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

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.

Subclinical-Dose Endotoxin Sustains Low-Grade Inflammation and Exacerbates Steatohepatitis in High-Fat Diet–Fed Mice

“…In line with a previous report with chronic injection of LPS (22), we documented that 4-week injection with super-low dose LPS exacerbated high-fat diet induced lipid accumulation in the liver (Figure 1B). The enhanced liver triglyceride (TG) accumulation in the LPS group was transient and not sustained after the stoppage of LPS injection at the 8 wk time point.…”

Improvement in the expression of hepatic genes involved in fatty acid metabolism in obese rats supplemented with taurine

“…Here, using MSGhypothalamic obese rats we observed, as earlier reported [4,30,47], that MSG treatment efficiently induced obesity, insulin resistance and classical features of NAFLD, as demonstrated by the higher serum and hepatic TG concentrations in the MSG group. In NAFLD patients and experimental rodents, the expressions and/or activities of the lipogenic factors and enzymes, such as SREBP-1c, ACC-1 and FASN were enhanced [7,12,17,28,44,45]. Here we found that increased TG content in the liver of MSG-obese rats was associated with increased FASN gene and protein expressions.…”

“…Previous observations from our laboratory demonstrate that Tau supplementation prevents obesity and reduces TG levels in the plasma and liver of MSG-obese rats [39]; however the mechanism of action by which Tau prevents dyslipidemia in MSG-hypothalamic Life Sciences 135 (2015) [15][16][17][18][19][20][21] obese rodents is unclear. Here, we verify whether Tau supplementation prevents hepatic lipid accumulation by regulation of the expression of the main transcription factors and enzymes involved in de novo lipogenesis and fatty acid oxidation.…”

Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease

“…Microbe PAMPs, which translocate to the liver through disrupted tight junctions, increase hepatic expression of TNF and levels of lipogenesis-related factors such as acetyl-CoA carboxylase, fatty acid synthase and SREBP-1c 115. Endogenous ethanol inhibits the tricarboxylic acid cycle, thus increases levels of acetate, thereby promoting triglyceride accumulation in hepatocytes 98.…”