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Impaired reverse cholesterol transport and hepatic steatosis contribute to pathogenesis of high fat dietinduced hyperlipidemia in murine models
Zeng, Xiaohui; Sun, Dongmei; Yao, Nan; Chen, Yuxing; Cai, Dake; Huang, Xuejun; Huang, Dane; Gan, Haining; Zeng, Qiaohuang; Zhao, Jingyu & Huang, Lin
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.
Keywords
Hyperlipidemic model; Hamster; Reverse cholesterol transport; Pathogenesis; Murine; mRNA; High-fat diet
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