Adipocyte reporter assays: Application for identification of anti‐inflammatory and antioxidant properties of mangosteen xanthones. Issue 2 (3rd September 2013)

• Record Type: Journal Article
• Authors: Shen, Qiwen; Chitchumroonchokchai, Chureeporn; Thomas, Jaisa L.; Gushchina, Liubov V.; DiSilvestro, David; Failla, Mark L.; Ziouzenkova, Ouliana
• Is Part Of: Molecular nutrition & food research. Volume 58:Issue 2(2014:Feb.)
• Page Start: 239
• Page End: 247
• Publication Date: 2013-09-03
• Subjects: Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201300181
• Languages: English
• ISSNs: 1613-4125

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mnfr2063-sec-0010" sec-type="section"> <title>Scope</title> <p>Three fluorescence biosensors were developed based on a 3T3‐L1 preadipocyte line that stably expressed <italic>Nfkb</italic>‐RE/GFP, <italic>Fabp4</italic>‐P/CFP, and <italic>Nrf2</italic>‐P/YFP fluorescent reporters. We hypothesized that nutraceuticals' inflammatory, adipogenic, and antioxidant status will be identified based on the change in fluorescence in reporter adipocytes. We validated these assays with activators of NFκB, FABP4‐regulating peroxisome proliferator activated receptor gamma, NFR2 and, thereafter, tested known and unknown properties of mangostines (MGs), the xanthone metabolites in mangosteen fruit.</p> </sec> <sec id="mnfr2063-sec-0020" sec-type="section"> <title>Methods and results</title> <p>We validated inflammatory and adipogenic properties of α‐MG using an <italic>Nfkb‐</italic>RE/GFP biosensor assay. Next, we identified unique properties of γ‐MG, a minor MG xanthone. γ‐MG suppressed adipogenesis and expression of adiponectin, but inhibited the <italic>Nfkb</italic>‐RE/GFP reporter and secretion of inflammatory monocyte chemotactic protein 1 as compared to the control adipocytes. We found that the inhibition of adipogenesis and <italic>Nfkb</italic>‐mediated inflammation depends on a dose‐dependent reduction of <italic>Nrf2</italic> promoter activity by α‐MG. The <italic>Nrf2</italic> inhibition resulted in the reduced <italic>Pparg</italic> expression. α‐MG did not directly influence <italic>Pparg</italic> activity in <italic>Fabp4</italic>‐P/CFP adipocytes.</p> </sec> <sec id="mnfr2063-sec-0030" sec-type="section"> <title>Conclusion</title> <p>α‐MG‐mediated antioxidant response via Nrf2 is a mechanism preventing adipogenesis and inflammation in adipocytes. Combined application of high‐throughput biosensors could provide an effective platform for the identification of nutraceuticals and the mechanism of their actions in adipocytes and, potentially, in obese patients.</p> </sec> </abstract>