The Effect Of Glucagon-like Peptide-1 Receptor Agonist On The Brown Adipose Tissue In High-fat Diet Induced Obese Rats

Part One Glucagon-like peptide-1 receptor agonist improve the function of brown adipose tissue in high-fat diet induced obese ratsObjective:To investigate the effects of glucagons-like peptide-1 (GLP-1) receptor agonist on the function of brown adipose tissue and the expression of its specific markers in high-fat diet induced obese rats.Methods:Fifty-four Sprague-Dawley (SD) rats (male, weight 220-260g) were established into obesity models by feeding them with high-fat diet 12weeks,and then randomly divided into six groups after selecting successful models:high-dose exenatide group(H-EXE group), low-dose exenatide group(L-EXE group), high-dose exenatide +Exendin 9-39 amide group(H-EXE+EX9 group), low-dose exenatide +Exendin 9-39 amide group(L-EXE+EX9 group), Metformin group(MET group),high-fat diet group(HF group).Besides, a normal group (NF group) was set up for control. Administration of exenatide、metformin、the integration of exenatide with Exendin 9-39 amide or normal saline lasted 10 weeks. At the 10th week, all rats were given general anesthetic in order to get the CT scan of interscapular brown adipose tissues by Gemstone CT, and then CT values of brown adipose tissues were measured. At the end of the experiment, the brown adipose tissue were collected. The mRNA expression and protein levels of uncoupling protein 1 (UCP1)、cell death-inducing DFFA (DNA fragmentation factor a)-like effector a (CIDEA)、 peroxisome proliferators-activated receptor γ coactive 1α (PGC1-α) were measured by RT-PCR and western blot. The single factor analysis was used for data analysis.Results:1.Compared with the control group, the protein levels of UCP-1、PGC1-a in the H-EXE group and L-EXE group increased significantly (P<0.05), as well as the mRNA level of UCP-1 (P<0.05); but the protein level of CIDEA was lower than the control group (P<0.05).With the intervention of Exendin 9-39 amide, the protein levels of UCP-1、PGC1-α and the mRNA level of UCP-1 decreased at the same time, the protein level of CIDEA increased.2. Compared with the control group, the level of Irisin in the H-EXE group increased significantly (P<0.05), but decreased after using Exendin 9-39 amide; 3. In the CT images, the CT values of interscapular brown adipose tissues in the H-EXE group and L-EXE group were higher than the control group, but become lower after using Exendin 9-39 amide.Conclusion:After administrating with the Glucagons-like peptide-1 (GLP-1) receptor agonist, the protein levels and mRNA levels of the functional markers in brown adipose tissues,enhance the function of brown adipose tissue were improved, the function of brown adipose tissue was enhanced, and it is more evident in higher concentration of GLP-1.Part Two Glucagon-like peptide-1 receptor agonist improve the quantity and differentiation of brown adipose tissue in high-fat diet induced obese ratsObjective:To investigate the effects of glucagons-like peptide-1 (GLP-1) receptoragonist on the quantity and differentiation of brown adipose tissue and the expression of its specific markers in high-fat diet induced obese rats.Methods:Fifty-four Sprague-Dawley (SD) rats (male, weight 220-260g) were established into obesity models by feeding them with high-fat diet 12weeks,and then randomly divided into six groups after selecting successful models:high-dose exenatide group(H-EXE group), low-dose exenatide group(L-EXE group), high-dose exenatide +Exendin 9-39 amide group(H-EXE+EX9 group), low-dose exenatide +Exendin 9-39 amide group(L-EXE+EX9 group), Metformin group(MET group),high-fat diet group(HF group).Besides, a normal group (NF group) was set up for control. Administration of exenatide、metformin、the integration of exenatide with Exendin 9-39 amide or normal saline lasted 10 weeks. At the 10th week, all rats were given general anesthetic in order to get the CT scan of interscapular brown adipose tissues by Gemstone CT, and then the areas and volumes of brown adipose tissue were measured. At the end of the experiment, the brown adipose tissues were collected. The mRNA expression and protein levels of peroxisome proliferators-activated receptor-γ (PPAR Y)、PRD1-BF1-RIZ1 homologous domain containing 16(PRDM16)were measured by RT-PCR and western blot. The single factor analysis was used for data analysis.Results:1.Compared with the control group, the protein levels of PPAR γ、 PRDM16 in the H-EXE group and L-EXE group increased significantly (P<0.05), as well as the mRNA level of PRDM16 (P<0.05).With the intervention of Exendin 9-39 amide, the protein levels of PPAR γ、PRDM16 and the mRNA level of PRDM16 decreased at the same tim.2. In the CT images, the areas and volumes of interscapular brown adipose tissues in the H-EXE group and L-EXE group were bigger than the control group, but become smaller after using Exendin 9-39 amide.Conclusion:After administrating with the Glucagons-like peptide-1 (GLP-1) receptor agonist, the protein levels and mRNA levels of the differentiation markers in brown adipose tissues were improved, the differentiation of brown adipose tissues was higher induced, and it is more evident in higher concentration of GLP-1.