Abstract
Background:
A good animal model was essential to understand the mechanism of NAFLD. It was needed to explore the NAFLD drug candidate target.

Aim:
This study aimed to determine the optimal fructose concentration and induction period for the NAFLD animal model.

Methods:
A total of 28 adult male Sprague Dawley rats were divided randomly into seven groups: standard diet (control, P1), three groups HFD-C with 30% w/v fructose for 4 weeks (P2), 6 weeks (P3), 8 weeks (P4), and three other groups HFD-C with 60% w/v fructose for 4 weeks (P5), 6 weeks (P6), and 8 weeks (P7). The blood sample and liver tissue were collected at the end of each period. We used spectrophotometry to measure the transaminase enzyme and metabolic parameter concentration. Liver tissue was evaluated by steatosis activity and fibrosis (SAF).

Results:
The steatosis of HFD-C with fructose groups (P2, P3, P4, P5, P6, and P7) were significantly higher than control group (P<0.05). The ballooning of HFD-C with fructose (P3, P4, P5, P6, and P7) were significantly higher than control (p<0.05). Ballooning of HFD-C with 30% w/v fructose increased with a prolonged period (p<0.05). The inflammation of all the tested groups was higher than that of the control (p<0.05). The fibrosis only appeared in the 8-week group; fibrosis in P7 was significantly higher than in the control (p<0.05). The AST of P4, P5, P6, and P7 were higher than the control (p<0.05), but not the ALT. The TC and LDL-C levels were raised in all HFD-C with fructose groups, but only the 8-week HFD-C with 30% w/v fructose group was higher than the control (p<0.05). Triglyceride levels also showed the same pattern as TC and LDL-C levels. The glucose level in the HFD-C with fructose groups was also higher than that of the control group. There was no statistically significant difference between 30% w/v and 60% w/v fructose at the same period.

Conclusion:
The Sprague Dawley rat fed by HFD-C with 30% w/v fructose in 4 weeks showed early-stage features of NAFLD, and the Sprague Dawley rat fed by HFD-C with 60% w/v fructose in 8 weeks showed more progressive NAFLD but still early fibrosis.

Key words: Animal model; Fatty liver; NAFLD; Sprague Dawley.