Research of mechanisms of liraglutide inducing expression of fibroblast growth factor 21 in white adipose tissues of obese type 2 diabetic rats / 中国药理学通报

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.