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Open Access Highly Accessed Research

The effects of obesity, diabetes and metabolic syndrome on the hydrolytic enzymes of the endocannabinoid system in animal and human adipocytes

Jemma C Cable1, Garry D Tan2, Stephen PH Alexander3 and Saoirse E O'Sullivan1*

Author Affiliations

1 Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, Faculty of Medicine & Health Sciences, University of Nottingham, Royal Derby Hospital Centre, Uttoxeter Road, Derby, DE22 3DT, UK

2 NIHR Biomedical Research Centre, Oxford University Hospitals NHS Trust, OCDEM, Churchill Hospital, Oxford, UK

3 School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK

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Lipids in Health and Disease 2014, 13:43  doi:10.1186/1476-511X-13-43

Published: 4 March 2014

Abstract

Background

Circulating 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.

Methods

Using 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).

Results

FAAH 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.

Conclusions

FAAH 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.

Keywords:
Endocannabinoid; Adipose; Adipocyte; Obesity; Type 2 diabetes; Fatty acid amide hydrolase (FAAH); Monoacylglycerol lipase (MGL); Rat; Human