title: Capsaicin, nonivamide and trans-pellitorine decrease free fatty acid uptake without TRPV1 activation and increase acetyl-coenzyme A synthetase activity in Caco-2 cells.
abstract: Red pepper and its major pungent component, capsaicin, have been associated with hypolipidemic effects in rats, although mechanistic studies on the effects of capsaicin and/or structurally related compounds on lipid metabolism are scarce. In this work, the effects of capsaicin and its structural analog nonivamide, the aliphatic alkamide trans-pellitorine and vanillin as the basic structural element of all vanilloids on the mechanisms of intestinal fatty acid uptake in differentiated intestinal Caco-2 cells were studied. Capsaicin and nonivamide were found to reduce fatty acid uptake, with IC₅₀ values of 0.49 μM and 1.08 μM, respectively. trans-Pellitorine was shown to reduce fatty acid uptake by 14.0±2.14% at 100 μM, whereas vanillin was not effective, indicating a pivotal role of the alkyl chain with the acid amide group in fatty acid uptake by Caco-2 cells. This effect was associated neither with the activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) or the epithelial sodium channel (ENaC) nor with effects on paracellular transport or glucose uptake. However, acetyl-coenzyme A synthetase activity increased (p<0.05) in the presence of 10 μM capsaicin, nonivamide or trans-pellitorine, pointing to an increased fatty acid biosynthesis that might counteract the decreased fatty acid uptake.
authors.affiliation: Christian Doppler Laboratory for Bioactive Aroma Compounds, Faculty of Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria. Veronika.Somoza@univie.ac.at.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rohm
authors.forename: Annett
authors.initials: A
authors.lastname: Riedel
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Ley
authors.forename: Sabine
authors.initials: S
authors.lastname: Widder
authors.forename: Gerhard E
authors.initials: GE
authors.lastname: Krammer
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
mesh_terms: D000106:Acetate-CoA Ligase / Q000737:chemistry / Q000378:metabolism*; D001547:Benzaldehydes / Q000009:adverse effects / Q000378:metabolism; D018938:Caco-2 Cells; D002211:Capsaicin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000378:metabolism*; D002470:Cell Survival; D019587:Dietary Supplements / Q000009:adverse effects; D015536:Down-Regulation; D020895:Enterocytes / Q000201:enzymology / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000378:metabolism*; D007408:Intestinal Absorption; D007700:Kinetics; D053284:Polyunsaturated Alkamides / Q000009:adverse effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D001547:Benzaldehydes; D053503:Epithelial Sodium Channels; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D005765:Gastrointestinal Agents; D000960:Hypolipidemic Agents; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C008778:pellitorine; C100058:vanillin; D000106:Acetate-CoA Ligase; D002211:Capsaicin; C040937:nonivamide