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.

Nonivamide Enhances miRNA let‐7d Expression and Decreases Adipogenesis PPARγ Expression in 3T3‐L1 Cells

“…Although data from long‐term human intervention studies with nonivamide are lacking, nonivamide seems to be a promising candidate to target different medicinal strategies in the treatment of obesity. Beside the inhibition of adipogenesis demonstrated here, nonivamide has also been shown to decrease fatty acid uptake in Caco‐2 cells [Rohm et al, ], which may support the prevention of hyperlipidemia. In addition, administration of 0.15 mg nonivamide in an oral glucose tolerance test reduced total energy intake from a standardized breakfast in slightly overweight male subjects [Hochkogler et al, ], supporting the effectiveness of the less pungent CAP‐analog.…”

Mechanistic study of nonivamide enhancement of hyperthermia-induced apoptosis in U937 cells

“…Nonivamide-containing cream is used for temporary relief of arthritis and muscle pain in clinical settings. In addition, nonivamide causes multiple physiological effects, including reduced lipid accumulation in pre-adipocyte cells [12], decreased free fatty acid uptake in Caco-2 cells [13], attenuated inflammatory properties in peripheral blood mononuclear 3 cells [14], and increased dopamine and serotonin release in SH-SY5Y cells [11].…”

Nonivamide, a capsaicin analogue, exhibits anti‐inflammatory properties in peripheral blood mononuclear cells and U‐937 macrophages

“…However, the influence of nonivamide on LPS‐induced inflammation has not yet been elucidated. Previously, the influence of the trigeminally active compounds on free fatty acid uptake has been demonstrated, showing that the less pungent nonivamide possessed similar efficacies as capsaicin and exploits an impact on human health beyond taste, pain, and heat .…”