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Open AccessArticle

Biological Evaluation of Natural and Synthesized Homovanillic Acid Esters as Inhibitors of Intestinal Fatty Acid Uptake in Differentiated Caco-2 Cells

1
Symrise AG, Muehlenfeldstrasse 1, 53479 Holzminden, Germany
2
Department of Physiological Chemistry, University of Vienna, CDL for Taste Research, Althanstrasse 14, Vienna 1090, Austria
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(19), 3599; https://doi.org/10.3390/molecules24193599
Received: 14 September 2019 / Revised: 29 September 2019 / Accepted: 4 October 2019 / Published: 7 October 2019
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes-II)
With raising prevalence of obesity, the regulation of human body fat is increasingly relevant. The modulation of fatty acid uptake by enterocytes represents a promising target for body weight maintenance. Recent results demonstrated that the trigeminal active compounds capsaicin, nonivamide, and trans-pellitorine dose-dependently reduce fatty acid uptake in differentiated Caco-2 cells as a model for the intestinal barrier. However, non-pungent alternatives have not been investigated and structural determinants for the modulation of intestinal fatty acid uptake have not been identified so far. Thus, based on the previous results, we synthesized 23 homovanillic acid esters in addition to the naturally occurring capsiate and screened them for their potential to reduce intestinal fatty acid uptake using the fluorescent fatty acid analog Bodipy-C12 in differentiated Caco‑2 cells as an enterocyte model. Whereas pre-incubation with 100 µM capsiate did not change fatty acid uptake by Caco-2 enterocytes, a maximum inhibition of −47% was reached using 100 µM 1‑methylpentyl-2-(4-hydroxy-3-methoxy-phenyl)acetate. Structural analysis of the 24 structural analogues tested in the present study revealed that a branched fatty acid side chain, independent of the chain length, is one of the most important structural motifs associated with inhibition of fatty acid uptake in Caco-2 enterocytes. The results of the present study may serve as an important basis for designing potent dietary inhibitors of fatty acid uptake. View Full-Text
Keywords: fatty acid uptake; capsiate; homovanillic acid esters; capsaicin; Caco-2 cells; obesity fatty acid uptake; capsiate; homovanillic acid esters; capsaicin; Caco-2 cells; obesity
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MDPI and ACS Style

Lieder, B.; Hans, J.; Hentschel, F.; Geissler, K.; Ley, J. Biological Evaluation of Natural and Synthesized Homovanillic Acid Esters as Inhibitors of Intestinal Fatty Acid Uptake in Differentiated Caco-2 Cells. Molecules 2019, 24, 3599.

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