Abstract
(1) Background: Capsaicin, a chief ingredient of natural chili peppers, enhances metabolism and energy expenditure and stimulates the browning of white adipose tissue (WAT) and brown fat activation to counter diet-induced obesity. Although capsaicin and its nonpungent analogs are shown to enhance energy expenditure, their efficiency to bind to and activate their receptor—transient receptor potential vanilloid subfamily 1 (TRPV1)—to mediate thermogenic effects remains unclear. (2) Methods: We analyzed the binding efficiency of capsaicin analogs by molecular docking. We fed wild type mice a normal chow or high fat diet (± 0.01% pungent or nonpungent capsaicin analog) and isolated inguinal WAT to analyze the expression of thermogenic genes and proteins. (3) Results: Capsaicin, but not its nonpungent analogs, efficiently binds to TRPV1, prevents high fat diet-induced weight gain, and upregulates thermogenic protein expression in WAT. Molecular docking studies indicate that capsaicin exhibits the highest binding efficacy to TRPV1 because it has a hydrogen bond that anchors it to TRPV1. Capsiate, which lacks the hydrogen bond, and therefore, does not anchor to TRPV1. (4) Conclusions: Long-term activation of TRPV1 is imminent for the anti-obesity effect of capsaicin. Efforts to decrease the pungency of capsaicin will help in advancing it to mitigate obesity and metabolic dysfunction in humans.
Highlights
Natural chili peppers contain both pungent capsaicinoids and non-pungent capsinoids [1].Capsaicin (CAP) is a pungent capsaicinoid [2] and Capsiate is a classic example of a non-pungent capsinoid [3]
The data presented in this work indicates that the structural differences among CAP, Capsiate, and CAP-β-Dgluco have significant impact on their binding to transient receptor potential vanilloid subfamily 1 (TRPV1) protein, activation of the channel, and upregulation of thermogenic protein expression in the inguinal white adipose tissues (WAT) of mice
The docking results suggest that the hydrogen bond between the CAP neck and T550 anchor this ligand to the binding channel
Summary
Natural chili peppers contain both pungent capsaicinoids and non-pungent capsinoids [1]. Capsaicin (CAP) is a pungent capsaicinoid [2] and Capsiate is a classic example of a non-pungent capsinoid [3] Both CAP and Capsiate bind to and activate their receptor, transient receptor potential vanilloid subfamily 1 (TRPV1) [4,5] protein, which is expressed in neuronal and non-neuronal tissues. Of equivalent is a lack of studies demonstrating the effect of long-term feeding of equivalent concentrations or doses concentrations or doses of pure CAP, Capsiate, and other non-pungent derivatives in rodents. Containing a defined effect of thirty-two (32)Capsiate, weeks ofor feeding wild type mice a highCAP- fat diet (HFD)We containing a defined quantity of pure CAP, another derivative of CAP, Dgluco. Our study presents novel dataefficiency on significant differences on significant differences between thein binding efficiency and thermogenic of pungent and nonpungent derivatives of CAP. Nonpungent derivatives of CAP on their pharmacological effects and therapeutic development
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