Capsaicin, nonivamide and trans-pellitorine decrease free fatty acid uptake without TRPV1 activation and increase...

Area of Science:

• Biochemistry
• Cell Biology
• Nutritional Science

Background:

• Red pepper and capsaicin are linked to hypolipidemic effects in rats.
• Mechanistic studies on capsaicin's impact on lipid metabolism are limited.

Purpose of the Study:

• To investigate the effects of capsaicin and related compounds on intestinal fatty acid uptake.
• To elucidate the mechanisms underlying these effects in Caco-2 cells.

Main Methods:

• Differentiated human intestinal Caco-2 cells were used.
• Fatty acid uptake was measured in the presence of capsaicin, nonivamide, trans-pellitorine, and vanillin.
• Enzyme activity assays (acetyl-CoA synthetase) and channel activation assessments (TRPV1, ENaC) were performed.

Main Results:

• Capsaicin (IC₅₀=0.49 μM) and nonivamide (IC₅₀=1.08 μM) significantly reduced fatty acid uptake.
• Trans-pellitorine showed a moderate reduction (14.0±2.14% at 100 μM), while vanillin had no effect.
• The inhibitory effect on fatty acid uptake was independent of TRPV1/ENaC activation and paracellular/glucose transport.
• Acetyl-CoA synthetase activity increased with capsaicin, nonivamide, and trans-pellitorine treatment.

Conclusions:

• The alkyl chain and amide group are crucial for the inhibitory effect on fatty acid uptake.
• Increased fatty acid biosynthesis may counteract the reduced uptake, suggesting a complex regulatory role.
• These findings provide mechanistic insights into capsaicin's potential lipid-lowering effects at the intestinal level.