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Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids

Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids
Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids
Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5–25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30–40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.
0143-5221
185-200
Fisk, Helena
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Childs, Caroline
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Miles, Elizabeth
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Ayres, Robert
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Noakes, Paul S.
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Paras Chavez, Carolina
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Kuda, Ondrej
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Kopecky, Jan
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Antoun, Elie
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Lillycrop, Karen
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Calder, Philip
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Fisk, Helena
2483d346-75dd-41b3-a481-10f8bb39cd9f
Childs, Caroline
ea17ccc1-2eac-4f67-96c7-a0c4d9dfd9c5
Miles, Elizabeth
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Ayres, Robert
da3a1f2b-432f-46f8-857f-ceae18ce7b40
Noakes, Paul S.
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Paras Chavez, Carolina
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Kuda, Ondrej
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Kopecky, Jan
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Antoun, Elie
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Lillycrop, Karen
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Calder, Philip
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Fisk, Helena, Childs, Caroline, Miles, Elizabeth, Ayres, Robert, Noakes, Paul S., Paras Chavez, Carolina, Kuda, Ondrej, Kopecky, Jan, Antoun, Elie, Lillycrop, Karen and Calder, Philip (2021) Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids. Clinical Science, 135 (1), 185-200. (doi:10.1042/CS20201060).

Record type: Article

Abstract

Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5–25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30–40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.

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Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity.. - Accepted Manuscript
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Table 1 - Accepted Manuscript
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Supplementary Table 1 - Accepted Manuscript
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Supplementary Table 2 - Accepted Manuscript
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endocannabinoid system overview Figure 1 - Accepted Manuscript
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Fig 2 study flow in weeks - Accepted Manuscript
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Figure 3 - Accepted Manuscript
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Figure 4 - Accepted Manuscript
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Figure 5 - Accepted Manuscript
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Figure 6 - Accepted Manuscript
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Figure 7 V2 % change in % EPA DPA and DHA revised - Accepted Manuscript
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New figure 8 % change in AEA 2AG EPEA DHEA - Accepted Manuscript
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More information

Accepted/In Press date: 4 January 2021
e-pub ahead of print date: 8 January 2021
Published date: January 2021

Identifiers

Local EPrints ID: 446258
URI: http://eprints.soton.ac.uk/id/eprint/446258
ISSN: 0143-5221
PURE UUID: 3b40d24d-c1a0-4c53-8e93-1f9ea0e5328b
ORCID for Helena Fisk: ORCID iD orcid.org/0000-0002-9534-3246
ORCID for Caroline Childs: ORCID iD orcid.org/0000-0001-6832-224X
ORCID for Elizabeth Miles: ORCID iD orcid.org/0000-0002-8643-0655
ORCID for Karen Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489
ORCID for Philip Calder: ORCID iD orcid.org/0000-0002-6038-710X

Catalogue record

Date deposited: 02 Feb 2021 17:30
Last modified: 11 Mar 2021 02:36

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Contributors

Author: Helena Fisk ORCID iD
Author: Caroline Childs ORCID iD
Author: Elizabeth Miles ORCID iD
Author: Robert Ayres
Author: Paul S. Noakes
Author: Carolina Paras Chavez
Author: Ondrej Kuda
Author: Jan Kopecky
Author: Elie Antoun
Author: Karen Lillycrop ORCID iD
Author: Philip Calder ORCID iD

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