Hyperlipidemic Guinea Pig Model: Mechanisms of Triglyceride Metabolism Disorder and Comparison to Rat

Abstract

Hyperlipidemia is an important risk factor for coronary heart disease. A proper animal model plays vital roles in the researches on mechanisms of lipid disorder. The advantages of using guinea pigs for cholesterol and lipoprotein metabolism investigations have been elucidated in many studies. The guinea pig is a suitable animal model for studying hyperlipidemia because of its similarities to humans in transporting the majority of its circulating cholesterol in low-density lipoprotein (LDL), exhibiting moderate rates of hepatic cholesterol synthesis and catabolism, having higher concentrations of free compared to esterified cholesterol in the liver and in many other aspects of lipid metabolism. [1][2][3][4][5] To date, however, little attention has been paid to triglyceride metabolism in guinea pigs.Rats have commonly been used for hyperlipidemia studies in the past, although their use has recently been in decline. They transport most of their serum cholesterol in the highdensity lipoprotein (HDL) fraction, have higher ability of plasma cholesterol clearance and couldn't develope a hypertriglyceridemia response to cholesterol feeding. More and more researchers indicated that the mechanisms by which diet interventions and drug treatments alter plasma lipids and lipoprotein metabolism in rats are different from humans. [6][7][8][9] In our previous studies, we also found that a high-fat diet containing 0.1% cholesterol and 10% lard induced typical hyperlipidemia and hypertriglyceridemia in guinea pigs but not in rats.10) And there is less number of good hypertriglyceridemic models. Therefore, it is very meaningful to further research the mechanisms of triglyceride metablism disorder in guinea pigs.The present study was designed to determine the comparative plasma and hepatic lipid responses of guinea pigs and rats to high-fat diets containing 0.1% cholesterol and 10% lard and to compare the enzyme activities and gene expression of molecules that closely related to triglyceride metabolism. MATERIALS AND METHODSReagents Acetyl-CoA, Triton WR-1339, malonyl-CoA, nicotinamide adenine dinucleotide phosphate (NADPH), DL-dithiothreitol (DTT), 5,5Ј-dithiobis(2-nitrobenzoate) (DTNB), palmitoyl-CoA, carnitine, 1,2-dipalmitoyl-sn-glycerol, palmitoyl-CoA lithium salt and glyceryl tripalmitate were purchased from Sigma-Aldrich. The solvents (chloroform, hexane, 2-propanol and methanol) were of HPLC grade (J. T. Baker, U.S.A.). All other reagents were of analytical grade and purchased from the Beijing Chemicals Company. The triglyceride (TG), total cholesterol (TC) and lowdensity lipoprotein cholesterol (LDL-C) assay kits were purchased from BioSino Bio-technology and Science, Inc. The lipoprotein lipase (LPL) and free fatty acids (FFA) kits were obtained from the Nanjing Jiancheng Bioengineering Institute. The RNApure high-purity total RNA rapid extraction kit, Super reverse transcription (RT) Kit (First Strand cDNA Synthesis Kit) and 2ϫSYBR real-time polymerase chain reaction (PCR) premixture were purchased from the BioTeke Corp...

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