title: Nonivamide enhances miRNA let-7d expression and decreases adipogenesis PPARγ expression in 3T3-L1 cells.
abstract: Red pepper and its major pungent principle, capsaicin (CAP), have been shown to be effective anti-obesity agents by reducing energy intake, enhancing energy metabolism, decreasing serum triacylglycerol content, and inhibiting adipogenesis via activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1). However, the binding of CAP to the TRPV1 receptor is also responsible for its pungent sensation, strongly limiting its dietary intake. Here, the effects of a less pungent structural CAP-analog, nonivamide, on adipogenesis and underlying mechanisms in 3T3-L1 cells were studied. Nonivamide was found to reduce mean lipid accumulation, a marker of adipogenesis, to a similar extent as CAP, up to 10.4% (P < 0.001). Blockage of the TRPV1 receptor with the specific inhibitor trans-tert-butylcyclohexanol revealed that the anti-adipogenic activity of nonivamide depends, as with CAP, on TRPV1 receptor activation. In addition, in cells treated with nonivamide during adipogenesis, protein levels of the pro-adipogenic transcription factor peroxisome-proliferator activated receptor γ (PPARγ) decreased. Results from miRNA microarrays and digital droplet PCR analysis demonstrated an increase in the expression of the miRNA mmu-let-7d-5p, which has been associated with decreased PPARγ levels.
authors.affiliation: Christian Doppler Laboratory for Bioactive Aroma Compounds, Althanstraße 14, 1090, Vienna, Austria; Department of Nutritional and Physiological Chemistry, Althanstraße 14, 1090, Vienna, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rohm
authors.forename: Ann-Katrin
authors.initials: AK
authors.lastname: Holik
authors.forename: Nicole
authors.initials: N
authors.lastname: Kretschy
authors.forename: Mark M
authors.initials: MM
authors.lastname: Somoza
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: Doris
authors.initials: D
authors.lastname: Marko
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D047495:PPAR gamma; D050916:TRPV Cation Channels; D002211:Capsaicin; C040937:nonivamide
keywords: 3T3-L1 ADIPOGENESIS; CELL DIFFERENTIATION; LIPID ACCUMULATION; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR (PPAR); TRPV1; microRNA; trans-tert-BUTYLCYCLOHEXANOL