Abstract
BackgroundCirculating endocannabinoid levels are increased in obesity and diabetes. We have shown that fatty acid amide hydrolase (FAAH, an endocannabinoid hydrolysing enzyme) in subcutaneous adipose tissue positively correlates with BMI in healthy volunteers. The aim of the present study was to investigate whether the hydrolytic enzymes of the endocannabinoid system are affected by diabetes or metabolic syndrome in obesity.MethodsUsing radiolabelled substrates, FAAH and monoacylglycerol lipase (MGL) activities were assessed in adipocytes from various adipose depots in Zucker rats (n = 22, subcutaneous abdominal, visceral and epididymal) and bariatric patients (n = 28, subcutaneous abdominal and omental).ResultsFAAH activity was significantly increased in adipocytes of obese (Zucker Fatty) compared to Zucker lean rats (P < 0.05) but was not raised in the Zucker Diabetic Fatty rats (ZDF). MGL activity was raised in both Zucker Fatty (P < 0.001-0.01) and ZDF rats (P < 0.05) and was positively correlated with body weight and plasma glucose levels (P < 0.01). In bariatric patients (BMI range 37–58 kg.m2), there was a trend for MGL activity to correlate positively with BMI, reaching significance when type 2 diabetic patients were removed. FAAH and MGL activities in obese humans were not correlated with blood pressure, skinfold thicknesses, fasting glucose, insulin, HbA1c, triglycerides or cholesterol levels.ConclusionsFAAH in adipocytes is differentially altered in animal models of obesity and diabetes, while MGL activity is increased by both. However, in obese humans, FAAH or MGL activity in adipocytes is not affected by diabetes, dyslipidaemia or other markers of metabolic dysfunction. This suggests increased circulating levels of endocannabinoids are not a result of altered degradation in adipose tissue.
Highlights
The endocannabinoid system (ECS) is crucial in the regulation of metabolism and energy homeostasis
fatty acid amide hydrolase (FAAH) in adipocytes is differentially altered in animal models of obesity and diabetes, while monoacylglycerol lipase (MGL)
In obese humans, FAAH or MGL activity in adipocytes is not affected by diabetes, dyslipidaemia or other markers of metabolic dysfunction
Summary
The endocannabinoid system (ECS) is crucial in the regulation of metabolism and energy homeostasis (see [1,2,3,4]). Full list of author information is available at the end of the article [5] and 2-arachidonoylglycerol (2-AG) [6,7] are the two best characterised endocannabinoids, and the enzymes which degrade them are predominantly fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL) respectively [8,9]. It has been suggested that the ECS is upregulated in human obesity on the basis that plasma concentrations of AEA [10,11], 2-AG [12] and other acyl-ethanolamides [13] correlate positively with body mass index (BMI). We have shown that fatty acid amide hydrolase (FAAH, an endocannabinoid hydrolysing enzyme) in subcutaneous adipose tissue positively correlates with BMI in healthy volunteers. The aim of the present study was to investigate whether the hydrolytic enzymes of the endocannabinoid system are affected by diabetes or metabolic syndrome in obesity
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