Parabens inhibit fatty acid amide hydrolase: A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation

Sean D. Kodani, Haley B. Overby, Christophe Morisseau, Jiangang Chen, Ling Zhao, Bruce D. Hammock

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Parabens are a class of small molecules that are regularly used as preservatives in a variety of personal care products. Several parabens, including butylparaben and benzylparaben, have been found to interfere with endocrine signaling and to stimulate adipocyte differentiation. We hypothesized these biological effects could be due to interference with the endocannabinoid system and identified fatty acid amide hydrolase (FAAH) as the direct molecular target of parabens. FAAH inhibition by parabens yields mixed-type and time-independent kinetics. Additionally, structure activity relationships indicate FAAH inhibition is selective for the paraben class of compounds and the more hydrophobic parabens have higher potency. Parabens enhanced 3T3-L1 adipocyte differentiation in a dose dependent fashion, different from two other FAAH inhibitors URB597 and PF622. Moreover, parabens, URB597 and PF622 all failed to enhance AEA-induced differentiation. Furthermore, rimonabant, a cannabinoid receptor 1 (CB1)-selective antagonist, did not attenuate paraben-induced adipocyte differentiation. Thus, adipogenesis mediated by parabens likely occurs through modulation of endocannabinoids, but cell differentiation is independent of direct activation of CB1 by endocannabinoids.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalToxicology Letters
Volume262
DOIs
StatePublished - Nov 16 2016

Fingerprint

Parabens
Adipocytes
Endocannabinoids
Cannabinoid Receptors
rimonabant
fatty-acid amide hydrolase
Adipogenesis
Structure-Activity Relationship
Cell Differentiation
Chemical activation

Keywords

  • Adipocyte
  • Benzylparaben
  • Fatty acid amide hydrolase
  • Parabens

ASJC Scopus subject areas

  • Toxicology

Cite this

Parabens inhibit fatty acid amide hydrolase : A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation. / Kodani, Sean D.; Overby, Haley B.; Morisseau, Christophe; Chen, Jiangang; Zhao, Ling; Hammock, Bruce D.

In: Toxicology Letters, Vol. 262, 16.11.2016, p. 92-99.

Research output: Contribution to journalArticle

Kodani, Sean D. ; Overby, Haley B. ; Morisseau, Christophe ; Chen, Jiangang ; Zhao, Ling ; Hammock, Bruce D. / Parabens inhibit fatty acid amide hydrolase : A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation. In: Toxicology Letters. 2016 ; Vol. 262. pp. 92-99.
@article{6d5aab1b7bc5455bbc92dfdcfceda993,
title = "Parabens inhibit fatty acid amide hydrolase: A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation",
abstract = "Parabens are a class of small molecules that are regularly used as preservatives in a variety of personal care products. Several parabens, including butylparaben and benzylparaben, have been found to interfere with endocrine signaling and to stimulate adipocyte differentiation. We hypothesized these biological effects could be due to interference with the endocannabinoid system and identified fatty acid amide hydrolase (FAAH) as the direct molecular target of parabens. FAAH inhibition by parabens yields mixed-type and time-independent kinetics. Additionally, structure activity relationships indicate FAAH inhibition is selective for the paraben class of compounds and the more hydrophobic parabens have higher potency. Parabens enhanced 3T3-L1 adipocyte differentiation in a dose dependent fashion, different from two other FAAH inhibitors URB597 and PF622. Moreover, parabens, URB597 and PF622 all failed to enhance AEA-induced differentiation. Furthermore, rimonabant, a cannabinoid receptor 1 (CB1)-selective antagonist, did not attenuate paraben-induced adipocyte differentiation. Thus, adipogenesis mediated by parabens likely occurs through modulation of endocannabinoids, but cell differentiation is independent of direct activation of CB1 by endocannabinoids.",
keywords = "Adipocyte, Benzylparaben, Fatty acid amide hydrolase, Parabens",
author = "Kodani, {Sean D.} and Overby, {Haley B.} and Christophe Morisseau and Jiangang Chen and Ling Zhao and Hammock, {Bruce D.}",
year = "2016",
month = "11",
day = "16",
doi = "10.1016/j.toxlet.2016.09.011",
language = "English (US)",
volume = "262",
pages = "92--99",
journal = "Toxicology Letters",
issn = "0378-4274",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Parabens inhibit fatty acid amide hydrolase

T2 - A potential role in paraben-enhanced 3T3-L1 adipocyte differentiation

AU - Kodani, Sean D.

AU - Overby, Haley B.

AU - Morisseau, Christophe

AU - Chen, Jiangang

AU - Zhao, Ling

AU - Hammock, Bruce D.

PY - 2016/11/16

Y1 - 2016/11/16

N2 - Parabens are a class of small molecules that are regularly used as preservatives in a variety of personal care products. Several parabens, including butylparaben and benzylparaben, have been found to interfere with endocrine signaling and to stimulate adipocyte differentiation. We hypothesized these biological effects could be due to interference with the endocannabinoid system and identified fatty acid amide hydrolase (FAAH) as the direct molecular target of parabens. FAAH inhibition by parabens yields mixed-type and time-independent kinetics. Additionally, structure activity relationships indicate FAAH inhibition is selective for the paraben class of compounds and the more hydrophobic parabens have higher potency. Parabens enhanced 3T3-L1 adipocyte differentiation in a dose dependent fashion, different from two other FAAH inhibitors URB597 and PF622. Moreover, parabens, URB597 and PF622 all failed to enhance AEA-induced differentiation. Furthermore, rimonabant, a cannabinoid receptor 1 (CB1)-selective antagonist, did not attenuate paraben-induced adipocyte differentiation. Thus, adipogenesis mediated by parabens likely occurs through modulation of endocannabinoids, but cell differentiation is independent of direct activation of CB1 by endocannabinoids.

AB - Parabens are a class of small molecules that are regularly used as preservatives in a variety of personal care products. Several parabens, including butylparaben and benzylparaben, have been found to interfere with endocrine signaling and to stimulate adipocyte differentiation. We hypothesized these biological effects could be due to interference with the endocannabinoid system and identified fatty acid amide hydrolase (FAAH) as the direct molecular target of parabens. FAAH inhibition by parabens yields mixed-type and time-independent kinetics. Additionally, structure activity relationships indicate FAAH inhibition is selective for the paraben class of compounds and the more hydrophobic parabens have higher potency. Parabens enhanced 3T3-L1 adipocyte differentiation in a dose dependent fashion, different from two other FAAH inhibitors URB597 and PF622. Moreover, parabens, URB597 and PF622 all failed to enhance AEA-induced differentiation. Furthermore, rimonabant, a cannabinoid receptor 1 (CB1)-selective antagonist, did not attenuate paraben-induced adipocyte differentiation. Thus, adipogenesis mediated by parabens likely occurs through modulation of endocannabinoids, but cell differentiation is independent of direct activation of CB1 by endocannabinoids.

KW - Adipocyte

KW - Benzylparaben

KW - Fatty acid amide hydrolase

KW - Parabens

UR - http://www.scopus.com/inward/record.url?scp=84990241474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990241474&partnerID=8YFLogxK

U2 - 10.1016/j.toxlet.2016.09.011

DO - 10.1016/j.toxlet.2016.09.011

M3 - Article

C2 - 27659731

AN - SCOPUS:84990241474

VL - 262

SP - 92

EP - 99

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -