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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.

Brown adipose tissue (BAT) activity is induced when humans are exposed to cold. Therefore, cold exposure prior to the 18F-FDG-PET/CT scan is used as a tool to quantify BAT. Several cooling protocols, including fixed and personalized ones are currently in use. The aim of the present study was to determine the effect of a new personalized cooling protocol where the shivering threshold was measured on a separate day, on BAT volume and activity in young adults. A total of 47 adults (n = 28 women) aged 22 ± 2 years participated in the study. We determined participants' shivering threshold (visually and self-reported) using a water perfused cooling vest in an air-conditioned cold room. 48–72 h later, participants wore the cooling vest set at ~4°C above the shivering threshold for 60 min prior to injection of 18F-FDG and ~5°C above the shivering threshold for ~60 min after injection, until PET/CT scan. We quantified BAT following BARCIST 1.0 recommendations. We identified 40 participants (85%, n = 25 women) as PET+ and 7 (n = 3 women) as PET–. The PET+ group presented significantly higher BAT volume and activity than PET– group (all P < 0.05). PET+ women had higher BAT mean activity than PET+ men (SUVmean: 5.0 ± 1.6 vs. 3.6 ± 0.9 g/ml respectively, P = 0.003), and there were no significant sex differences in BAT volume (P = 0.161). A total of 9 out of 47 participants did not shiver during the shivering threshold test. Our findings are similar to previous cold-stimulated human BAT studies; therefore, we conclude that our personalized cooling protocol is able to activate BAT in young adults.