BIOACTIVE FOOD COMPONENTS, SUCH AS OMEGA 3 POLYUNSATURATED FATTY ACIDS (Ω-3 PUFA) AND TART CHERRY ANTHOCYANINS (ACY) ARE PROMISING DIETARY INTERVENTIONS THAT REDUCE OBESITY-ASSOCIATED INFLAMMATION.WHILE EACH OF THESE COMPOUNDS HAS BEEN THE SUBJECT OF INTENSE STUDY INDIVIDUALLY, VERY FEW STUDIES HAVE INVESTIGATED COMBINATORIAL EFFECTS OF Ω-3 PUFA AND ACY IN THE CONTEXT OF OBESITY-ASSOCIATED INFLAMMATION. WE HYPOTHESIZE THAT COMBINED INTAKE OF THESE BIOACTIVES AT LOW DOSES PROVIDES GREATER AND SYNERGISTIC ANTI-INFLAMMATORY EFFECTS COMPARED TO EITHER COMPOUND ALONE, THROUGH MODULATION OF DISTINCT SIGNALING PATHWAYS IN TISSUES THAT CONTRIBUTE TO OBESITY-INDUCED INFLAMMATION. WE TEST THIS HYPOTHESIS IN ADIPOCYTES AND MACROPHAGES, KEY CELLS INVOLVED IN INFLAMMATION, AND IN A MOUSE MODEL OF HUMAN DIETARY OBESITY. MICE WILL BE FED A HIGH FAT DIET, COMPARABLE TO THE CURRENT AMERICAN DIET TO INDUCE CHRONIC INFLAMMATION. WE WILL FOCUS ON Ω-3 PUFA/ACY INTERACTIONS IN ADIPOCYTESAND MACROPHAGES, DUE TO THEIR ROLE AS A NEXUS BETWEEN ENERGY STORAGE AND INFLAMMATION. WE WILL DETERMINE EFFECTS OF THESE COMPOUNDS INDIVIDUALLY AND IN COMBINATION ON ADIPOSITY, INFLAMMATION, CELL SIGNALING, AND PROTEIN/GENE EXPRESSION IN ADIPOSE AND OTHER RELEVANT TISSUES. THESE STUDIES WILL BE COMPLEMENTED BY MECHANISTIC EXPERIMENTS IN CULTURED ADIPOCYTES AND MACROPHAGES TO DISSECT THE BASIS FOR Ω-3 PUFA/ACY INTERACTIVE ANTI-INFLAMMATORY ACTIONS.IN SUMMARY, THESE STUDIES WILL PROVIDE VALUABLE INSIGHT INTO INTERACTIONS AMONG IMPORTANT BIOACTIVE COMPOUNDS IN FOODS TO IMPROVE HUMAN HEALTH.
$499,742FY2019National Institute of Food and AgricultureUSDA
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