Projekte

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

Autor(en)
Barbara Lieder, Joachim Hans, Fabia Hentschel, Katrin Geissler, Jakob Ley
Abstrakt

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 mu M capsiate did not change fatty acid uptake by Caco-2 enterocytes, a maximum inhibition of -47% was reached using 100 mu M 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.

Organisation(en)
Institut für Physiologische Chemie
Externe Organisation(en)
Symrise AG
Journal
Molecules
Band
24
Anzahl der Seiten
14
ISSN
1420-3049
DOI
https://doi.org/10.3390/molecules24193599
Publikationsdatum
10-2019
Peer-reviewed
Ja
ÖFOS 2012
Ernährungswissenschaften, Chemische Biologie
Schlagwörter
Link zum Portal
https://ucris.univie.ac.at/portal/de/publications/biological-evaluation-of-natural-and-synthesized-homovanillic-acid-esters-as-inhibitors-of-intestinal-fatty-acid-uptake-in-differentiated-caco2-cells(2b00f800-5000-41c5-a58d-d59f5a5482b0).html

Publikationen

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

Autor(en)
Barbara Lieder, Joachim Hans, Fabia Hentschel, Katrin Geissler, Jakob Ley
Abstrakt

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 mu M capsiate did not change fatty acid uptake by Caco-2 enterocytes, a maximum inhibition of -47% was reached using 100 mu M 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.

Organisation(en)
Institut für Physiologische Chemie
Externe Organisation(en)
Symrise AG
Journal
Molecules
Band
24
Anzahl der Seiten
14
ISSN
1420-3049
DOI
https://doi.org/10.3390/molecules24193599
Publikationsdatum
10-2019
Peer-reviewed
Ja
ÖFOS 2012
Ernährungswissenschaften, Chemische Biologie
Schlagwörter
Link zum Portal
https://ucris.univie.ac.at/portal/de/publications/biological-evaluation-of-natural-and-synthesized-homovanillic-acid-esters-as-inhibitors-of-intestinal-fatty-acid-uptake-in-differentiated-caco2-cells(2b00f800-5000-41c5-a58d-d59f5a5482b0).html

Vortraege

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

Autor(en)
Barbara Lieder, Joachim Hans, Fabia Hentschel, Katrin Geissler, Jakob Ley
Abstrakt

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 mu M capsiate did not change fatty acid uptake by Caco-2 enterocytes, a maximum inhibition of -47% was reached using 100 mu M 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.

Organisation(en)
Institut für Physiologische Chemie
Externe Organisation(en)
Symrise AG
Journal
Molecules
Band
24
Anzahl der Seiten
14
ISSN
1420-3049
DOI
https://doi.org/10.3390/molecules24193599
Publikationsdatum
10-2019
Peer-reviewed
Ja
ÖFOS 2012
Ernährungswissenschaften, Chemische Biologie
Schlagwörter
Link zum Portal
https://ucris.univie.ac.at/portal/de/publications/biological-evaluation-of-natural-and-synthesized-homovanillic-acid-esters-as-inhibitors-of-intestinal-fatty-acid-uptake-in-differentiated-caco2-cells(2b00f800-5000-41c5-a58d-d59f5a5482b0).html