期刊论文详细信息
Lipids in Health and Disease
The activity of the endocannabinoid metabolising enzyme fatty acid amide hydrolase in subcutaneous adipocytes correlates with BMI in metabolically healthy humans
Saoirse E O'Sullivan2  Stephen PH Alexander1  Garry D Tan2  Jemma C Cable2 
[1] School of Biomedical Sciences, University of Nottingham, Nottingham, NG7 2UH, UK;School of Graduate Entry Medicine and Health, University of Nottingham, Derby, DE22 3DT, UK
关键词: Glucose;    Insulin;    BMI;    Adipocytes;    Human;    Monoacylglycerol lipase;    Fatty acid amide hydrolase;    Endocannabinoid system;   
Others  :  1212568
DOI  :  10.1186/1476-511X-10-129
 received in 2011-06-24, accepted in 2011-08-04,  发布年份 2011
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【 摘 要 】

Background

The endocannabinoid system (ECS) is a ubiquitously expressed signalling system, with involvement in lipid metabolism and obesity. There are reported changes in obesity of blood concentrations of the endocannabinoids anandamide (AEA) and 2-arachidonoylglcyerol (2-AG), and of adipose tissue expression levels of the two key catabolic enzymes of the ECS, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). Surprisingly, however, the activities of these enzymes have not been assayed in conditions of increasing adiposity. The aim of the current study was to investigate whether FAAH and MGL activities in human subcutaneous adipocytes are affected by body mass index (BMI), or other markers of adiposity and metabolism.

Methods

Subcutaneous abdominal mature adipocytes, fasting blood samples and anthropometric measurements were obtained from 28 metabolically healthy subjects representing a range of BMIs. FAAH and MGL activities were assayed in mature adipocytes using radiolabelled substrates. Serum glucose, insulin and adipokines were determined using ELISAs.

Results

MGL activity showed no relationship with BMI or other adiposity indices, metabolic markers (fasting serum insulin or glucose) or serum adipokine levels (adiponectin, leptin or resistin). In contrast, FAAH activity in subcutaneous adipocytes correlated positively with BMI and waist circumference, but not with skinfold thickness, metabolic markers or serum adipokine levels.

Conclusions

In this study, novel evidence is provided that FAAH activity in subcutaneous mature adipocytes increases with BMI, whereas MGL activity does not. These findings support the hypothesis that some components of the ECS are upregulated with increasing adiposity in humans, and that AEA and 2-AG may be regulated differently.

【 授权许可】

   
2011 Cable et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Devane W, Hanus L, Breuer A, Pertwee R, Stevenson L, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R: Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor. Science 1992, 258:1946-1949.
  • [2]Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, et al.: Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995, 50(1):83-90.
  • [3]Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, Yamashita A, Waku K: 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 1995, 215(1):89-97.
  • [4]Dinh TP, Freund TF, Piomelli D: A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Chem Phys Lipids 2002, 121(1-2):149-158.
  • [5]Cravatt B, Giang D, Mayfield S, Boger D, Lerner R, Gilula N: Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides. Nature 1996, 384:83-87.
  • [6]Engeli S: Dysregulation of the Endocannabinoid System in Obesity. J Neuroendocrinol 2008, 20(Suppl 1):110-115.
  • [7]Matias I, Gonthier MP, Orlando P, Martiadis V, De Petrocellis L, Cervino C, Petrosino S, Hoareau L, Festy F, Pasquali R, et al.: Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia. J Clin Endocrinol Metab 2006, 91(8):3171-3180.
  • [8]Gonthier M, Hoareau L, Festy F, Matias I, Valenti M, Bès-Houtmann S, Rouch C, Robert-Da Silva C, Chesne S, Lefebvre d'Hellencourt C, et al.: Identification of Endocannabinoids and Related Compounds in Human Fat Cells. Obesity 2007, 15(4):837-845.
  • [9]D'eon T, Pierce K, Roix J, Tyler A, Chen H, Teixeira S: The Role of Adipocyte Insulin Resistance in the Pathogenesis of Obesity-Related Elevations in Endocannabinoids. Diabetes 2008, 57:1262-1268.
  • [10]Bouaboula M, Hilairet S, Marchand J, Fajas L, Le Fur G, Casellas P: Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation. Eur J Pharmacol 2005, 517(3):174-181.
  • [11]Engeli S, Böhnke J, Feldpausch M, Gorzelniak K, Janke J, Bátkal S, Pacher P, Harvey-White J, Luft F, Sharma A, et al.: Activation of the Peripheral Endocannabinoid System in Human Obesity. Diabetes 2005, 54:2838-2834.
  • [12]Roche R, Hoareau L, Bes-Houtmann S, Gonthier MP, Laborde C, Baron JF, Haffaf Y, Cesari M, Festy F: Presence of the cannabinoid receptors, CB1 and CB2, in human omental and subcutaneous adipocytes. Histochem Cell Biol 2006, 126(2):177-187.
  • [13]Vettor R, Pagano C: The role of the endocannabinoid system in lipogenesis and fatty acid metabolism. Best Pract Res Clin Endocrinol Metab 2009, 23(1):51-63.
  • [14]Blüher M, Engeli S, Klöting N, Berndt J, Fasshauer M, Bátkai S, Pacher P, Schön M, Jordan J, Stumvoli M: Dysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity. Diabetes 2006, 55:3053-3060.
  • [15]Cote M, Matias I, Lemieux I, Petrosino S, Almeras N, Despres JP, Di Marzo V: Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int J Obes (Lond) 2007, 31(4):692-699.
  • [16]Di Marzo V, Cote M, Matias I, Lemieux I, Arsenault BJ, Cartier A, Piscitelli F, Petrosino S, Almeras N, Despres JP: Changes in plasma endocannabinoid levels in viscerally obese men following a 1 year lifestyle modification programme and waist circumference reduction: associations with changes in metabolic risk factors. Diabetologia 2009, 52(2):213-217.
  • [17]Pagano C, Pilon C, Calcagno A, Urbanet R, Rossato M, Milan G, Bianchi K, Rizzuto R, Bernante P, Federspil G, et al.: The endogenous cannabinoid system stimulates glucose uptake in human fat cells via phosphatidylinositol 3-kinase and calcium-dependent mechanisms. J Clin Endocrinol Metab 2007, 92(12):4810-4819.
  • [18]Murdolo G, Kempf K, Hammarstedt A, Herder C, Smith U, Jansson PA: Insulin differentially modulates the peripheral endocannabinoid system in human subcutaneous abdominal adipose tissue from lean and obese individuals. J Endocrinol Invest 2007, 30(8):RC17-21.
  • [19]Lofgren P, Sjolin E, Wahlen K, Hoffstedt J: Human adipose tissue cannabinoid receptor 1 gene expression is not related to fat cell function or adiponectin level. J Clin Endocrinol Metab 2007, 92(4):1555-1559.
  • [20]Sipe JC, Waalen J, Gerber A, Beutler E: Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int J Obes (Lond) 2005, 29(7):755-759.
  • [21]Spoto B, Fezza F, Parlongo G, Battista N, Sgro' E, Gasperi V, Zoccali C, Maccarrone M: Human adipose tissue binds and metabolizes the endocannabinoids anandamide and 2-arachidonoylglycerol. Biochimie 2006, 88:1889-1897.
  • [22]Norton K, Olds T: Measurement Techniques in Anthropometry. In Anthropometrica Edited by Norton K, Olds T. 1996, 47-53.
  • [23]Rodbell M: Metabolism of Isolated Fat Cells. J Biol Chem 1964, 239(2):375-380.
  • [24]Boldrup L, Wilson S, Barbier A, Fowler C: A simple stopped assay for fatty acid amide hydrolase avoiding the use of a chloroform extraction phase. J Biochem Biophys Meth 2004, 60:171-177.
  • [25]Bennetzen MF, Nielsen TS, Paulsen SK, Bendix J, Fisker S, Jessen N, Lund S, Richelsen B, Pedersen SB: Reduced cannabinoid receptor 1 protein in subcutaneous adipose tissue of obese. Eur J Clin Invest 2010, 40(2):121-126.
  • [26]Sun YX, Tsuboi K, Zhao LY, Okamoto Y, Lambert DM, Ueda N: Involvement of N-acylethanolamine-hydrolyzing acid amidase in the degradation of anandamide and other N-acylethanolamines in macrophages. Biochim Biophys Acta 2005, 1736(3):211-220.
  • [27]de Luis DA, Sagrado MG, Aller R, Izaola O, Conde R: Effects of C358A missense polymorphism of the degrading enzyme fatty acid amide hydrolase on weight loss, adipocytokines, and insulin resistance after 2 hypocaloric diets. Metabolism 2010, 59(9):1387-1392.
  • [28]Aurore A, Gonthier M-P: The endocannabinoid system: Its roles in energy balance and potential as a target for obesity treatment. Int J Biochem Cell Biol 2010, 42(11):1788-1801.
  • [29]Bermudez-Silva F, Viveros M, McPartland J, Rodriguez de Fonseca F: The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning? Pharm Biochem Behav 2010, 95(4):375-382.
  • [30]Annuzzi G, Piscitelli F, Di Marino L, Patti L, Giacco R, Costabile G, Bozzetto L, Riccardi G, Verde R, Petrosino S, et al.: Differential alterations of the concentrations of endocannabinoids and related lipids in the subcutaneous adipose tissue of obese diabetic patients. Lipids Health Dis 2010, 9:43. BioMed Central Full Text
  • [31]Després J, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodés-Cabau J, Bertrand O, Poirier P: Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arter Thromb Vasc Biol 2008, 28:1039-1049.
  • [32]de Luis D, Sagrado M, Aller R, Izaola O, Conde R, Romero E: C358A missense polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) and insulin resistance in patients with diabetes mellitus type 2. Diab Res Clin Pract 2010, 88(1):76-80.
  • [33]Maccarrone M, Di Rienzo M, Finazzi-Agrò A, Rossi A: Leptin activates the anandamide hydrolase promoter in human T lymphocytes through STAT3. J Biol Chem 2003, 278(15):13318-13324.
  • [34]Maccarrone M, Gasperi V, Fezza F, Finazzi-Agro A, Rossi A: Differential regulation of fatty acid amide hydrolase promoter in human immune cells and neuronal cells by leptin and progesterone. Eur J Biochem 2004, 271(23-24):4666-4676.
  • [35]Chanda P, Gao Y, Mark L, Btesh J, Strassle B, Lu P, Piesla M, Zhang M, Bingham B, Uveges A, et al.: Monoacylglycerol Lipase Activity Is a Critical Modulator of the Tone and Integrity of the Endocannabinoid System. Mol Pharmacol 2010, 78:996-1003.
  • [36]Schlosburg JE, Blankman JL, Long JZ, Nomura DK, Pan B, Kinsey SG, Nguyen PT, Ramesh D, Booker L, Burston JJ, et al.: Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neuro 2010, 13(9):1113-U1111.
  • [37]Bolinder J, Kerckhoffs D, Moberg E, Hagström-Toft E, Arner P: Rates of Skeletal Muscle and Adipose Tissue Glycerol Release in Nonobese and Obese Subjects. Diabetes 2000, 49:797-802.
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