Gene Expression of Endocannabinoid System Components in Skeletal Muscle and Adipose Tissue of South Asians and White Caucasians with Overweight.

ABSTRACT

OBJECTIVE: The study aimed to investigate whether markers of endocannabinoid signaling differed between men with overweight of South Asian and white Caucasian descent. METHODS: We included South Asian (n = 10) and white Caucasian (n = 10) men with overweight and prediabetes aged 35 to 50 years. Plasma samples were analyzed for endocannabinoids, their congeners, and lipids. In white adipose tissue (WAT) and skeletal muscle biopsies, mRNA expression of genes involved in the endocannabinoid system (ECS) was assessed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fasting lipid oxidation and glucose oxidation were determined with indirect calorimetry. RESULTS: Compared to white Caucasians, South Asians had higher levels of plasma 2-linoleoyl glycerol (P < 0.01) and N-linoleoylethanolamine (P < 0.05). Interestingly, in skeletal muscle of South Asians, expression of cannabinoid receptors CB1 and CB2 was 10-fold lower (P < 0.001) and that of the endocannabinoid degradation enzyme fatty acid amide hydrolase 2 (FAAH2) was 5-fold lower (P < 0.001) compared to white Caucasians. Expression of genes involved in the ECS in WAT were not different between the two ethnicities. After pooling of both ethnicities, plasma 2-arachidonoylglycerol (2-AG) positively correlated with plasma triglycerides (R = 0.77, P < 0.001) and lipid oxidation (R = 0.55, P < 0.05). CONCLUSIONS: South Asian men with overweight have higher plasma 2-linoleoyl glycerol and N-linoleoylethanolamine levels and lower expression of CB receptors and the endocannabinoid degradation enzyme FAAH2 in skeletal muscle compared to white Caucasians.