title: The effects of obesity, diabetes and metabolic syndrome on the hydrolytic enzymes of the endocannabinoid system in animal and human adipocytes.
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.
authors.forename: Jemma C
authors.initials: JC
authors.lastname: Cable
authors.forename: Garry D
authors.initials: GD
authors.lastname: Tan
authors.forename: Stephen P H
authors.initials: SP
authors.lastname: Alexander
authors.affiliation: 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. mbzso@nottingham.ac.uk.
authors.forename: Saoirse E
authors.initials: SE
authors.lastname: O'Sullivan
mesh_terms: D052438:Adipocytes, White / Q000201:enzymology*; D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D063388:Endocannabinoids / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology*; D008875:Middle Aged; D008994:Monoacylglycerol Lipases / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology*; D051381:Rats; D011924:Rats, Zucker; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D063388:Endocannabinoids; D008994:Monoacylglycerol Lipases; D000099252:Fatty Acid Amide Hydrolases