中国药理学通报2018，Vol.34Issue(6)：824-830,7.DOI:10.3969/j.issn.1001-1978.2018.06.017
利拉鲁肽诱导肥胖2型糖尿病大鼠白色脂肪组织中FGF21的表达及机制
Research of mechanisms of liraglutide inducing expression of fibroblast growth factor 21 in white adipose tissues of obese type 2 diabetic rats
摘要
Abstract
Aim To investigate the effect of liraglutide on expression of fibroblast growth factor 21 in white ad-ipose tissues and its mechanisms. Methods Male SD rats were subjected to a standard control diet or high-fat diet ( HFD) for 12 weeks, then the HFD group was in-jected introperitoneally with 30 mg · kg-1 streptozoto-cin to induce type 2 diabetes mellitus model. Half number of rats of type 2 diabetes mellitus were injected with liraglutide ( DM +LRG, 0. 4 mg · kg-1 · d-1 , two times one day ) for another 6 weeks. Serum bio-chemical indices and FGF21 levels were detected. The pathological changes in epididymal adipose tissues were detected by HE staining. The mRNA and protein ex-pression and phosphorylation of FGF21 , peroxisome proliferator-activated receptor γ ( PPARγ) , fibroblast growth factor receptor 3 (FGFR3),β-Klotho, liver ki-nase B1(LKB1), AMP-activated kinase (AMPK), a-cetyl-CoA carboxylase ( ACC ) and phosphorylation of signaling molecules in MAPK pathway were assessed by RT-PCR, immunohistochemistry and Western blot re-spectively. Results Body mass and serum lipid, ALT and AST levels increased in DM group, while FGF21 level decreased, and the volume of adipose cells in ep-ididymal adipose tissues was expanded. Expressions of FGF21, PPARγ, p-FGFR3, β-Klotho, p-LKB1, p-AMPK, p-ACC were down-regulated, while p-ERK, p-JNK and p-p38 expression were all increased. These indices were reverted by liraglutide treatment. Conclu-sion Liraglutide has significant lipid-lowering effect, which maybe related with increased FGF21 expression, activating AMPK pathway and inhibiting MAPK path-way.关键词
利拉鲁肽/肥胖2型糖尿病/白色脂肪组织/FGF21/AMPK/MAPKKey words
liraglutide/obese type 2 diabetes melli-tus/white adipose tissue FGF21/AMPK/MAPK分类
医药卫生引用本文复制引用
张楠,张一,章秋,鲁云霞..利拉鲁肽诱导肥胖2型糖尿病大鼠白色脂肪组织中FGF21的表达及机制[J].中国药理学通报,2018,34(6):824-830,7.基金项目
安徽省自然科学青年基金(No 1608085QH205) （No 1608085QH205）
国家自然科学基金青年科学基金培养计划项目(No 2013KJ15) （No 2013KJ15）
