Beneficial Effects of Alternate Dietary Regimen on Liver Inflammation, Atherosclerosis and Renal Activation

Wielinga, P. Y., Yakala, G. K., Heeringa, P., Kleemann, R. & Kooistra, T., 31-Mar-2011, In : PLoS ONE. 6, 3, 10 p., 18432.

Research output: Contribution to journalArticleAcademicpeer-review

  • Peter Y. Wielinga
  • Gopala K. Yakala
  • Peter Heeringa
  • Robert Kleemann
  • Teake Kooistra

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.

Design: 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-kappa B) 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 mu m(2) vs. 94664 +/- 16470 mu m(2); 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).

Conclusion: 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.

Original languageEnglish
Article number18432
Number of pages10
JournalPLoS ONE
Issue number3
Publication statusPublished - 31-Mar-2011



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