Comparison of dietary control and atorvastatin on high fat diet induced hepatic steatosis and hyperlipidemia in rats.
BACKGROUND
Treatment with atorvastatin (ATO) or dietary control has been demonstrated to benefit patients with non-alcoholic fatty liver disease (NAFLD) and hyperlipidemia. However, little is known on whether combination of dietary control and ATO treatment could enhance the therapeutic effect.


METHODS
We employed a rat model of NAFLD to examine the therapeutic efficacy of dietary control and/or ATO treatment. Sprague-Dawley rats were fed with normal chow diet as normal controls or with high fat diet (HFD) for 12 weeks to establish NAFLD. The NAFLD rats were randomized and continually fed with HFD, with normal chow diet, with HFD and treated with 30 mg/kg of ATO or with normal chow diet and treated with the same dose of ATO for 8 weeks. Subsequently, the rats were sacrificed and the serum lipids, aminotransferase, hepatic lipids, and liver pathology were characterized. The relative levels of fatty acid synthesis and β-oxidation gene expression in hepatic tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Hepatic expression of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was determined by Western blot assay.


RESULTS
While continual feeding with HFD deteriorated NAFLD and hyperlipidemia, treatment with dietary control, ATO or ATO with dietary control effectively improved serum and liver lipid metabolism and liver function. In comparison with ATO treatment, dietary control or combined with ATO treatment significantly reduced the liver weight and attenuated the HFD-induced hyperlipidemia and liver steatosis in rats. Compared to ATO treatment or dietary control, combination of ATO and dietary control significantly reduced the levels of serum total cholesterol and low density lipoprotein cholesterol (LDL-C). However, the combination therapy did not significantly improve triglyceride and free fatty acid metabolism, hepatic steatosis, and liver function, as compared with dietary control alone.


CONCLUSIONS
ATO treatment effectively improved NAFLD-related hyperlipidemia and inhibited liver steatosis, accompanied by modulating the expression of genes for regulating lipid metabolism. ATO enhanced the effect of dietary control on reducing the levels of serum total cholesterol and LDL-C, but not triglyceride, free fatty acid and hepatic steatosis in HFD-induced fatty liver and hyperlipidemia in rats.
Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
Guiyuan
G
Ji
Xihong
X
Zhao
Liang
L
Leng
Peiyi
P
Liu
Zhuoqin
Z
Jiang
D000818:Animals; D000069059:Atorvastatin; D003131:Combined Modality Therapy; D004041:Dietary Fats / Q000008:administration & dosage*; D005234:Fatty Liver / Q000178:diet therapy* / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000178:diet therapy* / Q000188:drug therapy* / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D009929:Organ Size; D047493:PPAR alpha / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D000637:Transaminases / Q000097:blood
D004041:Dietary Fats; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D047493:PPAR alpha; D011758:Pyrroles; D051780:Sterol Regulatory Element Binding Protein 1; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D000637:Transaminases
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