title: APOE*3Leiden.CETP transgenic mice as model for pharmaceutical treatment of the metabolic syndrome.
abstract: OBJECTIVE
  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).
authors.affiliation: Metabolic Health Research, TNO, Leiden, the Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: van den Hoek
authors.forename: J W A
authors.initials: JW
authors.lastname: van der Hoorn
authors.forename: A C
authors.initials: AC
authors.lastname: Maas
authors.forename: R M
authors.initials: RM
authors.lastname: van den Hoogen
authors.forename: A
authors.initials: A
authors.lastname: van Nieuwkoop
authors.forename: S
authors.initials: S
authors.lastname: Droog
authors.forename: E H
authors.initials: EH
authors.lastname: Offerman
authors.forename: E J
authors.initials: EJ
authors.lastname: Pieterman
authors.forename: L M
authors.initials: LM
authors.lastname: Havekes
authors.forename: H M G
authors.initials: HM
authors.lastname: Princen
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors; D000818:Animals; D053318:Apolipoprotein E3 / Q000235:genetics*; D000069059:Atorvastatin; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D011345:Fenofibrate / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D000069450:Liraglutide; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000235:genetics; D008822:Mice, Transgenic; D009525:Niacin / Q000494:pharmacology; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000235:genetics; D009765:Obesity / Q000188:drug therapy / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D053318:Apolipoprotein E3; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D006538:Heptanoic Acids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D011758:Pyrroles; D045162:Thiazolidinediones; C052720:apolipoprotein E3 (Leidein); D000077154:Rosiglitazone; D009525:Niacin; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000069059:Atorvastatin; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D011345:Fenofibrate
keywords: NAFLD; diabetic dyslipidemia; insulin resistance; obesity; pharmacological treatment