APOE*3Leiden.CETP transgenic mice as model for pharmaceutical treatment of the metabolic syndrome

Diabetes Obes Metab. 2014 Jun;16(6):537-44. doi: 10.1111/dom.12252. Epub 2014 Jan 16.

Abstract

Aims: This study aimed to investigate systematically (i) the appropriate dietary conditions to induce the features of the MetS in APOE*3Leiden.humanCholesteryl Ester Transfer Protein (E3L.CETP) mice and (ii) whether the response of this model to different antidiabetic and hypolipidemic drugs is similar as in humans.

Methods: Male obese, IR and dyslipidemic E3L.CETP mice were treated with antidiabetic drugs rosiglitazone, liraglutide or an experimental 11β-hydroxysteroid-dehydrogenase-1 (HSD-1) inhibitor, or with hypolipidemic drugs atorvastatin, fenofibrate or niacin for 4-6 weeks. The effects on bw, IR and plasma and liver lipids were assessed.

Results: Rosiglitazone, liraglutide and HSD-1 inhibitor significantly decreased glucose and insulin levels or IR. Liraglutide and HSD-1 inhibitor also decreased bw. Atorvastatin, fenofibrate and niacin improved the dyslipidemia and fenofibrate and niacin increased high-density lipoprotein (HDL) cholesterol. In addition, hepatic triglycerides were significantly decreased by treatment with rosiglitazone and liraglutide, while hepatic cholesterol esters were significantly decreased by rosiglitazone and atorvastatin.

Conclusions: We conclude that the E3L.CETP mouse is a promising novel translational model to investigate the effects of new drugs, alone or in combination, that affect IR, diabetic dyslipidemia and non-alcoholic fatty liver disease (NAFLD).

Keywords: NAFLD; diabetic dyslipidemia; insulin resistance; obesity; pharmacological treatment.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors
  • Animals
  • Apolipoprotein E3 / genetics*
  • Atorvastatin
  • Cholesterol Ester Transfer Proteins / genetics*
  • Disease Models, Animal*
  • Fenofibrate / pharmacology
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / pharmacology
  • Heptanoic Acids / pharmacology
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypolipidemic Agents / pharmacology*
  • Liraglutide
  • Male
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / genetics
  • Mice, Transgenic*
  • Niacin / pharmacology
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / genetics
  • Obesity / drug therapy
  • Obesity / genetics
  • Pyrroles / pharmacology
  • Rosiglitazone
  • Thiazolidinediones / pharmacology

Substances

  • Apolipoprotein E3
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Heptanoic Acids
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Pyrroles
  • Thiazolidinediones
  • apolipoprotein E3 (Leidein)
  • Rosiglitazone
  • Niacin
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Atorvastatin
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Fenofibrate