling pathway.Methods:Forty C57BL/6J mice were randomly divided into control group,model group,Yimai Granules group,and Simvastatin group using a random number table method,with 10 mice in each group.The control group was fed with regular feed,while the model group,Yimai Granules group,and Simvastatin group were continuously fed with high-fat feed for 44 weeks to establish a high-fat learning and memory impairment model.The Yimai Granules group(7.2 g/kg)and Simvastatin group(1.76 mg/kg)were gavaged with corresponding drugs at week 14,while the control group and model group were gavaged with an equal volume of 0.9％sodium chloride solution twice a day for 30 weeks.After 44 weeks,the learning and memory abilities of mice were tested using Morris water maze and spatial exploration experiments.HE staining was used to observe the morphology of the hippocampal CA1 region and the white adipose tissue near the epididymis.ELISA was used to detect the levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and the content of leptin(LP)in the supernatant of the white adipose tissue homogenate.The expression levels of UCP-1,PRDM16,p-JAK2,JAK2,p-STAT3,and STAT3 proteins in mice were detected.Results:Compared with the control group,the model group mice showed a decrease in escape latency and spatial directional shuttle ability(P＜0.01),uneven arrangement of neurons in the CA1 area of the hippocampus,liquefaction necrosis and nuclear pyknosis,significant increase in serum TC,TG,LDL-C levels(P＜0.01),and significant decrease in HDL-C levels(P＜0.01).The adipose tissue appeared as large molecule vacuoles,and the LP level in the supernatant of the adipose homogenate was significantly reduced(P＜0.01).The relative expression levels of PRDM16,UCP-1,p-JAK2/JAK2,p-STAT3/STAT3 proteins in adipose tissue were significantly reduced(P＜0.01).Compared with the model group,the targeted navigation and learning and memory abilities of mice in the Yimai Granules and Simvastatin groups were significantly improved(P＜0.01),while serum TC,TG,and LDL-C levels were significantly reduced(P＜0.01)and HDL-C levels were significantly increased(P＜0.01,P＜0.05),neurons in the CA1 area of the hippocampus gradually became intact,nuclei were evenly distributed,and multi lumen lipid droplet structures appeared in adipose tissue with a browning trend,LP levels in adipose homogenate were significantly increased(P＜0.01),and protein expression levels of PRDM16,UCP-1,p-JAK2/JAK2,p-STAT3/STAT3 in adipose tissue were significantly increased(P＜0.01,P＜0.05).Conclusion:Yimai Granules can reduce blood lipid levels and improve learning and memory abilities in high-fat learning and memory impairment model mice.Its mechanism of action may be related to activating the JAK2/STAT3 signaling pathway to promote white adipose browning.
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