It has been shown that severe hepatic steatosis was linked to increased atherogenesis in diabetic patients by increased plasma TG, LDL, and VLDL concentrations and decreased HDL level and insulin resistance. Moreover, the existence of cross talk between the liver and vascular wall might specifically account for the strong associations between liver steatosis and accelerated atherosclerosis. Studies in humans and experimental animals demonstrate that increased intake of fructose can result in hypertriglyceridemia, insulin resistance, and liver steatosis. However, recent data show that elevated consumption of fructose may also contribute to the development of those diseases. To date, increased fat consumption is considered the major pathogenic factor of MS and NAFLD. Recently, MS was also found to be a strong predictor of NAFLD, which is widely accepted to be the hepatic manifestation of MS. The metabolic syndrome (MS) is a cluster of interrelated risk factors that promote the development of cardiovascular disease (CVD). Although both CLA isomers (c9t11 and t10c12) display hepatoprotective activity, the hypolipemic action of the t10c12-CLA isomer proved to be more pronounced than that of c9t11-CLA. In summary, feeding rats with a high-fructose diet resulted in increased liver glycogen storage, indicating the induction of gluconeogenesis despite simultaneous upregulation of genes involved in de novo lipogenesis. In turn, the c9t11-CLA decreased LDL+VLDL cholesterol in the control group and downregulated liver expression of FAS without significant effects on liver weight, lipid content, and fatty acid composition. Specifically, t10c12-CLA decreased concentration of serum triacylglycerols and LDL + VLDL cholesterol, increased HDL cholesterol, and affected liver lipid content and fatty acid composition by downregulation of liver SCD-1 and FAS expression. Both CLA isomers prevented excessive accumulation of glycogen in the liver.
The high-fructose diet hampered body weight gain (without influencing food intake), increased liver weight and glycogen storage in hepatocytes, upregulated expression of fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 (SCD-1), and increased saturated fatty acid (SFA) content in the liver. This study assessed the effects of individual conjugated linoleic acid isomers, c9t11-CLA and t10c12-CLA, on nonalcoholic fatty liver disease (NAFLD) and systemic endothelial dysfunction in rats fed for four weeks with control or high-fructose diet.