Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats - PubMed (original) (raw)

Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats

Shinya Fukunishi et al. J Clin Biochem Nutr. 2014 Jan.

Abstract

Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide (LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.

Keywords: adiponectin; disaccharide; hepatic steatosis; lipopolysaccharides (LPS); nonalcoholic fatty liver disease (NAFLD).

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Figures

Fig. 1

Fig. 1

Hepatic effects of a diet rich in disaccharides, fed to Zucker (fa/fa) rats for 12 weeks or 24 weeks, with additional administration of LPS in one group. Hematoxylin and eosin staining (original magnification ×150). (A) D12 group; rats fed a disaccharide-rich diet for 12 weeks, (B) LPS group; rats fed an identical diet and treated with LPS, (C) D24 group; rats fed this diet for 24 weeks.

Fig. 2

Fig. 2

Levels of plasma adiponectin (A) and leptin (B) measured in all Zucker (fa/fa) rats. The results shown represent mean ± SD of five rats per group. *p<0.05 vs D24 group.

Fig. 3

Fig. 3

Expressions of TNF-α and TLR4 mRNA in specimens of hepatic tissue. TNF-α mRNA expression (A) and TLR4 mRNA expression (B) was evaluated by quantitative RT-PCR. The results shown represent mean ± SD of relative levels of target mRNA of five rats per group. *p<0.05 vs D24 group.

Fig. 4

Fig. 4

Expressions of lipogenic-related mRNA in specimens of hepatic tissue evaluated by quantitative RT-PCR. A, MCAD; B, LCAD; C, ACL; D, ACC; E, FAS; F, SREBP-1c. The results shown represent mean ± SD of relative levels of target mRNA of five rats per group. *p<0.05 vs D24 group.

Fig. 5

Fig. 5

Expression of TGF-β1 mRNA (A) and α-SMA mRNA (B) in specimens of hepatic tissue was evaluated by quantitative RT-PCR. The results shown represent mean ± SD of relative levels of target mRNA of five rats per group. *p<0.05 vs D24 group.

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