Downregulation of Macrophage Activation by PPARγ Suggests a Role for Conjugated Linoleic Acid in Prevention of Alzheimer's Disease and Atherosclerosis

Abstract

There is evidence that monocytes/macrophages, especially when activated, express the peroxisome proliferator-activated receptor γ(PPARγ) transcription factor and that activation of PPARγ with appropriate ligands downregulates induced macrophage production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Another report indicates that dietary conjugated linoleic acids (CLA) have a thiazolidinedione-like antidiabetic effect in Zucker fatty rats, associated with activation of PPARγ in adipocytes. This raises the prospect that CLA might exert antiinflammatory effects by suppressing macrophage cytokine production via PPARγ. Omega-3-rich fish oils likewise can downregulate production of IL-1 and TNF by macrophages, possibly because they inhibit autocrine positive feedback by thromboxane A₂. Therefore, supplemental CLA (fish oil) may be protective with respect to pathologies in which IL-1 and TNF play key etiological roles. Such pathologies may include atherogenesis and Alzheimer's disease. Antiatherogenic effects of both CLA and fish oil have been observed in animal models. With regard to Alzheimer's disease, the ability of dietary oils to reach the brain implies that CLA/fish oil may have greater clinical utility than drugs that have limited blood-brain barrier penetrance. Available epidemiological data are consistent with the possibility that frequent fish ingestion may decrease the risk of Alzheimer's disease.