Impaired reverse cholesterol transport and hepatic steatosis contribute to pathogenesis of high fat dietinduced hyperlipidemia in murine models

  • Xiaohui ZXH Zeng
  • Dongmei SDM Sun
  • Nan YN Yao
  • Yuxing CYX Chen
  • Dake CDK Cai
  • Xuejun HXJ Huang
  • Dane HDE Huang
  • Haining GHN Gan
  • Qiaohuang ZQH Zeng
  • Jingyu ZJY Zhao
  • Lin HL Huang
Keywords: Hyperlipidemic model, Murine, Hamster, mRNA, Reverse cholesterol transport, High-fat diet, Pathogenesis

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, Murine, Hamster, mRNA, Reverse cholesterol transport, High-fat diet, Pathogenesis

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eISSN: 1596-9827
print ISSN: 1596-5996