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Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin

(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 en...

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Autores principales: Baskaran, Padmamalini, Covington, Kyle, Bennis, Jane, Mohandass, Adithya, Lehmann, Teresa, Thyagarajan, Baskaran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321193/
https://www.ncbi.nlm.nih.gov/pubmed/30518154
http://dx.doi.org/10.3390/molecules23123198
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author Baskaran, Padmamalini
Covington, Kyle
Bennis, Jane
Mohandass, Adithya
Lehmann, Teresa
Thyagarajan, Baskaran
author_facet Baskaran, Padmamalini
Covington, Kyle
Bennis, Jane
Mohandass, Adithya
Lehmann, Teresa
Thyagarajan, Baskaran
author_sort Baskaran, Padmamalini
collection PubMed
description (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.
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spelling pubmed-63211932019-01-14 Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin Baskaran, Padmamalini Covington, Kyle Bennis, Jane Mohandass, Adithya Lehmann, Teresa Thyagarajan, Baskaran Molecules Article (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. MDPI 2018-12-04 /pmc/articles/PMC6321193/ /pubmed/30518154 http://dx.doi.org/10.3390/molecules23123198 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Baskaran, Padmamalini
Covington, Kyle
Bennis, Jane
Mohandass, Adithya
Lehmann, Teresa
Thyagarajan, Baskaran
Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin
title Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin
title_full Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin
title_fullStr Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin
title_full_unstemmed Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin
title_short Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin
title_sort binding efficacy and thermogenic efficiency of pungent and nonpungent analogs of capsaicin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321193/
https://www.ncbi.nlm.nih.gov/pubmed/30518154
http://dx.doi.org/10.3390/molecules23123198
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