Suppression of Postprandial Monocyte Activation by Fruit Rich in Anti-Inflammatory Polyphenols or Docosahexaenoic Acid in Humans

<P>NON-TECHNICAL SUMMARY: Dietary insult, such as ingestion of high saturated fat, is one of the major causes of chronic inflammation; whereas, another dietary component such as n-3 fatty acids or fruits containing anti-inflammatory phytochemicals alleviate chronic inflammation illustrating dynamic modulation of chronic inflammation by what we eat. Understanding the mechanisms of this modulation in humans will provide the scientific basis for establishing sound dietary guidelines aiming to promote public health and reduce health care costs in the long run. </P>
<P>APPROACH: 1) To determine whether high saturated fat diet-induced monocyte activation is suppressed by known dietary inhibitors of pattern recognition receptor (PRR) activation, we will investigate two potential dietary inhibitors: anti-inflammatory polyphenols (strawberry or blueberry powder as a source of polyphenols) and docosahexaenoic acid (DHA as capsule), and whether a combined mixture of strawberry or blueberry powder and DHA shows more potent inhibitory effects than strawberry or blueberry powder, or DHA alone in healthy human volunteers. Sixty healthy male and female subjects between the ages of 18-60 years of age will be recruited to the study which will follow a randomized, single-blinded, crossover design. Each subject will receive a brief dietary history and analysis prior to entering the study. For each study visit subjects will arrive at the Western Human Nutrition Research Center (WHNRC) in the morning following an over night fast (12 hours) and have blood sample (60 ml) taken by venipuncture. Subjects will then consume his or her high saturated-fat breakfast (40% fat, beef fat as a major source of fat) supplemented with strawberry or blueberry powder equivalent to 4 servings of fresh table grape. After consuming the test meal, subjects will be discharged from the WHNRC to resume their daily activity. After 3.5 and 6 hours subjects will return to the WHNRC to have another 60 ml of blood drawn. Collected blood samples will be used to prepare peripheral blood mononuclear cells (PBMC), serum and flow cytometric analyses. The time commitment required for each subject per study day will be approximately 1.5 hours. Following the completion of the first study day, the subjects will be discharged from WHNRC and asked to return to their usual diet. Following a 3-4 week wash-out period subjects will return to WHNRC after an overnight fast (12 hours) to repeat the study protocol. To complete the study, subjects will visit the WHNRC on four separate days upto 12-week period. 2) To determine the mechanism by which the high saturated fat diet activates but berry powder or DHA supplementation inhibits the monocyte activation. Our hypothesis is that saturated fatty acids derived from the high saturated fat meal activate PRRs (TLR4, TLR2 and inflammasome) leading to the expression of proinflammatory marker gene products including IL-1β in blood monocytes. We will determine first, whether saturated fatty acids derived from the high saturated fat activate TLR2 and TLR4 leading to the expression of pro-IL-1β and inflammasome-mediated IL-1β release, and second, whether the saturated fatty acid -induced monocyte activation is inhibited by DHA or anti-inflammatory polyphenols present in strawberries or blueberries. Monocytic or macrophage cell line, or whole blood will be used for thesein vitro studies. </P>