Endocannabinoid regulation in white and brown adipose tissue following thermogenic activation

被引:49
作者
Krott, Lucia M. [1 ]
Piscitelli, Fabiana [2 ]
Heine, Markus [1 ]
Borrino, Simona [2 ]
Scheja, Ludger [1 ]
Silvestri, Cristoforo [2 ]
Heeren, Joerg [1 ]
Di Marzo, Vincenzo [2 ]
机构
[1] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, D-20246 Hamburg, Germany
[2] CNR, Endocannabinoid Res Grp, Inst Biomol Chem, I-80078 Naples, Italy
关键词
cannabinoids; protein kinases/protein kinase A; gene expression; phospholipids; ADAPTIVE THERMOGENESIS; ENERGY-EXPENDITURE; FAT; RECEPTORS; ADIPOCYTES; SYSTEM; NEURONS; MASS; AGE;
D O I
10.1194/jlr.M065227
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The endocannabinoids and their main receptor, cannabinoid type-1 (CB1), suppress intracellular cyclic AMP levels and have emerged as key players in the control of energy metabolism. CB1 agonists and blockers have been reported to influence the thermogenic function of white and brown adipose tissue (WAT and BAT), affecting body weight through the inhibition and stimulation of energy expenditure, respectively. The purpose of the current study was to investigate the regulation of the endocannabinoid system in WAT and BAT following exposure to either cold or specific agonism of beta 3-adrenoceptors using CL316,243 (CL), conditions known to cause BAT activation and WAT browning. To address this question, we performed quantitative PCRbased mRNA profiling of genes important for endocannabinoid synthesis, degradation, and signaling, and determined endocannabinoid levels by LC-MS in WAT and BAT of control, cold-exposed, and CL-treated wild-type mice as well as primary brown adipocytes. Treatment with CL and exposure to cold caused an upregulation of endocannabinoid levels and biosynthetic enzymes in WAT. Acute beta 3-adrenoceptor activation increased endocannabinoids and a subset of genes of biosynthesis in BAT and primary brown adipocytes. We suggest that the cold-mediated increase in endocannabinoid tone is part of autocrine negative feed-back mechanisms controlling beta 3-adrenoceptor-induced BAT activation and WAT browning.
引用
收藏
页码:464 / 473
页数:10
相关论文
共 36 条
[1]   The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake [J].
Addy, Carol ;
Wright, Hamish ;
Van Laere, Koen ;
Gantz, Ira ;
Erondu, Ngozi ;
Musser, Bret J. ;
Lu, Kaifeng ;
Yuan, Jinyu ;
Sanabria-Bohorquez, Sandra M. ;
Stoch, Aubrey ;
Stevens, Cathy ;
Fong, Tung M. ;
De Lepeleire, Inge ;
Cilissen, Caroline ;
Cote, Josee ;
Rosko, Kim ;
Gendrano, Isaias N., III ;
Nguyen, Allison Martin ;
Gumbiner, Barry ;
Rothenberg, Paul ;
de Hoon, Jan ;
Bormans, Guy ;
Depre, Marleen ;
Eng, Wai-Si ;
Ravussin, Eric ;
Klein, Samuel ;
Blundell, John ;
Herman, Gary A. ;
Burns, H. Donald ;
Hargreaves, Richard J. ;
Wagner, John ;
Gottesdiener, Keith ;
Amatruda, John M. ;
Heymsfield, Steven B. .
CELL METABOLISM, 2008, 7 (01) :68-78
[2]   Cannabinoid receptor 1 (CB1) antagonism enhances glucose utilisation and activates brown adipose tissue in diet-induced obese mice [J].
Bajzer, M. ;
Olivieri, M. ;
Haas, M. K. ;
Pfluger, P. T. ;
Magrisso, I. J. ;
Foster, M. T. ;
Tschoep, M. H. ;
Krawczewski-Carhuatanta, K. A. ;
Cota, D. ;
Obici, S. .
DIABETOLOGIA, 2011, 54 (12) :3121-3131
[3]   Altered endocannabinoid signalling after a high-fat diet in Apoe-/- mice: relevance to adipose tissue inflammation, hepatic steatosis and insulin resistance [J].
Bartelt, A. ;
Orlando, P. ;
Mele, C. ;
Ligresti, A. ;
Toedter, K. ;
Scheja, L. ;
Heeren, J. ;
Di Marzo, V. .
DIABETOLOGIA, 2011, 54 (11) :2900-2910
[4]   Adipose tissue browning and metabolic health [J].
Bartelt, Alexander ;
Heeren, Joerg .
NATURE REVIEWS ENDOCRINOLOGY, 2014, 10 (01) :24-36
[5]   The holy grail of metabolic disease: brown adipose tissue [J].
Bartelt, Alexander ;
Heeren, Joerg .
CURRENT OPINION IN LIPIDOLOGY, 2012, 23 (03) :190-195
[6]   Brown adipose tissue activity controls triglyceride clearance [J].
Bartelt, Alexander ;
Bruns, Oliver T. ;
Reimer, Rudolph ;
Hohenberg, Heinz ;
Ittrich, Harald ;
Peldschus, Kersten ;
Kaul, Michael G. ;
Tromsdorf, Ulrich I. ;
Weller, Horst ;
Waurisch, Christian ;
Eychmueller, Alexander ;
Gordts, Philip L. S. M. ;
Rinninger, Franz ;
Bruegelmann, Karoline ;
Freund, Barbara ;
Nielsen, Peter ;
Merkel, Martin ;
Heeren, Joerg .
NATURE MEDICINE, 2011, 17 (02) :200-U93
[7]   Peripheral cannabinoid 1 receptor blockade activates brown adipose tissue and diminishes dyslipidemia and obesity [J].
Boon, Mariette R. ;
Kooijman, Sander ;
van Dam, Andrea D. ;
Pelgrom, Leonard R. ;
Berbee, Jimmy F. P. ;
Visseren, Cheryl A. R. ;
van Aggele, Robin C. ;
van den Hoek, Anita M. ;
Sips, Hetty C. M. ;
Lombes, Marc ;
Havekes, Louis M. ;
Tamsma, Jouke T. ;
Guigas, Bruno ;
Meijer, Onno C. ;
Jukema, J. Wouter ;
Rensen, Patrick C. N. .
FASEB JOURNAL, 2014, 28 (12) :5361-5375
[8]   Brown adipose tissue: Function and physiological significance [J].
Cannon, B ;
Nedergaard, J .
PHYSIOLOGICAL REVIEWS, 2004, 84 (01) :277-359
[9]   Cannabinoid Type 1 (CB1) Receptors on Sim1-Expressing Neurons Regulate Energy Expenditure in Male Mice [J].
Cardinal, Pierre ;
Bellocchio, Luigi ;
Guzman-Quevedo, Omar ;
Andre, Caroline ;
Clark, Samantha ;
Elie, Melissa ;
Leste-Lasserre, Thierry ;
Gonzales, Delphine ;
Cannich, Astrid ;
Marsicano, Giovanni ;
Cota, Daniela .
ENDOCRINOLOGY, 2015, 156 (02) :411-418
[10]   Identification and Importance of Brown Adipose Tissue in Adult Humans. [J].
Cypess, Aaron M. ;
Lehman, Sanaz ;
Williams, Gethin ;
Tal, Ilan ;
Rodman, Dean ;
Goldfine, Allison B. ;
Kuo, Frank C. ;
Palmer, Edwin L. ;
Tseng, Yu-Hua ;
Doria, Alessandro ;
Kolodny, Gerald M. ;
Kahn, C. Ronald .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 360 (15) :1509-1517