Non-alcoholic fatty liver disease (NAFLD) is a general term for fatty liver disease not caused by viruses or alcohol. Fibrotic hepatitis, cirrhosis, and hepatocellular carcinoma can develop. The recent increase in NAFLD incidence worldwide has stimulated drug development efforts. However, there is still no approved treatment. This may be due in part to the fact that non-alcoholic steatohepatitis (NASH) pathogenesis is very complex, and its mechanisms are not well understood. Studies with animals are very important for understanding the pathogenesis. Due to the close association between the establishment of human NASH pathology and metabolic syndrome, several animal models have been reported, especially in the context of overnutrition. In this study, we investigated the induction of NASH-like pathology by enhancing cholesterol absorption through treatment with hydroxypropyl-beta-cyclodextrin (CDX). Female Sprague-Dawley rats were fed a normal diet with normal water (control group); a high-fat (60 kcal%), cholesterol (1.25 %), and cholic acid (0.5 %) diet with normal water (HFCC group); or HFCC diet with 2 % CDX water (HFCC+CDX group) for 16 weeks. Compared to the control group, the HFCC and HFCC+CDX groups showed increased blood levels of total cholesterol, aspartate aminotransferase, and alanine aminotransferase. At autopsy, parameters related to hepatic lipid synthesis, oxidative stress, inflammation, and fibrosis were elevated, suggesting the development of NAFLD/NASH. Elevated levels of endoplasmic reticulum stress-related genes were evident in the HFCC+CDX group. In the novel rat model, excessive cholesterol intake and accelerated absorption contributed to NAFLD/NASH pathogenesis.

• MeSH
• Cholesterol MeSH
• Diet, High-Fat adverse effects   MeSH
• 2-Hydroxypropyl-beta-cyclodextrin metabolism   therapeutic use   MeSH
• Hypercholesterolemia * metabolism   MeSH
• Hyperlipidemias * MeSH
• Liver metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Non-alcoholic Fatty Liver Disease * chemically induced   MeSH
• Rats, Sprague-Dawley MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Amino acids are crucial compounds involved in most biochemical processes essential for life. Since their dynamic turnover reflects the actual physiology of the cell/organism, a turnover assessment may provide valuable information related to multiple physiological and pathophysiological conditions. The sensitive determination of amino acids is predominantly associated with their derivatization which might be laborious, time-consuming and difficult to standardize. However, capillary electrophoresis offers the automatic injection and mixing of reactants, incubation of the reaction mixture, separation and detection of the reaction products in one on-capillary procedure. Among the on-capillary mixing strategies, electrophoretically mediated microanalysis (EMMA) is superior in terms of mixing efficiency. In this paper, we present an optimization of EMMA for the simultaneous derivatization of standard amino acids by naphthalene-2,3-dicarboxaldehyde/NaCN and its application to targeted human embryo metabolomics. For such a purpose, novel separation conditions were developed involving the background electrolyte, comprised of 73mM sodium dodecyl sulfate, 6.7 % (v/v) 1-propanol, 0.5mM (2-hydroxypropyl)-β-cyclodextrin and 135mM boric acid/sodium hydroxide buffer (pH 9.00). Finally, the optimized EMMA was compared to a fundamentally different mixing strategy, namely the transverse diffusion of laminar flow profiles, and proved to be also suitable for human plasma analysis.

• MeSH
• Amino Acids chemistry   isolation & purification   MeSH
• beta-Cyclodextrins MeSH
• Chromatography, Micellar Electrokinetic Capillary instrumentation   methods   MeSH
• Fluorescence MeSH
• 2-Hydroxypropyl-beta-cyclodextrin MeSH
• Plasma chemistry   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH