Biomarkers of endocannabinoid system activation in severe obesity.

<h4>Background</h4>Obesity is a worldwide epidemic, and severe obesity is a risk factor for many diseases, including diabetes, heart disease, stroke, and some cancers. Endocannabinoid system (ECS) signaling in the brain and peripheral tissues is activated in obesity and plays a role in t...

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Autores principales: Jack C Sipe, T Michael Scott, Sarah Murray, Olivier Harismendy, Gabriel M Simon, Benjamin F Cravatt, Jill Waalen
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Publicado: Public Library of Science (PLoS) 2010
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spelling oai:doaj.org-article:d5f7a287e3b8456095f9e6dec8c459a42021-11-25T06:26:34ZBiomarkers of endocannabinoid system activation in severe obesity.1932-620310.1371/journal.pone.0008792https://doaj.org/article/d5f7a287e3b8456095f9e6dec8c459a42010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20098695/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Obesity is a worldwide epidemic, and severe obesity is a risk factor for many diseases, including diabetes, heart disease, stroke, and some cancers. Endocannabinoid system (ECS) signaling in the brain and peripheral tissues is activated in obesity and plays a role in the regulation of body weight. The main research question here was whether quantitative measurement of plasma endocannabinoids, anandamide, and related N-acylethanolamines (NAEs), combined with genotyping for mutations in fatty acid amide hydrolase (FAAH) would identify circulating biomarkers of ECS activation in severe obesity.<h4>Methodology/principal findings</h4>Plasma samples were obtained from 96 severely obese subjects with body mass index (BMI) of > or = 40 kg/m(2), and 48 normal weight subjects with BMI of < or = 26 kg/m(2). Triple-quadrupole mass spectroscopy methods were used to measure plasma ECS analogs. Subjects were genotyped for human FAAH gene mutations. The principal analysis focused on the FAAH 385 C-->A (P129T) mutation by comparing plasma ECS metabolite levels in the FAAH 385 minor A allele carriers versus wild-type C/C carriers in both groups. The main finding was significantly elevated mean plasma levels of anandamide (15.1+/-1.4 pmol/ml) and related NAEs in study subjects that carried the FAAH 385 A mutant alleles versus normal subjects (13.3+/-1.0 pmol/ml) with wild-type FAAH genotype (p = 0.04), and significance was maintained after controlling for BMI.<h4>Conclusions/significance</h4>Significantly increased levels of the endocannabinoid anandamide and related NAEs were found in carriers of the FAAH 385 A mutant alleles compared with wild-type FAAH controls. This evidence supports endocannabinoid system activation due to the effect of FAAH 385 mutant A genotype on plasma AEA and related NAE analogs. This is the first study to document that FAAH 385 A mutant alleles have a direct effect on elevated plasma levels of anandamide and related NAEs in humans. These biomarkers may indicate risk for severe obesity and may suggest novel ECS obesity treatment strategies.Jack C SipeT Michael ScottSarah MurrayOlivier HarismendyGabriel M SimonBenjamin F CravattJill WaalenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8792 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jack C Sipe
T Michael Scott
Sarah Murray
Olivier Harismendy
Gabriel M Simon
Benjamin F Cravatt
Jill Waalen
Biomarkers of endocannabinoid system activation in severe obesity.
description <h4>Background</h4>Obesity is a worldwide epidemic, and severe obesity is a risk factor for many diseases, including diabetes, heart disease, stroke, and some cancers. Endocannabinoid system (ECS) signaling in the brain and peripheral tissues is activated in obesity and plays a role in the regulation of body weight. The main research question here was whether quantitative measurement of plasma endocannabinoids, anandamide, and related N-acylethanolamines (NAEs), combined with genotyping for mutations in fatty acid amide hydrolase (FAAH) would identify circulating biomarkers of ECS activation in severe obesity.<h4>Methodology/principal findings</h4>Plasma samples were obtained from 96 severely obese subjects with body mass index (BMI) of > or = 40 kg/m(2), and 48 normal weight subjects with BMI of < or = 26 kg/m(2). Triple-quadrupole mass spectroscopy methods were used to measure plasma ECS analogs. Subjects were genotyped for human FAAH gene mutations. The principal analysis focused on the FAAH 385 C-->A (P129T) mutation by comparing plasma ECS metabolite levels in the FAAH 385 minor A allele carriers versus wild-type C/C carriers in both groups. The main finding was significantly elevated mean plasma levels of anandamide (15.1+/-1.4 pmol/ml) and related NAEs in study subjects that carried the FAAH 385 A mutant alleles versus normal subjects (13.3+/-1.0 pmol/ml) with wild-type FAAH genotype (p = 0.04), and significance was maintained after controlling for BMI.<h4>Conclusions/significance</h4>Significantly increased levels of the endocannabinoid anandamide and related NAEs were found in carriers of the FAAH 385 A mutant alleles compared with wild-type FAAH controls. This evidence supports endocannabinoid system activation due to the effect of FAAH 385 mutant A genotype on plasma AEA and related NAE analogs. This is the first study to document that FAAH 385 A mutant alleles have a direct effect on elevated plasma levels of anandamide and related NAEs in humans. These biomarkers may indicate risk for severe obesity and may suggest novel ECS obesity treatment strategies.
format article
author Jack C Sipe
T Michael Scott
Sarah Murray
Olivier Harismendy
Gabriel M Simon
Benjamin F Cravatt
Jill Waalen
author_facet Jack C Sipe
T Michael Scott
Sarah Murray
Olivier Harismendy
Gabriel M Simon
Benjamin F Cravatt
Jill Waalen
author_sort Jack C Sipe
title Biomarkers of endocannabinoid system activation in severe obesity.
title_short Biomarkers of endocannabinoid system activation in severe obesity.
title_full Biomarkers of endocannabinoid system activation in severe obesity.
title_fullStr Biomarkers of endocannabinoid system activation in severe obesity.
title_full_unstemmed Biomarkers of endocannabinoid system activation in severe obesity.
title_sort biomarkers of endocannabinoid system activation in severe obesity.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/d5f7a287e3b8456095f9e6dec8c459a4
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AT tmichaelscott biomarkersofendocannabinoidsystemactivationinsevereobesity
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AT olivierharismendy biomarkersofendocannabinoidsystemactivationinsevereobesity
AT gabrielmsimon biomarkersofendocannabinoidsystemactivationinsevereobesity
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