TY - JOUR
T1 - High fat diet increases circulating endocannabinoids accompanied by increased synthesis enzymes in adipose tissue
AU - Kuipers, Eline N.
AU - Kantae, Vasudev
AU - Eveleens Maarse, Boukje C.
AU - Van Den Berg, Susan M.
AU - Van Eenige, Robin
AU - Nahon, Kimberly J.
AU - Reifel-Miller, Anne
AU - Coskun, Tamer
AU - De Winther, Menno P.J.
AU - Lutgens, Esther
AU - Kooijman, Sander
AU - Harms, Amy C.
AU - Hankemeier, Thomas
AU - Van Der Stelt, Mario
AU - Rensen, Patrick C.N.
AU - Boon, Mariëtte R.
N1 - Publisher Copyright:
© 2019 Kuipers, Kantae, Maarse, van den Berg, van Eenige, Nahon, Reifel-Miller, Coskun, de Winther, Lutgens, Kooijman, Harms, Hankemeier, van der Stelt, Rensen and Boon.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Brown adipose tissue
KW - Diet-induced obesity
KW - Endocannabinoids
KW - NAPE-PLD
KW - White adipose tissue
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U2 - 10.3389/fphys.2018.01913
DO - 10.3389/fphys.2018.01913
M3 - Article
AN - SCOPUS:85065470763
SN - 1664-042X
VL - 10
JO - Frontiers in Physiology
JF - Frontiers in Physiology
IS - JAN
M1 - 1913
ER -