title: Characterisation of Atherogenic Effects of Low Carbohydrate, High Protein Diet (LCHP) in ApoE/LDLR-/- Mice.
abstract: BACKGROUND
  Low Carbohydrate High Protein diet represents a popular strategy to achieve weight loss.
  
  
  OBJECTIVE
  The aim of this study was to characterize effects of low carbohydrate, high protein diet (LCHP) on atherosclerotic plaque development in brachiocephalic artery (BCA) in apoE/LDLR-/- mice and to elucidate mechanisms of proatherogenic effects of LCHP diet.
  
  
  METHODS
  Atherosclerosis plaques in brachiocephalic artery (BCA) as well as in aortic roots, lipoprotein profile, inflammation biomarkers, expression of SREBP-1 in the liver as well as mortality were analyzed in Control diet (AIN-93G) or LCHP (Low Carbohydrate High Protein) diet fed mice.
  
  
  RESULTS
  Area of atherosclerotic plaques in aortic roots or BCA from LCHP diet fed mice was substantially increased as compared to mice fed control diet and was characterized by increased lipids and cholesterol contents (ORO staining, FT-IR analysis), increased macrophage infiltration (MOMA-2) and activity of MMPs (zymography). Pro-atherogenic phenotype of LCHP fed apoE/LDLR-/- mice was associated with increased plasma total cholesterol concentration, and in LDL and VLDL fractions, increased TG contents in VLDL, and a modest increase in plasma urea. LCHP diet increased SCD-1 index, activated SREBP-1 transcription factor in the liver and triggered acute phase response as evidence by an increased plasma concentration of haptoglobin, CRP or AGP. Finally, in long-term experiment survival of apoE/LDLR-/- mice fed LCHP diet was substantially reduced as compared to their counterparts fed control diet suggesting overall detrimental effects of LCHP diet on health.
  
  
  CONCLUSIONS
  The pro-atherogenic effect of LCHP diet in apoE/LDLR-/- mice is associated with profound increase in LDL and VLDL cholesterol, VLDL triglicerides, liver SREBP-1 upregulation, and systemic inflammation.
authors.affiliation: Renata B. Kostogrys, Department of Genetic Diagnostics and Nutrigenomics, Chair of Clinical Biochemistry, Jagiellonian University Medical College, ul. Kopernika 21, 31-531 Kraków, Poland, Phone/fax numbers: 48 12 662 48 21/ 48 12 662 48 12, email: rkostogrys@ar.krakow.pl.
authors.forename: R B
authors.initials: RB
authors.lastname: Kostogrys
authors.forename: C
authors.initials: C
authors.lastname: Johann
authors.forename: I
authors.initials: I
authors.lastname: Czyżyńska
authors.forename: M
authors.initials: M
authors.lastname: Franczyk-Żarów
authors.forename: A
authors.initials: A
authors.lastname: Drahun
authors.forename: E
authors.initials: E
authors.lastname: Maślak
authors.forename: A
authors.initials: A
authors.lastname: Jasztal
authors.forename: M
authors.initials: M
authors.lastname: Gajda
authors.forename: Ł
authors.initials: Ł
authors.lastname: Mateuszuk
authors.forename: T P
authors.initials: TP
authors.lastname: Wrobel
authors.forename: M
authors.initials: M
authors.lastname: Baranska
authors.forename: I
authors.initials: I
authors.lastname: Wybrańska
authors.forename: K
authors.initials: K
authors.lastname: Jezkova
authors.forename: P
authors.initials: P
authors.lastname: Nachtigal
authors.forename: S
authors.initials: S
authors.lastname: Chlopicki
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced*; D016122:Brachiocephalic Trunk / Q000187:drug effects / Q000473:pathology; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004036:Diet, Atherogenic / Q000009:adverse effects*; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007249:Inflammation / Q000139:chemically induced; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000139:chemically induced; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D016019:Survival Analysis; D014280:Triglycerides / Q000097:blood; D014508:Urea / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D004044:Dietary Proteins; D011973:Receptors, LDL; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D014508:Urea