Effects of ursodeoxycholic acid and/or low-calorie diet on steatohepatitis in rats with obesity and hyperlipidemia.
OBJECTIVE
To evaluate the effects of ursodeoxycholic acid (UDCA) and/or low-calorie diet (LCD) on a rat model of nonalcoholic steatohepatitis (NASH).


METHODS
Fifty-five Sprague-Dawley rats were divided into five groups. The control group (n = 9) was fed with standard rat diet for 12 wk, NASH group (n = 10) was fed with high-fat diet consisted of normal diet, 10% lard oil and 2% cholesterol for 12 wk, UDCA group (n = 10) was fed with high-fat diet supplemented with UDCA at a dose of 25 mg/(kg.d) in drinking water for 12 wk, LCD group (n = 10) was fed with high-fat diet for 10 wk and then LCD for 2 wk, and UDCA+LCD group (n = 15) was fed with high-fat diet for 10 wk, followed by LCD+UDCA for 2 wk. At the end of the experiment, body weight, serum biochemical index, and hepatopathologic changes were examined.


RESULTS
Compared with the control group, rats in the NASH group had significantly increased body weight, liver weight, and serum lipid and aminotransferase levels. All rats in the NASH group developed steatohepatitis, as determined by their liver histology. Compared with the NASH group, there were no significant changes in body weight, liver weight, blood biochemical index, the degree of hepatic steatosis, and histological activity index (HAI) score in the UDCA group; however, body and liver weights were significantly decreased, and the degree of steatosis was markedly improved in rats of both the LCD group and the UDCA+LCD group, but significant improvement with regard to serum lipid variables and hepatic inflammatory changes were seen only in rats of the UDCA+LCD group, and not in the LCD group.


CONCLUSIONS
LCD might play a role in the treatment of obesity and hepatic steatosis in rats, but it exerts no significant effect on both serum lipid disorders and hepatic inflammatory changes. UDCA may enhance the therapeutic effects of LCD on steatohepatitis accompanied by obesity and hyperlipidemia. However, UDCA alone is not effective in the prevention of steatohepatitis induced by high-fat diet.
Fan
Jian-Gao
JG
Department of Gastroenterology, Shanghai First People's Hospital, Shanghai 200080, China. fanjg@citiz.net
Zhong
Lan
L
Tia
Li-Yan
LY
Xu
Zheng-Jie
ZJ
Li
Min-Sheng
MS
Wang
Guo-Liang
GL
D000818:Animals; D031204:Caloric Restriction; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology; D005234:Fatty Liver / Q000178:diet therapy* / Q000188:drug therapy* / Q000473:pathology; D006949:Hyperlipidemias / Q000097:blood / Q000178:diet therapy / Q000473:pathology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D009765:Obesity / Q000097:blood / Q000178:diet therapy / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D002756:Cholagogues and Choleretics; D004041:Dietary Fats; D008055:Lipids; D014580:Ursodeoxycholic Acid