title: Beneficial effects of alternate dietary regimen on liver inflammation, atherosclerosis and renal activation.
abstract: BACKGROUND
  Alternate day calorie restriction (CR) has been shown to be almost as beneficial as daily CR. The question arises whether this concept is also applicable to alternating dietary composition.
  
  
  OBJECTIVE
  To seek evidence that alternating high cholesterol (HC)-cholesterol-free (CON) Western diet can effectively diminish hepatic and renal inflammation and cardiovascular risk factors as compared with daily HC-supplemented Western diet.
  
  
  METHODS
  Four groups of ApoE*3Leiden mice, a humanized model for atherosclerosis, were subjected to different feeding treatments for 16 weeks. Mice were fed CON diet; CON diet with 1% w/w cholesterol (HC); alternate (ALT) diet regimen of CON (4 days) and HC (3 days); or CON diet supplemented with 0.43% (w/w) cholesterol (MC), with overall dietary cholesterol intake equal to ALT. Plasma was analyzed for cardiovascular risk factors, aorta for atherosclerotic lesion formation, and liver and kidney for inflammation.
  
  
  RESULTS
  ALT diet but not MC was almost as effective as daily CON feeding in preventing disease development. Compared to HC, the ALT group showed 62% lower hepatic nuclear factor kappa B (NF-κB) activity (P<0.001), a reduction of the circulating inflammatory markers E-selectin (-20%; P<0.05), vascular cell adhesion molecule 1 (VCAM-1; -15%; P<0.05) and Serum Amyloid A (SAA; -31%; P<0.05), smaller atherosclerotic lesion sizes (-51%; 46497±10791 µm2 vs. 94664±16470 µm2; P<0.05) and diminished renal expression of specific inflammation and activation markers (VCAM-1, -27%; P<0.05; monocyte chemotactic protein-1 (MCP-1); -37%; P<0.01).
  
  
  CONCLUSIONS
  Alternate HC-CON feeding reproduced most of the beneficial effects of daily cholesterol-free diet, including strongly diminished hepatic, vascular and renal activation and inflammation; also atherosclerosis was reduced by half as compared to HC, albeit still higher compared to the CON group.
authors.affiliation: TNO-Metabolic Health Research, Leiden, The Netherlands. Peter.Wielinga@tno.nl
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Wielinga
authors.forename: Gopala K
authors.initials: GK
authors.lastname: Yakala
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
authors.forename: Teake
authors.initials: T
authors.lastname: Kooistra
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000178:diet therapy* / Q000378:metabolism*; D031204:Caloric Restriction / Q000379:methods*; D018932:Chemokine CCL2 / Q000378:metabolism; D002784:Cholesterol / Q000627:therapeutic use; D005260:Female; D007249:Inflammation / Q000178:diet therapy* / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver; D051379:Mice; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D019010:Vascular Cell Adhesion Molecule-1; D002784:Cholesterol