Acta Anatomica Sinica

AAS ›› 2014, Vol. 45 ›› Issue (6): 800-808.doi: 10.3969/j.issn.0529-1356.2014.06.012

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Molecular mechanism on nonalcoholic fatty liver disease by liraglutide regulation

NIU  Shi-wei 1,2 WU  Jun-zi 1,2 LI Xiao-bo2 WANG Wen-lin3 LI  Yan 1,2* LI Shu-de 4*   

  1. 1. Life Science and Technology College, Kunming University of Science and Technology, Kunming 650500, China;2. Department of Health Care,the First People’s Hospital of Yunnan Province, Kunming 650036, China;3. Department of Pathogenic Biology, Kunming Medical University,Kunming 650500, China; 4. Departent of Biochemistry and Molecular Biodogy,Kunming Medical University, Kunming 650500, China

  • Received:2014-05-16 Revised:2014-08-02 Online:2012-12-06 Published:2014-12-06

Abstract:

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.

Key words: Liraglutide, Nonalcoholic fatty liver disease, Sterol regulatory element binding transcription factor 1c, Acetyl-CoA carboxylase alpha, Reverse transcription-PCR, Rat