Endocannabinoid tone is higher in healthy lean South Asian than white Caucasian men

Vasudev Kantae,Mario Van Der Stelt,Kimberly J Nahon,Amy C Harms,Patrick C N Rensen,Mariëtte R Boon,Maaike E Straat,Thomas Hankemeier,Leontine E H Bakker,Ingrid M Jazet

doi:10.1038/s41598-017-07980-5

Vasudev Kantae, Mario Van Der Stelt + Show 8 more

Open Access

https://doi.org/10.1038/s41598-017-07980-5

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Abstract

South Asians have a higher risk to develop obesity and related disorders compared to white Caucasians. This is likely in part due to their lower resting energy expenditure (REE) as related with less energy-combusting brown adipose tissue (BAT). Since overactivation of the endocannabinoid system is associated with obesity and low BAT activity, we hypothesized that South Asians have a higher endocannabinoid tone. Healthy lean white Caucasian (n = 10) and South Asian (n = 10) men were cold-exposed to activate BAT. Before and after cooling, REE was assessed and plasma was collected for analysis of endocannabinoids and lipids. At thermoneutrality, South Asians had higher plasma levels of 2-arachidonoylglycerol (2-AG; 11.36 vs 8.19 pmol/mL, p < 0.05), N-arachidonylethanolamine (AEA; 1.04 vs 0.89 pmol/mL, p = 0.05) and arachidonic acid (AA; 23.24 vs 18.22 nmol/mL, p < 0.001). After pooling of both ethnicities, plasma 2-AG but not AEA positively correlated with triglycerides (R2 = 0.32, p < 0.05) and body fat percentage (R2 = 0.18, p < 0.05). Interestingly, AA negative correlated with REE (R2 = 0.46, p < 0.001) and positively with body fat percentage (R2 = 0.33, p < 0.01). Cooling increased endocannabinoids. In conclusion, South Asian compared to white Caucasian men have higher endocannabinoid tone. This suggests that endocannabinoids may, at least in part, underlie the disadvantageous metabolic phenotype of South Asians later in life.

Highlights

South Asians originally descend from the sub-Indian continent and comprise about 24% of the world population
brown adipose tissue (BAT) volume was lower in South Asians as compared to white Caucasians (185 mL vs 303 mL), which was borderline significant (p = 0.052) while the difference was significant in the original study[25] due to larger sample size
We showed that healthy lean South Asian men without an apparent disadvantageous metabolic phenotype have higher circulating levels of endocannabinoids (2-AG and AEA) and their metabolite arachidonic acid (AA) compared to matched white Caucasian men

Summary

Introduction

South Asians originally descend from the sub-Indian continent and comprise about 24% of the world population This population is at higher risk for developing a disadvantageous metabolic phenotype consisting of obesity, dyslipidemia and insulin resistance compared to white Caucasians, making them more prone to develop type 2 diabetes (T2D) at a younger age and lower body mass index (BMI)[1]. Elevated circulating AEA and 2-AG levels have been reported in obese individuals[8,9,10] and circulating 2-AG levels are positively correlated with different measures of adiposity, including BMI and body fat percentage[8], supporting a causal role of the ECS in energy metabolism. We have previously shown that South Asian individuals have lower BAT volume and activity, as measured with [18F] fluorodeoxyglucose ([18F]FDG) PET-CT scanning, compared to white Caucasians, which might, at least in part, contribute to their high susceptibility to develop obesity and T2D25. The underlying cause of the decreased BAT volume in South Asians is still a question that remains

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