Effect of High-Fat Diet on Hepatic Proteomics of Hamsters

Abstract

A high-fat diet contributes to the etiology of metabolic diseases. As the liver plays a crucial role in metabolism, an insight into the hepatic proteomics will help to illustrate the physiological effect of a high-fat diet. Fourteen nine-week old male Syrian hamsters were maintained on either control (C) or high-fat (HF) diets (0.2% cholesterol +22% fat) for 8 weeks. Hamsters were chosen because they show close similarity to human lipid metabolism. At the end of study, blood and livers were collected for analysis. Liver proteins were fractionated by electrophoresis, digested by trypsin, and then separated by label-free nano-LC/MS/MS. The TurboSequest algorithm was used to identify the peptide sequences against the hamster database in Universal Proteins Resource Knowledgebase (UniProt). The results indicate that 1191 hepatic proteins were identified and 135 of them were expressed differentially in the high-fat group (p < 0.05). Some of these 135 proteins that involve in metabolic diseases were further validated by Western blotting. The animals maintained on the high-fat diet had significantly (p < 0.05) higher serum triglyceride, cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and uric acid. Animals consuming a high-fat diet also had significantly (p < 0.05) more accumulation of triglyceride and cholesterol in livers. Xanthine dehydrogenase (XDH), which plays an important role in uric acid synthesis, was up-regulated by the high-fat diet (p < 0.05). The α-subunit of hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (HADHA), which catalyzes the second and third reactions of β-oxidation, was down-regulated by the high-fat diet (p < 0.05). Aconitate hydratase 2 (ACO2), which catalyzes the conversion of citrate to isocitrate in TCA cycle, was down-regulated in animals of the high-fat group (p < 0.05). Inflammatory markers annexin A3 (ANXA3) and annexin A5 (ANXA5) were up-regulated by the high-fat diet (p < 0.05). Moreover, enzymes involved in the urea cycle were suppressed by high-fat diet, including carbamoyl phosphate synthase 1 (CPS1), ornithine transcarbamoylase (OTC), argininosuccinate synthase (ASS), argininosuccinate lyase (ASL), and arginase 1 (ARG 1). Post-translational modifications (PTM) of ANXA3, ANXA5, and XDH were also analyzed. A set of differentially expressed proteins were identified as molecular markers for elucidating the pathological mechanism of high-fat diet.

An In Vivo Magnetic Resonance Spectroscopy Study of the Effects of Caloric and Non-Caloric Sweeteners on Liver Lipid Metabolism in Rats

“…This was in agreement with increased activities of glycolytic enzymes, in particular pyruvate kinase, a phenomenon also reported by others [50,51]. Decreased protein levels of several TCA cycle enzymes (ACO2, OGDH, SUCLA2, and SUCLG1), all of them catalyzing reactions downstream of citrate, suggest that TCA cycle activity might have been limited upon glucose and fructose feeding, favoring the translocation of citrate to the cytosol for lipogenesis [52]. Importantly, most of these effects were more profound in response to fructose compared with glucose.…”

Aqueous Extract of Black Maca Prevents Metabolism Disorder via Regulating the Glycolysis/Gluconeogenesis-TCA Cycle and PPARα Signaling Activation in Golden Hamsters Fed a High-Fat, High-Fructose Diet

“…After 20 weeks, the golden hamster model of metabolism disorder induced by HFD feeding was established, with substantially increased serum levels of biochemical indicators (including TG, CHO, LDL-C, and others). The model was very appropriate because golden hamsters respond consistently to dietary modulation and, compared with the profiles of other rodents, showed a close similarity to human lipoprotein profiles ( Liao et al, 2015 ). In this paper, we found that supplemental AEM (1,200 mg/kg) did not alter food intake but significantly prevented the increased in body weight, liver weight, and fat weight that occurred in golden hamsters fed a HFD for 20 weeks.…”

Mutations and common variants in the human arginase 1 (ARG1) gene: Impact on patients, diagnostics, and protein structure considerations

“…Factors such as diet, hormones, and numerous transcription factors and nuclear receptors are known to regulate ARG1 expression. For instance, hamsters, which have a lipid metabolism similar to humans, when fed with a high‐fat diet exhibited suppression of several urea cycle enzymes including ARG1 (Liao, Lin, & Kuo, ). In fetal rat, cortisol has been shown to stimulate liver ARG1 after an intraperitoneal injection (Husson & Vaillant, ).…”