Effect Of Intraventricular Chronic Injection Of Thyroid Hormone On Energy Metabolism In Mice

Objective More and more evidence shows that the hypothalamic pituitary thyroid axis(HPT)is closely related to energy balance.In the literature on the effects of thyroid hormones(THs)on energy metabolism,there are more reports on its peripheral effects,but there is relatively little literature on its direct effects in the central.Therefore,this study explored the changes of energy metabolism in mice by investigating the effects of T3(3,5,3'-triiodo-levothine-thyronine)directly in the lateral ventricle.Methods Forty-eight mice were randomly divided into two groups of 24 mice according to male and female,and then continued into two groups(CON group and T3 group),12 in each group.The lateral ventricle of the mice was positioned and placed in a tube with a stereotaxic apparatus.The chronic persistence of NAOH(CON group)and T3(T3 group)was injected into the lateral ventricle of the mouse for 28 days.The body weight and feeding status of the mice at 9 o'clock in the morning before the catheterization and after the catheterization were recorded.The mice were subjected to the peritoneal glucose tolerance test(GTT)and insulin tolerance test(ITT)on the 26 th and 28 th day after the catheterization.;on the 29 th day after catheterization,the eyelids were bled and the mice were sacrificed,and the mouse brown adipose tissue(BAT)and white adipose tissue(white adipose Tissue,WAT))were quickly isolated.and weighed to separate intact brain tissue.The changes of related hormones in mice were detected.Detection of agouti-related protein(AgRP),neuropeptide Y(NPY)and of proopiomelanocortin(POMC)in arcuate nucleus(ARC)by fluorescence in situ hybridization Changes in mRNA transcription;expression levels of AgRP,NPY,and POMC proteins were detected by immunofluorescence chemistry.Results After 28 days of chronic long-term injection of drug in the lateral ventricle,there was no significant difference in thyroid function between the T3 group and the CON group.The food intake of the T3 group was significantly higher than that of the CON group(P < 0.05).The weight of the mice in the T3 group was significantly higher than that in the CON group from the 5th day after the drug injection intervention.The weight of the mice in the T3 group was significantly higher than that in the CON group from the 6th day after the drug intervention.The total weight gain of the male and female T3 groups was significantly increased compared with the CON group(P < 0.05).The results of mouse GTT showed that there was no significant difference in blood glucose levels between T3 group and CON group in male and female mice at each monitoring time point.The ITT results showed that the blood glucose of the T3 group was higher at the 60 minute in male mice,and at the 15,30,45 minute in the female,respectively,compared to the CON group(P<0.05).The body fat percentage of WAT in the T3 group of mice was higher than that in the CON group(P <0.05),while the body fat percentage of BAT was lower in the T3 group than in the CON group(P <0.01).Leptin levels were reduced in mice after T3 administration.The expression of AgRP and NPY mRNA in the ARC region of the T3 group was significantly increased after drug intervention(P <0.05),while the expression of POMC mRNA in the T3 group decreased,compared to the CON group(P <0.05).The immunofluorescence showed that the expression of AgRP and NPY protein in ARC region of T3 group significantly increased,and the expression of POMC in the T3 group was significantly decreased.(P <0.05).Conclusion Chronic continuous injection of T3 into the lateral ventricle directly affects the central nervous system to affect energy metabolism.Intraventricular injection of T3 did not cause changes in thyroid function,and the effect of chronic injection of T3 into the lateral ventricle on thyroid function in mice was ruled out.Chronic injection of T3 can up-regulate the expression of appetite stimulating factors AgRP and NPY in ARC and down-regulate the expression of anorexia neuropeptide POMC,increase the food intake of mice,reduce the level of leptin,increase the body fat percentage of WAT,BAT The body fat percentage is reduced and the body weight is significantly increased.Chronic persistence of T3 in the center caused insulin resistance,but did not cause changes in glucose tolerance.