PROJECT SUMMARY All women experience menopause, putting a female at risk for a number of chronic diseases, including an increased risk of obesity. Although post-menopausal replacement of estrogen (hormone replacement therapy - HRT) has been shown to be effective at protecting against the metabolic and inflammatory perturbations linked to estrogen-deficiency, HRT has been shown to pose unwanted health risks including an increased risk of stroke, heart attack, and a variety of cancers. As such, it has become a priority of the National Center for Complementary and Integrative Health to invest in the development of therapies that are both safe AND effective at combating menopause-induced side effects, including excess fat mass accrual and its related negative metabolic and inflammatory perturbations. The parent K01 project (K01AT010348) is aimed at examining the therapeutic potential of the potent phytoestrogen from the Humulus Lupus plant (hops), 8-prenylnaringenin (8-PN). The long-term goal is to develop a safe and effective natural therapy for the clinical treatment of menopause- associated metabolic impairments and inflammatory-driven health perturbations. For this administrative supplement, we propose to examine how different modes of administration of 8-PN impact bioavailability of this potent phytoestrogen as well as elucidate the mechanism(s) by which 8-PN impacts the macrophage phenotype. Christian Unger, a PhD student of Native American heritage in Dr. Reilly Enos’ lab, will serve as the primary researcher in this supplementary project. Under the mentorship of Dr. Enos, the PI of the parent grant, Christian will be exposed to mass spectrometry, nutraceutical bioavailability assessment, large data analysis, as well as in vitro cell culture models. The research proposed in this supplement falls well within the scope of the research supported in the parent K01 award. In addition to the research experience Christian will garner from this supplement, Christian will also receive training in scientific writing, presentation skills, data analysis and interpretation, complementary and alternative medicine, immunology, and responsible conduct of research. This supplement will provide Christian with a stepping stone towards his long term goal of becoming a scientist examining nutraceutical therapies for the treatment of obesity.