High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose Tissue

The endocannabinoid system (ECS) controls energy balance by regulating both energy intake and energy expenditure. Endocannabinoid levels are elevated in obesity suggesting a potential causal relationship. This study aimed to elucidate the rate of dysregulation of the ECS, and the metabolic organs in...

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Main Authors: Eline N. Kuipers, Vasudev Kantae, Boukje C. Eveleens Maarse, Susan M. van den Berg, Robin van Eenige, Kimberly J. Nahon, Anne Reifel-Miller, Tamer Coskun, Menno P. J. de Winther, Esther Lutgens, Sander Kooijman, Amy C. Harms, Thomas Hankemeier, Mario van der Stelt, Patrick C. N. Rensen, Mariëtte R. Boon
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-01-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2018.01913/full
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author Eline N. Kuipers
Eline N. Kuipers
Vasudev Kantae
Boukje C. Eveleens Maarse
Boukje C. Eveleens Maarse
Susan M. van den Berg
Robin van Eenige
Robin van Eenige
Kimberly J. Nahon
Kimberly J. Nahon
Anne Reifel-Miller
Tamer Coskun
Menno P. J. de Winther
Esther Lutgens
Esther Lutgens
Sander Kooijman
Sander Kooijman
Sander Kooijman
Amy C. Harms
Thomas Hankemeier
Mario van der Stelt
Patrick C. N. Rensen
Patrick C. N. Rensen
Mariëtte R. Boon
Mariëtte R. Boon
spellingShingle Eline N. Kuipers
Eline N. Kuipers
Vasudev Kantae
Boukje C. Eveleens Maarse
Boukje C. Eveleens Maarse
Susan M. van den Berg
Robin van Eenige
Robin van Eenige
Kimberly J. Nahon
Kimberly J. Nahon
Anne Reifel-Miller
Tamer Coskun
Menno P. J. de Winther
Esther Lutgens
Esther Lutgens
Sander Kooijman
Sander Kooijman
Sander Kooijman
Amy C. Harms
Thomas Hankemeier
Mario van der Stelt
Patrick C. N. Rensen
Patrick C. N. Rensen
Mariëtte R. Boon
Mariëtte R. Boon
High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose Tissue
Frontiers in Physiology
brown adipose tissue
white adipose tissue
diet-induced obesity
endocannabinoids
NAPE-PLD
author_facet Eline N. Kuipers
Eline N. Kuipers
Vasudev Kantae
Boukje C. Eveleens Maarse
Boukje C. Eveleens Maarse
Susan M. van den Berg
Robin van Eenige
Robin van Eenige
Kimberly J. Nahon
Kimberly J. Nahon
Anne Reifel-Miller
Tamer Coskun
Menno P. J. de Winther
Esther Lutgens
Esther Lutgens
Sander Kooijman
Sander Kooijman
Sander Kooijman
Amy C. Harms
Thomas Hankemeier
Mario van der Stelt
Patrick C. N. Rensen
Patrick C. N. Rensen
Mariëtte R. Boon
Mariëtte R. Boon
author_sort Eline N. Kuipers
title High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose Tissue
title_short High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose Tissue
title_full High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose Tissue
title_fullStr High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose Tissue
title_full_unstemmed High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose Tissue
title_sort high fat diet increases circulating endocannabinoids accompanied by increased synthesis enzymes in adipose tissue
publisher Frontiers Media S.A.
series Frontiers in Physiology
issn 1664-042X
publishDate 2019-01-01
description The endocannabinoid system (ECS) controls energy balance by regulating both energy intake and energy expenditure. Endocannabinoid levels are elevated in obesity suggesting a potential causal relationship. This study aimed to elucidate the rate of dysregulation of the ECS, and the metabolic organs involved, in diet-induced obesity. Eight groups of age-matched male C57Bl/6J mice were randomized to receive a chow diet (control) or receive a high fat diet (HFD, 45% of calories derived from fat) ranging from 1 day up to 18 weeks before euthanasia. Plasma levels of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, AEA), and related N-acylethanolamines, were quantified by UPLC-MS/MS and gene expression of components of the ECS was determined in liver, muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) during the course of diet-induced obesity development. HFD feeding gradually increased 2-AG (+132% within 4 weeks, P < 0.05), accompanied by upregulated expression of its synthesizing enzymes Daglα and β in WAT and BAT. HFD also rapidly increased AEA (+81% within 1 week, P < 0.01), accompanied by increased expression of its synthesizing enzyme Nape-pld, specifically in BAT. Interestingly, Nape-pld expression in BAT correlated with plasma AEA levels (R2 = 0.171, β = 0.276, P < 0.001). We conclude that a HFD rapidly activates adipose tissue depots to increase the synthesis pathways of endocannabinoids that may aggravate the development of HFD-induced obesity.
topic brown adipose tissue
white adipose tissue
diet-induced obesity
endocannabinoids
NAPE-PLD
url https://www.frontiersin.org/article/10.3389/fphys.2018.01913/full
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spelling doaj-04969df25b384eee81b3288c63b30ff22020-11-24T22:53:41ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-01-01910.3389/fphys.2018.01913417815High Fat Diet Increases Circulating Endocannabinoids Accompanied by Increased Synthesis Enzymes in Adipose TissueEline N. Kuipers0Eline N. Kuipers1Vasudev Kantae2Boukje C. Eveleens Maarse3Boukje C. Eveleens Maarse4Susan M. van den Berg5Robin van Eenige6Robin van Eenige7Kimberly J. Nahon8Kimberly J. Nahon9Anne Reifel-Miller10Tamer Coskun11Menno P. J. de Winther12Esther Lutgens13Esther Lutgens14Sander Kooijman15Sander Kooijman16Sander Kooijman17Amy C. Harms18Thomas Hankemeier19Mario van der Stelt20Patrick C. N. Rensen21Patrick C. N. Rensen22Mariëtte R. Boon23Mariëtte R. Boon24Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDivision of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Medical Biochemistry, Academic Medical Center, Amsterdam, NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Diabetes/Endocrine, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, United StatesDepartment of Diabetes/Endocrine, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN, United StatesDepartment of Medical Biochemistry, Academic Medical Center, Amsterdam, NetherlandsDepartment of Medical Biochemistry, Academic Medical Center, Amsterdam, NetherlandsInstitute for Cardiovascular Prevention (IPEK), Ludwig Maximilian University of Munich, Munich, GermanyDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United KingdomDivision of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, NetherlandsDivision of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, NetherlandsDepartment of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, Leiden, NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, NetherlandsEinthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, NetherlandsThe endocannabinoid system (ECS) controls energy balance by regulating both energy intake and energy expenditure. Endocannabinoid levels are elevated in obesity suggesting a potential causal relationship. This study aimed to elucidate the rate of dysregulation of the ECS, and the metabolic organs involved, in diet-induced obesity. Eight groups of age-matched male C57Bl/6J mice were randomized to receive a chow diet (control) or receive a high fat diet (HFD, 45% of calories derived from fat) ranging from 1 day up to 18 weeks before euthanasia. Plasma levels of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, AEA), and related N-acylethanolamines, were quantified by UPLC-MS/MS and gene expression of components of the ECS was determined in liver, muscle, white adipose tissue (WAT) and brown adipose tissue (BAT) during the course of diet-induced obesity development. HFD feeding gradually increased 2-AG (+132% within 4 weeks, P < 0.05), accompanied by upregulated expression of its synthesizing enzymes Daglα and β in WAT and BAT. HFD also rapidly increased AEA (+81% within 1 week, P < 0.01), accompanied by increased expression of its synthesizing enzyme Nape-pld, specifically in BAT. Interestingly, Nape-pld expression in BAT correlated with plasma AEA levels (R2 = 0.171, β = 0.276, P < 0.001). We conclude that a HFD rapidly activates adipose tissue depots to increase the synthesis pathways of endocannabinoids that may aggravate the development of HFD-induced obesity.https://www.frontiersin.org/article/10.3389/fphys.2018.01913/fullbrown adipose tissuewhite adipose tissuediet-induced obesityendocannabinoidsNAPE-PLD