Overexpression 11β-HSD1 develops into fatty liver without obesity in C57BL/6

mice

Guoping Li1, Fengyi Gao2, Jie Xu1, Yong Man1 Shu Wang1, Jian Li1*

11The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of

Health, Beijing 100730, China2State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences,

Beijing 100101, China

*E-mail: lijian@bjhmoh.cn

The Project Sponsored by National Basic Research Program of China (2012CB517502), the National

Natural Science Foundation of China (No. 81270948, 81471071, 81270887, 81570789 , 81170381), the

Scientific Research Foundation for the Returned Overseas Chinese Scholars

Key word：11β-HSD1; Fatty liver; Adenovirus;

Objective: To establish a Non-alcoholic fatty liver disease (NAFLD) mouse model to mimic the

characteristics of fatty liver in Chinese population. Method: According to the latest

epidemiological survey, the characteristics of the Chinese population NAFLD presents

triglyceride accumulation with normal Body Mass Index (BMI). 11beta-hydroxysteroid

dehydrogenase type 1 (11β-HSD1) adenovirus (Ad-11βHSD1) was constructed．Ad-11βHSD1 and GFP adenovirus ( Ad-GFP) were amplified in 293A cells and purified before tail vein

injection．After adenovirus infection for 14 days, blood samples were collected and livers were

frozen. The levels of triglyceride, cholesterol and free fatty acid were measured. Lipoprotein

metabolism related genes were analyzed by Western blot and Q-PCR. Results: After Ad-11βHSD1

infection for 14 days, the mice develop into mild fatty liver but not obese with elevated plasma

nonesterified free fatty acids. However no difference was found in serum triglyceride and

cholesterol. The major lipogenesis regulator, sterol regulatory element binding protein-1

(SREBP1) was upregulated in protein levels, whether precursor or mature form, but not in

mRNA levels. Conclusion: The NAFLD mouse model was successfully constructed, which, at

least in part, has the characteristics of fatty liver in Chinese population, which lays a good

foundation for the further study.