Welcome to visit Acta Anatomica Sinica! Today is
Chinese
Molecular mechanism on nonalcoholic fatty liver disease by liraglutide regulation
NIU Shi-wei WU Jun-zi LI Xiao-bo WANG Wen-lin LI Yan1* LI Shu-de*
Acta Anatomica Sinica ›› 2014, Vol. 45 ›› Issue (6) : 800-808.
Molecular mechanism on nonalcoholic fatty liver disease by liraglutide regulation
Objective To investigate the effect of liraglutide on the reaction of inflammation and antioxidant capacity on the model of nonalcoholic fatty liver disease (NAFLD) rats and study the regulation of liraglutide to the expression of lipid metabolism enzyme. Methods Seventy SD rats, 25 SD rat were given normal cliet, the others were induced to produc NAFLD by high glucose and high fat diet by gavage for 12 weeks, five rats were killed randomly from control group and model group respectly. After the successful establishment of NAFLD model,the rats were randomly divided into the control group (n=20), the model group (n=20) and the liraglutide treatment group (n=20).The liraglutide treatment group was given liraglutide 60μg/(kg·d) by subcutaneous injection, while the model group received normal saline 1ml/(kg·d). The rats were killed 4 week or 8 weeks after the liraglutide injection, 50% from each group at each time point, so as to observe the changes of inflammatory factors, oxidant factors, antioxidant factors, liver function and lipids in the plasma, and to detect the liver morphological changes and the mRNA expressions of sterol regulatory element binding transcription factor -1c (SREBF-1c) and acetyl coenzyme A carboxylase alpha (ACCα) by the reverse transcription-PCR（RT-PCR）. The protein expressions of SREBF-1c and ACCα were detected by the immunohistochemistry and Western blotting. Results Compared with the model group, C-reactive protein (CRP), interleukin(IL)-1α, IL-1β, IL-6, gumor necrosis facto-α(TNF-α), malondialdehyde(MDA), aspartateamino trans ferase(AST), alanineamino transferase(ALT), triglyceride(TG), total cholesterol(TC) and low-density lipoprotein(LDL-C) contents in the plasma of the rats with the liraglutide treatment were reduced after 4 weeks(P<0.05), with superoxide dismutase(SOD), total antioxidant capacity(T-AOC) and glutathione (GSH) being increased (P<0.05), liver fat particle deposition reduced and the expressions of mRNA and protein of SREBF-1c and ACC α in the liver tissue regulated downward(P<0.05). After the liraglutide treatment for 8 weeks, the above indicators were improved were more obviously. Conclusion Liraglutide can reduce the inflammatory reaction in NAFLD and improve the antioxidant capacity as well as the liver function. It can also reduce the generation of lipid by down-regulating the expressions of SREBF-1c and ACCα in liver tissue possibly, and alleviate the liver fatty degeneration. With the increase of treatment time, the effect of liraglutide on the prevention and treatment of NAFLD becomes more obvious.
Liraglutide / Nonalcoholic fatty liver disease / Sterol regulatory element binding transcription factor 1c / Acetyl-CoA carboxylase alpha / Reverse transcription-PCR / Rat
［1］Alba LM, Lindor K. Non-alcoholic fatty liver disease［J］. Aliment Pharmacol Ther, 2003,17(8):977-986.
［2］Matsumoto S, Yamazaki M, Kadono M, et al. Effects of liraglutide on postprandial insulin and glucagon responses in Japanese patients with type 2 diabetes［J］.J Clin Biochem Nutr, 2013, 53(1):68-72.
［3］Ding J, Wang L, Li J, et al.Reliability of metabolic and pathologic parameters in the high fat diet-induced nonalcoholic fatty liver disease rat model established by gastric perfusion［J］. Journal of Clinical Hepatology, 2012, 28(7):531-534. (in Chinese)
丁洁，王亮，李娟,等. 高脂乳剂灌胃构建大鼠非酒精性脂肪性肝病模型可靠性的再研究［J］. 临床肝胆病杂志, 2012, 28(7):531-534.
［4］Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease［J］. Hepatology, 2005, 41(6): 1313-1321.
［5］Smith BW, Adams LA. Non-alcoholic fatty liver disease［J］. Crit Rev Clin Lab Sci, 2011, 48(3):97-113.
［6］Méndez-Sánchez N. Non alcoholic fatty liver disease［J］. Ann Hepatol, 2009, 8 Suppl 1:S3.
［7］Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes［J］. Hepatology, 2006, 44(4):865-873.
[8］Shen F, Wang YQ, Fan JG. The 2012 Shanghai International Conference on digestive system diseases［J］. Chinese Journal of the Frontiers of Medical Science(Electronic Version), 2012, 4(7):I-IV. (in Chinese)
沈峰，汪余勤，范建高. 2012上海国际消化系统疾病会议纪要［J］.中国医学前沿杂志(电子版), 2012, 4(7):I-IV.
［9］Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease［J］. Semin Liver Dis, 2008, 28(4):370-379
［10］Dai Y, Mehta JL, Chen M. Glucagon-like peptide-1 receptor agonist liraglutide inhibits endothelin-1 in endothelial cell by repressing nuclear factor-kappa B activation［J］. Cardiovasc Drugs Ther, 2013, 27(5):371-380.
［11］Parthsarathy V, Hlscher C. The type 2 diabetes drug liraglutide reduces chronic inflammation induced by irradiation in the mouse brain［J］. Eur J Pharmacol, 2013, 700(1-3):42-50.
［12］Shiraki A, Oyama J, Komoda H, et al. The glucagon-like peptide 1 analog liraglutide reduces TNF-α-induced oxidative stress and inflammation in endothelial cells［J］. Atherosclerosis, 2012, 221(2):375-382.
［13］Gao H, Xu L, Li D, et al. Effects of glucagon-like peptide-1 on liver oxidative stress, TNF-α and TGF-β1 in rats with non-alcoholic fatty liver disease［J］. Nan Fang Yi Ke Da Xue Xue Bao, 2013, 33(11):1661-1664.
［14］Guan LCh, Xu LSh, Gao HT, et al. Effects of liraglutide on biochemical and inflammatory index model of non alcoholic fatty liver in rats［J］. Journal of Practical Medicine, 2013, 29(14):2270-2272. (in Chinese)
关丽嫦，徐丽姝，高慧亭,等. 利拉鲁肽对非酒精性脂肪肝大鼠模型生化及炎症指标的影响［J］. 实用医学杂志, 2013, 29(14):2270-2272.
［15］Hu KC, Wang HY, Liu SC, et al. Nonalcoholic fatty liver disease: updates in noninvasive diagnosis and correlation with cardiovascular disease［J］. World J Gastroenterol, 2014, 20(24):7718-7729.
［16］Hagen RM, Rodriguez-Cuenca S, Vidal-Puig A. An allostatic control of membrane lipid composition by SREBP1［J］. FEBS Lett, 2010, 584( 12):2689-2698.
［17］Chen X, Zhang C, Zhao M, et al. Melatonin alleviates lipopolysaccharide-induced hepatic SREBP-1c activation and lipid accumulation in mice［J］. J Pineal Res, 2011, 51( 4):416-425.
［18］Fang DL, Wan Y, Shen W, et al. Endoplasmic reticulum stress leads to lipid accumulation through upregulation of SREBP-1c in normal hepatic and hepatoma cells［J］. Mol Cell Biochem, 2013, 381(1-2):127-137.
［19］Li JQ, Zheng ShX, Yu ZN, et al. Acetyl-coenzyme A carboxylase: a key Metabolic enzyme of fatty acid and progress of its gene clone［J］. Chinese Journal of Applied and Environmental Biology, 2011, 17 ( 5 ): 753-758. (in Chinese)
李洁琼，郑世学，喻子牛，等. 乙酰辅酶A羧化酶：脂肪酸代谢的关键酶及其基因克隆研究进展［J］. 应用与环境生物学报, 2011, 17 ( 5 ): 753-758.
［20］Chen SM，Yang SM，Zhang WL，et al.TNF-α promotes HepG2 hepatocytes lipid accumulation［J］. Journal of Third Military Medical Unviersity, 2013, 35( 11):1088-1092.
/
| 〈 |
|
〉 |
