Effects of Glucagon-Like Peptide-1 Analog on CDAA Diet-Induced Models of Nonalcoholic Fatty Liver Fibrosis in Rats

Objective To investigate the protective effects of glucagon-like peptide-1 （GLP-1） on Nonalcoholic fatty liver fibrosis（NAFLF） rats. Methods Sixty-three male SD rats were randomly divided into 2 groups, one of them（n=21） were fed with choline-supplemented L-amino acid-defined diet （CSAA） for the whole experiment process. Another group （n=43） were fed with choline deficent aminoacid-defined diet （CDAA） as the modeling group, and at the end of the tenth week, one of the CSAA group and two of the modeling group were sacrificed to confirm the modeling success, then the modeling group was divided randomly into 2 equal groups, both continued with CDAA diet, but one of the group were given with intraperitoneal injection of Liraglutide （GLP-1, administered in the later 8 weeks）, using saline as a control. The rats were sacrificed at the 2^nd、4^th、6^th、8^th week of the intervention process respectively to obtain blood samples and liver tissues for analyzing the levels of serum aminotransferase （ALT）, aspartate transferase （AST） using an automatic biochemical analyzer and the levels of liver fibrosis indexes such as hyaluronic acid （HA） and type Ⅲprocollagen （PCⅢ） in serum and α-SMA in the liver tissues by ELISA or radioimmunoassay. TLR4 and NF-κB protein levels in the liver tissues were detected by Western blot. Results All rats get a weight gain during the period. Compared with CDAA group, CDAA+GLP-1 group showed significantly decreased of body weight （F=3.407 9, P=0.006）and serum levels of AST （F=2.815 7, P=0.017）, while liver weight had no significant decrease until the end of the 4th week（F=2.103 1,P=0.059）, so did the serum levels of PCIII（F=11.797 4,P=0）, and the serum HA level decreased significantly at the end of the 2nd week （F=3.454 5, P=0.014）, liver index decreased significantly at the end of the 6th week（F=0.425 5, P=0.679）. Though serum levels of ALT of the CDAA+GLP-1 group decreased compared to the CDAA group, the difference was not significant（P>0.05）. Continous feeded with CDAA diet aggravated the liver steatosis and fibrosis, the pathological situation began to improve sinificantly after 4 weeks’ treatment with GLP-1 analog（F=3.674 2, P=0.003）. Conclusion CDAA diet can induce NAFLF rat model, while Liraglutide, the GLP-1 analog can reduce CDAA diet-induced hepatic fibrosis, improve liver function, suggesting its potential as a therapeutic agent for early liver fibrosis.