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Research Project: Prevention of Obesity Related Metabolic Diseases by Bioactive Components of Food Processing Waste Byproducts and Mitigation of Food Allergies

Location: Healthy Processed Foods Research

Title: Discovery of a novel bioactive compound in orange peel polar fraction on the inhibition of trimethylamine and trimethylamine N-oxide through metabolomics approaches and in vitro and vivo assays: feruloylputrescine inhibits

Author
item LEE, HANA - University Of Florida
item KOH, GAR YEE - Texas State University
item LEE, HANNA - US Department Of Agriculture (USDA)
item Alves Buongiorno, Priscila
item Yokoyama, Wallace - Wally
item WANG, YU - University Of Florida

Submitted to: Journal of Agriculture and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/19/2024
Publication Date: 4/1/2024
Citation: Lee, H., Koh, G., Lee, H., Alves, P.L., Yokoyama, W.H., Wang, Y. 2024. Discovery of a novel bioactive compound in orange peel polar fraction on the inhibition of trimethylamine and trimethylamine N-Oxide through metabolomics approaches and in vitro and in vivo assays: Feruloylputrescine inhibits trimethylamine via suppressing cntA/B enzyme. Journal of Agriculture and Food Chemistry. 72(14):7870-7881. https://doi.org/10.1021/acs.jafc.3c09005.
DOI: https://doi.org/10.1021/acs.jafc.3c09005

Interpretive Summary: Carnitine and choline are found in many foods. They contain a trimethylamine (TMA) substituent that is released by gut bacteria. TMA is translocated to the liver where it is metabolized to trimethylamine oxide (TMAO). TMAO has associated with inflammatory metabolic diseases. We found that orange peel extract inhibited the bacterial release of TMA and subsequent lower levels of TMA and TMAO in the blood. Further metabolic focusing of extract showed that a single molecule may be responsible for the inhibition.

Technical Abstract: This study compares inhibitory effects of orange peel polar fraction (OPP) and orange peel non-polar fraction (OPNP) on trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) production in response to L-carnitine treatment in vivo and in vitro. Metabolomics is used to identify bioactive compounds. The research demonstrates that OPP effectively regulates atherosclerosis-related markers, TMA, and TMAO in plasma and urine, compared to OPNP. Our investigation reveals that these inhibitory effects are independent of changes in gut microbiota composition. The effects are attributed to the modulation of cntA/B enzyme activity and FMO3 mRNA expression in vitro. Moreover, OPP exhibits stronger inhibitory effects on TMA production than OPNP, potentially due to its higher content of feruloylputrescine, which displays the highest inhibitory activity on the cntA/B enzyme and TMA production. These findings suggest that OPP containing feruloylputrescine has the potential to alleviate cardiovascular disease by modulating cntA/B and FMO3 enzymes without directly influencing gut microbiota composition.