Abstract
Purpose: To investigate the pathogenesis of high fat diet (HFD)-induced hyperlipidemia (HLP) in mice, rats and hamsters and to comparatively evaluate their sensitivity to HFD. Methods: Mice, rats and hamsters were fed with high-fat diet formulation (HFD, n = 8) or a control diet (control, n = 8) for 4 weeks. Changes in body weight, relative liver weight, serum lipid profile, expressions of hepatic marker gene of lipid metabolism and liver morphology were observed in three hyperlipidemic models. Results: Elevated total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) levels and body weight were observed in all hyperlipidemic animals (p < 0.05), while hepatic steatosis was manifested in rat and hamster HLP models, and increased hepatic TC level was only seen (p < 0.05) in hamster HLP model. Suppression of HMG-CoA reductase and up-regulation of lipoproteinlipase were observed in all HFD groups. Hepatic gene expression of LDLR, CYP7A1, LCAT, SR-B1, and ApoA I, which are a response to reverse cholesterol transport (RCT), were inhibited by HFD in the three models. Among these models, simultaneous suppression of HMG-CR, LCAT, LDLR and SR-BI and elevated LPL were features of the hamster model. Conclusion: As the results show, impaired RCT and excessive fat accumulation are major contributors to pathogenesis of HFD-induced murine HLP. Thus, the hamster model is more appropriate for hyperlipidemia research.
Highlights
Hyperlipidemia (HLP) is a disorder of lipid metabolism characterized by abnormally elevated levels of one or more lipids and/or lipoproteins in the blood [1], which has been identified as a clinical risk factor for atherosclerosis and cardiovascular disease [2]
Serum total cholesterol (TC), TG, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) are increased by high-fat diet (HFD) with statistically significant (p < 0.01), and liver TC and TG remain unchanged
Hepatic TC and TG level were significantly raised in hamster HLP models (p < 0.01)
Summary
Hyperlipidemia (HLP) is a disorder of lipid metabolism characterized by abnormally elevated levels of one or more lipids and/or lipoproteins in the blood [1], which has been identified as a clinical risk factor for atherosclerosis and cardiovascular disease [2]. It is one of the major predisposing factors for cancer [3] and diabetes [4]. The molecular basis of pathogenesis in hyperlipidemic rats, hamster and mice model induced by HFD remain unclear, which limits its predictability and accuracy on evaluating lipid-lowering agents for human HLP
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